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Enzymatic reactionDetermination of the cytotoxicity after contact of the test element. The assay is based on the ability of viable cells to incorporate and bind the supravital neutral red dye in the lysosomes.Early stage fertile hens eggs are used to determine if a substance is a severe ocular irritant or corrosive. Effects are measured by the onset of (1) hemorrhage; (2) coagulation; and (3) vessel lysis.Because early stage eggs are used this test is considered a non-animal test. Semi-quantitative assessment of the cytotoxicity (loss of viable cells) due to a test product after diffusion on agarose gel in contact with a fibroblasts monolayer. MTT, a yellow tetrazole dye that is reduced to an insoluble purple formazan product by the mitochondria of living cells, is used to evaluate cells viability.Assessment of the ability of a test chemical to induce cytotoxicity in a RhCE tissue. Tissue viability is measured by enzymatic conversion of the vital dye MTT by the viable cells of the tissue into a blue MTT formazan salt. Assessment of the ability of a test chemical to induce cytotoxicity in a RhCE tissue. Tissue viability is measured by enzymatic conversion of the vital dye MTT by the viable cells of the tissue into a blue MTT formazan salt. The method provides a UV spectral absorbance curve from which the UVA Protection Factor (UVA-PF) is determined.Test on reconstructed human epidermis (RHE). The cellular viability is measured by the the enzymatic change of the MTT colorant in the blue Formazan salt, measured after the tissue extraction.An adequate substrate on which the product has been spread is used. Measures are made by means of a spectrophotometric method.A UV spectral absorbance curve allows us to determine the Critical Wavelength (CW).This test is based upon an in vitro spectrophotometric measurement technique. After that, the product may be labeled as «Broad Spectrum» with SPF value on the front label.The level of photostability is measured from the collective effectiveness of UVA and UVB before and after UV exposure. This method consists in evaluating the IR protection levels expressed by the IR-CW (UV/VIS/IR balance) and the % IR (percentage of intensity of IR protection) from a sunscreen product through the full spectrum (from 290 nm to 2500 nm) measured by means of a spectrophotometric methodThis method consists in evaluating the Blue Light protection levels expressed by the BL-CW (UV/VIS balance) and the % BL (percentage of intensity of BL protection) from a sunscreen product through the spectrum (from 290 nm to 500 nm) measured by means of a spectrophotometric method. The method consists in assessing the Sun Protection Factor (SPF) before and after water immersion. The method consists in assessing the Sun Protection Factor (SPF) before and after double water immersions.Realisation of an automated textile rubbing on surface substrates with a controled pressure, speed and time. This method is based on the comparison of the Sun Protection Factor (SPF) on a dry then a wet substrate and the calculation of Wet Skin percentage. A spectrophotometric method, if the sunscreen product preserves its UV protection in extreme conditions.An adequate substrate on which the product has been spread is used. Measures are made by means of a spectrophotometric method.The method is based upon an in vitro spectrophotometric measurement technique in which the tested product is spread using adequate substrate.A test product is put in contact with calves’ corneas. The measurement of the opacity and permeability of the corneas to fluorescein is used to evaluate the corneal damage and, therefore, the irritant potential of the test product.The test substance is applied on the cornea of an enucleated chicken eye’s. Toxic effects to the cornea are measured through several parameters.The test substance is put in contact with a confluent monolayer of Statens Seruminstitut Rabbit Cornea (SIRC) cells. After five minutes, cytotoxicity is measured.to be completedThe test product is put in contact with a water-insoluble protein, zein protein, obtained from yellow corn, that is similar to keratin present in the skin and hair. Zein protein solubilization (= denaturation) gives information about the test product : the irritation potential of the product is directly proportional to the quantity of dissolved (denaturated) proteins.The test material (solid or liquid) is applied uniformly and topically to a three-dimensional human skin model. Corrosive materials are identified by their ability to produce a decrease in cell viability below defined threshold levels at specified exposure periods. https://www.oecd-ilibrary.org/fr/environment/test-no-431-in-vitro-skin-corrosion-human-skin-model-test_9789264071148-enThis method evaluate photo-cytotoxicity by the relative reduction in viability of cells exposed to the chemical in the presence versus absence of light. Cytotoxicity in this test is expressed as a concentration-dependent reduction of the uptake of the Vital dye Neutral Red (NR) when measured 24 hours after treatment with the test chemical and irradiation. https://www.oecd-ilibrary.org/fr/environment/test-no-432-in-vitro-3t3-nru-phototoxicity-test_9789264071162-enThe acute toxic response is defined after the first exposure of the reconstructed skin model to certain chemicals and subsequent exposure to light. The DPRA is proposed to address the molecular initiating event leading to the skin sensitisation, namely protein reactivity, by quantifying the reactivity of test chemicals towards model synthetic peptides containing either lysine or cysteine. https://www.oecd-ilibrary.org/fr/environment/test-no-442c-in-chemico-skin-sensitisation_9789264229709-enOECD 442D describes 2 test methods allowing the discrimination between skin sensitisers and non-sensitisers by assessing keratinocyte activation under test chemical application. KeratinoSens™ test method uses an immortalised adherent cell line derived from human keratinocytes which stably harbours a luciferase reporter gene under the control of the antioxidant response element (ARE) of the human AKR1C2 gene known to be up-regulated by skin sensitisers via the nuclear factor Nrf2. The principle of the LuSens test method is similar but uses the ARE of the rat NQO1 gene known to be up-regulated by contact sensitisers. In both cases, the luciferase signal intensity reflects the level of keratinocyte activation by sensitisers. These test methods either quantify the change in the expression of cell surface marker(s) associated with the process of activation of monocytes and DC following exposure to sensitisers (e.g. CD54, CD86) or the changes in IL-8 expression, a cytokine associated with the activation of DC. https://www.oecd-ilibrary.org/fr/environment/test-no-442e-in-vitro-skin-sensitisation_9789264264359-enQuantitatively measurement quantitatively the over expression of 62 specific biomarkers of skin sensitization and irritation by RT-PCRSuspensions of bacterial cells are exposed to the test substance in the presence and in the absence of an exogenous metabolic activation system. The principle of this test is that it detects mutations which revert mutations present in the test strains and restore the functional capability of the bacteria to synthesize an essential amino acid. The revertant bacteria are detected by their ability to grow in the absence of the amino acid required by the parent test strain. This method allows the detection of base substitution or frame-shifting point mutations. The assay detects the activity of clastogenic and aneugenic test substances in cells that have undergone cell division during or after exposure to the test substance.Cytotoxicity is determined by measuring the relative cloning efficiency (survival) or relative total growth of the cultures after the treatment period. Tests Using the Thymidine Kinase Gene.Purpose : identify agents that cause structural chromosome aberrations (chromosome or chromatid aberrations) in cultured mammalian somatic cells. Cell cultures are exposed to at least three concentrations of the test substance. At predetermined intervals after exposure, metaphase cells are analysed microscopically for the presence of chromosome aberrations. Caspase-14 is a protease initially expressed in the suprabasal layers of the epidermis in an inactive form and then converted into an active form essentially present in the stratum corneum. It is involved in the terminal differentiation of keratinocytes and thus the establishment of the skin barrier, but also in the filaggrin proteolysis and the formation of NMF (Natural Moisturizing Factor) allowing the hydration and thus the functionality of the skin barrier as well as in the protection of the skin against UVB. Caspase-14 is a protease initially expressed in the suprabasal layers of the epidermis in an inactive form and then converted into an active form essentially present in the stratum corneum. It is involved in the terminal differentiation of keratinocytes and thus the establishment of the skin barrier, but also in the filaggrin proteolysis and the formation of NMF (Natural Moisturizing Factor) allowing the hydration and thus the functionality of the skin barrier as well as in the protection of the skin against UVB. Caspase-14 is a protease initially expressed in the suprabasal layers of the epidermis in an inactive form and then converted into an active form essentially present in the stratum corneum. It is involved in the terminal differentiation of keratinocytes and thus the establishment of the skin barrier, but also in the filaggrin proteolysis and the formation of NMF (Natural Moisturizing Factor) allowing the hydration and thus the functionality of the skin barrier as well as in the protection of the skin against UVB. Claudin 1 (CLDN-1) and 4 (CLDN-4) are transmembrane proteins constituting the tight junctions which maintain the keratinocytes closely associated in the epidermis. A decrease of Claudin level beyond a threshold may alter skin barrier function and induce skin inflammation. This has been observed in some atopic dermatitis cases. Claudin 1 (CLDN-1) and 4 (CLDN-4) are transmembrane proteins constituting the tight junctions which maintain the keratinocytes closely associated in the epidermis. A decrease of Claudin level beyond a threshold may alter skin barrier function and induce skin inflammation. This has been observed in some atopic dermatitis cases. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Claudin 1 (CLDN-1) and 4 (CLDN-4) are transmembrane proteins constituting the tight junctions which maintain the keratinocytes closely associated in the epidermis. A decrease of Claudin level beyond a threshold may alter skin barrier function and induce skin inflammation. This has been observed in some atopic dermatitis cases. E-Cadherin is a protein belonging to adherens junctions that allow cell-cell adhesion. Its adhesive activity is also crucial for the assembly of other junctional complexes such as tight junctions and involved in the polarity of the keratinocytes and the epidermis. E-adherin is therefore crucial for the establishment of the skin barrier. E-Cadherin is a protein belonging to adherens junctions that allow cell-cell adhesion. Its adhesive activity is also crucial for the assembly of other junctional complexes such as tight junctions and involved in the polarity of the keratinocytes and the epidermis. E-adherin is therefore crucial for the establishment of the skin barrier. E-Cadherin is a protein belonging to adherens junctions that allow cell-cell adhesion. Its adhesive activity is also crucial for the assembly of other junctional complexes such as tight junctions and involved in the polarity of the keratinocytes and the epidermis. E-adherin is therefore crucial for the establishment of the skin barrier. E-Cadherin is a protein belonging to adherens junctions that allow cell-cell adhesion. Its adhesive activity is also crucial for the assembly of other junctional complexes such as tight junctions and involved in the polarity of the keratinocytes and the epidermis. E-adherin is therefore crucial for the establishment of the skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Filaggrin is a marker of the keratinocyte terminal differentiation. It derives from the cleavage of profilaggrin, a protein synthesised in granular keratinocytes, and associates with keratins inside the corneocytes to form, with other proteins, a resistant protein assembly which characterises the stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin also produces a mixture of amino acids constituting the NMF (Natural Moisturizing Factor) and thus participates in the hydration of the skin which is also involved in the barrier function.Filaggrin is a marker of the keratinocyte terminal differentiation. It derives from the cleavage of profilaggrin, a protein synthesised in granular keratinocytes, and associates with keratins inside the corneocytes to form, with other proteins, a resistant protein assembly which characterises the stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin also produces a mixture of amino acids constituting the NMF (Natural Moisturizing Factor) and thus participates in the hydration of the skin which is also involved in the barrier function.Filaggrin is a marker of the keratinocyte terminal differentiation. It derives from the cleavage of profilaggrin, a protein synthesised in granular keratinocytes, and associates with keratins inside the corneocytes to form, with other proteins, a resistant protein assembly which characterises the stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin also produces a mixture of amino acids constituting the NMF (Natural Moisturizing Factor) and thus participates in the hydration of the skin which is also involved in the barrier function.Filaggrin is a marker of the keratinocyte terminal differentiation. It derives from the cleavage of profilaggrin, a protein synthesised in granular keratinocytes, and associates with keratins inside the corneocytes to form, with other proteins, a resistant protein assembly which characterises the stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin also produces a mixture of amino acids constituting the NMF (Natural Moisturizing Factor) and thus participates in the hydration of the skin which is also involved in the barrier function. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Involucrin is a protein whose synthesis is stimulated by an increase in intracellular calcium level. Produced in the cytoplasm of stratum granulosum keratinocytes, it is involved in the initiation of horny envelope formation where its crosslinking with envoplakin / peripakin dimers is allowed by transglutaminase 1. It is therefore a marker of terminal differentiation and plays a major role in skin barrier function. Involucrin is a protein whose synthesis is stimulated by an increase in intracellular calcium level. Produced in the cytoplasm of stratum granulosum keratinocytes, it is involved in the initiation of horny envelope formation where its crosslinking with envoplakin / peripakin dimers is allowed by transglutaminase 1. It is therefore a marker of terminal differentiation and plays a major role in skin barrier function. Involucrin is a protein whose synthesis is stimulated by an increase in intracellular calcium level. Produced in the cytoplasm of stratum granulosum keratinocytes, it is involved in the initiation of horny envelope formation where its crosslinking with envoplakin / peripakin dimers is allowed by transglutaminase 1. It is therefore a marker of terminal differentiation and plays a major role in skin barrier function. Involucrin is a protein whose synthesis is stimulated by an increase in intracellular calcium level. Produced in the cytoplasm of stratum granulosum keratinocytes, it is involved in the initiation of horny envelope formation where its crosslinking with envoplakin / peripakin dimers is allowed by transglutaminase 1. It is therefore a marker of terminal differentiation and plays a major role in skin barrier function. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Laminin 332 (previously called Laminin V) is an essential component of the dermal-epidermal junction. It allows epidermal attachment and modulates the differentiation of epidermal stem cells. Thus, Laminin 332 synthesis may modulate the skin barrier integrity and its function.Laminin 332 (previously called Laminin V) is an essential component of the dermal-epidermal junction. It allows epidermal attachment and modulates the differentiation of epidermal stem cells. Thus, Laminin 332 synthesis may modulate the skin barrier integrity and its function.Laminin 332 (previously called Laminin V) is an essential component of the dermal-epidermal junction. It allows epidermal attachment and modulates the differentiation of epidermal stem cells. Thus, Laminin 332 synthesis may modulate the skin barrier integrity and its function.Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the skin barrier function. Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the skin barrier function. Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the skin barrier function. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the skin barrier function. Occludin is a transmembrane protein located at the tight junctions (TJs) of the granular layer. It is therefore a marker of keratinocyte differentiation and plays a role in skin barrier function. It also plays a role in the regeneration of the epidermis. A defect in the expression or distribution of this protein can lead to an alteration of the skin barrier.Occludin is a transmembrane protein located at the tight junctions (TJs) of the granular layer. It is therefore a marker of keratinocyte differentiation and plays a role in skin barrier function. It also plays a role in the regeneration of the epidermis. A defect in the expression or distribution of this protein can lead to an alteration of the skin barrier.Occludin is a transmembrane protein located at the tight junctions (TJs) of the granular layer. It is therefore a marker of keratinocyte differentiation and plays a role in skin barrier function. It also plays a role in the regeneration of the epidermis. A defect in the expression or distribution of this protein can lead to an alteration of the skin barrier.Occludin is a transmembrane protein located at the tight junctions (TJs) of the granular layer. It is therefore a marker of keratinocyte differentiation and plays a role in skin barrier function. It also plays a role in the regeneration of the epidermis. A defect in the expression or distribution of this protein can lead to an alteration of the skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Periplakin (PPL) is a small protein which expression increases during keratinocyte differentiation. With envoplakin [ENV], it connects intermediate filaments (including cytokeratins) to membrane and cellular junctions. Thus, it is involved in the assembly of the cornified envelope and therefore skin barrier formation.Periplakin (PPL) is a small protein which expression increases during keratinocyte differentiation. With envoplakin [ENV], it connects intermediate filaments (including cytokeratins) to membrane and cellular junctions. Thus, it is involved in the assembly of the cornified envelope and therefore skin barrier formation.Periplakin (PPL) is a small protein which expression increases during keratinocyte differentiation. With envoplakin [ENV], it connects intermediate filaments (including cytokeratins) to membrane and cellular junctions. Thus, it is involved in the assembly of the cornified envelope and therefore skin barrier formation.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Psoriasin (S100A7) is an antimicrobial peptide produced by keratinocytes which limits the development of pathogenic microorganisms. It is also involved in various processes including skin inflammation and keratinocyte differentiation. A modulation of its expression (e.g. psoriasis) affects the composition of the skin microbiota and may alter epidermal differentiation and thus the skin barrier. Psoriasin (S100A7) is an antimicrobial peptide produced by keratinocytes which limits the development of pathogenic microorganisms. It is also involved in various processes including skin inflammation and keratinocyte differentiation. A modulation of its expression (e.g. psoriasis) affects the composition of the skin microbiota and may alter epidermal differentiation and thus the skin barrier. Psoriasin (S100A7) is an antimicrobial peptide produced by keratinocytes which limits the development of pathogenic microorganisms. It is also involved in various processes including skin inflammation and keratinocyte differentiation. A modulation of its expression (e.g. psoriasis) affects the composition of the skin microbiota and may alter epidermal differentiation and thus the skin barrier. Psoriasin (S100A7) is an antimicrobial peptide produced by keratinocytes which limits the development of pathogenic microorganisms. It is also involved in various processes including skin inflammation and keratinocyte differentiation. A modulation of its expression (e.g. psoriasis) affects the composition of the skin microbiota and may alter epidermal differentiation and thus the skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.to be completedTransglutaminase (TGM) is a calcium-dependent enzyme catalyzing an intermolecular isopeptide bond formation between proteins. 9 TGMs have been identified in human. Among them, TGM 1, 3 and 5 are known to participate in the covalent cross-linking of constitutive proteins such as loricrin and involucrin ioccuring during the cornification process. Thus, TGMs are required for skin barrier function. to be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.α6β4 integrins are transmembrane proteins playing a key role in the formation and stabilization of junctional adhesion complexes called hemidesmosomes. They are connected to the intermediate filament system of basal keratinocytes and the laminin 332 of the dermal-epidermal junction. They are also involved in the regulation of a variety of signaling processes allowing for example keratinocyte migration. A defect in the expression of those molecules may therefore impair skin integrity and barrier function. Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in keratinocyte survival and differentiation. A decrease of Perlecan, which occurs for example during skin aging, may therefore induce an alteration of skin barrier integrity. Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in keratinocyte survival and differentiation. A decrease of Perlecan, which occurs for example during skin aging, may therefore induce an alteration of skin barrier integrity. Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in keratinocyte survival and differentiation. A decrease of Perlecan, which occurs for example during skin aging, may therefore induce an alteration of skin barrier integrity. Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in keratinocyte survival and differentiation. A decrease of Perlecan, which occurs for example during skin aging, may therefore induce an alteration of skin barrier integrity. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Langerin (CD207) is a C-type lectin receptor expressed on Langerhans cells and a specific population of dermal dendritic cells. It may therefore be used as a marker of those cells. It is also directly involved in specific processes such as the skin induced tolerance to protein antigens. Langerin (CD207) is a C-type lectin receptor expressed on Langerhans cells and a specific population of dermal dendritic cells. It may therefore be used as a marker of those cells. It is also directly involved in specific processes such as the skin induced tolerance to protein antigens. Langerin (CD207) is a C-type lectin receptor expressed on Langerhans cells and a specific population of dermal dendritic cells. It may therefore be used as a marker of those cells. It is also directly involved in specific processes such as the skin induced tolerance to protein antigens. Langerin (CD207) is a C-type lectin receptor expressed on Langerhans cells and a specific population of dermal dendritic cells. It may therefore be used as a marker of those cells. It is also directly involved in specific processes such as the skin induced tolerance to protein antigens. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Skin contains at least 20 matrix metalloproteinase (MMP) which degrade extracellular matrix (ECM) component under normal circumstances and thus allow ECM remodelling. A high MMP level has also been correlated with various skin inflammatory diseases as some peptides released by the activity of some MMPs (including MMP-2, MMP-9 or MMP-12) and called matrikines are able to induce inflammatory processes. Skin contains at least 20 matrix metalloproteinase (MMP) which degrade extracellular matrix (ECM) component under normal circumstances and thus allow ECM remodelling. A high MMP level has also been correlated with various skin inflammatory diseases as some peptides released by the activity of some MMPs (including MMP-2, MMP-9 or MMP-12) and called matrikines are able to induce inflammatory processes. Skin contains at least 20 matrix metalloproteinase (MMP) which degrade extracellular matrix (ECM) component under normal circumstances and thus allow ECM remodelling. A high MMP level has also been correlated with various skin inflammatory diseases as some peptides released by the activity of some MMPs (including MMP-2, MMP-9 or MMP-12) and called matrikines are able to induce inflammatory processes. Skin contains at least 20 matrix metalloproteinase (MMP) which degrade extracellular matrix (ECM) component under normal circumstances and thus allow ECM remodelling. A high MMP level has also been correlated with various skin inflammatory diseases as some peptides released by the activity of some MMPs (including MMP-2, MMP-9 or MMP-12) and called matrikines are able to induce inflammatory processes. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes and involved in many functions including wound healing, cell proliferation, differentiation, apoptosis, but also immune responses with cytokine/chemokine production, neutrophile migration and inflammation. Expressed at a low level in healthy skin, psoriasin is overexpressed in some tumors and inflammatory diseases such a psoriasis.Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes and involved in many functions including wound healing, cell proliferation, differentiation, apoptosis, but also immune responses with cytokine/chemokine production, neutrophile migration and inflammation. Expressed at a low level in healthy skin, psoriasin is overexpressed in some tumors and inflammatory diseases such a psoriasis.Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes and involved in many functions including wound healing, cell proliferation, differentiation, apoptosis, but also immune responses with cytokine/chemokine production, neutrophile migration and inflammation. Expressed at a low level in healthy skin, psoriasin is overexpressed in some tumors and inflammatory diseases such a psoriasis.Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes and involved in many functions including wound healing, cell proliferation, differentiation, apoptosis, but also immune responses with cytokine/chemokine production, neutrophile migration and inflammation. Expressed at a low level in healthy skin, psoriasin is overexpressed in some tumors and inflammatory diseases such a psoriasis. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. Its expression can be induced by cytokines, growth factors or microbial factors and it has been found at a high level in cutaneous inflammatory diseases such as psoriasis or atopic dermatitis. It exhibits a potent antimicrobial activity against various microorganisms including bacteria and virus, thus controlling skin microbiota composition. RNase 7 also exerts immunomodulatory activities. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. Its expression can be induced by cytokines, growth factors or microbial factors and it has been found at a high level in cutaneous inflammatory diseases such as psoriasis or atopic dermatitis. It exhibits a potent antimicrobial activity against various microorganisms including bacteria and virus, thus controlling skin microbiota composition. RNase 7 also exerts immunomodulatory activities. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. Its expression can be induced by cytokines, growth factors or microbial factors and it has been found at a high level in cutaneous inflammatory diseases such as psoriasis or atopic dermatitis. It exhibits a potent antimicrobial activity against various microorganisms including bacteria and virus, thus controlling skin microbiota composition. RNase 7 also exerts immunomodulatory activities. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. Its expression can be induced by cytokines, growth factors or microbial factors and it has been found at a high level in cutaneous inflammatory diseases such as psoriasis or atopic dermatitis. It exhibits a potent antimicrobial activity against various microorganisms including bacteria and virus, thus controlling skin microbiota composition. RNase 7 also exerts immunomodulatory activities. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification avoiding the development of inflammatory diseases such as atopic dermatitis. Moreover, it is required for the production of many cytokines and the recruitment of macrophages, neutrophils and mast cells. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification avoiding the development of inflammatory diseases such as atopic dermatitis. Moreover, it is required for the production of many cytokines and the recruitment of macrophages, neutrophils and mast cells. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification avoiding the development of inflammatory diseases such as atopic dermatitis. Moreover, it is required for the production of many cytokines and the recruitment of macrophages, neutrophils and mast cells. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification avoiding the development of inflammatory diseases such as atopic dermatitis. Moreover, it is required for the production of many cytokines and the recruitment of macrophages, neutrophils and mast cells. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Decorin is a key extracellular matrix component playing a role in fibrotic disorders, in cancer cancer as it present antitumor, antimetastatic and antiangiogenic properties, but also in inflammation as it can stimulate pro-inflammatory cytokines such as TNFalpha or IL-6. Initially identified as a natural inhibitor of TGF-β, soluble decorin is also able to target EGFR, IGF-IR, VEGFR2, and PDGFR, thus modulating various signaling pathways and inducing caveosomal internalization and receptor degradation. Decorin is a key extracellular matrix component playing a role in fibrotic disorders, in cancer cancer as it present antitumor, antimetastatic and antiangiogenic properties, but also in inflammation as it can stimulate pro-inflammatory cytokines such as TNFalpha or IL-6. Initially identified as a natural inhibitor of TGF-β, soluble decorin is also able to target EGFR, IGF-IR, VEGFR2, and PDGFR, thus modulating various signaling pathways and inducing caveosomal internalization and receptor degradation. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Decorin is a key extracellular matrix component playing a role in fibrotic disorders, in cancer cancer as it present antitumor, antimetastatic and antiangiogenic properties, but also in inflammation as it can stimulate pro-inflammatory cytokines such as TNFalpha or IL-6. Initially identified as a natural inhibitor of TGF-β, soluble decorin is also able to target EGFR, IGF-IR, VEGFR2, and PDGFR, thus modulating various signaling pathways and inducing caveosomal internalization and receptor degradation.Decorin is a key extracellular matrix component playing a role in fibrotic disorders, in cancer cancer as it present antitumor, antimetastatic and antiangiogenic properties, but also in inflammation as it can stimulate pro-inflammatory cytokines such as TNFalpha or IL-6. Initially identified as a natural inhibitor of TGF-β, soluble decorin is also able to target EGFR, IGF-IR, VEGFR2, and PDGFR, thus modulating various signaling pathways and inducing caveosomal internalization and receptor degradation. LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Besides direct antimicrobial effects it is also involved in inflammatory response, immune regulation, angiogenesis, tissue repair or cancer regulation. Skin inflammatory diseases such atopic dermatitis or psoriasis have been respectively correlated to a lack of LL37 or LL37 overexpression. LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Besides direct antimicrobial effects it is also involved in inflammatory response, immune regulation, angiogenesis, tissue repair or cancer regulation. Skin inflammatory diseases such atopic dermatitis or psoriasis have been respectively correlated to a lack of LL37 or LL37 overexpression. LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Besides direct antimicrobial effects it is also involved in inflammatory response, immune regulation, angiogenesis, tissue repair or cancer regulation. Skin inflammatory diseases such atopic dermatitis or psoriasis have been respectively correlated to a lack of LL37 or LL37 overexpression. LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Besides direct antimicrobial effects it is also involved in inflammatory response, immune regulation, angiogenesis, tissue repair or cancer regulation. Skin inflammatory diseases such atopic dermatitis or psoriasis have been respectively correlated to a lack of LL37 or LL37 overexpression. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects.Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects.Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects.Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Impairment of epidermal barrier function owing to filaggrin deficiency can promote inflammation and T cell infiltration and induce atopic dermatitis. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Impairment of epidermal barrier function owing to filaggrin deficiency can promote inflammation and T cell infiltration and induce atopic dermatitis. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Impairment of epidermal barrier function owing to filaggrin deficiency can promote inflammation and T cell infiltration and induce atopic dermatitis. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Impairment of epidermal barrier function owing to filaggrin deficiency can promote inflammation and T cell infiltration and induce atopic dermatitis. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Mainly involved in skin hydration, lubrication of joints and space filling, Hyaluronic Acid (HA) also constitutes a framework through which cells migrate. Almost all cells can attach HA via membrane receptors (either CD44 or RHAMM), including inflammatory cells which may be activated to enhance immune response. Interestingly, HA of high molecular size (>1,000kDa) is antiangiogenic and immunosuppressive, whereas smaller polymers of HA which accumulates during inflammation are potent inducers of inflammation and angiogenesis. Mainly involved in skin hydration, lubrication of joints and space filling, Hyaluronic Acid (HA) also constitutes a framework through which cells migrate. Almost all cells can attach HA via membrane receptors (either CD44 or RHAMM), including inflammatory cells which may be activated to enhance immune response. Interestingly, HA of high molecular size (>1,000kDa) is antiangiogenic and immunosuppressive, whereas smaller polymers of HA which accumulates during inflammation are potent inducers of inflammation and angiogenesis. Mainly involved in skin hydration, lubrication of joints and space filling, Hyaluronic Acid (HA) also constitutes a framework through which cells migrate. Almost all cells can attach HA via membrane receptors (either CD44 or RHAMM), including inflammatory cells which may be activated to enhance immune response. Interestingly, HA of high molecular size (>1,000kDa) is antiangiogenic and immunosuppressive, whereas smaller polymers of HA which accumulates during inflammation are potent inducers of inflammation and angiogenesis. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Mainly involved in skin hydration, lubrication of joints and space filling, Hyaluronic Acid (HA) also constitutes a framework through which cells migrate. Almost all cells can attach HA via membrane receptors (either CD44 or RHAMM), including inflammatory cells which may be activated to enhance immune response. Interestingly, HA of high molecular size (>1,000kDa) is antiangiogenic and immunosuppressive, whereas smaller polymers of HA which accumulates during inflammation are potent inducers of inflammation and angiogenesis. Skin kallikreins, including the well-known kallikreins 5 (KLK-5) and 7 (KLK-7) are proteolytic enzymes playing a crucial role in regulating both desquamation and skin inflammation. Thus, they allow to maintain skin homeostasis. They also play a key role in extracellular matrix remodeling and during wound healing inflammatory response. An abnormal activation of the KLK proteolytic cascade is reported in some inflammatory diseases such as atopic dermatitis (AD) and psoriasis. Thus, they represent an interesting target to treat inflammatory diseases or to improve wound healing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Under the activation of Toll-like receptors (by pathogens), some specific peripheral precursors differentiate into CD209+ (DC-SIGN) cells which are part of the innate immune system and located in the dermis, especially in inflamed cutaneous area. Either presenting a macrophage-like or a dendritic cell-like phenotype, they are actually macrophages and use CD209 to facilitate uptake of bacteria and achieve phagocytosis. Under the activation of Toll-like receptors (by pathogens), some specific peripheral precursors differentiate into CD209+ (DC-SIGN) cells which are part of the innate immune system and located in the dermis, especially in inflamed cutaneous area. Either presenting a macrophage-like or a dendritic cell-like phenotype, they are actually macrophages and use CD209 to facilitate uptake of bacteria and achieve phagocytosis. Under the activation of Toll-like receptors (by pathogens), some specific peripheral precursors differentiate into CD209+ (DC-SIGN) cells which are part of the innate immune system and located in the dermis, especially in inflamed cutaneous area. Either presenting a macrophage-like or a dendritic cell-like phenotype, they are actually macrophages and use CD209 to facilitate uptake of bacteria and achieve phagocytosis. Human Beta defensin 2, 3 and 4 are antimicrobial peptides produced by keratinocytes when stimulated by a contact with microorganisms or some inflammatory cytokines such as IL-1a or TNFa. Their level increases on inflammatory sites whereas a lack of bêta defensins can induce skin diseases such as psoriasis or atopic dermatitis.Human Beta defensin 2, 3 and 4 are antimicrobial peptides produced by keratinocytes when stimulated by a contact with microorganisms or some inflammatory cytokines such as IL-1a or TNFa. Their level increases on inflammatory sites whereas a lack of bêta defensins can induce skin diseases such as psoriasis or atopic dermatitis.Human Beta defensin 2, 3 and 4 are antimicrobial peptides produced by keratinocytes when stimulated by a contact with microorganisms or some inflammatory cytokines such as IL-1a or TNFa. Their level increases on inflammatory sites whereas a lack of bêta defensins can induce skin diseases such as psoriasis or atopic dermatitis.Human Beta defensin 2, 3 and 4 are antimicrobial peptides produced by keratinocytes when stimulated by a contact with microorganisms or some inflammatory cytokines such as IL-1a or TNFa. Their level increases on inflammatory sites whereas a lack of bêta defensins can induce skin diseases such as psoriasis or atopic dermatitis. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.CD1a is a lipid-presenting molecule expressed on Langerhans cells. It amplifies inflammatory responses mediated by TH17 cells reacting to self lipid antigens. Targeting CD1 may therefore be a strategy to alleviate inflammation in some inflammatory skin diseases such as psoriasis for example. CD1a is a lipid-presenting molecule expressed on Langerhans cells. It amplifies inflammatory responses mediated by TH17 cells reacting to self lipid antigens. Targeting CD1 may therefore be a strategy to alleviate inflammation in some inflammatory skin diseases such as psoriasis for example. CD1a is a lipid-presenting molecule expressed on Langerhans cells. It amplifies inflammatory responses mediated by TH17 cells reacting to self lipid antigens. Targeting CD1 may therefore be a strategy to alleviate inflammation in some inflammatory skin diseases such as psoriasis for example. CD1a is a lipid-presenting molecule expressed on Langerhans cells. It amplifies inflammatory responses mediated by TH17 cells reacting to self lipid antigens. Targeting CD1 may therefore be a strategy to alleviate inflammation in some inflammatory skin diseases such as psoriasis for example. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Prostaglandin E-2 (PGE-2) is a lipid-derived signaling molecule found in mammalian skin, especially in fibroblasts. Levels of Prostaglandin E-2 (PGE-2) increase with chronological aging and following sun exposure, inducing an inflammatory state and therefore skin damages associated to ageing such as collagen decrease. Desmogleins 1 - 4 are calcium-binding transmembrane glycoprotein belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes and corneocytes. Desmoglein 2 is more abundant in the basal layer whereas Desmoglein 1 level is higher in differentiated keratinocytes. But, even if the role of each desmoglein type vary, a defect in desmoglein expression may lead to an impaired skin barrier. Desmogleins 1 - 4 are calcium-binding transmembrane glycoprotein belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes and corneocytes. Desmoglein 2 is more abundant in the basal layer whereas Desmoglein 1 level is higher in differentiated keratinocytes. But, even if the role of each desmoglein type vary, a defect in desmoglein expression may lead to an impaired skin barrier. Desmogleins 1 - 4 are calcium-binding transmembrane glycoprotein belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes and corneocytes. Desmoglein 2 is more abundant in the basal layer whereas Desmoglein 1 level is higher in differentiated keratinocytes. But, even if the role of each desmoglein type vary, a defect in desmoglein expression may lead to an impaired skin barrier. Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Corneocytes, the final stage of keratinocyte differentiation, are linked together by protein complexes called corneodesmosomes composed of proteins such as corneodesmosin (CDSN), desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Kallikrein 7, capable of cleaving CDSN and DSC1, and kallikrein 5, capable of cleaving CDSN, DSC1 and DSG1, are two proteolytic enzymes involved in the loss of cohesion of corneocytes associated with desquamation. The synthesis and activity of these 2 enzymes must therefore be correctly regulated to ensure desquamation and therefore epidermal renewal at an appropriate level.Corneocytes, the final stage of keratinocyte differentiation, are linked together by protein complexes called corneodesmosomes composed of proteins such as corneodesmosin (CDSN), desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Kallikrein 7, capable of cleaving CDSN and DSC1, and kallikrein 5, capable of cleaving CDSN, DSC1 and DSG1, are two proteolytic enzymes involved in the loss of cohesion of corneocytes associated with desquamation. The synthesis and activity of these 2 enzymes must therefore be correctly regulated to ensure desquamation and therefore epidermal renewal at an appropriate level. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Corneocytes, the final stage of keratinocyte differentiation, are linked together by protein complexes called corneodesmosomes composed of proteins such as corneodesmosin (CDSN), desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Kallikrein 7, capable of cleaving CDSN and DSC1, and kallikrein 5, capable of cleaving CDSN, DSC1 and DSG1, are two proteolytic enzymes involved in the loss of cohesion of corneocytes associated with desquamation. The synthesis and activity of these 2 enzymes must therefore be correctly regulated to ensure desquamation and therefore epidermal renewal at an appropriate level.Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of this assay.To be completedProduced by fibroblasts and vascular smooth muscle cells, elastin is the main component of the skin's elastic fibers. It represents 2 to 4% of the adult cutaneous extracellular matrix (ECM) and is mainly responsible for the elasticity of the skin. Its production occurs mainly before sexual maturity and is considerably reduced thereafter in normal adult skin. Nevertheless, upon injury and during healing, elastin synthesis is stimulated. Some molecules can therefore modulate skin mechanical integrity by targeting elastin synthesis, distribution, arrangement and conservation.To be completedTo be completedFibrillin-1 (FBN-1) and fibrillin-2 (FBN-2) assemble into microfibrils. These microfibrils located in the extracellular matrix (ECM) form the core scaffolds for elastic fibre formation. They also decorate the surface of elastic fibres, and form an independent network of stretchable bundles. Thanks to their own mechanical properties and their role in elastin network formation, these fibres widely contribute to skin elasticity and pliability. Moreover FBN network stores and controls the bioavailability of growth factors such as TGFβ that control the remodeling and architecture of the ECM upon which its mechanical properties directly depend. To be completedTo be completedMatrix metalloproteinases (MMPs) are secreted or membrane proteolytic enzymes able to cleave various components of the extracellular matrix (ECM). There can be divided into several categories, depending on the types of matrix components they target. For example, MMPs 1, 8 and 13, also called collagenases 1, 2 and 3, cleave specifically collagens, while MMP12 is able to cleave elastin. All together, the different MMPs can degrade all the components of the ECM. Thus, they participate in ECM remodeling and regulate various biological processes (notably by releasing signaling molecules resulting from the cleavages), for example during the processes of wound healing, inflammation, etc... A fine control of MMP function is therefore necessary to maintain skin homeostasis and mechanical integrity. Various molecules can modulate this mechanical integrity by targeting MMP synthesis, activation or inhibition which depends on specific inhibitors called TIMPs. To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.To be completedThe α2β1 integrin is an heterodimeric transmembrane protein able to interact with collagen I and III. Abundantly and constitutively expressed by basal keratinocytes in intact skin, the α2β1 integrin is also upregulated in wounds. This integrin is also expressed by endothelial cells and able to interact with VEGF. The α2β1 integrin seems to regulate angiogenesis and inflammatory response, but also matrix remodeling during wound healing. The α2β1 integrin is an heterodimeric transmembrane protein able to interact with collagen I and III. Abundantly and constitutively expressed by basal keratinocytes in intact skin, the α2β1 integrin is also upregulated in wounds. This integrin is also expressed by endothelial cells and able to interact with VEGF. The α2β1 integrin seems to regulate angiogenesis and inflammatory response, but also matrix remodeling during wound healing. The α2β1 integrin is an heterodimeric transmembrane protein able to interact with collagen I and III. Abundantly and constitutively expressed by basal keratinocytes in intact skin, the α2β1 integrin is also upregulated in wounds. This integrin is also expressed by endothelial cells and able to interact with VEGF. The α2β1 integrin seems to regulate angiogenesis and inflammatory response, but also matrix remodeling during wound healing. Ki67 is a nuclear protein related to cell cycle and synthesized by all proliferating cells while deficient in resting cells. Proliferating cell nuclear antigen (PCNA) is another well-known nuclear protein which participates in cell proliferation by mediating DNA polymerase. Those two proteins are therefore two well-established proliferation-associated proteins used to probe cell proliferation during wound repair.Ki67 is a nuclear protein related to cell cycle and synthesized by all proliferating cells while deficient in resting cells. Proliferating cell nuclear antigen (PCNA) is another well-known nuclear protein which participates in cell proliferation by mediating DNA polymerase. Those two proteins are therefore two well-established proliferation-associated proteins used to probe cell proliferation during wound repair. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrix of several tissues including skin. Lumican regulates collagen fibrillogenesis, fibroblast contractility and keratinocyte phenotype, migration and proliferation. It is also involved in inflammatory cell recruitment and stimulation, in angiogenesis, and is the only member of the small leucine-rich proteoglycan famility expressed by the epithelia during wound healing. Overall, it promotes normal wound healing.Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrix of several tissues including skin. Lumican regulates collagen fibrillogenesis, fibroblast contractility and keratinocyte phenotype, migration and proliferation. It is also involved in inflammatory cell recruitment and stimulation, in angiogenesis, and is the only member of the small leucine-rich proteoglycan famility expressed by the epithelia during wound healing. Overall, it promotes normal wound healing.Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrix of several tissues including skin. Lumican regulates collagen fibrillogenesis, fibroblast contractility and keratinocyte phenotype, migration and proliferation. It is also involved in inflammatory cell recruitment and stimulation, in angiogenesis, and is the only member of the small leucine-rich proteoglycan famility expressed by the epithelia during wound healing. Overall, it promotes normal wound healing.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation. During wound healing, Perlecan promotes cellular proliferation, differentiation, extracellular matrix synthesis and therefore tissue repair and angiogenesis.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation. During wound healing, Perlecan promotes cellular proliferation, differentiation, extracellular matrix synthesis and therefore tissue repair and angiogenesis.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation. During wound healing, Perlecan promotes cellular proliferation, differentiation, extracellular matrix synthesis and therefore tissue repair and angiogenesis.Psoriasin (S100A7) is a calcium responsive signalling protein produced by keratinocytes. Besides its role as an antimicrobial peptide, it is also involved in various processes including skin inflammation and keratinocyte differentiation. Psoriasin expression is upregulated in wounds, particularly at the wound edges where it acts as a fundamental regulator of keratinocyte migration. Psoriasin is therefore essential in wound healing and has been suggested as a potential wound healing biomarker. Psoriasin (S100A7) is a calcium responsive signalling protein produced by keratinocytes. Besides its role as an antimicrobial peptide, it is also involved in various processes including skin inflammation and keratinocyte differentiation. Psoriasin expression is upregulated in wounds, particularly at the wound edges where it acts as a fundamental regulator of keratinocyte migration. Psoriasin is therefore essential in wound healing and has been suggested as a potential wound healing biomarker. Psoriasin (S100A7) is a calcium responsive signalling protein produced by keratinocytes. Besides its role as an antimicrobial peptide, it is also involved in various processes including skin inflammation and keratinocyte differentiation. Psoriasin expression is upregulated in wounds, particularly at the wound edges where it acts as a fundamental regulator of keratinocyte migration. Psoriasin is therefore essential in wound healing and has been suggested as a potential wound healing biomarker. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. It also regulates cell migration, redox response, inflammation, epidermis re-epithelialization, granulation formation and therefore proper wound healing.Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. It also regulates cell migration, redox response, inflammation, epidermis re-epithelialization, granulation formation and therefore proper wound healing.Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. It also regulates cell migration, redox response, inflammation, epidermis re-epithelialization, granulation formation and therefore proper wound healing.Desmogleins 1 - 4 are calcium-binding transmembrane glycoprotein belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes and corneocytes. Desmoglein 2 is more abundant in the basal layer whereas Desmoglein 1 level is higher in differentiated keratinocytes. But, even if the role of each desmoglein type vary, a defect in desmoglein expression may lead to an impaired skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Claudin 1 (CLDN-1) and 4 (CLDN-4) are transmembrane proteins constituting the tight junctions which maintain the keratinocytes closely associated in the epidermis. A decrease of Claudin level beyond a threshold may alter skin barrier function and induce skin inflammation. This has been observed in some atopic dermatitis cases. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Corneodesmosin is a protein secreted by granular keratinocytes via the lamellar bodies and incorporated into desmosomes shortly before their transformation into corneodesmosomes. Corneodesmosin displays adhesive properties by acting like a Velcro and is therefore involved in skin barrier function. Moreover, corneodesmosin is then sequentially proteolyzed as corneocytes migrate towards the skin surface, thus allowing appropriate desquamation and skin barrier renewal. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Caspase-14 is a protease initially expressed in the suprabasal layers of the epidermis in an inactive form and then converted into an active form essentially present in the stratum corneum. It is involved in the terminal differentiation of keratinocytes and thus the establishment of the skin barrier, but also in the filaggrin proteolysis and the formation of NMF (Natural Moisturizing Factor) allowing the hydration and thus the functionality of the skin barrier as well as in the protection of the skin against UVB. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The α2β1 integrin is an heterodimeric transmembrane protein able to interact with collagen I and III. Abundantly and constitutively expressed by basal keratinocytes in intact skin, the α2β1 integrin is also upregulated in wounds. This integrin is also expressed by endothelial cells and able to interact with VEGF. The α2β1 integrin seems to regulate angiogenesis and inflammatory response, but also matrix remodeling during wound healing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Ki67 is a nuclear protein related to cell cycle and synthesized by all proliferating cells while deficient in resting cells. Proliferating cell nuclear antigen (PCNA) is another well-known nuclear protein which participates in cell proliferation by mediating DNA polymerase. Those two proteins are therefore two well-established proliferation-associated proteins used to probe cell proliferation during wound repair. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrix of several tissues including skin. Lumican regulates collagen fibrillogenesis, fibroblast contractility and keratinocyte phenotype, migration and proliferation. It is also involved in inflammatory cell recruitment and stimulation, in angiogenesis, and is the only member of the small leucine-rich proteoglycan famility expressed by the epithelia during wound healing. Overall, it promotes normal wound healing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Perlecan is a heparan sulfate proteoglycan. Basal keratinocytes produce Perlecan which is accumulated at the dermal epidermal junction (DEJ) level while Perlecan coming from fibroblasts is accumulated in the dermal extracellular matrix. At the DEJ level, Perlecan allows to maintain the self-renewal capacities of keratinocytes and is involved in their survival and differentiation. During wound healing, Perlecan promotes cellular proliferation, differentiation, extracellular matrix synthesis and therefore tissue repair and angiogenesis. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Psoriasin (S100A7) is a calcium responsive signalling protein produced by keratinocytes. Besides its role as an antimicrobial peptide, it is also involved in various processes including skin inflammation and keratinocyte differentiation. Psoriasin expression is upregulated in wounds, particularly at the wound edges where it acts as a fundamental regulator of keratinocyte migration. Psoriasin is therefore essential in wound healing and has been suggested as a potential wound healing biomarker. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. It also regulates cell migration, redox response, inflammation, epidermis re-epithelialization, granulation formation and therefore proper wound healing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the accumulation of free amino-acids such as urocanic acid and pyrrolidone carboxylic acid which constitute the NMF involved in skin hydration. Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the accumulation of free amino-acids such as urocanic acid and pyrrolidone carboxylic acid which constitute the NMF involved in skin hydration. Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the accumulation of free amino-acids such as urocanic acid and pyrrolidone carboxylic acid which constitute the NMF involved in skin hydration. Matrix metallopeptidases (MMP) are various proteases located in dermal extracellular matrix and involved in extracellular matrix remodelling and therefore biological mechanisms such as wound healing or skin hydration. Matrix metallopeptidases (MMP) are various proteases located in dermal extracellular matrix and involved in extracellular matrix remodelling and therefore biological mechanisms such as wound healing or skin hydration. Matrix metallopeptidases (MMP) are various proteases located in dermal extracellular matrix and involved in extracellular matrix remodelling and therefore biological mechanisms such as wound healing or skin hydration. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. Derived from the cleavage of profilaggrin, a molecule present in the keratohyaline granules of granular keratinocytes, filaggrin is a known marker of terminal differentiation of keratinocytes and a major constituent of stratum corneum. It thus participates in the skin's barrier function. Under the action of proteases including caspase 14, filaggrin produces a mix of amino acids constituting NMF (Natural Moisturizing Factor) and is thus involved in skin hydration. The key molecule involved in skin moisture is hyaluronic acid (HA). It corresponds to the main skin extracellular matrix glycosaminoglycan and has unique capacity in retaining water, thus allowing for proper skin suppleness and stiffness. The key molecule involved in skin moisture is hyaluronic acid (HA). It corresponds to the main skin extracellular matrix glycosaminoglycan and has unique capacity in retaining water, thus allowing for proper skin suppleness and stiffness. Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Skin ageing is associated with an increase in senescent cell percentage. As β-galactosidase activity increases significantly in senescent cells, this marker is commonly used to assess the extent of skin ageing. An anti-ageing product can therefore decrease this activity.Skin ageing is associated with an increase in senescent cell percentage. As β-galactosidase activity increases significantly in senescent cells, this marker is commonly used to assess the extent of skin ageing. An anti-ageing product can therefore decrease this activity.Skin ageing is associated with an increase in senescent cell percentage. As β-galactosidase activity increases significantly in senescent cells, this marker is commonly used to assess the extent of skin ageing. An anti-ageing product can therefore decrease this activity. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Synthesised by the keratinocytes of the spinous layer and then secreted via the lamellar bodies, corneodesmosin is then incorporated into the corneodesmosomes which ensure cohesion between the corneocytes of the stratum corneum. During skin ageing, a degradation of this protein, notably linked to an increase in skin pH which activates certain proteases, leads to a weakening of the skin barrier. An anti-ageing agent can slow down the degradation of corneodesmosin and thus help maintain the skin barrier. Synthesised by the keratinocytes of the spinous layer and then secreted via the lamellar bodies, corneodesmosin is then incorporated into the corneodesmosomes which ensure cohesion between the corneocytes of the stratum corneum. During skin ageing, a degradation of this protein, notably linked to an increase in skin pH which activates certain proteases, leads to a weakening of the skin barrier. An anti-ageing agent can slow down the degradation of corneodesmosin and thus help maintain the skin barrier. Synthesised by the keratinocytes of the spinous layer and then secreted via the lamellar bodies, corneodesmosin is then incorporated into the corneodesmosomes which ensure cohesion between the corneocytes of the stratum corneum. During skin ageing, a degradation of this protein, notably linked to an increase in skin pH which activates certain proteases, leads to a weakening of the skin barrier. An anti-ageing agent can slow down the degradation of corneodesmosin and thus help maintain the skin barrier. Synthesised by the keratinocytes of the spinous layer and then secreted via the lamellar bodies, corneodesmosin is then incorporated into the corneodesmosomes which ensure cohesion between the corneocytes of the stratum corneum. During skin ageing, a degradation of this protein, notably linked to an increase in skin pH which activates certain proteases, leads to a weakening of the skin barrier. An anti-ageing agent can slow down the degradation of corneodesmosin and thus help maintain the skin barrier. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Sirtuin 1 is an enzyme with many functions. It limits oxidative stress, DNA damage, apoptosis, participates in inflammation, promotes barrier function, wound healing and endothelial function. By targeting this enzyme, anti-ageing products can promote its action and thus limit skin ageing. Sirtuin 1 is an enzyme with many functions. It limits oxidative stress, DNA damage, apoptosis, participates in inflammation, promotes barrier function, wound healing and endothelial function. By targeting this enzyme, anti-ageing products can promote its action and thus limit skin ageing. Sirtuin 1 is an enzyme with many functions. It limits oxidative stress, DNA damage, apoptosis, participates in inflammation, promotes barrier function, wound healing and endothelial function. By targeting this enzyme, anti-ageing products can promote its action and thus limit skin ageing. Sirtuin 1 is an enzyme with many functions. It limits oxidative stress, DNA damage, apoptosis, participates in inflammation, promotes barrier function, wound healing and endothelial function. By targeting this enzyme, anti-ageing products can promote its action and thus limit skin ageing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Type I and III collagens (Coll I and Coll III) are fibrous proteins whose structural role has long been known. They are among the main components of the extracellular matrix (ECM) and involved in the skin mechanical resistance to rupture. This resistance depends on collagen density, and thus on the balance between its synthesis and degradation, but also on the thickness of the fibers and the organization of the network. The coll I / coll III ratio also has an influence on this resistance. Any molecule likely to act on the enzymes controlling Coll I and Coll III synthesis and degradation, as well as on the network organization and its interactions with the other ECM components, can therefore influence the strength and mechanical integrity of the skin. To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Glycosaminoglycans (GAGs), also termed mucopolysaccharides, are a category of large linear polysaccharides in which the repeating disaccharide is composed of one amine sugar (N-acetylglucosamine or N-acetylgalactosamine) and an uronic acid (glucuronic acid or iduronic acid). GAGs are highly polar, attracting and binding water molecules, filling gaps between collagen fibrils within the ECM and thereby facilitating their role as both a lubricant and a shock absorber. Thus, they play a major role in skin mechanical properties. The structural diversity of GAGs also enables them to interact with a wide variety of biological molecules. Through these interactions, GAGs modulate various biological processes, such as cell adhesion, proliferation and migration, ECM assembly, tissue repair, coagulation, and immune responses, among many others. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.When cultivated in classical 3D collagen matrix, fibroblasts are able to induce lattice contraction by reoganizing the collagen more compactly and expelling fluid. All fibroblasts appear to have this capability, irrespective of the age of the donor, time in culture or the presence of various dermatoses. The contraction process can be assessed by measuring the size of the 3D model overtime. This contraction process resembles wound contraction in vivo and can be modulated by some culture conditions as well as certain factors able to modulate wound contraction in vivo. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Desmosomes are highly organized intercellular junctions composed of a number of interacting proteins that provide mechanical integrity to epithelial tissues. The ubiquitin- proteasome system (UPS) is an important regulatory system for the proper intracellular trafficking of proteins, the maintenance of desmoplakin at desmosomes, and the stabilization of cell–cell contacts in human keratinocytes. Proteasome is also involved in the regulated degradation of various cell proteins, including keratins. Proteasome therefore represents a potential target to strengthen skin mechanical integrity.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Skin mechanical integrity relies on a well-controlled network of intracellular and extracellular proteins. In the epidermis, keratins form a stable keratinocyte cytoskeleton that maintain stable intercellular adhesion and cell rigidity. Critical for bundling keratins, filaggrin (FLG) allows to attain flat squames in the cornified layer. During cornification, loricrin (LOR), S100 proteins, involucrin, the late cornified envelope (CE) family of proteins and hornerin (HRNR) are cross-linked by transglutaminase (TGM) to form a strong, indissoluble CE. At sites of attachment to the hemidesmosome and desmosome, the junction plakoglobin (JUP), plectin, desmoplakin (DSP), desmoglein1 (DSG1), desmocollin1 (DSC1) and corneodesmosin (CDSN) proteins are responsible for maintaining the mechanical integrity of the epidermal barrier by binding the intermediate filaments (IFs) to the cornified cells. At the dermis level, proteins such as collagens, elastin and glycosaminoglycans enable skin resistance, elasticity and hydration. Targeting the neosynthesis of these protein (especially in case of skin disease, and during skin ageing or wound healing) can therefore allow to modulate and strengthen skin mechanical integrity. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Caspase 9 is a protease initiating the activation cascade which leads to apoptosis. It can therefore be used as a marker for apoptotic cells. An anti-ageing product can aim to regulate apoptosis which is naturally altered during skin ageing.Caspase 9 is a protease initiating the activation cascade which leads to apoptosis. It can therefore be used as a marker for apoptotic cells. An anti-ageing product can aim to regulate apoptosis which is naturally altered during skin ageing.Caspase 9 is a protease initiating the activation cascade which leads to apoptosis. It can therefore be used as a marker for apoptotic cells. An anti-ageing product can aim to regulate apoptosis which is naturally altered during skin ageing.Caspase 9 is a protease initiating the activation cascade which leads to apoptosis. It can therefore be used as a marker for apoptotic cells. An anti-ageing product can aim to regulate apoptosis which is naturally altered during skin ageing. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Fibronectin is an extracellular matrix (ECM) protein that dictates cell adhesion, spreading, migration, proliferation and apoptosis. It is active through all stages of wound healing. Plasma fibronectin primarily helps to form the clot and assemble a cell-ECM matrix in the initial phase of wound healing. Cellular derived fibronectin regulates the later stages of tissue remodeling via locally expressed fibronectine assembly which regulates cell behaviour and granulation tissue formation. Fibronectin is also involved in the control of debris phagocytosis and the inflammation process preparing the site before cell recruitment and proliferation.Fibronectin is an extracellular matrix (ECM) protein that dictates cell adhesion, spreading, migration, proliferation and apoptosis. It is active through all stages of wound healing. Plasma fibronectin primarily helps to form the clot and assemble a cell-ECM matrix in the initial phase of wound healing. Cellular derived fibronectin regulates the later stages of tissue remodeling via locally expressed fibronectine assembly which regulates cell behaviour and granulation tissue formation. Fibronectin is also involved in the control of debris phagocytosis and the inflammation process preparing the site before cell recruitment and proliferation.Fibronectin is an extracellular matrix (ECM) protein that dictates cell adhesion, spreading, migration, proliferation and apoptosis. It is active through all stages of wound healing. Plasma fibronectin primarily helps to form the clot and assemble a cell-ECM matrix in the initial phase of wound healing. Cellular derived fibronectin regulates the later stages of tissue remodeling via locally expressed fibronectine assembly which regulates cell behaviour and granulation tissue formation. Fibronectin is also involved in the control of debris phagocytosis and the inflammation process preparing the site before cell recruitment and proliferation.Fibronectin is an extracellular matrix (ECM) protein that dictates cell adhesion, spreading, migration, proliferation and apoptosis. It is active through all stages of wound healing. Plasma fibronectin primarily helps to form the clot and assemble a cell-ECM matrix in the initial phase of wound healing. Cellular derived fibronectin regulates the later stages of tissue remodeling via locally expressed fibronectine assembly which regulates cell behaviour and granulation tissue formation. Fibronectin is also involved in the control of debris phagocytosis and the inflammation process preparing the site before cell recruitment and proliferation. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin inflammation or metastasis, and skin hydration as a key cell receptor for hyaluronic acid.The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin inflammation or metastasis, and skin hydration as a key cell receptor for hyaluronic acid. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The extracellular matrix synthesised by fibroblasts contains carbohydrate macromolecules called glycosaminoglycans (GAGs) which are generally covalently linked to a protein to form proteoglycans. These molecules (especially hyaluronic acid) contribute to the suppleness and firmness of the skin by promoting its hydration. The extracellular matrix synthesised by fibroblasts contains carbohydrate macromolecules called glycosaminoglycans (GAGs) which are generally covalently linked to a protein to form proteoglycans. These molecules (especially hyaluronic acid) contribute to the suppleness and firmness of the skin by promoting its hydration.Synthesised in the keratinocyte cytoplasm of stratum granulosum, involucrin is a major constituent of the cornified enveloppe, leads to the death of the keratinocytes and serves as a primer for the binding of other proteins such as loricrin. Known as differentiation marker of keratinocytes, it plays an active role in the skin's barrier function, limiting water loss and thus favouring appropriate skin hydration. Synthesised in the keratinocyte cytoplasm of stratum granulosum, involucrin is a major constituent of the cornified enveloppe, leads to the death of the keratinocytes and serves as a primer for the binding of other proteins such as loricrin. Known as differentiation marker of keratinocytes, it plays an active role in the skin's barrier function, limiting water loss and thus favouring appropriate skin hydration. Synthesised in the keratinocyte cytoplasm of stratum granulosum, involucrin is a major constituent of the cornified enveloppe, leads to the death of the keratinocytes and serves as a primer for the binding of other proteins such as loricrin. Known as differentiation marker of keratinocytes, it plays an active role in the skin's barrier function, limiting water loss and thus favouring appropriate skin hydration.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 14 (K14) and 5 (K5) are expressed in mitotically active basal layer cells and their expression is down-regulated as cells differentiate. Those markers therefore give an indication concerning the renewal abilities and differentiation level of the epidermis. Fibronectin is an extracellular matrix (ECM) protein that dictates cell adhesion, spreading, migration, proliferation and apoptosis, including during wound healing. Some changes concerning fibronectin synthesis, folding and organisation occur during skin ageing, thus modulating skin mechanical properties. Fibronectin thus represents a possible target to delay skin aging. To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.La pollution atmosphérique exerce des effets négatifs sur la peau humaine. Elle module l'expression des gènes dans les cellules cutanées et peut induire un vieillissement cutané plus précoce, notamment en provoquant une altération précoce du réseau de collagène de type IV (Coll IV), un composant majeur de la jonction dermo-épidermique (JDE).To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and notably stimulates pro-inflammatory cytokine production, increasing for example the levels of IL-1α, IL-1β, IL-6, IL-8, IL-33 andTNFα. To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Pollutant molecules penetrate skin either through hair follicles or transdermally, and exert negative effects on skin notably through the generation of reactive oxygen species (ROS). ROS activate the mitogen-activated protein kinase (MAPK) signaling pathway, and then the activated MAPK induces various transcription factors, such as Nuclear Factor Kappa B (NF-kB) and activator Protein-1 (AP-1). As a result, inflammatory cytokines, which are closely related to in- flammatory skin diseases and skin aging, are generated.To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and notably stimulates the expression and activity of various matrix metalloproteinases such as MMP-1, MMP-3 or MMP-9, thus favouring the skin matrix degradation and inducing an earlier skin ageing.To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and cell metabolism, notably decreasing ATP production. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Reactive oxygen species (ROS) mainly correspond to singlet oxygen (1O2), superoxide anion (O2•−), H2O2, and hydroxyl radical (•OH). ROS are generated during normal metabolism, are essential for cell function, and are usually of little harm because of intracellular mechanisms that reduce their damaging effects. Indeed, the skin employs a number of antioxidant agents to protect the oxidative balance, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), ascorbic acid, and tocopherols. However, endogenous factors such as skin ageing, or exogenous factors such as pathogens, chemicals or UV light can lead to increased or prolonged free radical action that can overwhelm ROS defense mechanisms, contributing to the development of cutaneous diseases and disorders such as non healing wound, psoriasis, acne, or vitiligo. In a context where ROS tend to accumulate, an antioxidant agent allows to decrease their level and to protect the cells against the associated damages. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.A lipid layer covers skin surface. This layer is mainly a mixture of triglycerides, wax esters and squalene produced by the sebaceous gland, and ceramides, free fatty acids and cholesterol from keratinocytes. Cholesterol, free fatty acids, and squalene are targets for lipid oxidation and yield bioactive products. Cholesterol is an important substrate for singlet oxygen and ozone. Polyunsaturated fatty acids are the substrates for free radical mediated lipid peroxidation and enzymatic oxidation. Squalene remains relatively stable against lipid peroxidation mediated by peroxyl radical but seems to have an antioxydant effect, acting as scavenger and quencher against some free radicals such as superoxyde anion. Oxidation of skin surface lipids may be important in connection with sunburn, wrinkle formation, hyperpigmentation, freckles, acne, atopic dermatitis, and cancer. The effect of an antioxidant product can therefore be determined by evaluating its effect on cholesterol, free fatty acids and/or squalene oxidation level. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Lipid peroxidation is the degradation of lipids that occurs as a result of oxidative damage. It represents a useful marker for oxidative stress. Polyunsaturated lipids (glycerophospholipids, sphingolipids, unsaturated fatty acids and cholesterol) are susceptible to an oxidative attack, typically by reactive oxygen species (ROS), resulting in a well-defined chain reaction with the production of end products such as malondialdehyde (MDA). An antioxidant product decreases lipid peroxidation and the accumulation of end products. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Skin cells contain several histone deacetylases called sirtuins (SIRT). SIRT1 is an active player in the prevention of H2O2-induced cell damages. SIRT2 and SIRT3 are also involved in oxidative stress regulation in skin. To prevent cell damages, an active molecule can therefore increase the expression or the activity of one of these enzymes. To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.The colour of the skin, hair and eyes is determined both by the quantity of melanin (darker skin with larger amounts) and the ratio between the two types of melanic pigments: eumelanin and pheomelanin. This pigments are the final products of complex biochemical reactions starting from the amino acid L-tyrosine and occuring in specific melanocyte organelles called melanosomes. The hydroxylation of the L-tyrosine at the L-DOPA (first reaction) is catalyzed by the tyrosinase (TYR), an enzyme located in the membrane of the melanosomes. The tyrosinase is therefore an indispensable enzyme of melanogenesis and the tyrosinase activity is correlated with the melanin production degree. To be completedTo be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Melanin is the main pigment responsible for the color of human skin, hair and eye. Its biosynthesis requires not only tyrosinase, but also 2 tyrosinase-related proteins: TYRP1 and TYRP2. These 2 enzymes are clearly important for melanin synthesis and they can also be used as markers of differentiated melanocytes. Tyrp1 is involved in stabilizing of tyrosinase protein and modulating its catalytic activity. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and melanocyte cell death. TYRP2 is also called dopachrome tautomerase (DCT) and is involved in the modification of the pigment color. The absence of TRP2 does not lead to a loss of pigmentation, but rather to a color modification. To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.To be completedThe analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of these specific studies.Beta defensin 2 is an antimicrobial peptide with pro-inflammatory and chemotactic properties presenting greater amounts in the epidermis of acne-prone skin. An anti-acne product should decrease this amount. Beta defensin 2 is an antimicrobial peptide with pro-inflammatory and chemotactic properties presenting greater amounts in the epidermis of acne-prone skin. An anti-acne product should decrease this amount. Beta defensin 2 is an antimicrobial peptide with pro-inflammatory and chemotactic properties presenting greater amounts in the epidermis of acne-prone skin. An anti-acne product should decrease this amount. Beta defensin 2 is an antimicrobial peptide with pro-inflammatory and chemotactic properties presenting greater amounts in the epidermis of acne-prone skin. An anti-acne product should decrease this amount. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.In acne-prone skin, MMP1 and MMP3 are overexpressed, inducing remodelling of the extracellular matrix in the dermis. Anti-acne products can decrease the expression level of these enzymes.In acne-prone skin, MMP1 and MMP3 are overexpressed, inducing remodelling of the extracellular matrix in the dermis. Anti-acne products can decrease the expression level of these enzymes. In acne-prone skin, MMP1 and MMP3 are overexpressed, inducing remodelling of the extracellular matrix in the dermis. Anti-acne products can decrease the expression level of these enzymes.The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Squalene overproduction and oxydation are observed in acne-prone skin. An anti-acne product decreases both the amount of squalene produced and the ratio of peroxidised squalene to squalene.Acne is an inflammatory disease, characterised by higher levels of inflammatory cytokines such as interleukin 8. An anti-acne product should reduce this level. Acne is an inflammatory disease, characterised by higher levels of inflammatory cytokines such as interleukin 8. An anti-acne product should reduce this level. Acne is an inflammatory disease, characterised by higher levels of inflammatory cytokines such as interleukin 8. An anti-acne product should reduce this level. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Acne is an inflammatory disease, characterised by higher levels of inflammatory cytokines such as interleukin 8. An anti-acne product should reduce this level. In acne-prone skin, the IA strain of P. acnes is more abundant and stimulates the production of IGF-1 by keratinocytes. An anti-acne product can reduce this production, which is correlated with keratinocyte proliferation and differentiation.In acne-prone skin, the IA strain of P. acnes is more abundant and stimulates the production of IGF-1 by keratinocytes. An anti-acne product can reduce this production, which is correlated with keratinocyte proliferation and differentiation.In acne-prone skin, the IA strain of P. acnes is more abundant and stimulates the production of IGF-1 by keratinocytes. An anti-acne product can reduce this production, which is correlated with keratinocyte proliferation and differentiation. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.In acne-prone skin, the IA strain of the P. acnes bacterium is more present and stimulates the production of involucrin by the keratinocytes. An anti-acne product can reduce this production, which is correlated with the differentiation of keratinocytes.In acne-prone skin, the IA strain of the P. acnes bacterium is more present and stimulates the production of involucrin by the keratinocytes. An anti-acne product can reduce this production, which is correlated with the differentiation of keratinocytes.In acne-prone skin, the IA strain of the P. acnes bacterium is more present and stimulates the production of involucrin by the keratinocytes. An anti-acne product can reduce this production, which is correlated with the differentiation of keratinocytes.KGF is a growth factor stimulating sebocyte and keratinocyte proliferation and differentiation. In acne-prone skin, overproliferation of keratinocytes and overproduction of sebum related to the proliferation and differentiation of sebocytes are observed. KGF is a growth factor stimulating sebocyte and keratinocyte proliferation and differentiation. In acne-prone skin, overproliferation of keratinocytes and overproduction of sebum related to the proliferation and differentiation of sebocytes are observed. KGF is a growth factor stimulating sebocyte and keratinocyte proliferation and differentiation. In acne-prone skin, overproliferation of keratinocytes and overproduction of sebum related to the proliferation and differentiation of sebocytes are observed. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.C. acnes is the dominant resident bacterial species in the sebaceous follicles. It includes various subtypes. The proportion of phylotype IA1, which virulence and inflammatory potential is higher than other phylotypes, is usually more abundant in acne-prone skin. An anti-acneic product acts by decreasing phylotype IA1 proportion.C. acnes is the dominant resident bacterial species in the sebaceous follicles. It includes various subtypes. The proportion of phylotype IA1, which virulence and inflammatory potential is higher than other phylotypes, is usually more abundant in acne-prone skin. An anti-acneic product acts by decreasing phylotype IA1 proportion.C. acnes is the dominant resident bacterial species in the sebaceous follicles. It includes various subtypes. The proportion of phylotype IA1, which virulence and inflammatory potential is higher than other phylotypes, is usually more abundant in acne-prone skin. An anti-acneic product acts by decreasing phylotype IA1 proportion. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of this assayPlease contact directly the testing laboratory to define the details of these specific studies.In acne-prone skin, high levels of testosterone, which is then converted to dihydrotestosterone (DHT) by 5-alpha reductase, leads to an overproduction of sebum. An acne product can restore normal sebum production by specifically targeting 5-alpha reductase. In acne-prone skin, high levels of testosterone, which is then converted to dihydrotestosterone (DHT) by 5-alpha reductase, leads to an overproduction of sebum. An acne product can restore normal sebum production by specifically targeting 5-alpha reductase. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Please contact directly the testing laboratory to define the details of this assay.Please contact directly the testing laboratory to define the details of this assay.Collagen IV is a major component of the dermal-epidermal junction and the basement membrane on which endothelial cells are attached. It is therefore essential for anchoring the epidermis and maintaining the integrity of the skin barrier. It is also involved in the skin barrier restoration during wound healing and it modulates keratinocyte proliferation and differentiationas well as endothelial cells.Collagen IV is a major component of the dermal-epidermal junction and the basement membrane on which endothelial cells are attached. It is therefore essential for anchoring the epidermis and maintaining the integrity of the skin barrier. It is also involved in the skin barrier restoration during wound healing and it modulates keratinocyte proliferation and differentiationas well as endothelial cells.Collagen IV is a major component of the dermal-epidermal junction and the basement membrane on which endothelial cells are attached. It is therefore essential for anchoring the epidermis and maintaining the integrity of the skin barrier. It is also involved in the skin barrier restoration during wound healing and it modulates keratinocyte proliferation and differentiationas well as endothelial cells.Collagen IV is a major component of the dermal-epidermal junction and the basement membrane on which endothelial cells are attached. It is therefore essential for anchoring the epidermis and maintaining the integrity of the skin barrier. It is also involved in the skin barrier restoration during wound healing and it modulates keratinocyte proliferation and differentiationas well as endothelial cells.Squalene overproduction and oxydation are observed in acne-prone skin. An anti-acne product decreases both the amount of squalene produced and the ratio of peroxidised squalene to squalene. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Biodegradability is used to assess the environmental characteristics of decomposition and mineralization by microorganisms of organic substances. The OECD distinguishes between “easy” biodegradability and “intrinsic” biodegradability. OECD testing methods are chosen based on the properties of each substance.Biodegradability is used to assess the environmental characteristics of decomposition and mineralization by microorganisms of organic substances. The OECD distinguishes between “easy” biodegradability and “intrinsic” biodegradability. OECD testing methods are chosen based on the properties of each substance.Biodegradability is used to assess the environmental characteristics of decomposition and mineralization by microorganisms of organic substances. The OECD distinguishes between “easy” biodegradability and “intrinsic” biodegradability. OECD testing methods are chosen based on the properties of each substance.Biodegradability is used to assess the environmental characteristics of decomposition and mineralization by microorganisms of organic substances. The OECD distinguishes between “easy” biodegradability and “intrinsic” biodegradability. OECD testing methods are chosen based on the properties of each substance.Biodegradability is used to assess the environmental characteristics of decomposition and mineralization by microorganisms of organic substances. The OECD distinguishes between “easy” biodegradability and “intrinsic” biodegradability. OECD testing methods are chosen based on the properties of each substance.Laminin 332 (previously called Laminin V) is an essential component of the dermal-epidermal junction. It allows epidermal attachment and modulates the differentiation of epidermal stem cells. Thus, Laminin 332 synthesis may modulate the skin barrier integrity and its function. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by immune cells, keratinocytes or sebocytes. Under the exposition of microorganisms such as S. epidermidis, C. acnes or S. aureus, it potentiates the skin resistance against pathogens. LL-37 shows broad antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungi including yeasts. LL 37 is overexpressed in various skin diseases such as Hidradenitis suppurativa, Rosacea or Psoriasis, and decreased in atopic dermatitis. In addition to its direct antimicrobial effects, it is also involved in many processes including the induction of the inflammatory response. To be completedTo be completedTo be completedConstantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. The expression of RNase 7 in keratinocytes can be induced by diverse stimuli such as cytokines, growth factors, and microbial factors. RNase 7 exhibits a potent broad spectrum of antimicrobial activity against various microorganisms and contributes to control bacterial growth on the skin surface. The ribonuclease and antimicrobial activity of RNase 7 can be blocked by the endogenous ribonuclease inhibitor. There is also increasing evidence that RNase 7 exerts immunomodulatory activities and may participate in antiviral defense.To be completedTo be completedTo be completedHuman beta-defensin-2 (BD-2) is a cysteine-rich low molecular weight antimicrobial peptide. It is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive Staphylococcus aureus. BD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as Pseudomonas aeruginosa or cytokines such as TNF-alpha and IL-1 beta. BD-2 has also pro-inflammatory and chemotactic properties. To be completedTo be completedTo be completedThe skin is colonized by a diverse microbiota which composition depends on many factors including the body location (moist, dry or sebaceous area), the age, the climate, individual variations, etc... A disturbance of skin microbiota composition (dysbiosis) may lead to or be correlated with various skin diseases. For example, a disturbance affecting either Staphylococcus aureus (S. aureus) or epidermis (S. epidermidis) and Cutibacterium acnes (C. acnes) is respectively associated with atopic dermatitis or common acne, Studying its composition, in vitro or in vivo, may therefore be of great interest.To be completedTo be completedThe skin is colonized by a diverse microbiota which composition depends on many factors including the body location (moist, dry or sebaceous area), the age, the climate, individual variations, etc... A disturbance of skin microbiota composition (dysbiosis) may lead to or be correlated with various skin diseases. Evaluating the resistance of one or more microorganisms to a particular product or ingredient can ensure its safety or, on the contrary, its targeted effectiveness in stopping the development of a particular microorganism. For example, Staphylococcus aureus (S. aureus), which tends to overproliferate, can be targeted in the context of atopic dermatitis, whereas Cutibacterium acnes (C. acnes) or sometimes Staphylococcus epidermidis (S. epidermidis) will be targeted in the context of acne.To be completedThe skin is colonized by a diverse microbiota whose composition depends on many factors such as the location of the body (wet, dry or sebaceous zone), age, climate, inter-individual variations, etc. A disturbance in the composition of the skin microbiota (dysbiosis) can lead to or be correlated with various skin diseases. Targeting specifically the microorganism that overproliferates without affecting the others can then be an effective treatment of the disease. For example, Staphylococcus aureus (S. aureus) can be targeted in the context of atopic dermatitis where it overproliferates, while Cutibacterium acnes (C. acnes) will be targeted in the context of acne. Determining the Minimum Inhibitory Concentration (MIC) of a product or an ingredient is to determine the lowest concentration for which this product or active ingredient inhibits the growth of a particular bacteria. This product can be used when the MIC is low with the targeted bacteria and higher with non-targeted bacteria. To be completedThe bacterial pathogen Staphylococcus aureus (S. aureus) plays an important role in atopic dermatitis (AD). As the outermost layer of the skin is the stratum corneum composed by corneocytes, S. aureus-corneocyte adhesion constitutes the first step in skin colonization. A correlation between the strength of S. aureus-corneocyte adhesion and AD symptom severity has been established. Measuring the effect of a molecule on the ability of S. aureus to adhere to corneocytes is therefore a possible way to demonstrate the potential effect of that molecule on AD.To be completedSeveral skin diseases are correlated with skin colonization by pathogens. For example, an overproliferation of Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes) are respectively correlated with atopic dermatitis and acne. In both cases, skin colonization induces the production of various pro-inflammatory cytokines which level may be measured to evaluate the severity of the inflammatory response. These cytokines can be for example TSLP, TNFα, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17,IL-18, IL-19, IL-31 or IL-33.To be completedPlease contact directly the testing laboratory to define the details of these specific studies.To be completedPlease contact directly the testing laboratory to define the details of this assay. To be completedTo be completedTo be completedTo be completedSterol regulatory element binding proteins (SREBPs) are a family of transcription factors which promote fatty acid production (SREBP1a/c) and cholesterol synthesis (SREBP2) involved in adipocyte lipogenesis. SREBP1 therefore represents a key target for a slimming agent. To be completedTo be completedTo be completedTo be completedTo be completedPPARγ is a nuclear receptor regulating many functions in diverse cell types, including especially the development of adipose tissue by coordinating many hundreds of genes responsible for the establishment of the mature adipocyte phenotype. It stimulates in particular the expression of the Fatty Acid Transporter FATP1, which main role in adipocytes is to favor insulin-induced fatty acid uptake. FATP4 is also expressed in adipocytes and its expression level correlates well with obesity, thus representing an interesting target to prevent or treat obesity. Nevertheless,it seems to regulate PPARgamma expression and participate in lipolysis rather than playing a role in fatty acid uptake. PPARγ is a nuclear receptor regulating many functions in diverse cell types, including especially the development of adipose tissue by coordinating many hundreds of genes responsible for the establishment of the mature adipocyte phenotype. It stimulates in particular the expression of the Fatty Acid Transporter FATP1, which main role in adipocytes is to favor insulin-induced fatty acid uptake. FATP4 is also expressed in adipocytes and its expression level correlates well with obesity, thus representing an interesting target to prevent or treat obesity. Nevertheless,it seems to regulate PPARgamma expression and participate in lipolysis rather than playing a role in fatty acid uptake. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Adipose tissue (visceral or subcutaneous fat) has an important store of triacylglycerol that can be hydrolysed in a regulated way to release free fatty acids (FFA) into the circulation for delivery to other tissues. Fat storage thus depends on the balance between FFA uptake and release by adipocytes. These mechanisms are regulated for example by insulin wich stimulates fat storage and inhibits fat mobilization. On the contrary, a slimming product will promote the release and the use of fatty acids while limiting their uptake and storage.To be completedAdipose tissue mainly contain adipocytes, a cell type that is specialized to synthesize and store large globules of fat. The white adipose tissue expands in response to over-nutrition so that the excess calories can be safely stored as triacylglycerol (TAG), preventing toxic lipid accumulation in non-adipose tissues. De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. A series of coordinated enzymatic reactions are involved in the flow of carbons from glucose to fatty acids. A slimming agent can target one of these reactions to limit fat accumulation, possibly by affecting their control system. DNL is controlled by various factors such as the mechanistic target of rapamycin complex 2 (mTORC2) which regulates glucose uptake and de novo lipogenesis, or adiponectin, which is produced by adipocytes and increases as fat mass decreases, thus favoring GLUT4-mediated glucose uptake and enhancing adipogenesis and adipocyte lipid storage. A slimming agent can also favor lipolysis. To be completedTo be completedTo be completedPlease contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of this assay. To be completedTo be completedCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingCountingTheoretical analysis: hypothesis that the entire container is solubilised in the contents. It defines critical substances when there is accurate data on material composition. The different materials of the packaging are separated and subjected each to specific incubation conditions (3 hours to 100°C for example). 4 solvents of different polarity are used to isolate extractables and potentially critical migrants. Visual and olfactory assessment of packaging and product variations after specific temperature and duration incubationExposure of packaging materials to physically-chemically defined excipients as close to the container years from normal operating conditions (duration, humidity, temperature) Analysis of interactions with the complete product after specific incubation (temperature, humidity, duration) In acne-prone skin, high levels of testosterone, which is then converted to dihydrotestosterone (DHT) by 5-alpha reductase, leads to an overproduction of sebum. An acne product can restore normal sebum production by specifically targeting 5-alpha reductase. In acne-prone skin, high levels of testosterone, which is then converted to dihydrotestosterone (DHT) by 5-alpha reductase, leads to an overproduction of sebum. An acne product can restore normal sebum production by specifically targeting 5-alpha reductase. To be completedTo be completedThe analysis method is defined by each laboratory in function of each searched substance: HPLC, UV, HPLC-MS, HPLC/MSMS, GC/FID, GC/MS, QTOF-MS, ORBI-TRAP, ICP/AES, ICP/MS, ICP/MSMS, MEB-EDX, DRX, DSC, ATG, ...To be completedTo be completedEvaluation of the decrease in contamination to levels ensuring the microbial limits established for Categories 1 and 2, after an artificial contamination of the product by Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus brasiliensisMeasurement of water activity in oil, powders and other low water content productsDetection on a non-selective agar of viable microorganisms and the microbial growth inhibitionDetection on a non-selective agar of viable microorganisms and the microbial growth inhibitionEvaluation of the contamination level of the yeast and moulds except pathogens Determination of the DLU (date of minimum durability). Evaluation of the microbiological, chemical, physical stability of the product under specific storage conditions of temperature, humidity and light : laboratory conditions, accelerated conditions or real time conditions of use, specific for each product.Theoritical definition for products durability under 30 months. Evaluation of the microbiological, chemical, physical stability of the product under specific storage conditions of temperature, humidity and light : laboratory conditions, accelerated conditions or real time conditions of use, specific for each product. Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.The HPRT system detects base pair mutations, frameshift mutations, small deletions and insertions.It is a genomic test measuring changes in gene expression of 200 genes relevant to the skin sensitization adverse outcome pathways (AOP).To assess distinction between sensitizing skin products and non- sensitizing skin products to classify and label the dangers of the product in an IATA (Integrated Approaches to Testing and Assessment). cf.OECD TGP 4.106MTT (3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide; thiazolyl blue) is a water soluble tetrazolium salt yielding a yellowish solution when prepared in media or salt solutions lacking phenol red. Dissolved MTT is converted to an insoluble purple formazan by cleavage of the tetrazolium ring by dehydrogenase enzymes. This water-insoluble formazan can be solubilized using isopropanol or other solvents, and the dissolved material is measured spectrophotometrically using absorbance as a function of concentration of converted dye.Measure of the cellular viability on oral epithelium. Other endpoints other than MTT/Histology are considered: e.g. TEER, LDH release, IL-1a release, ultrastructural analysis by SEM (partnered),…Assessment of the ability of a test chemical to induce cytotoxicity in a RhCE tissue. Tissue viability is measured by enzymatic conversion of the vital dye MTT by the viable cells of the tissue into a blue MTT formazan salt. Genomic Allergen Rapid Detection. Measurement of levels of gene transcripts in human myeloid origin cells. GARDpotency is an add-on to GARDskin, able to cf. OECD TGP 4.106.The goal of the study is to evaluate the potential toxicity of reference compounds on daily exposure. The viability, cytotoxicity and inflammation to small and large airways can be also evaluated.Identification of skin sensitisers and to rank sensitisers according to their potency. It combines viability measurement (MTT-Assay) with the detection of Interleukin-18 secretion from epiCS.This Skin Sensitisation and Potency. It is easy to perform and results strongly correlate with LLNA and human DSA data..Skin ageing is associated with an increase in senescent cell percentage. As β-galactosidase activity increases significantly in senescent cells, this marker is commonly used to assess the extent of skin ageing. An anti-ageing product can therefore decrease this activity.Method for identifying water soluble ocular corrosives and severe irritants as defined by the UN Globally Harmonized System of Classification and Labelling, Category 1. The assay is performed in a well where a confluent monolayer of Madin-Darby Canine Kidney (MDCK) is used as a separation between two chambers. It uses a fluorescein dye as marqueur. The test substance has the potential to impair the junctions of the MDCK cells and thus to increase the monolayer¡¯s permeability. Consequently the fluorescein passes through the monolayer and the fluorescein leakage (FL) increases. This Test method has been designed to provide information on a test substance absorption after its application to the surface of a skin sample separating the two chambers (a donor chamber and a receptor chamber) of a diffusion cell (Franz cell). The substance application should mimic human exposure, normally 1-5 mg/cm2 of skin for a solid and up to 10 µl/cm2 for liquids. Passage kinetics are determined by dosing the active substance at regular intervals in the fluid of the receiving compartment. As the skin is able to metabolize certain substances during percutaneous absorption, the metabolites of the test substance can also be analyzed. The cleavage product of XTT is soluble in water; a solubilization step is therefore not required. The tetrazolium salt XTT is cleaved to formazan by a complex cellular mechanism. This bioreduction occurs in viable cells only, and is related to NAD(P)H production through glycolysis. The test material (150 µL for liquids or solid with 150 µL of deionised water added on the top) is applied for up to 24 hours to the epidermal surfaces of skin discs (three skin discs are used for each test and control substance) in a two-compartment test system in which the skin discs function as the separation between the compartments. A dye-binding step incorporated into the test procedure permits to determine if the increase in ionic permeability is due to physical destruction of the stratum corneumThe time (in minutes) elapsed between application of the test substance to the membrane barrier and barrier penetration is used to predict the corrosivity of the test substance.The test method utilizes an artificial membrane designed to respond to corrosive substances in a manner similar to animal skin in situ. The test system is composed of two components, a synthetic macromolecular bio-barrier and a Chemical Detection System (which one detect the test substance). This test provides information on the availability by measuring the absorption of a test substance, applied to the surface of a skin sample separating two chambers (a donor chamber and a receptor chamber) of a diffusion cell. Static and flow-through diffusion cells are both acceptable. The NRU assays test eight concentrations of the test substance or the positive control (PC) by diluting the stock test substance solution in log dilutions to cover a large concentration range. This method evaluate cytotoxicity by the relative reduction in viability of cells exposed to the chemical in the presence versus absence of light. Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Please contact directly the testing laboratory to define the details of these specific studies.Interleukin 1 alpha (IL-1α) is a key pro-inflammatory cytokine of the innate immune response. It is released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. It is involved in various inflammatory skin diseases and is overexpressed in atopic dermatitis.Interleukin 1 alpha (IL-1α) is a key pro-inflammatory cytokine of the innate immune response. It is released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. It is involved in various inflammatory skin diseases and is overexpressed in atopic dermatitis.Interleukin 1 alpha (IL-1α) is a key pro-inflammatory cytokine of the innate immune response. It is released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. It is involved in various inflammatory skin diseases and is overexpressed in atopic dermatitis.CD1a is abundantly expressed on epidermal Langerhans cells and dermal dendritic cells which are implicated in contact dermatitis. After binding to allergens, CD1a is involved in T cell activation and therefore inflammatory response. It has been shown that a higher expression of CD1a augments intradermal T cell responses to some allergens. Moreover, a higher density of CD1a-positive Langerhans cells has been found in atopic dermatitis skin patients compared to healthy skin, with differences in the location and appearances of the cells. Spontaneous mutations or various factors such as UV radiation can cause cellular DNA damages. Some enzymes normally repair DNA. However, more and more alterations tend to accumulate during skin aging increasing the risk of cancer development. More or less innovative techniques can be used to assess the efficiency and relevance of DNA repair systems in cell cultures or biopsies. Spontaneous mutations or various factors such as UV radiation can cause cellular DNA damages. Some enzymes normally repair DNA. However, more and more alterations tend to accumulate during skin aging increasing the risk of cancer development. More or less innovative techniques can be used to assess the efficiency and relevance of DNA repair systems in cell cultures or biopsies. Spontaneous mutations or various factors such as UV radiation can cause cellular DNA damages. Some enzymes normally repair DNA. However, more and more alterations tend to accumulate during skin aging increasing the risk of cancer development. More or less innovative techniques can be used to assess the efficiency and relevance of DNA repair systems in cell cultures or biopsies. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Free radicals are produced in cells by cellular metabolism and exogenous agents. These species react with biomolecules in cells, including DNA, leading for example to H- and OH- abstraction and addition. Further reactions of these radicals yield numerous products such as glycol, dTG, and 8-hydroxy-2-deoxyguanosine (oxidative nucleotides), and result in DNA base modifications leading to abnormalities at genomic level (mutations, translocations, gene inactivation). Thus, the oxidative damage to DNA is implicated in mutagenesis, carcinogenesis, and aging. Various analytical techniques exist for the measurement of oxidative damage to DNA and associated products, allowing to screen antioxidant molecules able to prevent these damages. Some enzymes normally repair DNA. However, more and more alterations tend to accumulate during skin aging increasing the risk of cancer development. More or less innovative techniques can be used to assess the efficiency and relevance of DNA repair systems in cell cultures or biopsies.To be completedTo be completedAdipocytes secrete numerous factors that circulate in blood and act on distal tissues, and they also mediate local autocrine/paracrine effects, to influence food intake, energy expenditure, and carbohydrate and lipid metabolism. Adiponectin (also known as apM1, AdipoQ, Gbp28, and Acrp30) is one of these adipocyte-derived factors. Adiponectin, which increases as fat mass decreases, enhances insulin sensitivity and acts locally on the adipocyte to increase GLUT4-mediated glucose uptake while enhancing adipogenesis and adipocyte lipid storage. The key molecule involved in skin moisture is hyaluronic acid (HA). It corresponds to the main skin extracellular matrix glycosaminoglycan and has unique capacity in retaining water, thus allowing for proper skin suppleness and stiffness. Mainly involved in skin hydration, lubrication of joints and space filling, Hyaluronic Acid (HA) also constitutes a framework through which cells migrate. Almost all cells can attach HA via membrane receptors (either CD44 or RHAMM), including inflammatory cells which may be activated to enhance immune response. Interestingly, HA of high molecular size (>1,000kDa) is antiangiogenic and immunosuppressive, whereas smaller polymers of HA which accumulates during inflammation are potent inducers of inflammation and angiogenesis. Enzymes are used to cleave RNA into a small single-stranded fragment of 21 to 24 long nucleotides. Thus matured, microRNAs can regulate gene expression, by pairing with messenger RNAs carrying a homologous sequence. These are then degraded, or their translation is inhibited. Enzymes are used to cleave RNA into a small single-stranded fragment of 21 to 24 long nucleotides. Thus matured, microRNAs can regulate gene expression, by pairing with messenger RNAs carrying a homologous sequence. These are then degraded, or their translation is inhibited. Enzymes are used to cleave RNA into a small single-stranded fragment of 21 to 24 long nucleotides. Thus matured, microRNAs can regulate gene expression, by pairing with messenger RNAs carrying a homologous sequence. These are then degraded, or their translation is inhibited. Measure of the O2 consumption and the mitochondry activity. Measure of the O2 consumption and the mitochondry activity. Measure of the O2 consumption and the mitochondry activity. Mitochondria is the place of breathing and cellular energy production with the conversion of glucose to ATP. This process also involves O2 consumption and the production of reactive oxygen species (ROS) which level increases with ageing. ROS modulate epidermal differentiation but also collagen biosynthesis and degradation. They play therefore a role in skin regeneration and healing. An active ingredient may thus target mitochondria activity to improve skin regeneration either by boosting ATP production or by scavenging the excess amounts of free radicals. Mitochondria is the place of breathing and cellular energy production with the conversion of glucose to ATP. This process also involves O2 consumption and the production of reactive oxygen species (ROS) which level increases with ageing. ROS modulate epidermal differentiation but also collagen biosynthesis and degradation. They play therefore a role in skin regeneration and healing. An active ingredient may thus target mitochondria activity to improve skin regeneration either by boosting ATP production or by scavenging the excess amounts of free radicals. Mitochondria is the place of breathing and cellular energy production with the conversion of glucose to ATP. This process also involves O2 consumption and the production of reactive oxygen species (ROS) which level increases with ageing. ROS modulate epidermal differentiation but also collagen biosynthesis and degradation. They play therefore a role in skin regeneration and healing. An active ingredient may thus target mitochondria activity to improve skin regeneration either by boosting ATP production or by scavenging the excess amounts of free radicals. Mitochondria is the place of breathing and cellular energy production with the conversion of glucose to ATP. This process also involves O2 consumption and the production of reactive oxygen species (ROS) which level increases with ageing. ROS modulate epidermal differentiation but also collagen biosynthesis and degradation. They play therefore a role in skin regeneration and healing. An active ingredient may thus target mitochondria activity to improve skin regeneration either by boosting ATP production or by scavenging the excess amounts of free radicals. Cell respiration and cellular energy production occur in mitochondria with the conversion of glucose into ATP, particularly during the Krebs cycle and the respiratory chain. This process involves O2 consumption and leads to the production of reactive oxygen species (ROS). Physiologically, an increase in ROS production related to mitochondrial activity is correlated with an increase in O2 consumption. An antioxidant agent can target mitochondrial activity to decrease ROS production. Mitochondria is the place of breathing and cellular energy with the conversion of glucose to ATP. This process includes several stages of metabolic reactions, including the "Krebs cycle." Mitochondria is the place of breathing and cellular energy with the conversion of glucose to ATP. This process includes several stages of metabolic reactions, including the "Krebs cycle." Mitochondria is the place of breathing and cellular energy with the conversion of glucose to ATP. This process includes several stages of metabolic reactions, including the "Krebs cycle." Measure of the O2 consumption and the mitochondry activity. The extracellular matrix synthesised by fibroblasts contains carbohydrate macromolecules called glycosaminoglycans (GAGs) which are generally covalently linked to a protein to form proteoglycans. These molecules (especially hyaluronic acid) contribute to the suppleness and firmness of the skin by promoting its hydration. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Sebaceous gland sensitivity to androgens relies on the presence of AR in sebocytes. Its presence allows the in vitro model used to be validated and anti-acne products can specifically target this receptor to reduce the amount of sebum produced. Sebaceous gland sensitivity to androgens relies on the presence of AR in sebocytes. Its presence allows the in vitro model used to be validated and anti-acne products can specifically target this receptor to reduce the amount of sebum produced. Sebaceous gland sensitivity to androgens relies on the presence of AR in sebocytes. Its presence allows the in vitro model used to be validated and anti-acne products can specifically target this receptor to reduce the amount of sebum produced. Sebaceous gland sensitivity to androgens relies on the presence of AR in sebocytes. Its presence allows the in vitro model used to be validated and anti-acne products can specifically target this receptor to reduce the amount of sebum produced. Aquaporins correspond to channels facilitating the transfer of water and small molecules across cell membranes. During skin ageing, the decreased expression level of genes coding for aquaporins seems to be correlated with the progressive dehydration of the skin. An anti-ageing product will therefore be able to promote skin hydration by maintaining a greater quantity of aquaporins.Aquaporins correspond to channels facilitating the transfer of water and small molecules across cell membranes. During skin ageing, the decreased expression level of genes coding for aquaporins seems to be correlated with the progressive dehydration of the skin. An anti-ageing product will therefore be able to promote skin hydration by maintaining a greater quantity of aquaporins.Aquaporines correspond to channels facilitating the transfer of water and small molecules across cell membranes. During skin ageing, the decreased expression level of genes coding for aquaporins seems to be correlated with the progressive dehydration of the skin. An anti-ageing product will therefore be able to promote skin hydration by maintaining a greater quantity of aquaporins.Characterisation of the visco-elastic properties of skin with Atomic Force Microscopy.To be completedCCAAT/enhancer binding protein β (C/EBPβ) plays a key role in preadipocyte differentiation. Induced early, C/EBPβ elicits the expression of C/EBPα and peroxisome proliferator-activated receptor gamma (PPARγ), two master transcription factors for terminal adipocyte differentiation. CCAAT/enhancer binding protein α (C/EBPα) stimulates the expression of many genes such as adipose P2 protein (aP2), stearoyl-CoA desaturase 1 (SCD1), and glucose transporter 4 (GLUT4), thus allowing the accumulation of cytoplasmic triglyceride. PPARγ is a nuclear receptor also regulating many functions in diverse cell types, including especially the development of adipose tissue by coordinating many hundreds of genes responsible for the establishment of the mature adipocyte phenotype. These 3 molecules therefore represent potentially very interesting targets in the treatment of obesity. To be completedElastic fibers are an essential component of the extracellular matrix (ECM), allowing skin recoil after transient stretching. Elastic fibers consist of an elastin core covered by a sheath of microfibrils, which are composed of several distinct glycoproteins including fibrillin. Elastin is a highly hydrophobic protein (≈750 amino acids long). Soluble tropoelastin is secreted into the extracellular space, where it forms lysine cross-links to other tropoelastin molecules to generate a large network of elastin fibers and sheets. Elastin-binding fibrillin is also essential for the integrity of the elastic fibers. Microfibrils appear before elastin in developing tissues and seem to form a scaffold on which the secreted elastin molecules are deposited. Elastic fiber network is progressively established during late gestation and in early life, remaining stable throughout life as elastin turnover approaches the life span (in circumstances not involving a wound). A progressive degradation is correlated with ageing, affecting skin mechanical integrity. The synthesis and degradation of elastic fibers, which are thus a major component of skin mechanical integrity, can be modulated by several growth factors (such as IGF-1, TGF-β, FGF) or other components thus targeting skin mechanical integrity. To be completedTo be completedTo be completedThe colour of the skin, hair and eyes is determined both by the quantity of melanin (darker skin with larger amounts) and the ratio between the two types of melanic pigments: eumelanin and pheomelanin. This pigments are the final products of complex biochemical reactions occuring in specific melanocyte organelles called melanosomes. Melanosomes are then distributed to neighbouring cells and stored in the basal layer keratinocytes, as well as in dermal macrophages which become melanophores. The process of melanin synthesis and distribution is called melanogenesis. Skin pigmentation directly depends on this mecanism and the degree of pigmentation is well-reflected by the dosage of melanin. Melanin has a major role in skin homeostasis by absorbing and/or reflecting ultraviolet radiation but also by neutralizing free radicals and reactive oxygen species. To be completedHuman primary adipocytes are spherical monovacuolar cells, typically 50 to 200 μm in diameter, that contain a single centrally located lipid droplet taking up to 90% of the cytoplasm, and displacing the nucleus to the periphery of the cell. The lipid droplet is stabilized by a surrounding monolayer of phospholipids, which is decorated with adherent proteins, in particular Perilipin 1 (PLIN1). PLIN1 regulates lipid metabolism in adipocytes by serving as a physical barrier as well as a recruitment site for lipases to the lipid droplet. Its phosphorylation by protein kinase A is known to rapidly initiate lipolysis. When testing the slimming effect of a product, PLIN1 can therefore be used as a marker to follow the evolution of lipid droplets. PLIN1 can also constitute a target to limit or promote lipolysis. The blocking capacity of the sweat production of an antiperspirant is measured by studying the interaction between sweat and product. SOD4 and Smart-Pore™ allow us to visualize this phenomenon. Smart-Pore™ is a microfluidic consumable that mimics human sweat pore. SOD4 is a fluid control instrument that mimics sweat production. SOD4 measures in real time the interaction between sweat and the product. It provides information on the kinetics of the formed cap as well as the unblocking pressure required to expel the pore. It is possible to link this unblocking pressure to commercial efficiency claims (24 hours a day). By counting the colonies on agar medium after aerobic incubation, or by checking the absence of bacterial growth after enrichment.Detection on a non-selective liquid of viable microorganisms and the microbial growth inhibitionDetection on a non-selective liquid medium of viable microorganisms and the microbial growth inhibitionDetection on a non-selective liquid medium of viable microorganisms and the microbial growth inhibitionDetection in a non-selective liquid medium of viable microorganisms and the microbial growth inhibition. NF18416. EN18416. ISO18416Genomic method5α-reductases are microsomal enzymes responsible for the formation of 5α-dihydrotestosterone (DHT), either through conversion of androstenedione (4-dione) to androstanedione (A-dione) and subsequent 17-oxidoreduction, or through direct conversion of testosterone (testo) to DHT. In adipose tissue, androgens such as DHT and testo inhibit preadipocyte differentiation, decrease triglyceride synthesis and increase lipolysis. 4-dione is the main source of DHT in human preadipocytes and DHT formation through 5α-reductase activity mediates most of the inhibitory effects of 4-dione and testo on preadipocyte differentiation. 5α-reductase type 3 seems to be the main isoform in adipose tissue.To be completedTo be completedThe epidermis is a stratified squamous epithelium composed primarily of keratinocytes that undergo sequential changes in gene expression during differentiation. The epidermis is a stratified squamous epithelium composed primarily of keratinocytes that undergo sequential changes in gene expression during differentiation. ColVI exerts different roles in the tissues where it is expressed, spanning from mechanical roles, which are typical of collagen components of the ECM, to more specific cytoprotective functions; these include inhibition of apoptosis and oxidative damage, the regulation of cell differentiation and of the autophagic machinery, and maintenance of cell stemness.ColVI exerts different roles in the tissues where it is expressed, spanning from mechanical roles, which are typical of collagen components of the ECM, to more specific cytoprotective functions; these include inhibition of apoptosis and oxidative damage, the regulation of cell differentiation and of the autophagic machinery, and maintenance of cell stemness.The intercellular lipids are composed of free fatty acids, cholesterol, and ceramides. In conjunction with the other stratum corneum lipids, they form ordered structures. An essential factor is the physical state of the lipid chains in the nonpolar regions of the bilayers.The extracellular matrix synthesised by fibroblasts contains carbohydrate macromolecules called glycosaminoglycans (GAGs) which are generally covalently linked to a protein to form proteoglycans. These molecules (especially hyaluronic acid) contribute to the suppleness and firmness of the skin by promoting its hydration. Malassezia furfur is a lipid-dependent yeast commonly found in the healthy skin areas rich in sebaceous glands, especially the trunk, face and scalp. M. furfur has also been associated with the development of several skin diseases such as seborrheic dermatitis (SD), pityriasis versicolor (PV), and Malassezia folliculitis (MF). Infection results when the dimorphic yeast changes to its mycelial form. Infection is associated with inflammation in SD and MF. Targeting M. furfur can therefore help to reduce the infection, rebalance skin microbiota, and reduce inflammation. This effect can be assessed by monitoring M. furfur shape. NMF is mainly composed of amino acids derived from filaggrin degradation. It is involved in the maintenance of skin hydration, on which the barrier function, the skin suppleness and plasticity, the desquamation process and skin homeostasis depend. During skin aging, the NMF content decreases, thus increasing skin dryness. Confocal microscopy, most frequently confocal laser scanning microscopy (CLSM) or laser confocal scanning microscopy (LCSM), is an optical imaging technique for increasing optical resolution and contrast of a micrograph by means of using a spatial pinhole to block out-of-focus light in image formation. AFM analysis of subcutaneous adipoe tissue taken from an explant and cryosection of this tissueAFM analysis of the physical behaviour of fibroblasts coated upon collagen matrix.AFM imaging of newly-formed cell-cell junctions and mechanical measurements of cell junction stiffness and actin cytoskeleton.Mechanical studies of skin's cells and tissues behaviour under external factors, by studying applied forces.Confocal microscopy, most frequently confocal laser scanning microscopy (CLSM) or laser confocal scanning microscopy (LCSM), is an optical imaging technique for increasing optical resolution and contrast of a micrograph by means of using a spatial pinhole to block out-of-focus light in image formation.Study with AFM of morphometric parameters of collagen network.Visualisation and characterisation of the lipid matrix within the stratum corneum through skin explants with AFM technology.BioMeca visualizes and characterizes organization of collagen network, strength of cell-matrix interaction and cell traction force by Atomic Force Microscopy.Second-harmonic imaging microscopy (SHIM) is based on a nonlinear optical effect known as second-harmonic generation (SHG). SHIM has been established as a viable microscope imaging contrast mechanism for visualization of cell and tissue structure and function. XPolar® technology is an imaging polarization solution for measuring the birefringence of the samples. The birefringence value is measured in each pixel of the image. The method is based on a non-contact technique that does not cause any degradation in the handling of samples. XPolar® technology is an imaging polarization solution for measuring the birefringence of the samples. The birefringence value is measured in each pixel of the image. The method is based on a non-contact technique that does not cause any degradation in the handling of samples. XPolar® technology is an imaging polarization solution for measuring the birefringence of the samples. The birefringence value is measured in each pixel of the image. The method is based on a non-contact technique that does not cause any degradation in the handling of samples. The principle of the trial is to generate intracellular radical species in a controlled way through an induction photo process based on the use of the orange thiazole (TO). The presence of ROS species leads to cellular alteration and an increase in the level of fluorescence.The assay relies on the stimulation of Nrf2 transcription factor and its binding on the Antioxidant Response Element, an enhancer sequence of many genes coding for antioxidant, detoxification and cytoprotective proteins. The increase of gene expression is measured by luminescence. The assay is based on the intracellular presence of a DNA biosensor whose fluorescence increases in presence of H2O2. Decrease or time delayed increase of fluorescence indicates capacity of sample to neutralize (scavenge) H2O2 in a catalase-like reaction. The LUCS technology is based on photo-induction of Thiazole Orange (TO) leading to a fluorescence signal. A fluorescence increase is only observed on cells in homeostasis prior to TO addition. Calculation of the fluorescence ratios before and after LED application leads to an accurate and dose-dependent measurement of the state of cellular damage that follows chemical or physical toxicity induced by the sample.The different skin flora bacterial strains are pre-grown in appropriate conditions. Bacteria are then re-seeded at low optical density [OD] in order to record bacterial growth on a large window of time, which allow to assess the sample protective effect at the beginning of exponentially growing stage and then for the time needed, at least 4h30.When cells are treated with a radical generator such as 2,2'-azobis (2-amidinopropane) dihydrochloride [AAPH], peroxyl radicals [ROO.] are produced at the plasma membrane level, triggering transformation of intracellular non-fluorescent DCFH into fluorescent dichlorofluorescein [DCF]. Consequently, a decrease in cellular fluorescence in AAPH-treated cells indicates an antioxidant effect of the sample at the level of ROO.s.The Ocular Irritection® Assay System is a standardized, quantitative in vitro test method which utilizes changes of relevant macromolecules to predict the ocular irritancy of chemicals, mixtures and product formulations. Changes in protein structure induced by the test substance can be easily quantified by measuring the resulting changes in turbidity (OD405) of the reagent solution.The Dermal Irritection® Assay System is a standardized, quantitative in vitro test method which utilizes changes of relevant macromolecules to predict the dermal irritancy of chemicals, mixtures and product formulations. Changes in protein structure induced by the test substance can be easily quantified by measuring the resulting changes in turbidity (OD405) of the reagent solution.A glass vial is filled with a chemical detection liquid, coated with a proprietary bio-barrier membrane. The test sample is applied to the membrane. The speed at which it passes through the membrane correlates with its corrosion potential and is revealed by the speed at which the underlying liquid becomes colored. The test substance is placed in the presence of a bacterial suspension and, after a given time, the survival rate of the bacteria is evaluated. The test substance is placed on a surface formed from a bacterial or fungal suspension and, after a given time, the survival rate of the organisms is evaluated.The test substance is placed on a surface formed from a fungal or yeast suspension and, after a given time, the survival rate of the organisms is evaluated. Search for the genetic signatures of plant species and verification of their identity and authenticity using a DNA sequencer using the Sanger sequencing technique.Traceability of plant raw materials and identification of contamination and fraud on ingredients and finished products. Search for the genetic signatures of plant species and verification of their identity and authenticity using a DNA sequencer using the Sanger sequencing technique.In-vitro evaluation on the packaging of the SPF and UVAPF and critical walenlenght with or without pre-irradiation.Measurement of the protection index and of the critical walenlenght under specific conditions of ageing.The substance to test is first placed in the presence of a bacterial suspension and, after a given time, the survival rate of the bacteria is evaluated. Then, this rate is evaluated after application on hands, instruments or surfaces. The fungicide or yeast killer effect of the product is assessed on Candida albicans and Aspergillus brasiliensis under the following conditions: - Hand rubbing (hand scrub) or hygienic hand washing ; - Friction (surgical hand scrub) or surgical hand washing ; - Disinfection of medical equipment.The product to be tested is applied on the hands previously contaminated with Escherichia coli of volunteers. The survival rate of the bacteria is then evaluated and compared to that obtained with a reference product. The product to be tested is applied on the hands previously contaminated with Escherichia coli of volunteers. The survival rate of the bacteria is then evaluated and compared to that obtained with a reference product. Based on the elements of the asset bibliography, the scientific concept and the desired claims, the choice of the tests and assay supports most relevant to objective and/or enhance the effectiveness of the actives ingredients and finished products. From the choice of biomarkers, analysis methods and testing materials, recommendation of the most suitable providers. Review of protocols, follow-up of the study, processing of raw data and interpretation of results.Based on the results of in-vitro or ex-vivo studies and the most relevant results, reflection on innovative concepts, writing scientific media and storytelling.Alternative toxicity assay to Draize Rabbit Eye test. Visual exam. The CAMVA uses the vascularized membrane of fertile chicken eggs to assess a test material's potential to cause vascular changes (hemorraghing, capillary injection, ghost vessels). Resazurin Assay/HistologyThe TRPV1 channel is a well characterized pain receptor that is present in tissues associated with the eye. This channel can be activated by chemical stimuli (or heat) and is thought to be a general mediator of chemically induced pain on the surface of the eye, which can cause a stinging sensation in a clinical setting. This assay predicts the eye stinging potential of materials, such as cosmetics, sunscreens, surfactants, and ophthalmic products. Rather than classify a test material’s irritation potential into discrete regulatory categories, the ET50 screening protocol allows one to determine the irritation potential for materials covering a wide range of irritation responses from highly irritant materials to those which are extremely well tolerated.The amount of absorption is referred to as molar extinction coefficient (MEC)RSMN is used to evaluate the genotoxicity/mutagenicity potential of the test article to the EpiDerm™ Skin Model. Genotoxicity potential is determined by assessing whether the micronucleus frequency in tissues exposed to the test article showed a statistically significant increase relative to the tissues exposed to the solvent (negative) control. This method is based on the comparison of the Sun Protection Factor (SPF) on a dry then a sweat substrate and the calculation of sweat Skin percentage. The in chemico photo-DPRA incorporates a light exposure step into the standard DPRA protocol to determine if a compound becomes photoreactive in the presence of light.This method evaluate photo-cytotoxicity by the relative reduction in viability of cells exposed to the chemical in the presence versus absence of light. Cytotoxicity in this test is expressed as a concentration-dependent reduction of the uptake of the Vital dye Neutral Red (NR) when measured 24 hours after treatment with the test chemical and irradiation. Cell proliferation and differentiation allow to regenerate tissues. At the elderly, the regenerative capacity of the skin decreases, especially because the proportion of stem cells, which are able to multiply, decreases. The suggested methods therefore make it possible to assess the percentage of cells undergoing cell division (dermis and/or epidermis), or the speed at which they multiply. The skin acts as a barrier controlling exchanges between the external environment and the body. This function is maintained by the continuous proliferation and differentiation of keratinocytes. Several markers can be used to determine the differentiation status of keratinocytes. Following a skin lesion, cell migration towards the altered area (keratinocytes, fibroblasts, endothelial cells) allows tissue repair. The speed of healing therefore depends in particular on this migration capacity, which can be measured using various techniques.At the elderly, cell metabolism tends to slow down. At the skin level, this is highlited for example by a decrease in extracellular matrix production by fibroblasts. Various techniques measuring the secretion of molecules (collagen, elastin, etc.) or dosing biosynthesis enzymes make it possible to evaluate the intensity of metabolism. Cell proliferation and differentiation allow to regenerate tissues. At the elderly, the regenerative capacity of the skin decreases, especially because the proportion of stem cells, which are able to multiply, decreases. The suggested methods therefore make it possible to assess the percentage of cells undergoing cell division (dermis and/or epidermis), or the speed at which they multiply. The skin acts as a barrier controlling exchanges between the external environment and the body. This function is maintained by the continuous proliferation and differentiation of keratinocytes. Several markers can be used to determine the differentiation status of keratinocytes. KGF is a growth factor stimulating sebocyte and keratinocyte proliferation and differentiation. In acne-prone skin, overproliferation of keratinocytes and overproduction of sebum related to the proliferation and differentiation of sebocytes are observed. Air pollution can have a significant impact on the skin. It notably induces oxidative stress that may promote lipid peroxidation by reactive oxygen species (ROS), leading to the formation of malondialdehyde (MDA) and squalene monohydroperoxide. Thus, squalene peroxydation level and malondialdehyde formation may serve as potent biomarkers for evaluating potential anti-pollution claims of cosmetics products. The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin inflammation or metastasis, and skin hydration as a key cell receptor for hyaluronic acid.The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin inflammation or metastasis, and skin hydration as a key cell receptor for hyaluronic acid.The intercellular lipids are composed of free fatty acids, cholesterol, and ceramides. In conjunction with the other stratum corneum lipids, they form ordered structures. An essential factor is the physical state of the lipid chains in the nonpolar regions of the bilayers.The intercellular lipids are composed of free fatty acids, cholesterol, and ceramides. In conjunction with the other stratum corneum lipids, they form ordered structures. An essential factor is the physical state of the lipid chains in the nonpolar regions of the bilayers.Certification by a toxicologist that the product is safe for human health when used under normal or reasonably foreseeable conditions of useThe safety is evaluated on the basis of the relevant information according to Annex I of the regulation (EC) n°1223/2009.Compliance with the Part B of the Product Information File (PIF).Literature search. Advice in the choice of tests to be conducted in silico or in vitro to confirm the safety of products. Expertise in formula analysis. Advice in cosmetovigilance.Specific protocol developed by each laboratory. Safety Data Sheets [SDS] gather information on the safety of substances and mixtures and on hazards to the environment and human health, and on safety precautions.Analysis and advice in the valorization of the results of in-vitro or in-vivo evaluation studies.At the elderly, cell metabolism tends to slow down. At the skin level, this is highlited for example by a decrease in extracellular matrix production by fibroblasts. Various techniques measuring the secretion of molecules (collagen, elastin, etc.) or dosing biosynthesis enzymes make it possible to evaluate the intensity of metabolism. Following a skin lesion, cell migration towards the altered area (keratinocytes, fibroblasts, endothelial cells) allows tissue repair. The speed of healing therefore depends in particular on this migration capacity, which can be measured using various techniques.Cell proliferation and differentiation allow to regenerate tissues. At the elderly, the regenerative capacity of the skin decreases, especially because the proportion of stem cells, which are able to multiply, decreases. The suggested methods therefore make it possible to assess the percentage of cells undergoing cell division (dermis and/or epidermis), or the speed at which they multiply. The skin acts as a barrier controlling exchanges between the external environment and the body. This function is maintained by the continuous proliferation and differentiation of keratinocytes. Several markers can be used to determine the differentiation status of keratinocytes. Following a skin lesion, cell migration towards the altered area (keratinocytes, fibroblasts, endothelial cells) allows tissue repair. The speed of healing therefore depends in particular on this migration capacity, which can be measured using various techniques.At the elderly, cell metabolism tends to slow down. At the skin level, this is highlited for example by a decrease in extracellular matrix production by fibroblasts. Various techniques measuring the secretion of molecules (collagen, elastin, etc.) or dosing biosynthesis enzymes make it possible to evaluate the intensity of metabolism. At the elderly, cell metabolism tends to slow down. At the skin level, this is highlited for example by a decrease in extracellular matrix production by fibroblasts. Various techniques measuring the secretion of molecules (collagen, elastin, etc.) or dosing biosynthesis enzymes make it possible to evaluate the intensity of metabolism. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Collagen IV is a major component of the dermal-epidermal junction. It is therefore essential for anchoring the epidermis and maintaining the integrity of the skin barrier. It is also involved in the skin barrier restoration during wound healing and modulates keratinocyte proliferation and differentiation.In acne-prone skin, the IA strain of P. acnes is more abundant and stimulates the production of IGF-1 by keratinocytes. An anti-acne product can reduce this production, which is correlated with keratinocyte proliferation and differentiation.Corneocytes, the final stage of keratinocyte differentiation, are linked together by protein complexes called corneodesmosomes composed of proteins such as corneodesmosin (CDSN), desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Kallikrein 7, capable of cleaving CDSN and DSC1, and kallikrein 5, capable of cleaving CDSN, DSC1 and DSG1, are two proteolytic enzymes involved in the loss of cohesion of corneocytes associated with desquamation. The synthesis and activity of these 2 enzymes must therefore be correctly regulated to ensure desquamation and therefore epidermal renewal at an appropriate level.A film containing various lipids produced by sebaceous glands and keratinocytes covers the skin. Under various factors, including the production of reactive free radicals, skin lipids may be peroxidised. Reactive free radicals also induce cell and tissue damages. A correlation between the level of peroxidised lipids and a defect in wound healing has been reported and an active ingredient may improve skin regeneration or wound healing by decreasing lipid peroxidation. Adipocyte progenitor cells (APCs) provide the reservoir of regenerative cells to produce new adipocytes. They reside within the stromal vascular fraction of adipose tissue which contains a lot of CD34+ cells. CD34 is a membrane protein often used as a stemness marker. CD34+ / CD31+ / CD144+ cells correspond to endothelial cells while CD34+/ CD31- / CD144- cells are considered as APCs. Nevertheless, a recent study revealed that CD34 allows to distinguish 3 APC populations. Adipocytes derived from APCs with high CD34 expression exhibit exceedingly high rates of lipid flux compared with APCs with low or no CD34 expression, while adipocytes produced from CD34− APCs display beige-like adipocyte properties and a unique endocrine profile.SLC3A2 is an integrin coreceptor that has been shown to maintain (1) collagen and elastin fiber length and reticulation (2) consequently elastic modulus which gives skin stiffness and (3) a proper TGFbeta location and activation but also (4) sphingolipid metabolism which is involved in mechanosensing signalling. As SLCA3A2 is decreased during skin aging it represents a relevant target to treat aging skin.KN motif and Ankyrin repeat domain containing protein 4 (KANK4) is expressed in papillary fibroblasts at an increased level in both chronologically-aged and photo-damaged skin. Inhibiting this molecule allows to reduce fibroblast contractility which tends to increase with skin aging. Resulting from a mutation of Lamin A protein, Progerin is known to induce a premature aging disease called Progeria. Progerin is also accumulated in skin cells during natural skin aging, thus inducing cell proliferation decrease and cell senescence stimulation. Targeting Progerin may therefore be of great interest to slow down skin aging.TGFβ is involved in various skin processes: epidermis differentiation, extracellular matrix formation and maintenance, wound healing, maintenance of skin-resident immune cells, etc... During skin ageing, the expression level of TGFβ tends to decrease, leading to a greater skin fragility.SLC3A2 is an integrin coreceptor that has been shown to maintain (1) collagen and elastin fiber length and reticulation (2) consequently elastic modulus which gives skin stiffness and (3) a proper TGFbeta location and activation but also (4) sphingolipid metabolism which is involved in mechanosensing signalling. As SLCA3A2 is decreased during skin aging it represents a relevant target to treat aging skin.SLC3A2 is an integrin coreceptor that has been shown to maintain (1) collagen and elastin fiber length and reticulation (2) consequently elastic modulus which gives skin stiffness and (3) a proper TGFbeta location and activation but also (4) sphingolipid metabolism which is involved in mechanosensing signalling. As SLCA3A2 is decreased during skin aging it represents a relevant target to treat aging skin.KN motif and Ankyrin repeat domain containing protein 4 (KANK4) is expressed in papillary fibroblasts at an increased level in both chronologically-aged and photo-damaged skin. Inhibiting this molecule allows to reduce fibroblast contractility which tends to increase with skin aging. KN motif and Ankyrin repeat domain containing protein 4 (KANK4) is expressed in papillary fibroblasts at an increased level in both chronologically-aged and photo-damaged skin. Inhibiting this molecule allows to reduce fibroblast contractility which tends to increase with skin aging. Resulting from a mutation of Lamin A protein, Progerin is known to induce a premature aging disease called Progeria. Progerin is also accumulated in skin cells during natural skin aging, thus inducing cell proliferation decrease and cell senescence stimulation. Targeting Progerin may therefore be of great interest to slow down skin aging.Resulting from a mutation of Lamin A protein, Progerin is known to induce a premature aging disease called Progeria. Progerin is also accumulated in skin cells during natural skin aging, thus inducing cell proliferation decrease and cell senescence stimulation. Targeting Progerin may therefore be of great interest to slow down skin aging.TGFβ is involved in various skin processes: epidermis differentiation, extracellular matrix formation and maintenance, wound healing, maintenance of skin-resident immune cells, etc... During skin ageing, the expression level of TGFβ tends to decrease, leading to a greater skin fragility.TGFβ is involved in various skin processes: epidermis differentiation, extracellular matrix formation and maintenance, wound healing, maintenance of skin-resident immune cells, etc... During skin ageing, the expression level of TGFβ tends to decrease, leading to a greater skin fragility.Keratin 7 (K7) is a well-known marker of sebaceous glands (SG) and sweat glands. In SG, K7-positive cells are progenitor cells located in the periphery of the gland. K7 expression is then lost during sebocyte maturation. As sebum is a holocrine secretion originating from SG cell disintegration into follicular duct of pilosebaceous unit, SG renewal and sebum secretion depend on K7-positive sebocyte proliferation and maturation. In acne-prone skin, these phenomena are simulated, leading to higher sebum production.The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin hydration as a key cell receptor for hyaluronic acid and skin inflammation or metastasis. Permeability barrier disruption and inflammation stimulate epidermal CD44 expression which is involved in leucocyte recruitment and it has been shown that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model. Skin ageing is associated with a decrease in dermal collagen I proportion. This has been correlated to a decrease in procollagen I synthesis and an increase in collagen I degradation by MMP-1. An anti-ageing product can therefore increase Procollagen I synthesis and decrease MMP-1 activity.Skin ageing is associated with an increase in the senescent cell percentage. As senescent human cells overexpress cell growth inhibitors such as p16 and p21, these markers can be used to assess the extent of skin ageing. An anti-ageing product can therefore decrease their expression.Keratin 7 (K7) is a well-known marker of sebaceous glands (SG) and sweat glands. In SG, K7-positive cells are progenitor cells located in the periphery of the gland. K7 expression is then lost during sebocyte maturation. As sebum is a holocrine secretion originating from SG cell disintegration into follicular duct of pilosebaceous unit, SG renewal and sebum secretion depend on K7-positive sebocyte proliferation and maturation. In acne-prone skin, these phenomena are simulated, leading to higher sebum production.Keratin 7 (K7) is a well-known marker of sebaceous glands (SG) and sweat glands. In SG, K7-positive cells are progenitor cells located in the periphery of the gland. K7 expression is then lost during sebocyte maturation. As sebum is a holocrine secretion originating from SG cell disintegration into follicular duct of pilosebaceous unit, SG renewal and sebum secretion depend on K7-positive sebocyte proliferation and maturation. In acne-prone skin, these phenomena are simulated, leading to higher sebum production.Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Decreased expression of K1 or K10 may be correlated with a defect in keratinocyte differentiation and impairment of the skin barrier.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact. Thus, they belong to the "alarmines" whose expression is activated following alteration of the skin barrier, particularly following skin injury, and until the restoration of its functionality.Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number, which can lead to reduce the renewal and induce a higher fragility of the skin barrier. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. Upon skin injury, the expression of keratins 16 / 17 (K16/ K17) and 6 (K6) is stimulated in suprabasal keratinocytes. K17 can combine with K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and protein synthesis. K17 can also induce the production of Th1/Th17 cytokines by keratinocytes, and K17 peptides can serve as self-antigens to promote the activation of antigen-presenting cells and T cells. K17 is thus considered as an alarmine, i.e. a molecules whose expression is activated following injury and which act on the skin barrier by modulating the epidermis structure and the innate immune response. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratin 19 (K19) is a known marker of epidermal stem cells located in both hair follicle and interfollicular areas. Even if its expression in some specific stem cell population is discussed, a decrease of K19 expression may be correlated with a decrease of stem cell number and lead to a more fragile skin barrier. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratin 19 (K19) is a known marker of epidermal stem cells located in both hair follicle and interfollicular areas. Even if its expression in some specific stem cell population is discussed, a decrease of K19 expression may be correlated with a decrease of stem cell number. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratin 19 (K19) is a known marker of epidermal stem cells located in both hair follicle and interfollicular areas. Even if its expression in some specific stem cell population is discussed, a decrease of K19 expression may be correlated with a decrease of stem cell number. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. Kruppel-like factor 4 (KLF4) is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Owing to an increased post-transcriptional expression of Klf4, Klf4 protein decreases during keratinocyte replicative senescence and during physiological skin aging, while its mRNA level does not change. KLF4 is therefore a possible marker of skin aging which may be targeted by antiaging products. Specific analyse developed by each expert. Multicriteria approach with the analysis of biodegradation, acute and chronic aquatic toxicity, bioaccumulation in organisms, endocrine effect, sediment toxicity and terrestrial toxicity.Part A: Cosmetic Product Safety Information. Part B of the CSR is a safety assessment leading to a conclusion on the safety of the product. Literature search. Advice in the choice of tests to be conducted in silico or in vitro to confirm the safety of the ingredients.Interleukin 1 alpha (IL-1α) and bêta (IL-1β) are key pro-inflammatory cytokines released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. They are therefore involved in various skin inflammation diseases and constitute appropriate markers of skin inflammatory state. Keratinocytes constitute the interface between the body and the external environment. Various aggressions due to factors such as microorganisms or UV light stimulate these cells and induce the production of TNFα, a cytokine involved in immunity and inflammation. The TNFα assay allows to assess the intensity of the inflammatory response. Epidermal integrity is regulated by a tight communication between keratinocytes and leucocytes, particularly under cytokine control. Imbalance of the cytokine network leads to inflammatory diseases such as psoriasis. The combination of five cytokines (IL-22, Oncostatin M, IL-17, TNFα and IL-1) all overexpressed in vivo in psoriatic lesions has been shown in vitro to induce a “psoriasis-like” epidermis phenotype, both at the histological and molecular levels.Overexpressed in psoriatic lesions, Oncostatin M (OSM) potently regulates the expression of genes involved in skin inflammation and epidermal differentiation. For example, OSM stimulates the expression of antimicrobial peptides and various cytokines such as Th1/Th2 cytokines, whereas it decreases the expression of some epidermal differentiation markers such as K10 or filaggrin. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. Interleukin 17 (IL-17) is an essential proinflammatory cytokine secreted by the Th17 cells (CD4+ helper T cells) and subsets of innate lymphoid cells. IL-17 targets many cells including keratinocytes, fibroblasts, neutrophils or endothelial cells and is associated with the pathogenesis of many inflammatory diseases including psoriasis and atopic dermatitis. Interleukin 23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. IL-17 and IL-23 level may therefore be used as markers of inflammatory state. Interleukin 22 (IL-22) is a cytokine involved in the modulation of tissue responses during inflammation. Produced by Th17 and Th22 T helper cells, IL-22 induces keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and promotes the production of antimicrobial proteins. Th22 cells reside in the normal skin and are enriched in the lesional skin of inflammatory skin diseases. IL-22 plays a role in psoriasis, atopic dermatitis and other inflammatory skin diseases. IFNγ orchestrates numerous protective functions including antigen processing and presentation, leukocyte trafficking, anti-microbial functions, cellular proliferation and apoptosis or the initiation of a cascade of pro-inflammatory responses. Produced by many immune cells including Th1 Tcells, macrophages or dendritic cells (DCs), IFNγ is overexpressed in psoriatic skin and enhances IL-23 and IL-1 production by DCs, leading to Th17 cell activation and initiating psoriasis lesions. On the contrary, its expression is reduced in atopic dermatitis.Interleukin 4 (IL-4) promotes the development of Th2 cells, while interleukin 13 (IL-13) is critical in promoting tissue inflammation. They both play a key role in allergic inflammation and therefore in atopic dermatitis (AD) genesis. In AD, IL-4 and IL-13 are overexpressed and consequently decrease the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. IL-6 is a pro-inflammatory cytokine associated with skin healing and inflammation. Released early in response to injury, IL-6 plays a central role in acute inflammation and reparative process occuring successively during wound healing. Overexpressed in skin inflammatory diseases such as psoriasis, IL-6 stimulates both other pro-inflammatory cytokine secretion and keratinocyte hyperproliferation leading to epidermal thickening. IL-6 is produced by immune cells such as lymphocytes, monocyte / macrophages, dendritic cells but also by keratinocytes, fibroblasts, endothelial cells or sebocytes. Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in allergen stimulated keratinocytes. It plays a key role in allergic inflammation by stimulating eosinophil infiltration and Th2 cytokine secretion (IL-4, IL-5, IL-13) by T helper cells. TSLP can therefore be used as a marker of allergic inflammation. The Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a pro-inflammatory cytokine produced by many cell types including keratinocytes activated by hapten, irritant or IL-1a. GM-CSF can be therefore used as an inflammatory response marker in skin following hapten or irritant application. Transforming Growth Factor beta (TGFβ) has many effects highly cell and context-dependent. Among all its effects, TGF-β1 is a potent chemoattractant for endothelial cells and fibroblasts as well as neutrophils and monocytes and stimulates pro-inflammatory cytokine release by these cells. TGF-β overexpression in the epidermal basal layers is also associated with inflammation, keratinocyte hyperproliferation and delayed wound healing. Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.Keratins 6 (K6) and 16 (K16) are constitutive keratins of stratified epithelia built up by keratinocytes of relatively high proliferative state such as mucosal tissues, palmoplantar epidermis, and certain skin appendages. Usually absent in interfollicular epidermis of hairy skin, they are rapidly switched on after injury, UV-irradiation and also present in inflammation and some hyperproliferative disorders such as psoriasis. The K16-K6 keratin pair maintains mechanical integrity by increasing cell-cell and cell-matrix contact.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.During skin injury or in psoriasis, suprabasal keratinocytes strongly induce the expression of keratin 16 / 17 (K16/ K17) and 6 (K6). K17 can pair with either K6 or K5 to drive keratinocyte hyperproliferation by increasing cell size and increasing protein synthesis. K17 can also induce Th1/Th17 cytokine production from keratinocytes, and K17 peptides can also serve as an autoantigen to promote antigen presenting cell (APC)-T cell activation, leading to autoimmune amplification during psoriasis pathogenesis.Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 15 (K15) is a known marker of basal and bulge stem cells. Consequently, a decrease of K15 expression may be correlated with a decrease of stem cell number. Nevertheless, as this marker is also expressed in differentiated cells, a special attention should be paid to the interpretation of K15 expression level and location. Phototoxicity (photoirritation) is defined as an acute toxic response elicited by topically or systemically administered photoreactive chemicals after body exposure to environmental light. In OECD 498 test, a chemical is topically applied (at 3 or 5 concentrations) on a reconstructed human epidermis (RhE) in the presence and absence of simulated sunlight (6 J/cm2). After a post-exposure incubation period of 18 to 24 hours, cell viability is determined in both the irradiated and non-irradiated groups by using the MTT test. The more the viability is different between the two groups, the higher the phototoxic potential of the product. Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.The human ribonuclease RNase 7, which is continuously secreted by keratinocytes, accumulates on the skin surface and has potent antimicrobial activity. It is overexpressed in psoriatic lesions which, on the one hand, stimulates the production of interferon gamma and the triggering of an inflammatory reaction and, on the other hand, limits bacterial superinfections despite the loss of skin barrier integrity. Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Overexpressed in psoriasis, it limits the risk of infection despite a defective skin barrier. In addition to its direct antimicrobial effects, it is also involved in many processes and has been identified as an activating and regulating agent of the inflammatory response characteristic of psoriasis. Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes. It is involved in many functions including inflammation and keratinocyte differentiation. Its synthesis is low in healthy skin but stimulated by IL-22, IL-17 and TNFα in psoriatic lesions, thus participating in inducing the inflammatory response and dysregulating the epidermal differentiation. Psoriasis initiation begins with environmental triggers and/or loss of tolerance, which leads to the activation of several pro-inflammatory dendritic cell populations, including some producing interleukin 23 (IL-23). Under the regulation of IL-23, some T cell populations produce high levels of IL-17 and IL-22 driving inflammatory response and immune cell recruitment, skin thickening and the alteration of keratinocyte proliferation and differentiation. Calcoprotectin (S100A8/9), is a dimer of calgranulin A (S100A8) and B (S100A9) belonging to the antimicrobial peptides produced by keratinocytes. Expressed at low level in healthy skin, it is overexpressed in psoriasis as in other inflammatory diseases or under the action of various stimuli (tape stripping, detergents, UV, interleukins IL-1α and IL-22). Calcoprotectin is involved in inflammatory response, prevents keratinocyte proliferation and induces their differentiation. Koebnerisin S100A15, which has a sequence almost identical to that of psoriasin, is overexpressed in psoriatic skin lesions and known for its antimicrobial, proinflammatory and chemotaxis properties. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. In psoriatic lesions, caspase 9 is expressed at a lower level in epidermis compared to normal skin, highlighting a decreased apoptosis in psoriatic epidermis, whereas there are no differences in the dermal perivascular areas. Legal representative by a Responsible Person in a given territory guaranteeing compliance with the requirements of the regulations.The interleukins 4 (IL-4) and 13 (IL-13) are overexpressed in atopic dermatitis (AD). This stimulates inflammation and decreases the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. Thus, they both play a key role in atopic dermatitis (AD) genesis.Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on various immune cells. IL-8 is therefore a pro-inflammatory cytokine that is overexpressed in atopic dermatitis (AD) and it has been shown that the concentration of IL-8 in the stratum corneum is closely correlated with the severity of AD. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Atopic dermatitis (AD) is associated with a decrease in filaggrin expression and/or loss of function. This leads to impaired barrier function which facilitates the stratum corneum dehydration, allergen entry and T-cell infiltration. Filaggrin is thus a key player in AD. Claudin-1 is a transmembrane protein which is also the major component of epidermal tight junctions. In atopic dermatitis (AD), a downregulation of Claudin-1 has been associated with tight junction and barrier function impairment. In AD, Claudin-1 decrease also induces inflammation in human epidermis. A new relevant and reliable in vitro method has been developped to allow the evaluation of the Sand Resistance percentage of a sunscreen product by comparing the in vitro SPF before and after a specific agitation in a standardized sand.TNFα is a pro-inflammatory cytokine overexpressed in atopic dermatitis (AD). It acts in synergy with Th2-type cytokines (IL-4, IL-13 and IL-31). It promotes the development of inflammation, in particular by stimulating TSLP expression by keratinocytes, and alters the skin barrier by modulating the synthesis of ceramides and marker proteins for epidermal differentiation. TNFα is a possible target in the treatment of AD.LIGHT (TNSF14) belongs to the tumor necrosis factor (TNF) superfamily overexpressed in atopic dermatitis (AD). This molecule directly stimulates keratinocyte hyperplasia and the production of periostin, a matrix protein, thus contributing to the onset of AD symptoms. This was recently demonstrated in mice. Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the formation of Natural Moisturizing Factor (NMF) involved in skin hydration. In Atopic Dermatitis (AD), Caspase 14 is decreased, inducing skin dryness. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. Its expression is modulated by various factors such as cytokines and microorganisms. It exhibits a potent antimicrobial activity in healthy skin and also exerts potent immunomodulatory activities. In Atopic Dermatitis (AD), RNAse 7 is overexpressed, but its ability to regulate immune response is decreased as well as the ability of keratinocytes to produce RNAse 7 in response to S aureus infection. Interleukin 18 (IL-18) is a pro-inflammatory cytokine produced by keratinocytes and monocytes. It is more abundant in the stratum corneum (SC) of skin with atopic dermatitis (AD) than in healthy skin and its abundance in both SC and blood correlates with the severity of AD. This interleukin stimulates both the Th1 immune response and the production of Th2 type interleukins and histamine by T lymphocytes and mast cells. It thus participates in the genesis of AD and the associated pruritus. Vascular endothelial growth factor (VEGF) is produced by keratinocytes and endothelial cells in skin vessels. A higher level has been observed in the stratum corneum of skins affected by atopic dermatitis than in healthy skins. Moreover, its abundance in both stratum corneum and blood of affected subjects correlates with the severity of atopic dermatitis. Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Prostaglandin E-2 (PGE-2) is a lipid-derived signalling molecule found in mammalian skin, particularly in fibroblasts. It is overexpressed in atopic skin and stimulates the production of interleukin 22 (IL-22) by T cells. It is thus involved in the genesis of atopic dermatitis, at least in mice. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. The expression of these two keratins is decreased in atopic lesions, probably due to the effect of interleukins 4 and 13. This results in an alteration of the skin barrier. Loricrin and involucrin are two proteins synthesised in the keratinocyte cytoplasm of stratum granulosum. They are markers of terminal differentiation and essential components of the stratum corneum. The expression of these two proteins is decreased in atopic dermatitis and the skin barrier is thus impaired. Human beta-defensin 2 is an antimicrobial peptide produced by keratinocytes when stimulated by microorganisms and/or certain inflammatory cytokines such as IL-1a or TNFa. Its synthesis increases in atopic lesions and its expression level has been correlated with the severity of atopic dermatitis.The interleukins 4 (IL-4) and 13 (IL-13) are overexpressed in atopic dermatitis (AD). This stimulates inflammation and decreases the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. Thus, they both play a key role in atopic dermatitis (AD) genesis.The interleukins 4 (IL-4) and 13 (IL-13) are overexpressed in atopic dermatitis (AD). This stimulates inflammation and decreases the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. Thus, they both play a key role in atopic dermatitis (AD) genesis.Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on various immune cells. IL-8 is therefore a pro-inflammatory cytokine that is overexpressed in atopic dermatitis (AD) and it has been shown that the concentration of IL-8 in the stratum corneum is closely correlated with the severity of AD. Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on various immune cells. IL-8 is therefore a pro-inflammatory cytokine that is overexpressed in atopic dermatitis (AD) and it has been shown that the concentration of IL-8 in the stratum corneum is closely correlated with the severity of AD. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Atopic dermatitis (AD) is associated with a decrease in filaggrin expression and/or loss of function. This leads to impaired barrier function which facilitates the stratum corneum dehydration, allergen entry and T-cell infiltration. Filaggrin is thus a key player in AD. Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Atopic dermatitis (AD) is associated with a decrease in filaggrin expression and/or loss of function. This leads to impaired barrier function which facilitates the stratum corneum dehydration, allergen entry and T-cell infiltration. Filaggrin is thus a key player in AD. Claudin-1 is a transmembrane protein which is also the major component of epidermal tight junctions. In atopic dermatitis (AD), a downregulation of Claudin-1 has been associated with tight junction and barrier function impairment. In AD, Claudin-1 decrease also induces inflammation in human epidermis. Claudin-1 is a transmembrane protein which is also the major component of epidermal tight junctions. In atopic dermatitis (AD), a downregulation of Claudin-1 has been associated with tight junction and barrier function impairment. In AD, Claudin-1 decrease also induces inflammation in human epidermis. TNFα is a pro-inflammatory cytokine overexpressed in atopic dermatitis (AD). It acts in synergy with Th2-type cytokines (IL-4, IL-13 and IL-31). It promotes the development of inflammation, in particular by stimulating TSLP expression by keratinocytes, and alters the skin barrier by modulating the synthesis of ceramides and marker proteins for epidermal differentiation. TNFα is a possible target in the treatment of AD.TNFα is a pro-inflammatory cytokine overexpressed in atopic dermatitis (AD). It acts in synergy with Th2-type cytokines (IL-4, IL-13 and IL-31). It promotes the development of inflammation, in particular by stimulating TSLP expression by keratinocytes, and alters the skin barrier by modulating the synthesis of ceramides and marker proteins for epidermal differentiation. TNFα is a possible target in the treatment of AD.LIGHT (TNSF14) belongs to the tumor necrosis factor (TNF) superfamily overexpressed in atopic dermatitis (AD). This molecule directly stimulates keratinocyte hyperplasia and the production of periostin, a matrix protein, thus contributing to the onset of AD symptoms. This was recently demonstrated in mice. LIGHT (TNSF14) belongs to the tumor necrosis factor (TNF) superfamily overexpressed in atopic dermatitis (AD). This molecule directly stimulates keratinocyte hyperplasia and the production of periostin, a matrix protein, thus contributing to the onset of AD symptoms. This was recently demonstrated in mice. Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the formation of Natural Moisturizing Factor (NMF) involved in skin hydration. In Atopic Dermatitis (AD), Caspase 14 is decreased, inducing skin dryness. Mainly expressed in suprabasal layers and activated during keratinocyte cornification, Caspase 14 is a protease inducing filaggrin proteolysis. This allows the formation of Natural Moisturizing Factor (NMF) involved in skin hydration. In Atopic Dermatitis (AD), Caspase 14 is decreased, inducing skin dryness. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Sirtuin 1 is produced by keratinocytes and, among various functions, is required for skin barrier formation and inflammatory response. Indeed, by stimulating filaggrin expression, it allows appropriate skin cornification. In Atopic Dermatitis (AD), its expression is decreased, inducing a more fragile skin barrier. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. It exhibits a potent antimicrobial activity in healthy skin and also exerts potent immunomodulatory activities. In Atopic Dermatitis (AD), RNAse 7 is overexpressed, but its ability to regulate immune response is decreased as well as the ability of keratinocytes to produce RNAse 7 in response to S aureus infection. Constantly released by keratinocytes, the human ribonuclease RNase 7 accumulates on the skin surface. It exhibits a potent antimicrobial activity in healthy skin and also exerts potent immunomodulatory activities. In Atopic Dermatitis (AD), RNAse 7 is overexpressed, but its ability to regulate immune response is decreased as well as the ability of keratinocytes to produce RNAse 7 in response to S aureus infection. Interleukin 18 (IL-18) is a pro-inflammatory cytokine produced by keratinocytes and monocytes. It is more abundant in the stratum corneum (SC) of skin with atopic dermatitis (AD) than in healthy skin and its abundance in both SC and blood correlates with the severity of AD. This interleukin stimulates both the Th1 immune response and the production of Th2 type interleukins and histamine by T lymphocytes and mast cells. It thus participates in the genesis of AD and the associated pruritus. Interleukin 18 (IL-18) is a pro-inflammatory cytokine produced by keratinocytes and monocytes. It is more abundant in the stratum corneum (SC) of skin with atopic dermatitis (AD) than in healthy skin and its abundance in both SC and blood correlates with the severity of AD. This interleukin stimulates both the Th1 immune response and the production of Th2 type interleukins and histamine by T lymphocytes and mast cells. It thus participates in the genesis of AD and the associated pruritus. Vascular endothelial growth factor (VEGF) is produced by keratinocytes and endothelial cells in skin vessels. A higher level has been observed in the stratum corneum of skins affected by atopic dermatitis than in healthy skins. Moreover, its abundance in both stratum corneum and blood of affected subjects correlates with the severity of atopic dermatitis. Vascular endothelial growth factor (VEGF) is produced by keratinocytes and endothelial cells in skin vessels. A higher level has been observed in the stratum corneum of skins affected by atopic dermatitis than in healthy skins. Moreover, its abundance in both stratum corneum and blood of affected subjects correlates with the severity of atopic dermatitis. Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Prostaglandin E-2 (PGE-2) is a lipid-derived signalling molecule found in mammalian skin, particularly in fibroblasts. It is overexpressed in atopic skin and stimulates the production of interleukin 22 (IL-22) by T cells. It is thus involved in the genesis of atopic dermatitis, at least in mice. Prostaglandin E-2 (PGE-2) is a lipid-derived signalling molecule found in mammalian skin, particularly in fibroblasts. It is overexpressed in atopic skin and stimulates the production of interleukin 22 (IL-22) by T cells. It is thus involved in the genesis of atopic dermatitis, at least in mice. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. The expression of these two keratins is decreased in atopic lesions, probably due to the effect of interleukins 4 and 13. This results in an alteration of the skin barrier. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. In the suprabasal layers, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. The expression of these two keratins is decreased in atopic lesions, probably due to the effect of interleukins 4 and 13. This results in an alteration of the skin barrier. Loricrin and involucrin are two proteins synthesised in the cytoplasm of stratum granulosum keratinocytes. They are markers of terminal differentiation and essential components of the stratum corneum. The expression of these two proteins is decreased in atopic dermatitis and the skin barrier is thus impaired. Loricrin and involucrin are two proteins synthesised in the cytoplasm of stratum granulosum keratinocytes. They are markers of terminal differentiation and essential components of the stratum corneum. The expression of these two proteins is decreased in atopic dermatitis and the skin barrier is thus impaired. Human beta-defensin 2 is an antimicrobial peptide produced by keratinocytes when stimulated by microorganisms and/or certain inflammatory cytokines such as IL-1a or TNFa. Its synthesis increases in atopic lesions and its expression level has been correlated with the severity of atopic dermatitis.Human beta-defensin 2 is an antimicrobial peptide produced by keratinocytes when stimulated by microorganisms and/or certain inflammatory cytokines such as IL-1a or TNFa. Its synthesis increases in atopic lesions and its expression level has been correlated with the severity of atopic dermatitis.Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.The human ribonuclease RNase 7, which is continuously secreted by keratinocytes, accumulates on the skin surface and has potent antimicrobial activity. It is overexpressed in psoriatic lesions which, on the one hand, stimulates the production of interferon gamma and the triggering of an inflammatory reaction and, on the other hand, limits bacterial superinfections despite the loss of skin barrier integrity. The human ribonuclease RNase 7, which is continuously secreted by keratinocytes, accumulates on the skin surface and has potent antimicrobial activity. It is overexpressed in psoriatic lesions which, on the one hand, stimulates the production of interferon gamma and the triggering of an inflammatory reaction and, on the other hand, limits bacterial superinfections despite the loss of skin barrier integrity. Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.Elafin (SKALP) is mainly produced by epithelial cells and keratinocytes but almost undetectable in normal skin. Its level increases in psoriatic lesions and is enhanced by IL-1 and TNF-alpha (i.e. a pro-inflammatory microenvironment). It inhibits various proteases including elastase and thus protects tissues against the damage caused by pathological acute and chronic inflammation, limits immune response during chronic inflammation and exhibits antimicrobial effects. The analysis of this biomarker is carried out by a specific method whose details will be given to you by the testing laboratory. Please contact them directly.LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Overexpressed in psoriasis, it limits the risk of infection despite a defective skin barrier. In addition to its direct antimicrobial effects, it is also involved in many processes and has been identified as an activating and regulating agent of the inflammatory response characteristic of psoriasis. LL37 / hCAP18 is the single known human cathelicidin. It is a small antimicrobial peptide released by neutrophils, macrophages or keratinocytes. Overexpressed in psoriasis, it limits the risk of infection despite a defective skin barrier. In addition to its direct antimicrobial effects, it is also involved in many processes and has been identified as an activating and regulating agent of the inflammatory response characteristic of psoriasis. Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes. It is involved in many functions including inflammation and keratinocyte differentiation. Its synthesis is low in healthy skin but stimulated by IL-22, IL-17 and TNFα in psoriatic lesions, thus participating in inducing the inflammatory response and dysregulating the epidermal differentiation. Psoriasin (S100A7), is an antimicrobial peptide expressed by keratinocytes. It is involved in many functions including inflammation and keratinocyte differentiation. Its synthesis is low in healthy skin but stimulated by IL-22, IL-17 and TNFα in psoriatic lesions, thus participating in inducing the inflammatory response and dysregulating the epidermal differentiation. Psoriasis initiation begins with environmental triggers and/or loss of tolerance, which leads to the activation of several pro-inflammatory dendritic cell populations, including some producing interleukin 23 (IL-23). Under the regulation of IL-23, some T cell populations produce high levels of IL-17 and IL-22 driving inflammatory response and immune cell recruitment, skin thickening and the alteration of keratinocyte proliferation and differentiation. Psoriasis initiation begins with environmental triggers and/or loss of tolerance, which leads to the activation of several pro-inflammatory dendritic cell populations, including some producing interleukin 23 (IL-23). Under the regulation of IL-23, some T cell populations produce high levels of IL-17 and IL-22 driving inflammatory response and immune cell recruitment, skin thickening and the alteration of keratinocyte proliferation and differentiation. Calcoprotectin (S100A8/9), is a dimer of calgranulin A (S100A8) and B (S100A9) belonging to the antimicrobial peptides produced by keratinocytes. Expressed at low level in healthy skin, it is overexpressed in psoriasis as in other inflammatory diseases or under the action of various stimuli (tape stripping, detergents, UV, interleukins IL-1α and IL-22). Calcoprotectin is involved in inflammatory response, prevents keratinocyte proliferation and induces their differentiation. Calcoprotectin (S100A8/9), is a dimer of calgranulin A (S100A8) and B (S100A9) belonging to the antimicrobial peptides produced by keratinocytes. Expressed at low level in healthy skin, it is overexpressed in psoriasis as in other inflammatory diseases or under the action of various stimuli (tape stripping, detergents, UV, interleukins IL-1α and IL-22). Calcoprotectin is involved in inflammatory response, prevents keratinocyte proliferation and induces their differentiation. Koebnerisin S100A15, which has a sequence almost identical to that of psoriasin, is overexpressed in psoriatic skin lesions and known for its antimicrobial, proinflammatory and chemotaxis properties. Koebnerisin S100A15, which has a sequence almost identical to that of psoriasin, is overexpressed in psoriatic skin lesions and known for its antimicrobial, proinflammatory and chemotaxis properties. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. In psoriatic lesions, caspase 9 is expressed at a lower level in epidermis compared to normal skin, highlighting a decreased apoptosis in psoriatic epidermis, whereas there are no differences in the dermal perivascular areas. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. In psoriatic lesions, caspase 9 is expressed at a lower level in epidermis compared to normal skin, highlighting a decreased apoptosis in psoriatic epidermis, whereas there are no differences in the dermal perivascular areas. β1-containing integrin dimers are ubiquitously expressed receptor that mediate cell-cell and cell-extracellular matrix interactions. Keratinocytes express α2β1 and α3β1 receptors and β1 has been found to be a marker for proliferation competent cells as its expression decreases during keratinocyte differentiation. β1 plays a key role in the processing of the basement membrane components, including the dermal-epidermal junction, the formation and/or maintenance of hemidesmosomes, and keratinocyte proliferation and differentiation. A defect in β1 expression may therefore impair skin integrity and barrier function. Calprotectin (S100A8/9) is a heterodimer composed of calgranuline A (S100A8) and calgranuline B (S100A9). It is produced by keratinocytes and forms an antimicrobial peptide which limits the development of pathogenic microorganisms, thus participating in skin barrier function. Its expression is low in normal skin but stimulated by various skin stresses such as tape stripping, exposure to detergent, UV, or cytokines (IL-1α, IL-22). Koebnerisin (S100A15) is an antimicrobial peptide produced by keratinocytes with a sequence very similar to psoriasin. Overexpressed in psoriatic lesions or in the case of infection of keratinocytes by Escherischia coli, koebnerisin also has anti-inflammatory and chemotactic properties. It thus contributes to the skin's barrier function. Zonula Occludens 1 (ZO1) is a transmembrane protein linked to the cytosqueleton and providing the structural basis for the assembly of the proteins composing the tight junctions. It therefore participates in the keratinocyte close association and thus in the proper functionning of the skin barrier. Besides this structural function, a role of ZO proteins in the regulation of cell growth and proliferation has also been reported. Transepidermal Water Loss (TEWL) corresponds to the loss of water through the epidermis via diffusion and evaporation processes. TEWL is evaluated by using an evaporimeter and normal rates range from 2.3 g/m2/h to 44 g/m2/h depending on the anatomical region. These values can be increased due to injury, burns, infection or various diseases affecting the stratum corneum. TEWL measurement therefore allows to evaluate skin barrier functionality. Transepithelial/transendothelial electrical resistance (TEER) is a quantitative technique to measure the integrity of tight junction dynamics in cell culture models such as reconstructed human epidermis. TEER values are then strong indicators of the skin barrier integrity. TEER measurements can be performed in real-time without cell damage and generally are based on measuring ohmic resistance or measuring impedance across a wide spectrum of frequencies. This Test method has been designed to provide information on a test substance absorption after its application to the surface of a skin sample separating the two chambers (a donor chamber and a receptor chamber) of a diffusion cell (Franz cell). The substance application should mimic human exposure, normally 1-5 mg/cm2 of skin for a solid and up to 10 µl/cm2 for liquids. Passage kinetics are determined by dosing the active substance at regular intervals in the fluid of the receiving compartment. As the skin is able to metabolize certain substances during percutaneous absorption, the metabolites of the test substance can also be analyzed. In the case of sterile articles packaged in multiple-dose containers, antimicrobial preservatives are added to inhibit the growth of microorganisms that may be introduced from repeatedly withdrawing individual doses. The most widely used method to evaluate the effectiveness of added antimicrobial preservatives to aqueous based products consists in evaluating the effect of those products against 5 representative microorganisms (bacteria, yeast and mold). The microorganism density is commonly evaluated at day (7), 14 and 28. Considering the log reduction of microorganisms obtained from each sampling interval, a product either conforms or does not conform to the USP <51> acceptance criteria.The M-3 method evaluates whether preservatives are effective in limiting contamination of water-miscible cosmetic products. This method has been established as an alternative to the USP <51> testing methodology with more stringent pass/fail criteria. Some personal care products are anhydrous and cannot be sampled using conventional methods. Those include oils, powders and wax-like products. The M-6 method, adapted from the USP <51> method, evaluates whether preservatives are effective in limiting contamination of anhydrous cosmetic products. The M-7 method allows the selection of preservatives that appear to be the most effective in limiting the contamination of a water-miscible cosmetic product. This method saves time in screening but does not replace the M-3 or USP <51> methods for the final validation of a preservative. Type VII collagen (Coll VII) is primarily synthesized by keratinocytes and fibroblasts. It is an anchoring fibril binding Dermal Epidermal Junction (DEJ) proteins such as Laminin 5, 6 or Collagen IV with ExtraCellular Matrix (ECM) proteins of the dermis such as Collagen I, III and V. The quality of the DEJ and the dermis anchoring to the epidermis therefore depends on Coll VII expression level and location.Type XVII collagen (Coll XVII), also called 180-kDa bullous pemphigoid antigen (BP180) is a keratinocyte transmembrane protein located in hemidesmosomes. It binds to other hemidesmosome components such as β4 integrins and plectin, but also to laminin 332 which a component of the Dermal Epidermal Junction (DEJ). The main function of type XVII collagen in skin is therefore to stabilize adhesion of epidermal cells to the DEJ. Skin renewal involves the renewal of the dermal extracellular matrix and in particular of its main component, the collagen I. The density and structure of the collagen I network depend on the synthesis of procollagen I, its assembly into collagen fibrils, the cross-linking of the fibrils and their degradation. A modulation of procollagen I synthesis, observed for example during skin ageing, therefore has consequences for skin renewal and firmness.Kruppel-like factor 4 (KLF4) is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Owing to an increased post-transcriptional expression of Klf4, Klf4 protein decreases during keratinocyte replicative senescence and during physiological skin aging, while its mRNA level does not change. Modulating the synthesis or post-transcriptional regulation of KLF4 should therefore influence epidermal renewal. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. In addition to its effect on angiogenesis, V-EGF is also involved in maintaining the stemness and renewal abilities of cancer cells in squamous tumours. Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity.Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Skin barrier function mainly relies on stratum corneum which is composed of corneocytes embedded in a lipid-enriched lamellar matrix. Rab11a is a GTPase type enzyme highly expressed in terminally differentiated keratinocytes and partly associated with lamellar bodies. Rab11a is involved in lamellar body biogenesis, associated secretion and the production of stratum corneum lipids. Rab11a is therefore essential for skin barrier function. Following pretreatment with a systemic analgesic and instillation of appropriate topical anesthesia, the test chemical (liquid, solid or aerosol) is applied in a single dose to one of the eyes of the experimental animal. The untreated eye serves as the control. The degree of eye irritation/serious eye damage is evaluated by scoring lesions of conjunctiva, cornea, and iris, at specific intervals (at least 1 hour after application and daily for 21 days). Other effects in the eye and adverse systemic effects are also described to provide a complete evaluation of the effects. The duration of the study should be sufficient to evaluate the reversibility or irreversibility of the effects.The objective of OECD 263 is to establish an Integrated Approach on Testing and Assessment (IATA) for hazard identification of serious eye damage and eye irritation potential of test chemicals allowing their classification and labelling according to the United Nations Globally Harmonised System (UN GHS, 2015). Briefly, this guideline suggests to consider first the existing information (human data, in vivo animal data, in vitro animal data, physico-chemical properties and other non testing data) before either taking a conclusive decision regarding classification and labelling (if possible) or formulating a hypothesis which will then guide the sequence of prospective testing. This prospective testing includes 1/ testing on OECD adopted in vitro test methods, 2/ testing on other non-OECD adopted alternative test methods and 3/ As a last resort, testing on in vivo animal test method according to OECD TG 405. The Vitrigel®-EIT method is an in vitro assay using human corneal epithelium (hCE) models fabricated in a collagen vitrigel® membrane chamber. The test chemical is dissolved or suspended in the culture medium before exposure of the hCE model. Immediately after its application, the time-dependent changes in TEER values are registered for a few minutes. When low, the TEER decrease speed and intensity reflect the absence of real damages to the barrier function of the corneal epithelium. In this case, the test chemical is identified as not requiring classification and labelling according to UN GHS (No Category). In this case, no further testing with another test method is considered necessary.The Comet assay is an agarose gel electrophoresis technique. It allows the measurement of breaks induced directly by a genotoxic agent and indirectly during enzymatic damage repair processes or during secondary DNA fragmentation processes such as apoptosis. The formation of micronuclei (MN) is a widely used and accepted endpoint of genotoxicity testing. The MN assay provides a simple and rapid indirect measure of the induction of structural or numerical chromosome aberrations. The hen's egg test for MN induction (HET-MN) is an ex vivo assay for the detection of MN formation in young erythrocytes of chick embryo peripheral blood. Adductomics is the study of DNA adducts in the context of an entire genome. DNA adducts are compounds that bind to DNA, causing damage and mutations. These mutations can result in cancer, aging and birth defects in multicellular organisms. The science of adductomics seeks to identify all DNA adducts and the target sequence of each adduct. Various methods such as for example liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) may allow to detect multiple DNA adducts.The Comet assay is an agarose gel electrophoresis technique. It allows the measurement of breaks induced directly by a genotoxic agent and indirectly during enzymatic damage repair processes or during secondary DNA fragmentation processes such as apoptosis. The 3D Comet assay is an adaptation of this test. It is performed from 3D full thickness human skin models in order to assess the effect of a topical application on keratinocytes and fibroblasts located deeper, as in real-life conditions. Photo-Comet Assay allows to assess the ability of chemical compounds to increase the sensitivity of the skin to radiation (280 - 800nm) through the generation of intermediates and/or reactive oxygen species giving rise to phototoxic or photoallergic reactions. Cell cultures are irradiated with a spectrum covering UVA, UVB and visible wavelengths. Then, DNA damages are evaluated at different time points following irradiation with Comet Assay which allows the measurement of the breaks (single or double strand) induced. Photo-Ames test allows to assess the ability of chemical compounds to increase the frequency of radiation-induced bacterial mutations. Suspensions of bacterial cells are exposed to radiations and the tested substance. They are cultured in the presence and in the absence of an amino-acid which is normally necessary to grow the seeded bacteria (parent strain). Only the revertant bacteria which mutation restore the functional capability of the bacteria to synthesize this essential amino acid are able to grow without the amino-acid. This method allows to assess the mutation frequency under radiation exposure with or without the chemical compound to test, and therefore to determine the potential increase of mutation frequency due to the compound.Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the barrier function, thus limiting water loss and favouring appropriate skin hydration. The h-CLAT method consists of quantifying the variation in the expression of markers such as CD54 or CD86, some cell surface markers involved in the activation of dendritic cells, on cell lines after exposure to sensitising agents. The Photo-hCLAT method is an adaptation of this test performed in the presence or absence of light radiation and with or without the chemical compound to be tested. This allows the effects of the product when placed in the presence of light radiation to be determined and thus the photo-sensitising properties of the product to be assessed.This test consists of detecting estrogen receptor agonists and antagonists (nuclear receptors alpha ERα and/or beta ERβ) via in vitro stable transfection transactivation assays. Luciferase or β-galactosidase reporter genes are used. The cells are placed in the presence of the test substance. If the test substance binds to ERα and/or ERβ, the ligand/receptor complex binds to the ER response element and the reporter gene placed under the control of this response element is transactivated. A system for measuring the level of expression of the protein corresponding to the reporter gene makes it possible to assess the degree of activation of expression by the molecule tested and thus the ability of this molecule to activate ERα and/or ERβ. This assay uses a recombinant human estrogen receptor (ERα) to detect molecules with binding affinity to estrogen receptors. Whether via the Freyberger-Wilson (FW) assay using a full-length human ERα receptor or the Chemical Evaluation and Research Institute (CERI) assay using simply the ligand-binding domain of a human ERα, the principle of the assay is to measure the ability of a radiolabelled ligand ([3H]-17β-estradiol) to bind to ERs in the presence of increasing concentrations of the test chemical (called 'competitor'). The greater the affinity of the competitor for the ER receptor, the more it reduces the ability of the radiolabelled ligand to bind. The measurement of radioactivity after rinsing is therefore a way of assessing the affinity of a test molecule for the oestrogen receptor. Desmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healingKeratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. In the suprabasal layers of the epidermis, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Monitoring the expression of these two keratins during the healing phase allows to visualise the progressive differentiation of the epidermis and the the correct regeneration of the skin barrier. Type VII collagen (Coll VII) is primarily synthesized by keratinocytes and fibroblasts. It is an anchoring fibril binding Dermal Epidermal Junction (DEJ) proteins such as Laminin 5, 6 or Collagen IV with ExtraCellular Matrix (ECM) proteins of the dermis such as Collagen I, III and V. The quality of the DEJ and the dermis anchoring to the epidermis therefore depends on Coll VII expression level and location.Type VII collagen (Coll VII) is primarily synthesized by keratinocytes and fibroblasts. It is an anchoring fibril binding Dermal Epidermal Junction (DEJ) proteins such as Laminin 5, 6 or Collagen IV with ExtraCellular Matrix (ECM) proteins of the dermis such as Collagen I, III and V. The quality of the DEJ and the dermis anchoring to the epidermis therefore depends on Coll VII expression level and location.Type XVII collagen (Coll XVII), also called 180-kDa bullous pemphigoid antigen (BP180) is a keratinocyte transmembrane protein located in hemidesmosomes. It binds to other hemidesmosome components such as β4 integrins and plectin, but also to laminin 332 which a component of the Dermal Epidermal Junction (DEJ). The main function of type XVII collagen in skin is therefore to stabilize adhesion of epidermal cells to the DEJ. Type XVII collagen (Coll XVII), also called 180-kDa bullous pemphigoid antigen (BP180) is a keratinocyte transmembrane protein located in hemidesmosomes. It binds to other hemidesmosome components such as β4 integrins and plectin, but also to laminin 332 which a component of the Dermal Epidermal Junction (DEJ). The main function of type XVII collagen in skin is therefore to stabilize adhesion of epidermal cells to the DEJ. In the suprabasal layers of the epidermis, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Monitoring the expression of these two keratins during the healing phase allows to visualise the progressive differentiation of the epidermis and the the correct regeneration of the skin barrier. In the suprabasal layers of the epidermis, the differentiation-specific keratins K1 and K10 are expressed. K10 plays a role in proliferation inhibition and, ultrastructurally, keratin filaments composed of the pair K1/K10 form particularly dense bundles that contribute to the mechanical integrity to the cells and the whole epidermis. Monitoring the expression of these two keratins during the healing phase allows to visualise the progressive differentiation of the epidermis and the the correct regeneration of the skin barrier. Interleukin 17 (IL-17) is an essential proinflammatory cytokine secreted by the Th17 cells (CD4+ helper T cells) and subsets of innate lymphoid cells. IL-17 targets many cells including keratinocytes, fibroblasts, neutrophils or endothelial cells and is associated with the pathogenesis of many inflammatory diseases including psoriasis and atopic dermatitis. Interleukin 23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. IL-17 and IL-23 level may therefore be used as markers of inflammatory state. Interleukin 17 (IL-17) is an essential proinflammatory cytokine secreted by the Th17 cells (CD4+ helper T cells) and subsets of innate lymphoid cells. IL-17 targets many cells including keratinocytes, fibroblasts, neutrophils or endothelial cells and is associated with the pathogenesis of many inflammatory diseases including psoriasis and atopic dermatitis. Interleukin 23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. IL-17 and IL-23 level may therefore be used as markers of inflammatory state. Interleukin 22 (IL-22) is a cytokine involved in the modulation of tissue responses during inflammation. Produced by Th17 and Th22 T helper cells, IL-22 induces keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and promotes the production of antimicrobial proteins. Th22 cells reside in the normal skin and are enriched in the lesional skin of inflammatory skin diseases. IL-22 plays a role in psoriasis, atopic dermatitis and other inflammatory skin diseases. Interleukin 22 (IL-22) is a cytokine involved in the modulation of tissue responses during inflammation. Produced by Th17 and Th22 T helper cells, IL-22 induces keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and promotes the production of antimicrobial proteins. Th22 cells reside in the normal skin and are enriched in the lesional skin of inflammatory skin diseases. IL-22 plays a role in psoriasis, atopic dermatitis and other inflammatory skin diseases. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. IL-31 belongs to pro-inflammatory cytokines and plays a role in various human inflammatory disorders including atopic dermatitis (AD). Overexpressed in AD lesional skin, IL-31 is produced by TH2 T cells and immature dendritic cells. It can activate various cells including keratinocytes and plays a key role in puritus and pruritic disorders. IL-6 is a pro-inflammatory cytokine associated with skin healing and inflammation. Released early in response to injury, IL-6 plays a central role in acute inflammation and reparative process occuring successively during wound healing. Overexpressed in skin inflammatory diseases such as psoriasis, IL-6 stimulates both other pro-inflammatory cytokine secretion and keratinocyte hyperproliferation leading to epidermal thickening. IL-6 is produced by immune cells such as lymphocytes, monocyte / macrophages, dendritic cells but also by keratinocytes, fibroblasts, endothelial cells or sebocytes. IL-6 is a pro-inflammatory cytokine associated with skin healing and inflammation. Released early in response to injury, IL-6 plays a central role in acute inflammation and reparative process occuring successively during wound healing. Overexpressed in skin inflammatory diseases such as psoriasis, IL-6 stimulates both other pro-inflammatory cytokine secretion and keratinocyte hyperproliferation leading to epidermal thickening. IL-6 is produced by immune cells such as lymphocytes, monocyte / macrophages, dendritic cells but also by keratinocytes, fibroblasts, endothelial cells or sebocytes. Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.Produced by activated monocytes, endothelial cells, keratinocytes, fibroblasts and sebocytes, interleukin 8 (IL-8) exerts a chemotactic effect on neutrophils, T cells and basophils. Thus involved in the inflammatory response,especially in the case of bacterial infection, it is locally overproduced in several inflammatory skin diseases involving neutrophilic infiltration, such as psoriasis.Interleukin 1 alpha (IL-1α) and bêta (IL-1β) are key pro-inflammatory cytokines released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. They are therefore involved in various skin inflammation diseases and constitute appropriate markers of skin inflammatory state. Interleukin 1 alpha (IL-1α) and bêta (IL-1β) are key pro-inflammatory cytokines released by immune cells such as monocytes and macrophages but also by keratinocytes after their activation or alteration. They are therefore involved in various skin inflammation diseases and constitute appropriate markers of skin inflammatory state. Interleukin 4 (IL-4) promotes the development of Th2 cells, while interleukin 13 (IL-13) is critical in promoting tissue inflammation. They both play a key role in allergic inflammation and therefore in atopic dermatitis (AD) genesis. In AD, IL-4 and IL-13 are overexpressed and consequently decrease the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. Interleukin 4 (IL-4) promotes the development of Th2 cells, while interleukin 13 (IL-13) is critical in promoting tissue inflammation. They both play a key role in allergic inflammation and therefore in atopic dermatitis (AD) genesis. In AD, IL-4 and IL-13 are overexpressed and consequently decrease the expression of multiple genes associated with innate defense, including some associated with epidermal differentiation such as filaggrin, therefore impairing epidermal barrier function. Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the barrier function, thus limiting water loss and favouring appropriate skin hydration. Loricrin is an insoluble protein that is synthesised and stored as granules in the keratinocytes of the stratum granulosum. It then enters the composition of the stratum corneum where it is linked by covalent bonds to other proteins by transglutaminases. As a major component of the stratum corneum, it represents a marker of the terminal differentiation of the epidermis and plays an essential role in the barrier function, thus limiting water loss and favouring appropriate skin hydration. The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin hydration as a key cell receptor for hyaluronic acid and skin inflammation or metastasis. Permeability barrier disruption and inflammation stimulate epidermal CD44 expression which is involved in leucocyte recruitment and it has been shown that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model. The cluster of differentiation 44 (CD44) is on all skin cells. This membrane receptor is involved in cell adhesion and migration, skin hydration as a key cell receptor for hyaluronic acid and skin inflammation or metastasis. Permeability barrier disruption and inflammation stimulate epidermal CD44 expression which is involved in leucocyte recruitment and it has been shown that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model. Desmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healingDesmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healingSpontaneous mutations or various factors such as UV radiation can cause cellular DNA damages. Some enzymes normally repair DNA. However, more and more alterations tend to accumulate during skin aging increasing the risk of cancer development. More or less innovative techniques can be used to assess the efficiency and relevance of DNA repair systems in cell cultures or biopsies. The Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a pro-inflammatory cytokine produced by many cell types including keratinocytes activated by hapten, irritant or IL-1a. GM-CSF can be therefore used as an inflammatory response marker in skin following hapten or irritant application. The Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a pro-inflammatory cytokine produced by many cell types including keratinocytes activated by hapten, irritant or IL-1a. GM-CSF can be therefore used as an inflammatory response marker in skin following hapten or irritant application. Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Hornerin is a component of cornified cell enveloppes of human epidermis. Its reduced expression in atopic dermatitis contributes to the epidermal barrier defect observed in the disease. Epidermal integrity is regulated by a tight communication between keratinocytes and leucocytes, particularly under cytokine control. Imbalance of the cytokine network leads to inflammatory diseases such as psoriasis. The combination of five cytokines (IL-22, Oncostatin M, IL-17, TNFα and IL-1) all overexpressed in vivo in psoriatic lesions has been shown in vitro to induce a “psoriasis-like” epidermis phenotype, both at the histological and molecular levels.Epidermal integrity is regulated by a tight communication between keratinocytes and leucocytes, particularly under cytokine control. Imbalance of the cytokine network leads to inflammatory diseases such as psoriasis. The combination of five cytokines (IL-22, Oncostatin M, IL-17, TNFα and IL-1) all overexpressed in vivo in psoriatic lesions has been shown in vitro to induce a “psoriasis-like” epidermis phenotype, both at the histological and molecular levels.α6β4 integrins are transmembrane proteins playing a key role in the formation and stabilization of junctional adhesion complexes called hemidesmosomes. They are connected to the intermediate filament system of basal keratinocytes and the laminin 332 of the dermal-epidermal junction. They are also involved in the regulation of a variety of signaling processes allowing for example keratinocyte migration. A defect in the expression of those molecules may therefore impair skin integrity and barrier function. α6β4 integrins are transmembrane proteins playing a key role in the formation and stabilization of junctional adhesion complexes called hemidesmosomes. They are connected to the intermediate filament system of basal keratinocytes and the laminin 332 of the dermal-epidermal junction. They are also involved in the regulation of a variety of signaling processes allowing for example keratinocyte migration. A defect in the expression of those molecules may therefore impair skin integrity and barrier function. IFNγ orchestrates numerous protective functions including antigen processing and presentation, leukocyte trafficking, anti-microbial functions, cellular proliferation and apoptosis or the initiation of a cascade of pro-inflammatory responses. Produced by many immune cells including Th1 Tcells, macrophages or dendritic cells (DCs), IFNγ is overexpressed in psoriatic skin and enhances IL-23 and IL-1 production by DCs, leading to Th17 cell activation and initiating psoriasis lesions. On the contrary, its expression is reduced in atopic dermatitis.IFNγ orchestrates numerous protective functions including antigen processing and presentation, leukocyte trafficking, anti-microbial functions, cellular proliferation and apoptosis or the initiation of a cascade of pro-inflammatory responses. Produced by many immune cells including Th1 Tcells, macrophages or dendritic cells (DCs), IFNγ is overexpressed in psoriatic skin and enhances IL-23 and IL-1 production by DCs, leading to Th17 cell activation and initiating psoriasis lesions. On the contrary, its expression is reduced in atopic dermatitis.Koebnerisin (S100A15) is an antimicrobial peptide produced by keratinocytes with a sequence very similar to psoriasin. Overexpressed in psoriatic lesions or in the case of infection of keratinocytes by Escherischia coli, koebnerisin also has anti-inflammatory and chemotactic properties. It thus contributes to the skin's barrier function. Koebnerisin (S100A15) is an antimicrobial peptide produced by keratinocytes with a sequence very similar to psoriasin. Overexpressed in psoriatic lesions or in the case of infection of keratinocytes by Escherischia coli, koebnerisin also has anti-inflammatory and chemotactic properties. It thus contributes to the skin's barrier function. Overexpressed in psoriatic lesions, Oncostatin M (OSM) potently regulates the expression of genes involved in skin inflammation and epidermal differentiation. For example, OSM stimulates the expression of antimicrobial peptides and various cytokines such as Th1/Th2 cytokines, whereas it decreases the expression of some epidermal differentiation markers such as K10 or filaggrin. Overexpressed in psoriatic lesions, Oncostatin M (OSM) potently regulates the expression of genes involved in skin inflammation and epidermal differentiation. For example, OSM stimulates the expression of antimicrobial peptides and various cytokines such as Th1/Th2 cytokines, whereas it decreases the expression of some epidermal differentiation markers such as K10 or filaggrin. Skin ageing is associated with a decrease in dermal collagen I proportion. This has been correlated to a decrease in procollagen I synthesis and an increase in collagen I degradation by MMP-1. An anti-ageing product can therefore increase Procollagen I synthesis and decrease MMP-1 activity.Skin ageing is associated with a decrease in dermal collagen I proportion. This has been correlated to a decrease in procollagen I synthesis and an increase in collagen I degradation by MMP-1. An anti-ageing product can therefore increase Procollagen I synthesis and decrease MMP-1 activity.Skin renewal involves the renewal of the dermal extracellular matrix and in particular of its main component, the collagen I. The density and structure of the collagen I network depend on the synthesis of procollagen I, its assembly into collagen fibrils, the cross-linking of the fibrils and their degradation. A modulation of procollagen I synthesis, observed for example during skin ageing, therefore has consequences for skin renewal and firmness.Skin renewal involves the renewal of the dermal extracellular matrix and in particular of its main component, the collagen I. The density and structure of the collagen I network depend on the synthesis of procollagen I, its assembly into collagen fibrils, the cross-linking of the fibrils and their degradation. A modulation of procollagen I synthesis, observed for example during skin ageing, therefore has consequences for skin renewal and firmness.Prostaglandin E-2 (PGE-2) is a lipid-derived signaling molecule found in mammalian skin, especially in fibroblasts. Levels of Prostaglandin E-2 (PGE-2) increase with chronological aging and following sun exposure, inducing an inflammatory state and therefore skin damages associated to ageing such as collagen decrease. Prostaglandin E-2 (PGE-2) is a lipid-derived signaling molecule found in mammalian skin, especially in fibroblasts. Levels of Prostaglandin E-2 (PGE-2) increase with chronological aging and following sun exposure, inducing an inflammatory state and therefore skin damages associated to ageing such as collagen decrease. Loricrin and involucrin are two proteins synthesised in the keratinocyte cytoplasm of stratum granulosum. They are markers of terminal differentiation and essential components of the stratum corneum. Monitoring the expression of these two proteins allows to ensure that the skin barrier is correctly established during wound healing. Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Its cleavage also leads to the formation of Natural Moisturising Factor (NMF) which is involved in skin hydration. Monitoring the synthesis, abundance, localisation and cleavage of filaggrin therefore makes it possible to verify the correct restoration of the skin barrier and its hydration during wound healing.Specific to smooth muscle cells, α-SMA is also an abundant actin in the cytoskeleton of myofibroblasts. The specificity of myofibroblasts is their ability to contract and to produce a very large amount of matrix elements. These myofibroblasts are derived from the differentiation of fibroblasts and appear in the dermis approximately one week after a skin injury. By contracting synchronously after the wound has been filled with granulation tissue and re-epithelialised, they actively participate in wound closure and tissue remodelling. Myofibroblasts are therefore necessary for wound healing, but an excess of myofibroblasts is also correlated to skin diseases such as hypertrophic scars or other fibrotic diseases. Evaluating the synthesis and distribution of α-SMA therefore allows monitoring the differentiation of fibroblasts into myofibroblasts, the contraction of the tissue and its appropriate remodelling.Vimentin is an intermediate filament protein composing the cytosqueletton and participating in numerous cellular processes including cell adhesion, migration, signaling, differentiation, cytoskeletal rearrangements, and regulation of cell morphology and plasticity. Following skin or eye injury and cell lesion, vimentin is released in extracellular matrix and stimulates inflammatory cell migration, keratinocyte differentiation and fibroblast proliferation, migration and differentiation in myofibroblasts. Vimentin therefore supports wound healing but may also be responsible of fibrosis. Vimentin is therefore an interesting marker to follow wound healing. Integrins are transmembrane cell surface receptors allowing interactions between cells or between cells and extracellular matrix (ECM) molecules. They are involved in cell adhesion, movement and migration but also in signal transduction. A modification of the number, type, and distribution of integrins is observed during wound healing. For instance, α2β1 integrin constitutively expressed in intact skin is upregulated in wounds. α3β1 integrin is up-regulated in keratinocytes during reepithelialization. Indirectly involved in this phenomenon, it also stimulates angiogenesis by inducing a cross-talk between keratinocytes and endothelial cells. α5β1 integrin is not present in normal epidermis but appears shortly after wounding, interacting with the initial clot, and lasts only for a short duration. This integrin is the major cell receptor of fibronectin (keratinocytes, fibroblasts, endothelial cells, immune cells) and is involved in keratinocyte migration, angiogenesis and inflammation. It also plays a key role in fibrosis. The integrin subunit α11 is highly induced during wound healing both at the mRNA and protein levels. Some data suggest that α11β1 integrin stimulates granulation tissue formation, wound contraction, fibroblast migration, cell differentiation in myofibroblasts and collagen remodeling during wound healing. In response to injury, collagen exposure induces platelet activation and aggregation leading to the formation of a fibrin clot. Collagen fragments also contributes in the inflammatory stage as a chemoattractant for neutrophiles and macrophages. Inflammation drives the proliferation of fibroblasts and myofibroblasts which contribute to collagen deposition. Simultaneously, collagen degradation releases fragments that promote fibroblast proliferation and synthesis of growth factors that lead to angiogenesis and reepithelialization. Finally, the remodeling of the extracellular matrix (ECM), which results from the balance of new matrix synthesis and matrix metalloproteinase (MMPs) degradative activities, determines the acquisition of tensile strength. Types I and III collagens (Col I & Col III) are the two main components of extracellular matrix. Col III is the first to be synthesized in the early stages of wound healing and is replaced by Col I, the dominant skin collagen. Col I and Col III are preferentially cleaved by MMP-1 (also called collagenase-1) and MMP-8 (collagenase-2). Abnormalities in the ECM reconstitution during wound healing result in hypertrophic and keloid scars. Scarring is characterized by high levels of Col I, Col III, fibronectin and laminin. Collagen fiber orientation in all scars is parallel to the epithelial surface unlike that of normal skin where the fibers form a three-dimensional basketweave-like network. Keloid scars are characterized by abnormally thick bundles of collagen that are poorly organized with fewer cross-links that are found in the deep dermis compared to superficial dermic. Hypertrophic scars have thinner collagen bundles than keloid or normotrophic scars. The ratio of collagen I to III is higher in keloids than normotrophic scars. Even within the keloid scar, there is a heterogeneity to the collagen I/III ratio. Following skin injury, damaged blood vessels are replaced by "sprouts" from intact capillaries in the local vicinity of the wound. Approximately on day 2 postwounding, endothelial cells (ECs) which will constitute the future vessels begin to migrate. Platelet endothelial cell adhesion molecule (PECAM 1), also called CD31, is an ECs marker which staining or dosage allow to monitor angiogenesis progression. CD34 may also be used, even if other skin cells such as bulge stem cells or dendritic cells also express this marker. ECs migration into the wound involves many factors including the αVβ3 integrin. This transmembrane protein helps ECs adhesion on extracellular matrix proteins including fibrin, one of the major component of the clot formed at the begining of wound healing. It also favors MMP2 collagenase location on ECs surface thus facilitating collagen digestion. This integrin is the most important integrin regarding angiogenesis. Absent in normal tissue, its expression is stimulated during wound healing. Produced by fibroblasts and vascular smooth muscle cells, elastin is the main component of skin elastic fibres. Responsible of skin elasticity, it represents 2 - 4% of the dermal extracellular matrix (ECM) in adult skin. Its production occurs mainly before sexual maturity and is drastically reduced thereafter in adult normal skin. Nevertheless, elastin synthesis is stimulated upon injury and during wound healing. This leads to the formation of elastin fragments called elastikines and stimulating dermal cells, thus attenuating wound contraction and improving dermal regeneration. Elastin deposition is usually observed many months after injury and remains more or less efficient to regenerate elastin network and skin elasticity. During wound healing, the inflammation phase succeeds to the hemostasis. Various pro-inflammatory cytokines and growth factors released by the clot and wound tissue induce inflammatory cell migration by the process of chemotaxis. Mast cells come first and assist in the recruitment of neutrophils which protect against infectious agents and starts the removal of debris from damaged cells and extracellular matrix. The neutrophil population peaks in the first 48 hr after injury and is eventually replaced by macrophages differentiated from monocytes. Various histological markers can be used to locate and quantify white blood cells, including CD203 or Mas-related G-protein coupled receptor member X2 (MRGPRX2) for mast cells. Myeloperoxidase (MPO) is an enzyme contained in neutrophil cytoplasmic granules and participating in innate immune response while N-acetylglucosaminidase (NAG) is a lysosomal enzyme highly expressed in activated macrophages. Staining or evaluating the enzyme activity of MPO and NAG can therefore respectively allow to localise or assess the level of accumulation in the tissue of neutrophils and macrophages. During the inflammatory phase of wound healing, various leukocytes are involved and recruited, including lymphocytes that can be divided in 3 categories : T cells, B cells and Natural Killer (NK) cells. The skin contains resident T cells that participates in normal skin homeostasis and are activated under skin injury, thus contributing to wound healing by producing epithelial growth factors and inflammatory cytokines. Some data also suggest that T helper (Th) cells recruited during wound healing delay wound closure, decrease inflammation, stimulate neovascularization and limit scarring. Live B cells mediate pro-healing responses, helping to reduce scar size and increase collagen deposition and maturation, enhancing angiogenesis, and increasing nerve growth into and under the healing wound. Natural Killer (NK) cells regulate the early onset and resolution of the inflammatory phase. Some data also suggest their contribution to re-epithelialization, angiogenesis, granulation tissue formation, and remodelling. Various markers can be used to monitor the leukocyte infiltration and abundance during wound healing. CD3 is a marker of mature T cells. The human skin-resident T cells express specifically the cutaneous leukocyte antigen (CLA) which is almost absent in peripheral blood T cells. CD4 is specific of Th cells while CD8 may be used to identify T cytotoxic (Tc) cells and partially NK cells. CD19 or CD20 are B cell markers, while NK cells may be identified with CD16 or CD56. Wound healing begins with hemostasis. The clot formed minutes after injury is mainly composed by fibrin and platelets. Produced by the cleavage of fibrinogen by thrombin, fibrin monomers are cross linked by factor XIII and binds to platelets to produce a clot. Fibrin is then involved in cellular migration and extracellular matrix (ECM) production occurring after hemostasis. For example, fibrin participates in the inflammatory phase by binding αMβ2 integrin, a receptor found on monocytes and neutrophils. Endothelial cells and fibroblasts also bind to fibrin via αvβ3 integrin. Fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) bind fibrin and stimulate angiogenesis, whereas insulin-like growth factor (IGF)-1 binds fibrin and stimulates stromal cell function and proliferation. Despite its important function throughout wound healing, fibrin degradation begins shortly after the formation of a clot thanks to plasminogen which is activated by a synthetic product of endothelial cells. Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein produced by endothelial cells, fibroblasts, smooth muscle cells, platelets, neutrophils, and macrophages. It plays a key role during wound healing by stimulating angiogenesis, collagen deposition and epithelialization but also by mediating vascular permeability, the chemotactic response of neutrophils and macrophages, and the expression of matrix metalloproteinases in vascular smooth muscle cells. The time course of VEGF expression provides insight into the progression of wound healing. Maximal activity occurs during a “window” period approximately 3 to 7 days after injury. Once the wound is granulated, angiogenesis ceases and blood vessels decline as endothelial cells undergo apoptosis. The reduction in VEGF and the loss of apoptosis may contribute to this transition from hypercellular granulation tissue to a hypocellular scar. Integrins associated with VEGF activity follow a similar pattern of expression in wound healing. In full thickness wounds at days 3 and 4, αvβ3 integrin is localized on hypertrophied vessels at the wound margin as well as on the tips of capillary sprouts invading the fibrin clot. Expression of αvβ3 disappears by day 7, as VEGF returns to baseline levels.Platelet-derived growth factor (PDGF) is released from platelets into the serum during blood clotting. It is also secreted by macrophages, endothelial cells, fibroblasts, and keratinocytes. PDGF has been found to regulate cell growth and division and plays a role in angiogenesis. It is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells. It also stimulates general protein and collagen synthesis and collagenase activity. Nevertheless, it seems to have an effect on wound healing only in combination with other growth factors such as Insulin-like Growth Factor (IGF-I) Despite there are only few data for human, IGF-I seems to play a key role in wound healing. Indeed, according to these data, it promotes the migration and proliferation of keratinocytes, thus playing an important role in wound epithelialization. It also enables wound bed contraction, and stimulates hyaluronan synthesis thus participating in skin remodeling. Fibroblast growth factor (FGF2) strongly activates not only fibroblasts but also other mesoderm-derived cells, including vascular endothelial and smooth muscle cells. It plays an important role during wound healing. Indeed, the administration of recombinant FGF2 to skin wounds accelerates acute and chronic wound healing. Local FGF2 administration also has an anti-fibrotic effect for the wound to antagonize myofibroblast differentiation and dampen fibrosis. In addition, FGF2 is considered to accelerate reepithelization and has been recently shown to accelerates the epithelial–mesenchymal transition in keratinocytes during wound healing. Epidermal Growth Factor (EGF) is produced by platelets, macrophages and monocytes. It plays an important role by binding to epidermal growth factor receptor (EGFR) on cell surface. EGFR is expressed on various cell surfaces, obviously epidermal cells but also fibroblasts, endothelial cells and smooth muscle cells. After binding with EGF, the intrinsic protein tyrosine kinase activity of EGFR is stimulated, leading to a variety of biochemical processes in cells. For example, it can promote DNA synthesis and cell proliferation, regulate cell metabolism, promote chemotaxis, granulation tissue and epidermis formation. Transforming Growth Factor bêta (TGF-β) is a family of growth factors (TGF-β1, TGF-β2 and TGF-β3) involved in a number of essential cellular functions. All three isoforms are believed to bind and signal through the two TGF- β receptors (TβRI and TβRII) and mainly act via SMAD pathway. All 3 isoforms of TGF-β notably play a key role during wound healing, being involved in the inflammation phase, and stimulating angiogenesis, fibroblast proliferation, collagen synthesis and deposition and remodelling of the new extracellular matrix. Interestingly chronic, non-healing wounds often show a loss of TGF-β1 signalling, whereas fibroblasts derived from hypertrophic scars have been shown to synthetise more TGF-β1 and to express TGF-β receptors for a longer period of time than fibroblasts derived from normal skin. Thus, an alteration of TGF-β signaling (correlated to TGF-β or its receptors) has often been correlated to abnormal wound healing. Assessing TGF-β synthesis and/or the expression of its receptors may be of great interest when studying this phenomenon. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. In addition to its effect on angiogenesis, V-EGF is also involved in maintaining the stemness and renewal abilities of cancer cells in squamous tumours. A decrease in the number of dermal blood vessels is observed during skin aging. This seems to be due to an impairment of Vascular Endothelial Growth Factor (V-EGF) signaling. Some antiaging molecules may restore V-EGF cell level and therefore an appropriate dermal microcirculation. In addition to its effect on angiogenesis, V-EGF is also involved in maintaining the stemness and renewal abilities of cancer cells in squamous tumours. Proinflammatory cytokines, particularly interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNFα) are up-regulated during the inflammatory phase of wound healing. Upon wound healing IL-1 and TNFα are immediately released by keratinocytes. IL-1 is also released by neutrophils, monocytes and macrophages. IL-1 increases keratinocyte migration and proliferation, activates fibroblasts and increases the secretion of FGF-7. IL-6 is produced by neutrophils and monocytes and initiates the healing response. Its expression is increased after wounding and tends to persist in older wounds. It stimulates keratinocyte proliferation and is chemoattractive to neutrophils. TNFα, at low levels, can promote wound healing by indirectly stimulating inflammation and increasing macrophage produced growth factors. However, at higher levels and especially for a long period, TNFα, as well as IL-1β, favors extracellular matrix degradation and has a detrimental effect on healing. Levels of TNFα and IL-1β are elevated in chronic wounds.Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar (HS), which limits patients' joint movement and generates an aesthetic problem. This HS results from the enhanced proliferation of fibroblasts, the increased transdifferentiation of fibroblasts into myofibroblasts, and the increased deposition of extracellular matrix proteins, such as type I collagen. Interleukine-17 (IL-17) is a pro-inflammatory cytokine whose overexpression promotes the formation of cutaneous scar with the help of increased levels of several chemokines and the infiltration of macrophages. Interleukine-10 (IL-10) is a potent anti-inflammatory cytokine produced by various cell types such as Tcells, monocytes and macrophages, but also by keratinocytes after skin injury. IL-10 plays a key role in the ability of the fetus to heal regeneratively. Overexpression of IL-10 is also able to recapitulate scarless healing in postnatal tissue through its wide-ranging pleiotropic effects, attenuating the inflammatory response, regulating the extracellular matrix, enhancing fibroblast function, and modulating stem cell function. Interferon gamma (IFNγ) is a cytokine mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. IFNγ contributes to the activation of the immune cells during the inflammatory phase of wound healing, the recruitment of neutrophils and cell clearance through apoptosis. IFNγ also regulates collagen synthesis and angiogenesis, and there is also a crosstalk between IFNγ and the Transforming Growth Factor beta (TGFβ)/Smad signaling pathway. Thus, a defect in IFNγ secretion can lead to a delayed wound closure associated with inappropriate neutrophil accumulation and defective extracellular matrix formation. Histopathology of wounds is a very helpful tool to monitor healing progress.A biopsy of the wound, including the edges to compare the ulcerated area and the surrounding skin, is collected. After fixation or freezing in appropriate conditions, cutting and staining, the general structure of the wound can be observed. The most widely used stain in dermatopathology is haematoxylin and eosin (H&E). Haematoxylin dyes the cellular nuclei blue, while eosin dyes the non-nuclear cells and structures pink/orange, such as cytoplasm and collagen. This allows to observe the evolution of the epidermis, the dermis or the skin appendages. The abundance of immune cells can also be observed. HES staining combines HE staining with Saffron to better highlight collagen fibers whose arrangement and orientation play a vital role during the remodelling phase. Picrosirius Red is a special stain that demonstrates both thin and thick collagen fibres. Thrichrome stainings such as Masson's trichrome reveals muscle and intercellular or extracellular fibres (collagen, keratins).Type VII collagen (Coll VII), type IV collagen (Coll IV) and Laminin 332 (previously called Laminin V) are major components of the dermal-epidermal junction (DEJ). Studying the synthesis and the location of these molecules allow to monitor DEJ repair during wound healing, which is mandatory to restore barrier function. Moreover, Coll IV fragments can be mediators of inflammation by stimulating neutrophil migration, phagocytosis and immune responses. They also regulate angiogenesis. Coll VII is required for re-epithelialization. Its loss perturbs the organization of laminin-332 during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Coll VII also supports dermal fibroblast migration and regulates their cytokine production in the granulation tissue. Laminin 332 also regulates keratinocyte turnover and differentiation on which the efficiency of the barrier function depends. In addition, laminin-332 and Coll IV are major components of the basement membrane of skin vessels on which endothelial cells are attached and they play a key role in angiogenesis. Calprotectin (S100A8/9) is a heterodimer composed of calgranuline A (S100A8) and calgranuline B (S100A9). It is produced by keratinocytes and forms an antimicrobial peptide which limits the development of pathogenic microorganisms, thus participating in skin barrier function. Its expression is low in normal skin but stimulated by various skin stresses such as tape stripping, exposure to detergent, UV, or cytokines (IL-1α, IL-22). Calprotectin (S100A8/9) is a heterodimer composed of calgranuline A (S100A8) and calgranuline B (S100A9). It is produced by keratinocytes and forms an antimicrobial peptide which limits the development of pathogenic microorganisms, thus participating in skin barrier function. Its expression is low in normal skin but stimulated by various skin stresses such as tape stripping, exposure to detergent, UV, or cytokines (IL-1α, IL-22). β1-containing integrin dimers are ubiquitously expressed receptor that mediate cell-cell and cell-extracellular matrix interactions. Keratinocytes express α2β1 and α3β1 receptors and β1 has been found to be a marker for proliferation competent cells as its expression decreases during keratinocyte differentiation. β1 plays a key role in the processing of the basement membrane components, including the dermal-epidermal junction, the formation and/or maintenance of hemidesmosomes, and keratinocyte proliferation and differentiation. A defect in β1 expression may therefore impair skin integrity and barrier function. β1-containing integrin dimers are ubiquitously expressed receptor that mediate cell-cell and cell-extracellular matrix interactions. Keratinocytes express α2β1 and α3β1 receptors and β1 has been found to be a marker for proliferation competent cells as its expression decreases during keratinocyte differentiation. β1 plays a key role in the processing of the basement membrane components, including the dermal-epidermal junction, the formation and/or maintenance of hemidesmosomes, and keratinocyte proliferation and differentiation. A defect in β1 expression may therefore impair skin integrity and barrier function. Skin barrier function mainly relies on stratum corneum which is composed of corneocytes embedded in a lipid-enriched lamellar matrix. Rab11a is a GTPase type enzyme highly expressed in terminally differentiated keratinocytes and partly associated with lamellar bodies. Rab11a is involved in lamellar body biogenesis, associated secretion and the production of stratum corneum lipids. Rab11a is therefore essential for skin barrier function. Skin barrier function mainly relies on stratum corneum which is composed of corneocytes embedded in a lipid-enriched lamellar matrix. Rab11a is a GTPase type enzyme highly expressed in terminally differentiated keratinocytes and partly associated with lamellar bodies. Rab11a is involved in lamellar body biogenesis, associated secretion and the production of stratum corneum lipids. Rab11a is therefore essential for skin barrier function. Transglutaminase (TGM) is a calcium-dependent enzyme catalyzing an intermolecular isopeptide bond formation between proteins. 9 TGMs have been identified in human. Among them, TGM 1, 3 and 5 are known to participate in the covalent cross-linking of constitutive proteins such as loricrin and involucrin ioccuring during the cornification process. Thus, TGMs are required for skin barrier function. Transglutaminase (TGM) is a calcium-dependent enzyme catalyzing an intermolecular isopeptide bond formation between proteins. 9 TGMs have been identified in human. Among them, TGM 1, 3 and 5 are known to participate in the covalent cross-linking of constitutive proteins such as loricrin and involucrin ioccuring during the cornification process. Thus, TGMs are required for skin barrier function. Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. The surface of healthy cells is composed of lipids that are asymmetrically distributed on the inner and outer leaflet of the plasma membrane. One of these lipids, phosphatidylserine (PS), is normally restricted to the inner leaflet of the plasma membrane and is, therefore, only exposed to the cell cytoplasm. However, during apoptosis lipid asymmetry is lost and PS becomes exposed on the outer leaflet of the plasma membrane. Annexin V, a 36-kDa calcium-binding protein, binds to PS; therefore, fluorescently labeled Annexin V can be used to detect PS that is exposed on the outside of apoptotic cells. Annexin V can also stain necrotic cells because these cells have ruptured membranes that permit Annexin V to access the entire plasma membrane. However, apoptotic cells can be distinguished from necrotic cells by co-staining with propidium iodide (PI) because PI enters necrotic cells but is excluded from apoptotic cells. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay detects DNA breakage by labeling the free 3'-hydroxyl termini. Given that genomic DNA breaks arise during early and late stages of apoptosis, TUNEL staining can also be used to measure apoptotic cell death. Collagen is the major protein component of connective tissue and is composed primarily of glycine, proline and hydroxyproline. Collagen synthesis requires hydroxylation of lysine and proline, and co-factors such as ferrous iron and vitamin C. Breakdown of collagen liberates free hydroxyproline and its peptides. Hence, measurement of hydroxyproline can be used as a biochemical marker for tissue collagen and an index for collagen turnover. Increase in the hydroxyproline content indicates increased collagen synthesis, which corresponds to an enhanced wound healing. Hydroxyproline can be analysed in tissue (biopsies) and in cell culture supernatants. Measurement of hydroxyproline can be carried out by colorimetric methods, high-performance liquid chromatography (HPLC), gas chromatography/mass spectrometry and enzymatic methods.Macrophages, which classical marker is CD68, are one of the key regulators of the wound healing process and as it progresses, their phenotype changes, reflecting a differentiation process that shifts their functions from inflammation to proliferation and it is called polarization. During acute wound healing, inflammatory macrophages, traditionally referred to as M1, infiltrate after injury to clean the wound of microorganisms, foreign debris and dead cells. As the tissue begins to repair, the overall macrophage population transitions to reparative macrophages (M2) along with migration and proliferation of fibroblasts, keratinocytes and endothelial cells to restore the dermis, epidermis and vasculature. M1 macrophages are induced by Th-1 cytokines, such as IFN-γ and TNF-α, or by bacterial lipopolysaccharide (LPS) recognition. They produce and secrete high levels of pro-inflammatory cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-12, IL-23 and cyclooxygenase-2 (COX-2), and low levels of IL-10. M1 macrophages have robust antimicrobial and anti-tumoral activity but mediate ROS-induced tissue damage, and impair tissue repair. The inflammatory response is inhibited by regulatory mechanisms driven by anti-inflammatory function of M2 macrophages in order to protect against tissue damage. Induced by Th-2 cytokines, IL-10, TGF-β, IL-4, IL-13, IL-33 and IL-21, M2 cells orchestrate the promotion of tissue remodelling, angiogenesis, immunoregulation, tumour formation and progression. Zonula Occludens 1 (ZO1) is a transmembrane protein linked to the cytosqueleton and providing the structural basis for the assembly of the proteins composing the tight junctions. It therefore participates in the keratinocyte close association and thus in the proper functionning of the skin barrier. Besides this structural function, a role of ZO proteins in the regulation of cell growth and proliferation has also been reported. Zonula Occludens 1 (ZO1) is a transmembrane protein linked to the cytosqueleton and providing the structural basis for the assembly of the proteins composing the tight junctions. It therefore participates in the keratinocyte close association and thus in the proper functionning of the skin barrier. Besides this structural function, a role of ZO proteins in the regulation of cell growth and proliferation has also been reported. C. acnes is the dominant resident bacterial species in the sebaceous follicles. It includes various subtypes. The proportion of phylotype IA1, which virulence and inflammatory potential is higher than other phylotypes, is usually more abundant in acne-prone skin. An anti-acneic product acts by decreasing phylotype IA1 proportion.Squalene overproduction and oxydation are observed in acne-prone skin. An anti-acne product decreases both the amount of squalene produced and the ratio of peroxidised squalene to squalene.Squalene overproduction and oxydation are observed in acne-prone skin. An anti-acne product decreases both the amount of squalene produced and the ratio of peroxidised squalene to squalene.Transforming Growth Factor beta (TGFβ) has many effects highly cell and context-dependent. Among all its effects, TGF-β1 is a potent chemoattractant for endothelial cells and fibroblasts as well as neutrophils and monocytes and stimulates pro-inflammatory cytokine release by these cells. TGF-β overexpression in the epidermal basal layers is also associated with inflammation, keratinocyte hyperproliferation and delayed wound healing. Transforming Growth Factor beta (TGFβ) has many effects highly cell and context-dependent. Among all its effects, TGF-β1 is a potent chemoattractant for endothelial cells and fibroblasts as well as neutrophils and monocytes and stimulates pro-inflammatory cytokine release by these cells. TGF-β overexpression in the epidermal basal layers is also associated with inflammation, keratinocyte hyperproliferation and delayed wound healing. Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in allergen stimulated keratinocytes. It plays a key role in allergic inflammation by stimulating eosinophil infiltration and Th2 cytokine secretion (IL-4, IL-5, IL-13) by T helper cells. TSLP can therefore be used as a marker of allergic inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in allergen stimulated keratinocytes. It plays a key role in allergic inflammation by stimulating eosinophil infiltration and Th2 cytokine secretion (IL-4, IL-5, IL-13) by T helper cells. TSLP can therefore be used as a marker of allergic inflammation. Decorin (DCN) is a small leucine-rich proteoglycan expressed in the extracellular matrix of several tissues and considered as the predominant proteoglycan in human skin. DCN interacts with various extracellular (ECM) proteins, especially collagen I, and plays a key role in collagen fibrillogenesis and ECM assembly. Its role in cell adhesion, migration, and proliferation has also been shown, partly due to its ability to regulate various growth factors including PDGF, IGF-I, FGF-2, TGFβ and TNFα. Although not essential for the process of cutaneous wound repair, DCN regulates ECM regeneration, modulates the length of the healing process and limits scar formation. Moreover, DCN seems to be involved in angiogenesis regulation.Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan in the extracellular matrix, and is expressed at high levels in tissues during development and remodeling in pathological conditions. Versican is a component of the elastic fibres and is involved in elastogenesis, extracellular matrix remodeling, cell phenotype, proliferation, adhesion and migration. During wound healing, Versican has been shown to stimulate endothelial cell proliferation, myofibroblast formation, types I and III collagen accumulation, and immune cell infiltration, especially inflammatory macrophages.As the endpoint of a successful treatment is the complete wound closure, the first approach to quantify the healing progress is to obtain the wound healing rate. In vitro, scratch assays, also called wound healing assays, are performed. The basic steps involve creating a “scratch” in a keratinocyte monolayer (with mechanical, chemical or thermal technic), capturing the images at the beginning and at regular intervals during cell migration to close the scratch, and comparing the images to quantify the migration rate of the cells. The Wound Healing Rate (WHR) can be calculated following the equation: [(Ai − Af)/Ai], where Ai represents the initial scratched area and Af represents the final area/measurement.Ki67 is a nuclear protein related to cell cycle and synthesized by all proliferating cells while deficient in resting cells. Proliferating cell nuclear antigen (PCNA) is another well-known nuclear protein which participates in cell proliferation by mediating DNA polymerase. Those two proteins are therefore two well-established proliferation-associated proteins used to probe cell proliferation during wound repair. Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity. Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity. Kruppel-like factor 4 (KLF4) is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Owing to an increased post-transcriptional expression of Klf4, Klf4 protein decreases during keratinocyte replicative senescence and during physiological skin aging, while its mRNA level does not change. Modulating the synthesis or post-transcriptional regulation of KLF4 should therefore influence epidermal renewal. Kruppel-like factor 4 (KLF4) is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Owing to an increased post-transcriptional expression of Klf4, Klf4 protein decreases during keratinocyte replicative senescence and during physiological skin aging, while its mRNA level does not change. Modulating the synthesis or post-transcriptional regulation of KLF4 should therefore influence epidermal renewal. Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity.Versican is a large extracellular matrix proteoglycan known to bind to elastic fibers and hyaluronan for maintaining the skin hydration and elasticity. Versican V0 isoform expression has been shown to decrease with aging in human dermis. Moreover, Versican size and sulfation pattern are also modified with aging. An anti-aging product can therefore restore an appropriate Versican level and skin elasticity.A film containing various lipids produced by sebaceous glands and keratinocytes covers the skin. Under various factors, including the production of reactive free radicals, skin lipids may be peroxidised. Reactive free radicals also induce cell and tissue damages. A correlation between the level of peroxidised lipids and a defect in wound healing has been reported and an active ingredient may improve skin regeneration or wound healing by decreasing lipid peroxidation. A film containing various lipids produced by sebaceous glands and keratinocytes covers the skin. Under various factors, including the production of reactive free radicals, skin lipids may be peroxidised. Reactive free radicals also induce cell and tissue damages. A correlation between the level of peroxidised lipids and a defect in wound healing has been reported and an active ingredient may improve skin regeneration or wound healing by decreasing lipid peroxidation. Keratinocytes constitute the interface between the body and the external environment. Various aggressions due to factors such as microorganisms or UV light stimulate these cells and induce the production of TNFα, a cytokine involved in immunity and inflammation. The TNFα assay allows to assess the intensity of the inflammatory response. Keratinocytes constitute the interface between the body and the external environment. Various aggressions due to factors such as microorganisms or UV light stimulate these cells and induce the production of TNFα, a cytokine involved in immunity and inflammation. The TNFα assay allows to assess the intensity of the inflammatory response. CD1a is abundantly expressed on epidermal Langerhans cells and dermal dendritic cells which are implicated in contact dermatitis. After binding to allergens, CD1a is involved in T cell activation and therefore inflammatory response. It has been shown that a higher expression of CD1a augments intradermal T cell responses to some allergens. Moreover, a higher density of CD1a-positive Langerhans cells has been found in atopic dermatitis skin patients compared to healthy skin, with differences in the location and appearances of the cells. CD1a is abundantly expressed on epidermal Langerhans cells and dermal dendritic cells which are implicated in contact dermatitis. After binding to allergens, CD1a is involved in T cell activation and therefore inflammatory response. It has been shown that a higher expression of CD1a augments intradermal T cell responses to some allergens. Moreover, a higher density of CD1a-positive Langerhans cells has been found in atopic dermatitis skin patients compared to healthy skin, with differences in the location and appearances of the cells. Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and notably decreases the synthesis of collagen I and elastin, the two main components of the dermal matrix, notably by decreasing TGFβ synthesis. This, coupled with increased degradation of the matrix by metalloproteases, leads to premature ageing of the skin.Air pollution can have a significant impact on the skin, notably by modulating gene expression in skin cells. For example, it stimulates the synthesis of the inducible nitric oxide synthase (iNOS), thus increasing nitric oxide (NO) level that plays a key role in skin perfusion as well as in inflammation and collagen metabolism. Translucent embryos are used as an in vitro test to measure androgenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.Translucent embryos are used as an in vitro test to measure androgenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.Translucent embryos are used as an in vitro test to measure androgenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.Translucent embryos are used as an in vitro test to measure estrogenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.y.Translucent embryos are used as an in vitro test to measure estrogenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.y.Translucent embryos are used as an in vitro test to measure estrogenic activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.y.Translucent embryos are used as an in vitro test to measure thyroid activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.Translucent embryos are used as an in vitro test to measure thyroid activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.Translucent embryos are used as an in vitro test to measure thyroid activity of an ingredient or a formula. A fluorescent biomarker reveals the endocrine activity.The colour of the skin, hair and eyes is determined both by the quantity of melanin (darker skin with larger amounts) and the ratio between the two types of melanic pigments: eumelanin and pheomelanin. This pigments are the final products of complex biochemical reactions occuring in specific melanocyte organelles called melanosomes, and thanks to tyrosinase and related proteins. Through cytoplasmic extensions called dendrites, the melanosomes are transferred to the surrounding keratinocytes where they distribute uniformly in order to insure a homogeneous pigmentation and create a screen which covers the nucleus of keratinocytes. Under UV radiations, the synthesis of the alpha melanocyte stimulating hormon (α-MSH) and its receptor the melanocortin 1 receptor (MC1R) are increased in keratinocytes and melanocytes. This allows to stimulate skin pigmentation as α-MSH enhances tyrosinase synthesis and activity, but also the synthesis of eumelanin at the expense of phaeomelanin, the proliferation and distribution of the epidemic melanocytes, the number of dendrites of melanocytes and the transfer rate of melanosomes. The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of melanin. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses also involved in skin protoprotection. Many MC1R actions rely on cAMP-dependent activation of the microphthalmia-associated transcription factor (MITF). This transcription factor upregulates expression of a set of melanogenic enzymes, mainly the rate-limiting Tyrosinase and the Tyr-related proteins Tyrp1 and Tyrp2/Dct. MITF is also involved in cell cycle control, in melanosome transport,and in the control of the distribution of melanosomes and their transfer to keratinocytes. Thus, the MC1R/cAMP/MITF pathway is a key determinant for growth, differentiation, and survival of melanocytes and melanoma. Glucose represents the major source of energy for most tissues of the body and enter the cells via specific glucose transporters such as glucose GLUT2 or GLUT4. Intake of carbohydrates leads to an immediate increase in circulating blood glucose levels after absorption of the glucose from the intestine. As a direct response, pancreatic beta cells sense the elevated blood glucose concentrations via a GLUT2-dependent process and increase secretion of insulin. Consequently, insulin binding to its receptors leads to enhanced glucose transport into skeletal muscle, adipose tissue, and the heart. In adipocytes In adipocytes, the rapid entry of glucose is mainly mediated by a rapid translocation of intracellular vesicles containing the GLUT4 transporter to the plasma membrane. Glucose is then stored as triglycerides through de novo lipogenesis. The regulation of the density of GLUT4 receptors on the surface of adipocytes thus plays a major role in the regulation of blood glucose and lipid storage in adipocytes. Insulin plays a major role in this regulation and high levels of GLUT4 in adipose tissue are correlated with high insulin sensitivity and glucose tolerance. This cell diagnostic targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic or similar molecules). Evaluation of the agonist or antagonist character.This cell diagnostic targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic or similar molecules). Evaluation of the agonist or antagonist character.This cell diagnostic targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic or similar molecules). Evaluation of the agonist or antagonist character.The minimal inhibitory concentration is measured in microplates, in liquid media. Adapatation of the challenge test on 96-deep micro-plaques. This method enables the discovery of new preservatives or the control steps of anti-microbial efficacy where the regulatory method is not absolutely required.The anti-microbial or pro-microbial activity is measured according to a method performed in microplates, in liquid media, followed by a second part dedicated to the determination of the microorganisms concentration. The co-culture method is applied in a liquid medium in a 96well microplate format. GLYcoDiag elaborates various models of co-culture allowing the study of activity of a product on the growing parameters of each strain and the equilibrium between strains populations living together in the same environment and culture conditions (culture media, temperature, humidity, oxygen).Screening of products to determine their potential effects in the framework of the interaction with microbial strains (previously fluorescent labelled) on corneocytes (taken from voluntaries) or cultured human normal keratinocytes.Determination of the interaction profile of a product with a panel of glycans binding protein (GLYcoPROFILE) by gas chromatography (GC). The molecular weight is determined by size exclusion chromatography (SEC) coupled to a refractometer, a UV detector and a three angle light scaterring (MALS) detector.Determination of the interaction profile of a product with a panel of glycans binding protein (GLYcoPROFILE). Determination of the interaction profile of a product with Human recombinant lectins involved in innate immunity (DC-SIGN, langerin, Dectin-1). The inhibition profile is determined at 3 concentrations Determination of the interaction profile of a sample with a panel of glycan-binding proteins (GLYcoPROFILE) selected in order to highlight specific interactions with lectins recognizing specific glycans involved in wellness feeling. Determination of the interaction profile of a sample with a panel of glycans binding proteins (GLYcoPROFILE) whose specificities correspond to those involved in melanin transfert. Determination of the interaction profile of a sample on the surface of keratinocytes (cellular GLYcoPROFILE). Determination of the interaction profile of a sample with a panel of human recombinant lectins (CD44, layilin) recognizing glycoaminoglycan motifs. These receptors are expressed on the surface of skin cells or in their close environment and are involved in cell development, tissue remodeling and inflammation. Adapatation of the challenge test by QACS which has replaced all animal-by products with a selection of plant-based ingredients and developed a vegan challenge test. The in-vitro diagnostic test is of the molecular type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active. The in-vitro diagnostic test is of the molecular type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active. Our in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character. Our in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character. The in-vitro test is a cellular type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogens or molecules with similar structures). Once complexed to these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of reporter genes. In case of binding, the expression of the reporter genes allows to quantify the activation or not of the estrogenic receptor = evaluation of the agonist or antagonist character. The agonistic character can be considered as an ""Estrogen-Like". The in-vitro test is a cellular type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogens or molecules with similar structures). Once complexed to these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of reporter genes. In case of binding, the expression of the reporter genes allows to quantify the activation or not of the estrogenic receptor = evaluation of the agonist or antagonist character. The agonistic character can be considered as an ""Estrogen-Like". This in-vitro test is a cellular type. It directly targets the androgen receptor, a protein that binds only to natural androgens and/or to any androgen mimetic (synthetic androgens or molecules with similar structures). Once complexed to these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of reporter genes. In case of binding, the reporter genes allow to quantify the activation or not of the androgenic receptor = evaluation of the agonist or antagonist character. The agonistic character can be qualified as ""Androgen-like".This in-vitro diagnostic test is of the cell type. It directly targets the thyroidic receptors, proteins that bind only to natural thyroid hormones and/or to any thyromimetic (synthetic thyroid hormones or molecules with similar structures). Once complexed with these thyroidic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the thyroidic receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the thyroidic receptors, proteins that bind only to natural thyroid hormones and/or to any thyromimetic (synthetic thyroid hormones or molecules with similar structures). Once complexed with these thyroidic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the thyroidic receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the progesteron receptors, proteins that bind only to natural progesteron and/or to any progesteron mimetic (synthetic progesteron or molecules with similar structures). Once complexed with these progesteronic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the progesteron receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptors, proteins that bind only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the androgen receptors, proteins that bind only to natural androgens and/or to any androgen mimetic (synthetic testosteron or molecules with similar structures). Once complexed with these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the androgen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the progesteron receptors, proteins that bind only to natural progesteron and/or to any progesteron mimetic (synthetic progesteron or molecules with similar structures). Once complexed with these progesteronic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the progesteron receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the progesteron receptors, proteins that bind only to natural progesteron and/or to any progesteron mimetic (synthetic progesteron or molecules with similar structures). Once complexed with these progesteronic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the progesteron receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the androgen receptors, proteins that bind only to natural androgens and/or to any androgen mimetic (synthetic testosteron or molecules with similar structures). Once complexed with these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the androgen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptors, proteins that bind only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the progesteron receptors, proteins that bind only to natural progesteron and/or to any progesteron mimetic (synthetic progesteron or molecules with similar structures). Once complexed with these progesteronic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the progesteron receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the thyroidic receptors, proteins that bind only to natural thyroid hormones and/or to any thyromimetic (synthetic thyroid hormones or molecules with similar structures). Once complexed with these thyroidic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the thyroidic receptor = evaluation of the agonist or antagonist character.This in-vitro test is a cellular type. It directly targets the androgen receptor, a protein that binds only to natural androgens and/or to any androgen mimetic (synthetic androgens or molecules with similar structures). Once complexed to these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of reporter genes. In case of binding, the reporter genes allow to quantify the activation or not of the androgenic receptor = evaluation of the agonist or antagonist character. The agonistic character can be qualified as ""Androgen-like".The in-vitro test is a cellular type. It directly targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic estrogens or molecules with similar structures). Once complexed to these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of reporter genes. In case of binding, the expression of the reporter genes allows to quantify the activation or not of the estrogenic receptor = evaluation of the agonist or antagonist character. The agonistic character can be considered as an ""Estrogen-Like". This cell diagnostic targets the estrogen receptor, a protein that binds only to natural estrogens and/or to any estrogen mimetic (synthetic or similar molecules). Evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptors, proteins that bind only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the estrogen receptors, proteins that bind only to natural estrogens and/or to any estrogen mimetic (synthetic estrogen or molecules with similar structures). Once complexed with these estrogenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the estrogen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the androgen receptors, proteins that bind only to natural androgens and/or to any androgen mimetic (synthetic testosteron or molecules with similar structures). Once complexed with these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the androgen receptor = evaluation of the agonist or antagonist character.This in-vitro diagnostic test is of the cell type. It directly targets the androgen receptors, proteins that bind only to natural androgens and/or to any androgen mimetic (synthetic testosteron or molecules with similar structures). Once complexed with these androgenic molecules, the receptor becomes active and, binding to specific DNA sequences, leads to the abnormal expression of genes. In case of binding, evaluation of the activation or not of the androgen receptor = evaluation of the agonist or antagonist character.Internal method. By implementing biological tests on 50 different coral species using a standardized method. Toxic effects or booster effects are measured in the laboratory by exposing these indicator organisms to the sample against a control. We rely on the principle of causality between dose and response.The differentiation of pre-adipocytes into adipocytes is characterized by the accumulation of lipid droplets that fuse and take up more and more space in the cytoplasm. Lipid accumulation is directly or indirectly enabled by enhanced expression of GLUT4 (glucose transporter), insulin receptors, aP2 (lipid transport protein), perilipins and PPARgamma (nuclear factors stimulating adipogenesis). Lipid mobilization capacity also increases, marked by an increase in β-adrenergic receptors and lipase. A slimming agent is therefore likely to act on the expression of these different markers.PPARγ is a nuclear receptor regulating many functions in diverse cell types, including especially the development of adipose tissue by coordinating many hundreds of genes responsible for the establishment of the mature adipocyte phenotype. It stimulates in particular the expression of the Fatty Acid Transporter FATP1, which main role in adipocytes is to favor insulin-induced fatty acid uptake. FATP4 is also expressed in adipocytes and its expression level correlates well with obesity, thus representing an interesting target to prevent or treat obesity. Nevertheless,it seems to regulate PPARgamma expression and participate in lipolysis rather than playing a role in fatty acid uptake. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors which promote fatty acid production (SREBP1a/c) and cholesterol synthesis (SREBP2) involved in adipocyte lipogenesis. SREBP1 therefore represents a key target for a slimming agent. The differentiation of pre-adipocytes into adipocytes is characterized by the accumulation of lipid droplets that fuse and take up more and more space in the cytoplasm. Lipid accumulation is directly or indirectly enabled by enhanced expression of GLUT4 (glucose transporter), insulin receptors, aP2 (lipid transport protein), perilipins and PPARgamma (nuclear factors stimulating adipogenesis). Lipid mobilization capacity also increases, marked by an increase in β-adrenergic receptors and lipase. A slimming agent is therefore likely to act on the expression of these different markers.Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. The surface of healthy cells is composed of lipids that are asymmetrically distributed on the inner and outer leaflet of the plasma membrane. One of these lipids, phosphatidylserine (PS), is normally restricted to the inner leaflet of the plasma membrane and is, therefore, only exposed to the cell cytoplasm. However, during apoptosis lipid asymmetry is lost and PS becomes exposed on the outer leaflet of the plasma membrane. Annexin V, a 36-kDa calcium-binding protein, binds to PS; therefore, fluorescently labeled Annexin V can be used to detect PS that is exposed on the outside of apoptotic cells. Annexin V can also stain necrotic cells because these cells have ruptured membranes that permit Annexin V to access the entire plasma membrane. However, apoptotic cells can be distinguished from necrotic cells by co-staining with propidium iodide (PI) because PI enters necrotic cells but is excluded from apoptotic cells. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay detects DNA breakage by labeling the free 3'-hydroxyl termini. Given that genomic DNA breaks arise during early and late stages of apoptosis, TUNEL staining can also be used to measure apoptotic cell death. Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. Vimentin is an intermediate filament protein composing the cytosqueletton and participating in numerous cellular processes including cell adhesion, migration, signaling, differentiation, cytoskeletal rearrangements, and regulation of cell morphology and plasticity. Following skin or eye injury and cell lesion, vimentin is released in extracellular matrix and stimulates inflammatory cell migration, keratinocyte differentiation and fibroblast proliferation, migration and differentiation in myofibroblasts. Vimentin therefore supports wound healing but may also be responsible of fibrosis. Vimentin is therefore an interesting marker to follow wound healing. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. Keratins 14 (K14) and 5 (K5) are expressed in mitotically active basal layer cells and their expression is down-regulated as cells differentiate. Those markers therefore give an indication concerning the renewal abilities and differentiation level of the epidermis. The skin is colonized by a diverse microbiota which composition depends on many factors including the body location (moist, dry or sebaceous area), the age, the climate, individual variations, etc... A disturbance of skin microbiota composition (dysbiosis) may lead to or be correlated with various skin diseases. For example, a disturbance affecting either Staphylococcus aureus (S. aureus) or epidermis (S. epidermidis) and Cutibacterium acnes (C. acnes) is respectively associated with atopic dermatitis or common acne, Studying its composition, in vitro or in vivo, may therefore be of great interest.In response to injury, collagen exposure induces platelet activation and aggregation leading to the formation of a fibrin clot. Collagen fragments also contributes in the inflammatory stage as a chemoattractant for neutrophiles and macrophages. Inflammation drives the proliferation of fibroblasts and myofibroblasts which contribute to collagen deposition. Simultaneously, collagen degradation releases fragments that promote fibroblast proliferation and synthesis of growth factors that lead to angiogenesis and reepithelialization. Finally, the remodeling of the extracellular matrix (ECM), which results from the balance of new matrix synthesis and matrix metalloproteinase (MMPs) degradative activities, determines the acquisition of tensile strength. Types I and III collagens (Col I & Col III) are the two main components of extracellular matrix. Col III is the first to be synthesized in the early stages of wound healing and is replaced by Col I, the dominant skin collagen. Col I and Col III are preferentially cleaved by MMP-1 (also called collagenase-1) and MMP-8 (collagenase-2). Abnormalities in the ECM reconstitution during wound healing result in hypertrophic and keloid scars. Scarring is characterized by high levels of Col I, Col III, fibronectin and laminin. Collagen fiber orientation in all scars is parallel to the epithelial surface unlike that of normal skin where the fibers form a three-dimensional basketweave-like network. Keloid scars are characterized by abnormally thick bundles of collagen that are poorly organized with fewer cross-links that are found in the deep dermis compared to superficial dermic. Hypertrophic scars have thinner collagen bundles than keloid or normotrophic scars. The ratio of collagen I to III is higher in keloids than normotrophic scars. Even within the keloid scar, there is a heterogeneity to the collagen I/III ratio. In response to injury, collagen exposure induces platelet activation and aggregation leading to the formation of a fibrin clot. Collagen fragments also contributes in the inflammatory stage as a chemoattractant for neutrophiles and macrophages. Inflammation drives the proliferation of fibroblasts and myofibroblasts which contribute to collagen deposition. Simultaneously, collagen degradation releases fragments that promote fibroblast proliferation and synthesis of growth factors that lead to angiogenesis and reepithelialization. Finally, the remodeling of the extracellular matrix (ECM), which results from the balance of new matrix synthesis and matrix metalloproteinase (MMPs) degradative activities, determines the acquisition of tensile strength. Types I and III collagens (Col I & Col III) are the two main components of extracellular matrix. Col III is the first to be synthesized in the early stages of wound healing and is replaced by Col I, the dominant skin collagen. Col I and Col III are preferentially cleaved by MMP-1 (also called collagenase-1) and MMP-8 (collagenase-2). Abnormalities in the ECM reconstitution during wound healing result in hypertrophic and keloid scars. Scarring is characterized by high levels of Col I, Col III, fibronectin and laminin. Collagen fiber orientation in all scars is parallel to the epithelial surface unlike that of normal skin where the fibers form a three-dimensional basketweave-like network. Keloid scars are characterized by abnormally thick bundles of collagen that are poorly organized with fewer cross-links that are found in the deep dermis compared to superficial dermic. Hypertrophic scars have thinner collagen bundles than keloid or normotrophic scars. The ratio of collagen I to III is higher in keloids than normotrophic scars. Even within the keloid scar, there is a heterogeneity to the collagen I/III ratio. Type VII collagen (Coll VII), type IV collagen (Coll IV) and Laminin 332 (previously called Laminin V) are major components of the dermal-epidermal junction (DEJ). Studying the synthesis and the location of these molecules allow to monitor DEJ repair during wound healing, which is mandatory to restore barrier function. Moreover, Coll IV fragments can be mediators of inflammation by stimulating neutrophil migration, phagocytosis and immune responses. They also regulate angiogenesis. Coll VII is required for re-epithelialization. Its loss perturbs the organization of laminin-332 during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Coll VII also supports dermal fibroblast migration and regulates their cytokine production in the granulation tissue. Laminin 332 also regulates keratinocyte turnover and differentiation on which the efficiency of the barrier function depends. In addition, laminin-332 and Coll IV are major components of the basement membrane of skin vessels on which endothelial cells are attached and they play a key role in angiogenesis. Type VII collagen (Coll VII), type IV collagen (Coll IV) and Laminin 332 (previously called Laminin V) are major components of the dermal-epidermal junction (DEJ). Studying the synthesis and the location of these molecules allow to monitor DEJ repair during wound healing, which is mandatory to restore barrier function. Moreover, Coll IV fragments can be mediators of inflammation by stimulating neutrophil migration, phagocytosis and immune responses. They also regulate angiogenesis. Coll VII is required for re-epithelialization. Its loss perturbs the organization of laminin-332 during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Coll VII also supports dermal fibroblast migration and regulates their cytokine production in the granulation tissue. Laminin 332 also regulates keratinocyte turnover and differentiation on which the efficiency of the barrier function depends. In addition, laminin-332 and Coll IV are major components of the basement membrane of skin vessels on which endothelial cells are attached and they play a key role in angiogenesis. Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. The colour of the skin, hair and eyes is determined both by the quantity of melanin (darker skin with larger amounts) and the ratio between the two types of melanic pigments: eumelanin and pheomelanin. This pigments are the final products of complex biochemical reactions occuring in specific melanocyte organelles called melanosomes, and thanks to tyrosinase and related proteins. Through cytoplasmic extensions called dendrites, the melanosomes are transferred to the surrounding keratinocytes where they distribute uniformly in order to insure a homogeneous pigmentation and create a screen which covers the nucleus of keratinocytes. Under UV radiations, the synthesis of the alpha melanocyte stimulating hormon (α-MSH) and its receptor the melanocortin 1 receptor (MC1R) are increased in keratinocytes and melanocytes. This allows to stimulate skin pigmentation as α-MSH enhances tyrosinase synthesis and activity, but also the synthesis of eumelanin at the expense of phaeomelanin, the proliferation and distribution of the epidemic melanocytes, the number of dendrites of melanocytes and the transfer rate of melanosomes. The colour of the skin, hair and eyes is determined both by the quantity of melanin (darker skin with larger amounts) and the ratio between the two types of melanic pigments: eumelanin and pheomelanin. This pigments are the final products of complex biochemical reactions occuring in specific melanocyte organelles called melanosomes, and thanks to tyrosinase and related proteins. Through cytoplasmic extensions called dendrites, the melanosomes are transferred to the surrounding keratinocytes where they distribute uniformly in order to insure a homogeneous pigmentation and create a screen which covers the nucleus of keratinocytes. Under UV radiations, the synthesis of the alpha melanocyte stimulating hormon (α-MSH) and its receptor the melanocortin 1 receptor (MC1R) are increased in keratinocytes and melanocytes. This allows to stimulate skin pigmentation as α-MSH enhances tyrosinase synthesis and activity, but also the synthesis of eumelanin at the expense of phaeomelanin, the proliferation and distribution of the epidemic melanocytes, the number of dendrites of melanocytes and the transfer rate of melanosomes. To be completedSpecific to smooth muscle cells, α-SMA is also an abundant actin in the cytoskeleton of myofibroblasts. The specificity of myofibroblasts is their ability to contract and to produce a very large amount of matrix elements. These myofibroblasts are derived from the differentiation of fibroblasts and appear in the dermis approximately one week after a skin injury. By contracting synchronously after the wound has been filled with granulation tissue and re-epithelialised, they actively participate in wound closure and tissue remodelling. Myofibroblasts are therefore necessary for wound healing, but an excess of myofibroblasts is also correlated to skin diseases such as hypertrophic scars or other fibrotic diseases. Evaluating the synthesis and distribution of α-SMA therefore allows monitoring the differentiation of fibroblasts into myofibroblasts, the contraction of the tissue and its appropriate remodelling.Specific to smooth muscle cells, α-SMA is also an abundant actin in the cytoskeleton of myofibroblasts. The specificity of myofibroblasts is their ability to contract and to produce a very large amount of matrix elements. These myofibroblasts are derived from the differentiation of fibroblasts and appear in the dermis approximately one week after a skin injury. By contracting synchronously after the wound has been filled with granulation tissue and re-epithelialised, they actively participate in wound closure and tissue remodelling. Myofibroblasts are therefore necessary for wound healing, but an excess of myofibroblasts is also correlated to skin diseases such as hypertrophic scars or other fibrotic diseases. Evaluating the synthesis and distribution of α-SMA therefore allows monitoring the differentiation of fibroblasts into myofibroblasts, the contraction of the tissue and its appropriate remodelling.Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. The surface of healthy cells is composed of lipids that are asymmetrically distributed on the inner and outer leaflet of the plasma membrane. One of these lipids, phosphatidylserine (PS), is normally restricted to the inner leaflet of the plasma membrane and is, therefore, only exposed to the cell cytoplasm. However, during apoptosis lipid asymmetry is lost and PS becomes exposed on the outer leaflet of the plasma membrane. Annexin V, a 36-kDa calcium-binding protein, binds to PS; therefore, fluorescently labeled Annexin V can be used to detect PS that is exposed on the outside of apoptotic cells. Annexin V can also stain necrotic cells because these cells have ruptured membranes that permit Annexin V to access the entire plasma membrane. However, apoptotic cells can be distinguished from necrotic cells by co-staining with propidium iodide (PI) because PI enters necrotic cells but is excluded from apoptotic cells. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay detects DNA breakage by labeling the free 3'-hydroxyl termini. Given that genomic DNA breaks arise during early and late stages of apoptosis, TUNEL staining can also be used to measure apoptotic cell death. During wound healing, the inflammation phase succeeds to the hemostasis. Various pro-inflammatory cytokines and growth factors released by the clot and wound tissue induce inflammatory cell migration by the process of chemotaxis. Mast cells come first and assist in the recruitment of neutrophils which protect against infectious agents and starts the removal of debris from damaged cells and extracellular matrix. The neutrophil population peaks in the first 48 hr after injury and is eventually replaced by macrophages differentiated from monocytes. Various histological markers can be used to locate and quantify white blood cells, including CD203 or Mas-related G-protein coupled receptor member X2 (MRGPRX2) for mast cells. Myeloperoxidase (MPO) is an enzyme contained in neutrophil cytoplasmic granules and participating in innate immune response while N-acetylglucosaminidase (NAG) is a lysosomal enzyme highly expressed in activated macrophages. Staining or evaluating the enzyme activity of MPO and NAG can therefore respectively allow to localise or assess the level of accumulation in the tissue of neutrophils and macrophages. During wound healing, the inflammation phase succeeds to the hemostasis. Various pro-inflammatory cytokines and growth factors released by the clot and wound tissue induce inflammatory cell migration by the process of chemotaxis. Mast cells come first and assist in the recruitment of neutrophils which protect against infectious agents and starts the removal of debris from damaged cells and extracellular matrix. The neutrophil population peaks in the first 48 hr after injury and is eventually replaced by macrophages differentiated from monocytes. Various histological markers can be used to locate and quantify white blood cells, including CD203 or Mas-related G-protein coupled receptor member X2 (MRGPRX2) for mast cells. Myeloperoxidase (MPO) is an enzyme contained in neutrophil cytoplasmic granules and participating in innate immune response while N-acetylglucosaminidase (NAG) is a lysosomal enzyme highly expressed in activated macrophages. Staining or evaluating the enzyme activity of MPO and NAG can therefore respectively allow to localise or assess the level of accumulation in the tissue of neutrophils and macrophages. During the inflammatory phase of wound healing, various leukocytes are involved and recruited, including lymphocytes that can be divided in 3 categories : T cells, B cells and Natural Killer (NK) cells. The skin contains resident T cells that participates in normal skin homeostasis and are activated under skin injury, thus contributing to wound healing by producing epithelial growth factors and inflammatory cytokines. Some data also suggest that T helper (Th) cells recruited during wound healing delay wound closure, decrease inflammation, stimulate neovascularization and limit scarring. Live B cells mediate pro-healing responses, helping to reduce scar size and increase collagen deposition and maturation, enhancing angiogenesis, and increasing nerve growth into and under the healing wound. Natural Killer (NK) cells regulate the early onset and resolution of the inflammatory phase. Some data also suggest their contribution to re-epithelialization, angiogenesis, granulation tissue formation, and remodelling. Various markers can be used to monitor the leukocyte infiltration and abundance during wound healing. CD3 is a marker of mature T cells. The human skin-resident T cells express specifically the cutaneous leukocyte antigen (CLA) which is almost absent in peripheral blood T cells. CD4 is specific of Th cells while CD8 may be used to identify T cytotoxic (Tc) cells and partially NK cells. CD19 or CD20 are B cell markers, while NK cells may be identified with CD16 or CD56. During the inflammatory phase of wound healing, various leukocytes are involved and recruited, including lymphocytes that can be divided in 3 categories : T cells, B cells and Natural Killer (NK) cells. The skin contains resident T cells that participates in normal skin homeostasis and are activated under skin injury, thus contributing to wound healing by producing epithelial growth factors and inflammatory cytokines. Some data also suggest that T helper (Th) cells recruited during wound healing delay wound closure, decrease inflammation, stimulate neovascularization and limit scarring. Live B cells mediate pro-healing responses, helping to reduce scar size and increase collagen deposition and maturation, enhancing angiogenesis, and increasing nerve growth into and under the healing wound. Natural Killer (NK) cells regulate the early onset and resolution of the inflammatory phase. Some data also suggest their contribution to re-epithelialization, angiogenesis, granulation tissue formation, and remodelling. Various markers can be used to monitor the leukocyte infiltration and abundance during wound healing. CD3 is a marker of mature T cells. The human skin-resident T cells express specifically the cutaneous leukocyte antigen (CLA) which is almost absent in peripheral blood T cells. CD4 is specific of Th cells while CD8 may be used to identify T cytotoxic (Tc) cells and partially NK cells. CD19 or CD20 are B cell markers, while NK cells may be identified with CD16 or CD56. Macrophages, which classical marker is CD68, are one of the key regulators of the wound healing process and as it progresses, their phenotype changes, reflecting a differentiation process that shifts their functions from inflammation to proliferation and it is called polarization. During acute wound healing, inflammatory macrophages, traditionally referred to as M1, infiltrate after injury to clean the wound of microorganisms, foreign debris and dead cells. As the tissue begins to repair, the overall macrophage population transitions to reparative macrophages (M2) along with migration and proliferation of fibroblasts, keratinocytes and endothelial cells to restore the dermis, epidermis and vasculature. M1 macrophages are induced by Th-1 cytokines, such as IFN-γ and TNF-α, or by bacterial lipopolysaccharide (LPS) recognition. They produce and secrete high levels of pro-inflammatory cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-12, IL-23 and cyclooxygenase-2 (COX-2), and low levels of IL-10. M1 macrophages have robust antimicrobial and anti-tumoral activity but mediate ROS-induced tissue damage, and impair tissue repair. The inflammatory response is inhibited by regulatory mechanisms driven by anti-inflammatory function of M2 macrophages in order to protect against tissue damage. Induced by Th-2 cytokines, IL-10, TGF-β, IL-4, IL-13, IL-33 and IL-21, M2 cells orchestrate the promotion of tissue remodelling, angiogenesis, immunoregulation, tumour formation and progression. Macrophages, which classical marker is CD68, are one of the key regulators of the wound healing process and as it progresses, their phenotype changes, reflecting a differentiation process that shifts their functions from inflammation to proliferation and it is called polarization. During acute wound healing, inflammatory macrophages, traditionally referred to as M1, infiltrate after injury to clean the wound of microorganisms, foreign debris and dead cells. As the tissue begins to repair, the overall macrophage population transitions to reparative macrophages (M2) along with migration and proliferation of fibroblasts, keratinocytes and endothelial cells to restore the dermis, epidermis and vasculature. M1 macrophages are induced by Th-1 cytokines, such as IFN-γ and TNF-α, or by bacterial lipopolysaccharide (LPS) recognition. They produce and secrete high levels of pro-inflammatory cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-12, IL-23 and cyclooxygenase-2 (COX-2), and low levels of IL-10. M1 macrophages have robust antimicrobial and anti-tumoral activity but mediate ROS-induced tissue damage, and impair tissue repair. The inflammatory response is inhibited by regulatory mechanisms driven by anti-inflammatory function of M2 macrophages in order to protect against tissue damage. Induced by Th-2 cytokines, IL-10, TGF-β, IL-4, IL-13, IL-33 and IL-21, M2 cells orchestrate the promotion of tissue remodelling, angiogenesis, immunoregulation, tumour formation and progression. Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate. K5 and K14 thus make it possible to monitor the re-epithelialisation phase characteristic of wound healing, first by detecting the existence or not of a newly formed epidermis in the injured area and, secondly, by monitoring the proliferation and differentiation of this epidermis. Decorin (DCN) is a small leucine-rich proteoglycan expressed in the extracellular matrix of several tissues and considered as the predominant proteoglycan in human skin. DCN interacts with various extracellular (ECM) proteins, especially collagen I, and plays a key role in collagen fibrillogenesis and ECM assembly. Its role in cell adhesion, migration, and proliferation has also been shown, partly due to its ability to regulate various growth factors including PDGF, IGF-I, FGF-2, TGFβ and TNFα. Although not essential for the process of cutaneous wound repair, DCN regulates ECM regeneration, modulates the length of the healing process and limits scar formation. Moreover, DCN seems to be involved in angiogenesis regulation.Decorin (DCN) is a small leucine-rich proteoglycan expressed in the extracellular matrix of several tissues and considered as the predominant proteoglycan in human skin. DCN interacts with various extracellular (ECM) proteins, especially collagen I, and plays a key role in collagen fibrillogenesis and ECM assembly. Its role in cell adhesion, migration, and proliferation has also been shown, partly due to its ability to regulate various growth factors including PDGF, IGF-I, FGF-2, TGFβ and TNFα. Although not essential for the process of cutaneous wound repair, DCN regulates ECM regeneration, modulates the length of the healing process and limits scar formation. Moreover, DCN seems to be involved in angiogenesis regulation.Produced by fibroblasts and vascular smooth muscle cells, elastin is the main component of skin elastic fibres. Responsible of skin elasticity, it represents 2 - 4% of the dermal extracellular matrix (ECM) in adult skin. Its production occurs mainly before sexual maturity and is drastically reduced thereafter in adult normal skin. Nevertheless, elastin synthesis is stimulated upon injury and during wound healing. This leads to the formation of elastin fragments called elastikines and stimulating dermal cells, thus attenuating wound contraction and improving dermal regeneration. Elastin deposition is usually observed many months after injury and remains more or less efficient to regenerate elastin network and skin elasticity. Produced by fibroblasts and vascular smooth muscle cells, elastin is the main component of skin elastic fibres. Responsible of skin elasticity, it represents 2 - 4% of the dermal extracellular matrix (ECM) in adult skin. Its production occurs mainly before sexual maturity and is drastically reduced thereafter in adult normal skin. Nevertheless, elastin synthesis is stimulated upon injury and during wound healing. This leads to the formation of elastin fragments called elastikines and stimulating dermal cells, thus attenuating wound contraction and improving dermal regeneration. Elastin deposition is usually observed many months after injury and remains more or less efficient to regenerate elastin network and skin elasticity. Epidermal Growth Factor (EGF) is produced by platelets, macrophages and monocytes. It plays an important role by binding to epidermal growth factor receptor (EGFR) on cell surface. EGFR is expressed on various cell surfaces, obviously epidermal cells but also fibroblasts, endothelial cells and smooth muscle cells. After binding with EGF, the intrinsic protein tyrosine kinase activity of EGFR is stimulated, leading to a variety of biochemical processes in cells. For example, it can promote DNA synthesis and cell proliferation, regulate cell metabolism, promote chemotaxis, granulation tissue and epidermis formation. Epidermal Growth Factor (EGF) is produced by platelets, macrophages and monocytes. It plays an important role by binding to epidermal growth factor receptor (EGFR) on cell surface. EGFR is expressed on various cell surfaces, obviously epidermal cells but also fibroblasts, endothelial cells and smooth muscle cells. After binding with EGF, the intrinsic protein tyrosine kinase activity of EGFR is stimulated, leading to a variety of biochemical processes in cells. For example, it can promote DNA synthesis and cell proliferation, regulate cell metabolism, promote chemotaxis, granulation tissue and epidermis formation. Wound healing begins with hemostasis. The clot formed minutes after injury is mainly composed by fibrin and platelets. Produced by the cleavage of fibrinogen by thrombin, fibrin monomers are cross linked by factor XIII and binds to platelets to produce a clot. Fibrin is then involved in cellular migration and extracellular matrix (ECM) production occurring after hemostasis. For example, fibrin participates in the inflammatory phase by binding αMβ2 integrin, a receptor found on monocytes and neutrophils. Endothelial cells and fibroblasts also bind to fibrin via αvβ3 integrin. Fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) bind fibrin and stimulate angiogenesis, whereas insulin-like growth factor (IGF)-1 binds fibrin and stimulates stromal cell function and proliferation. Despite its important function throughout wound healing, fibrin degradation begins shortly after the formation of a clot thanks to plasminogen which is activated by a synthetic product of endothelial cells. Wound healing begins with hemostasis. The clot formed minutes after injury is mainly composed by fibrin and platelets. Produced by the cleavage of fibrinogen by thrombin, fibrin monomers are cross linked by factor XIII and binds to platelets to produce a clot. Fibrin is then involved in cellular migration and extracellular matrix (ECM) production occurring after hemostasis. For example, fibrin participates in the inflammatory phase by binding αMβ2 integrin, a receptor found on monocytes and neutrophils. Endothelial cells and fibroblasts also bind to fibrin via αvβ3 integrin. Fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) bind fibrin and stimulate angiogenesis, whereas insulin-like growth factor (IGF)-1 binds fibrin and stimulates stromal cell function and proliferation. Despite its important function throughout wound healing, fibrin degradation begins shortly after the formation of a clot thanks to plasminogen which is activated by a synthetic product of endothelial cells. Fibroblast growth factor (FGF2) strongly activates not only fibroblasts but also other mesoderm-derived cells, including vascular endothelial and smooth muscle cells. It plays an important role during wound healing. Indeed, the administration of recombinant FGF2 to skin wounds accelerates acute and chronic wound healing. Local FGF2 administration also has an anti-fibrotic effect for the wound to antagonize myofibroblast differentiation and dampen fibrosis. In addition, FGF2 is considered to accelerate reepithelization and has been recently shown to accelerates the epithelial–mesenchymal transition in keratinocytes during wound healing. Fibroblast growth factor (FGF2) strongly activates not only fibroblasts but also other mesoderm-derived cells, including vascular endothelial and smooth muscle cells. It plays an important role during wound healing. Indeed, the administration of recombinant FGF2 to skin wounds accelerates acute and chronic wound healing. Local FGF2 administration also has an anti-fibrotic effect for the wound to antagonize myofibroblast differentiation and dampen fibrosis. In addition, FGF2 is considered to accelerate reepithelization and has been recently shown to accelerates the epithelial–mesenchymal transition in keratinocytes during wound healing. Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar (HS), which limits patients' joint movement and generates an aesthetic problem. This HS results from the enhanced proliferation of fibroblasts, the increased transdifferentiation of fibroblasts into myofibroblasts, and the increased deposition of extracellular matrix proteins, such as type I collagen. Interleukine-17 (IL-17) is a pro-inflammatory cytokine whose overexpression promotes the formation of cutaneous scar with the help of increased levels of several chemokines and the infiltration of macrophages. Interleukine-10 (IL-10) is a potent anti-inflammatory cytokine produced by various cell types such as Tcells, monocytes and macrophages, but also by keratinocytes after skin injury. IL-10 plays a key role in the ability of the fetus to heal regeneratively. Overexpression of IL-10 is also able to recapitulate scarless healing in postnatal tissue through its wide-ranging pleiotropic effects, attenuating the inflammatory response, regulating the extracellular matrix, enhancing fibroblast function, and modulating stem cell function. Proinflammatory cytokines, particularly interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNFα) are up-regulated during the inflammatory phase of wound healing. Upon wound healing IL-1 and TNFα are immediately released by keratinocytes. IL-1 is also released by neutrophils, monocytes and macrophages. IL-1 increases keratinocyte migration and proliferation, activates fibroblasts and increases the secretion of FGF-7. IL-6 is produced by neutrophils and monocytes and initiates the healing response. Its expression is increased after wounding and tends to persist in older wounds. It stimulates keratinocyte proliferation and is chemoattractive to neutrophils. TNFα, at low levels, can promote wound healing by indirectly stimulating inflammation and increasing macrophage produced growth factors. However, at higher levels and especially for a long period, TNFα, as well as IL-1β, favors extracellular matrix degradation and has a detrimental effect on healing. Levels of TNFα and IL-1β are elevated in chronic wounds.Histopathology of wounds is a very helpful tool to monitor healing progress.A biopsy of the wound, including the edges to compare the ulcerated area and the surrounding skin, is collected. After fixation or freezing in appropriate conditions, cutting and staining, the general structure of the wound can be observed. The most widely used stain in dermatopathology is haematoxylin and eosin (H&E). Haematoxylin dyes the cellular nuclei blue, while eosin dyes the non-nuclear cells and structures pink/orange, such as cytoplasm and collagen. This allows to observe the evolution of the epidermis, the dermis or the skin appendages. The abundance of immune cells can also be observed. HES staining combines HE staining with Saffron to better highlight collagen fibers whose arrangement and orientation play a vital role during the remodelling phase. Picrosirius Red is a special stain that demonstrates both thin and thick collagen fibres. Thrichrome stainings such as Masson's trichrome reveals muscle and intercellular or extracellular fibres (collagen, keratins).Histopathology of wounds is a very helpful tool to monitor healing progress.A biopsy of the wound, including the edges to compare the ulcerated area and the surrounding skin, is collected. After fixation or freezing in appropriate conditions, cutting and staining, the general structure of the wound can be observed. The most widely used stain in dermatopathology is haematoxylin and eosin (H&E). Haematoxylin dyes the cellular nuclei blue, while eosin dyes the non-nuclear cells and structures pink/orange, such as cytoplasm and collagen. This allows to observe the evolution of the epidermis, the dermis or the skin appendages. The abundance of immune cells can also be observed. HES staining combines HE staining with Saffron to better highlight collagen fibers whose arrangement and orientation play a vital role during the remodelling phase. Picrosirius Red is a special stain that demonstrates both thin and thick collagen fibres. Thrichrome stainings such as Masson's trichrome reveals muscle and intercellular or extracellular fibres (collagen, keratins).Collagen is the major protein component of connective tissue and is composed primarily of glycine, proline and hydroxyproline. Collagen synthesis requires hydroxylation of lysine and proline, and co-factors such as ferrous iron and vitamin C. Breakdown of collagen liberates free hydroxyproline and its peptides. Hence, measurement of hydroxyproline can be used as a biochemical marker for tissue collagen and an index for collagen turnover. Increase in the hydroxyproline content indicates increased collagen synthesis, which corresponds to an enhanced wound healing. Hydroxyproline can be analysed in tissue (biopsies) and in cell culture supernatants. Measurement of hydroxyproline can be carried out by colorimetric methods, high-performance liquid chromatography (HPLC), gas chromatography/mass spectrometry and enzymatic methods.Collagen is the major protein component of connective tissue and is composed primarily of glycine, proline and hydroxyproline. Collagen synthesis requires hydroxylation of lysine and proline, and co-factors such as ferrous iron and vitamin C. Breakdown of collagen liberates free hydroxyproline and its peptides. Hence, measurement of hydroxyproline can be used as a biochemical marker for tissue collagen and an index for collagen turnover. Increase in the hydroxyproline content indicates increased collagen synthesis, which corresponds to an enhanced wound healing. Hydroxyproline can be analysed in tissue (biopsies) and in cell culture supernatants. Measurement of hydroxyproline can be carried out by colorimetric methods, high-performance liquid chromatography (HPLC), gas chromatography/mass spectrometry and enzymatic methods.As the endpoint of a successful treatment is the complete wound closure, the first approach to quantify the healing progress is to obtain the wound healing rate. In vitro, scratch assays, also called wound healing assays, are performed. The basic steps involve creating a “scratch” in a keratinocyte monolayer (with mechanical, chemical or thermal technic), capturing the images at the beginning and at regular intervals during cell migration to close the scratch, and comparing the images to quantify the migration rate of the cells. The Wound Healing Rate (WHR) can be calculated following the equation: [(Ai − Af)/Ai], where Ai represents the initial scratched area and Af represents the final area/measurement.As the endpoint of a successful treatment is the complete wound closure, the first approach to quantify the healing progress is to obtain the wound healing rate. In vitro, scratch assays, also called wound healing assays, are performed. The basic steps involve creating a “scratch” in a keratinocyte monolayer (with mechanical, chemical or thermal technic), capturing the images at the beginning and at regular intervals during cell migration to close the scratch, and comparing the images to quantify the migration rate of the cells. The Wound Healing Rate (WHR) can be calculated following the equation: [(Ai − Af)/Ai], where Ai represents the initial scratched area and Af represents the final area/measurement.Platelet-derived growth factor (PDGF) is released from platelets into the serum during blood clotting. It is also secreted by macrophages, endothelial cells, fibroblasts, and keratinocytes. PDGF has been found to regulate cell growth and division and plays a role in angiogenesis. It is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells. It also stimulates general protein and collagen synthesis and collagenase activity. Nevertheless, it seems to have an effect on wound healing only in combination with other growth factors such as Insulin-like Growth Factor (IGF-I) Despite there are only few data for human, IGF-I seems to play a key role in wound healing. Indeed, according to these data, it promotes the migration and proliferation of keratinocytes, thus playing an important role in wound epithelialization. It also enables wound bed contraction, and stimulates hyaluronan synthesis thus participating in skin remodeling. Platelet-derived growth factor (PDGF) is released from platelets into the serum during blood clotting. It is also secreted by macrophages, endothelial cells, fibroblasts, and keratinocytes. PDGF has been found to regulate cell growth and division and plays a role in angiogenesis. It is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells. It also stimulates general protein and collagen synthesis and collagenase activity. Nevertheless, it seems to have an effect on wound healing only in combination with other growth factors such as Insulin-like Growth Factor (IGF-I) Despite there are only few data for human, IGF-I seems to play a key role in wound healing. Indeed, according to these data, it promotes the migration and proliferation of keratinocytes, thus playing an important role in wound epithelialization. It also enables wound bed contraction, and stimulates hyaluronan synthesis thus participating in skin remodeling. Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Its cleavage also leads to the formation of Natural Moisturising Factor (NMF) which is involved in skin hydration. Monitoring the synthesis, abundance, localisation and cleavage of filaggrin therefore makes it possible to verify the correct restoration of the skin barrier and its hydration during wound healing.Derived from the cleavage of profilaggrin coming from granular keratinocytes, filaggrin is a major component of the stratum corneum and actively participates in the skin's barrier function. Its cleavage also leads to the formation of Natural Moisturising Factor (NMF) which is involved in skin hydration. Monitoring the synthesis, abundance, localisation and cleavage of filaggrin therefore makes it possible to verify the correct restoration of the skin barrier and its hydration during wound healing.Integrins are transmembrane cell surface receptors allowing interactions between cells or between cells and extracellular matrix (ECM) molecules. They are involved in cell adhesion, movement and migration but also in signal transduction. A modification of the number, type, and distribution of integrins is observed during wound healing. For instance, α2β1 integrin constitutively expressed in intact skin is upregulated in wounds. α3β1 integrin is up-regulated in keratinocytes during reepithelialization. Indirectly involved in this phenomenon, it also stimulates angiogenesis by inducing a cross-talk between keratinocytes and endothelial cells. α5β1 integrin is not present in normal epidermis but appears shortly after wounding, interacting with the initial clot, and lasts only for a short duration. This integrin is the major cell receptor of fibronectin (keratinocytes, fibroblasts, endothelial cells, immune cells) and is involved in keratinocyte migration, angiogenesis and inflammation. It also plays a key role in fibrosis. The integrin subunit α11 is highly induced during wound healing both at the mRNA and protein levels. Some data suggest that α11β1 integrin stimulates granulation tissue formation, wound contraction, fibroblast migration, cell differentiation in myofibroblasts and collagen remodeling during wound healing. Integrins are transmembrane cell surface receptors allowing interactions between cells or between cells and extracellular matrix (ECM) molecules. They are involved in cell adhesion, movement and migration but also in signal transduction. A modification of the number, type, and distribution of integrins is observed during wound healing. For instance, α2β1 integrin constitutively expressed in intact skin is upregulated in wounds. α3β1 integrin is up-regulated in keratinocytes during reepithelialization. Indirectly involved in this phenomenon, it also stimulates angiogenesis by inducing a cross-talk between keratinocytes and endothelial cells. α5β1 integrin is not present in normal epidermis but appears shortly after wounding, interacting with the initial clot, and lasts only for a short duration. This integrin is the major cell receptor of fibronectin (keratinocytes, fibroblasts, endothelial cells, immune cells) and is involved in keratinocyte migration, angiogenesis and inflammation. It also plays a key role in fibrosis. The integrin subunit α11 is highly induced during wound healing both at the mRNA and protein levels. Some data suggest that α11β1 integrin stimulates granulation tissue formation, wound contraction, fibroblast migration, cell differentiation in myofibroblasts and collagen remodeling during wound healing. Interferon gamma (IFNγ) is a cytokine mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. IFNγ contributes to the activation of the immune cells during the inflammatory phase of wound healing, the recruitment of neutrophils and cell clearance through apoptosis. IFNγ also regulates collagen synthesis and angiogenesis, and there is also a crosstalk between IFNγ and the Transforming Growth Factor beta (TGFβ)/Smad signaling pathway. Thus, a defect in IFNγ secretion can lead to a delayed wound closure associated with inappropriate neutrophil accumulation and defective extracellular matrix formation. Interferon gamma (IFNγ) is a cytokine mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. IFNγ contributes to the activation of the immune cells during the inflammatory phase of wound healing, the recruitment of neutrophils and cell clearance through apoptosis. IFNγ also regulates collagen synthesis and angiogenesis, and there is also a crosstalk between IFNγ and the Transforming Growth Factor beta (TGFβ)/Smad signaling pathway. Thus, a defect in IFNγ secretion can lead to a delayed wound closure associated with inappropriate neutrophil accumulation and defective extracellular matrix formation. Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar (HS), which limits patients' joint movement and generates an aesthetic problem. This HS results from the enhanced proliferation of fibroblasts, the increased transdifferentiation of fibroblasts into myofibroblasts, and the increased deposition of extracellular matrix proteins, such as type I collagen. Interleukine-17 (IL-17) is a pro-inflammatory cytokine whose overexpression promotes the formation of cutaneous scar with the help of increased levels of several chemokines and the infiltration of macrophages. Interleukine-10 (IL-10) is a potent anti-inflammatory cytokine produced by various cell types such as Tcells, monocytes and macrophages, but also by keratinocytes after skin injury. IL-10 plays a key role in the ability of the fetus to heal regeneratively. Overexpression of IL-10 is also able to recapitulate scarless healing in postnatal tissue through its wide-ranging pleiotropic effects, attenuating the inflammatory response, regulating the extracellular matrix, enhancing fibroblast function, and modulating stem cell function. Proinflammatory cytokines, particularly interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNFα) are up-regulated during the inflammatory phase of wound healing. Upon wound healing IL-1 and TNFα are immediately released by keratinocytes. IL-1 is also released by neutrophils, monocytes and macrophages. IL-1 increases keratinocyte migration and proliferation, activates fibroblasts and increases the secretion of FGF-7. IL-6 is produced by neutrophils and monocytes and initiates the healing response. Its expression is increased after wounding and tends to persist in older wounds. It stimulates keratinocyte proliferation and is chemoattractive to neutrophils. TNFα, at low levels, can promote wound healing by indirectly stimulating inflammation and increasing macrophage produced growth factors. However, at higher levels and especially for a long period, TNFα, as well as IL-1β, favors extracellular matrix degradation and has a detrimental effect on healing. Levels of TNFα and IL-1β are elevated in chronic wounds.Loricrin and involucrin are two proteins synthesised in the keratinocyte cytoplasm of stratum granulosum. They are markers of terminal differentiation and essential components of the stratum corneum. Monitoring the expression of these two proteins allows to ensure that the skin barrier is correctly established during wound healing. Loricrin and involucrin are two proteins synthesised in the keratinocyte cytoplasm of stratum granulosum. They are markers of terminal differentiation and essential components of the stratum corneum. Monitoring the expression of these two proteins allows to ensure that the skin barrier is correctly established during wound healing. Following skin injury, damaged blood vessels are replaced by "sprouts" from intact capillaries in the local vicinity of the wound. Approximately on day 2 postwounding, endothelial cells (ECs) which will constitute the future vessels begin to migrate. Platelet endothelial cell adhesion molecule (PECAM 1), also called CD31, is an ECs marker which staining or dosage allow to monitor angiogenesis progression. CD34 may also be used, even if other skin cells such as bulge stem cells or dendritic cells also express this marker. ECs migration into the wound involves many factors including the αVβ3 integrin. This transmembrane protein helps ECs adhesion on extracellular matrix proteins including fibrin, one of the major component of the clot formed at the begining of wound healing. It also favors MMP2 collagenase location on ECs surface thus facilitating collagen digestion. This integrin is the most important integrin regarding angiogenesis. Absent in normal tissue, its expression is stimulated during wound healing. Following skin injury, damaged blood vessels are replaced by "sprouts" from intact capillaries in the local vicinity of the wound. Approximately on day 2 postwounding, endothelial cells (ECs) which will constitute the future vessels begin to migrate. Platelet endothelial cell adhesion molecule (PECAM 1), also called CD31, is an ECs marker which staining or dosage allow to monitor angiogenesis progression. CD34 may also be used, even if other skin cells such as bulge stem cells or dendritic cells also express this marker. ECs migration into the wound involves many factors including the αVβ3 integrin. This transmembrane protein helps ECs adhesion on extracellular matrix proteins including fibrin, one of the major component of the clot formed at the begining of wound healing. It also favors MMP2 collagenase location on ECs surface thus facilitating collagen digestion. This integrin is the most important integrin regarding angiogenesis. Absent in normal tissue, its expression is stimulated during wound healing. Transforming Growth Factor bêta (TGF-β) is a family of growth factors (TGF-β1, TGF-β2 and TGF-β3) involved in a number of essential cellular functions. All three isoforms are believed to bind and signal through the two TGF- β receptors (TβRI and TβRII) and mainly act via SMAD pathway. All 3 isoforms of TGF-β notably play a key role during wound healing, being involved in the inflammation phase, and stimulating angiogenesis, fibroblast proliferation, collagen synthesis and deposition and remodelling of the new extracellular matrix. Interestingly chronic, non-healing wounds often show a loss of TGF-β1 signalling, whereas fibroblasts derived from hypertrophic scars have been shown to synthetise more TGF-β1 and to express TGF-β receptors for a longer period of time than fibroblasts derived from normal skin. Thus, an alteration of TGF-β signaling (correlated to TGF-β or its receptors) has often been correlated to abnormal wound healing. Assessing TGF-β synthesis and/or the expression of its receptors may be of great interest when studying this phenomenon. Transforming Growth Factor bêta (TGF-β) is a family of growth factors (TGF-β1, TGF-β2 and TGF-β3) involved in a number of essential cellular functions. All three isoforms are believed to bind and signal through the two TGF- β receptors (TβRI and TβRII) and mainly act via SMAD pathway. All 3 isoforms of TGF-β notably play a key role during wound healing, being involved in the inflammation phase, and stimulating angiogenesis, fibroblast proliferation, collagen synthesis and deposition and remodelling of the new extracellular matrix. Interestingly chronic, non-healing wounds often show a loss of TGF-β1 signalling, whereas fibroblasts derived from hypertrophic scars have been shown to synthetise more TGF-β1 and to express TGF-β receptors for a longer period of time than fibroblasts derived from normal skin. Thus, an alteration of TGF-β signaling (correlated to TGF-β or its receptors) has often been correlated to abnormal wound healing. Assessing TGF-β synthesis and/or the expression of its receptors may be of great interest when studying this phenomenon. Vimentin is an intermediate filament protein composing the cytosqueletton and participating in numerous cellular processes including cell adhesion, migration, signaling, differentiation, cytoskeletal rearrangements, and regulation of cell morphology and plasticity. Following skin or eye injury and cell lesion, vimentin is released in extracellular matrix and stimulates inflammatory cell migration, keratinocyte differentiation and fibroblast proliferation, migration and differentiation in myofibroblasts. Vimentin therefore supports wound healing but may also be responsible of fibrosis. Vimentin is therefore an interesting marker to follow wound healing. Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan in the extracellular matrix, and is expressed at high levels in tissues during development and remodeling in pathological conditions. Versican is a component of the elastic fibres and is involved in elastogenesis, extracellular matrix remodeling, cell phenotype, proliferation, adhesion and migration. During wound healing, Versican has been shown to stimulate endothelial cell proliferation, myofibroblast formation, types I and III collagen accumulation, and immune cell infiltration, especially inflammatory macrophages.Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan in the extracellular matrix, and is expressed at high levels in tissues during development and remodeling in pathological conditions. Versican is a component of the elastic fibres and is involved in elastogenesis, extracellular matrix remodeling, cell phenotype, proliferation, adhesion and migration. During wound healing, Versican has been shown to stimulate endothelial cell proliferation, myofibroblast formation, types I and III collagen accumulation, and immune cell infiltration, especially inflammatory macrophages.Keratins 5 and 14 (K5 and K14) are expressed in dividing keratinocytes in the basal layer of the epidermis. Their expression decreases as the keratinocytes differentiate, while other keratins such as K1 or K10 begin to be expressed. In acne-prone skin, hyperkeratinisation correlated with a decrease in the ratio of K1 or K10 to K14 or K5 is observed. An anti-acne product should restore a normal ratio.Desmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healing. NMF is mainly composed of free amino acids and derived components such as pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA), which come from filaggrin degradation. NMF is involved in the maintenance of skin hydration, on which the barrier function, the skin suppleness and plasticity, the desquamation process and skin homeostasis depend. Atopic dermatitis (AD) is often correlated with a decrease in NMF level and a treatment against AD can improve NMF production. Skin kallikreins, including the well-known kallikreins 5 (KLK-5) and 7 (KLK-7) are proteolytic enzymes playing a crucial role in regulating both desquamation and skin inflammation. Thus, they allow to maintain skin homeostasis. They also play a key role in extracellular matrix remodeling and during wound healing inflammatory response. An abnormal activation of the KLK proteolytic cascade is reported in some inflammatory diseases such as atopic dermatitis (AD) and psoriasis. Thus, they represent an interesting target to treat inflammatory diseases or to improve wound healing. The conversion of saturated fatty acids (FAs) palmitate (16:0) and stearate (18:0) into monounsaturated FAs palmitoleate (16:1n-7) and oleate (18:1n-9) is catalyzed by stearoyl-CoA desaturase 1 (SCD1). These FAs represent the dominant constituents of adipocyte triacylglycerols (TAGs) and phospholipids (PLs). Given the critical role of SCD1 in lipid metabolism and the notable increase in its expression during adipogenesis, reductions in SCD1 activity have the potential to compromise the adipocyte's ability to accumulate lipid. Slimming agent can therefore target SCD1 to reduce fat level and modulate adipocyte lipid composition. Fibrillin-1 (FBN-1) and fibrillin-2 (FBN-2) assemble into microfibrils (FMF). These FMF are located in the extracellular matrix (ECM) and form the core scaffolds for elastic fibre formation. They also decorate the surface of elastic fibres, and form an independent network of stretchable bundles. Thanks to their own mechanical properties and their role in elastin network formation, these fibres widely contribute to skin elasticity and pliability. Moreover FBN network stores and controls the bioavailability of growth factors such as TGFβ that control the remodeling and architecture of the ECM upon which its mechanical properties directly depend. A degradation or loss of FMF occurs with ageing or sun exposure at the dermo-epidermal junction. This is believed to be the primary reason for wrinkling and sagging of the skin.FBNs thus represent potential targets for anti-ageing products. Sensitive skin syndrome is defined as the occurrence of unpleasant sensations in response to various stimuli that normally should not provoke such sensations. This syndrome, which is independent of any other skin disease, can be detected in many cases by the lowering of the skin's sensitivity threshold to capsaicin. Capsaicin can indeed trigger unpleasant sensations (pain, itching), in particular by binding to the transient receptor potential vanilloid 1 (TRPV1) carried by keratinocytes and nerve fibers. It thus induces the activation of the peptidergic sensory neurons. These then release the calcitonin gene related peptide (CGRP), a factor promoting skin inflammation (neurogenic inflammation). In vitro, capsaicin is used to induce the release of CGRP and a molecule will be considered as having a soothing effect if it decreases this release. Glucose represents the major source of energy for most tissues of the body and enter the cells via specific glucose transporters such as glucose GLUT2 or GLUT4. Intake of carbohydrates leads to an immediate increase in circulating blood glucose levels after absorption of the glucose from the intestine. As a direct response, pancreatic beta cells sense the elevated blood glucose concentrations via a GLUT2-dependent process and increase secretion of insulin. Consequently, insulin binding to its receptors leads to enhanced glucose transport into skeletal muscle, adipose tissue, and the heart. In adipocytes In adipocytes, the rapid entry of glucose is mainly mediated by a rapid translocation of intracellular vesicles containing the GLUT4 transporter to the plasma membrane. Glucose is then stored as triglycerides through de novo lipogenesis. The regulation of the density of GLUT4 receptors on the surface of adipocytes thus plays a major role in the regulation of blood glucose and lipid storage in adipocytes. Insulin plays a major role in this regulation and high levels of GLUT4 in adipose tissue are correlated with high insulin sensitivity and glucose tolerance. Glucose represents the major source of energy for most tissues of the body and enter the cells via specific glucose transporters such as glucose GLUT2 or GLUT4. Intake of carbohydrates leads to an immediate increase in circulating blood glucose levels after absorption of the glucose from the intestine. As a direct response, pancreatic beta cells sense the elevated blood glucose concentrations via a GLUT2-dependent process and increase secretion of insulin. Consequently, insulin binding to its receptors leads to enhanced glucose transport into skeletal muscle, adipose tissue, and the heart. In adipocytes In adipocytes, the rapid entry of glucose is mainly mediated by a rapid translocation of intracellular vesicles containing the GLUT4 transporter to the plasma membrane. Glucose is then stored as triglycerides through de novo lipogenesis. The regulation of the density of GLUT4 receptors on the surface of adipocytes thus plays a major role in the regulation of blood glucose and lipid storage in adipocytes. Insulin plays a major role in this regulation and high levels of GLUT4 in adipose tissue are correlated with high insulin sensitivity and glucose tolerance. PPARγ is a nuclear receptor regulating many functions in diverse cell types, including especially the development of adipose tissue by coordinating many hundreds of genes responsible for the establishment of the mature adipocyte phenotype. It stimulates in particular the expression of the Fatty Acid Transporter FATP1, which main role in adipocytes is to favor insulin-induced fatty acid uptake. FATP4 is also expressed in adipocytes and its expression level correlates well with obesity, thus representing an interesting target to prevent or treat obesity. Nevertheless,it seems to regulate PPARgamma expression and participate in lipolysis rather than playing a role in fatty acid uptake. The conversion of saturated fatty acids (FAs) palmitate (16:0) and stearate (18:0) into monounsaturated FAs palmitoleate (16:1n-7) and oleate (18:1n-9) is catalyzed by stearoyl-CoA desaturase 1 (SCD1). These FAs represent the dominant constituents of adipocyte triacylglycerols (TAGs) and phospholipids (PLs). Given the critical role of SCD1 in lipid metabolism and the notable increase in its expression during adipogenesis, reductions in SCD1 activity have the potential to compromise the adipocyte's ability to accumulate lipid. Slimming agent can therefore target SCD1 to reduce fat level and modulate adipocyte lipid composition. The conversion of saturated fatty acids (FAs) palmitate (16:0) and stearate (18:0) into monounsaturated FAs palmitoleate (16:1n-7) and oleate (18:1n-9) is catalyzed by stearoyl-CoA desaturase 1 (SCD1). These FAs represent the dominant constituents of adipocyte triacylglycerols (TAGs) and phospholipids (PLs). Given the critical role of SCD1 in lipid metabolism and the notable increase in its expression during adipogenesis, reductions in SCD1 activity have the potential to compromise the adipocyte's ability to accumulate lipid. Slimming agent can therefore target SCD1 to reduce fat level and modulate adipocyte lipid composition. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors which promote fatty acid production (SREBP1a/c) and cholesterol synthesis (SREBP2) involved in adipocyte lipogenesis. SREBP1 therefore represents a key target for a slimming agent. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors which promote fatty acid production (SREBP1a/c) and cholesterol synthesis (SREBP2) involved in adipocyte lipogenesis. SREBP1 therefore represents a key target for a slimming agent. Desmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healing. Desmogleins and desmocollins are calcium-binding transmembrane glycoproteins belonging to the cadherin superfamily. As components of desmosomes, they are involved in the cohesion between keratinocytes. The exact composition of desmosoms varies depending on the location. For example, Desmoglein 2 is more abundant in the basal layer while Desmoglein 1 level is higher in differentiated keratinocytes. Monitoring the synthesis, abundance and location of all those proteins allow to ensure the correct regeneration of the skin barrier during wound healing. Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and notably decreases the synthesis of collagen I and elastin, the two main components of the dermal matrix, notably by decreasing TGFβ synthesis. This, coupled with increased degradation of the matrix by metalloproteases, leads to premature ageing of the skin.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and notably decreases the synthesis of collagen I and elastin, the two main components of the dermal matrix, notably by decreasing TGFβ synthesis. This, coupled with increased degradation of the matrix by metalloproteases, leads to premature ageing of the skin.Air pollution can have a significant impact on the skin, notably by modulating gene expression in skin cells. For example, it stimulates the synthesis of the inducible nitric oxide synthase (iNOS), thus increasing nitric oxide (NO) level that plays a key role in skin perfusion as well as in inflammation and collagen metabolism. Air pollution can have a significant impact on the skin, notably by modulating gene expression in skin cells. For example, it stimulates the synthesis of the inducible nitric oxide synthase (iNOS), thus increasing nitric oxide (NO) level that plays a key role in skin perfusion as well as in inflammation and collagen metabolism. Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and cell metabolism, notably decreasing ATP production.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and cell metabolism, notably decreasing ATP production.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and cell metabolism, notably decreasing ATP production.Air pollution exerts negative effects on the human skin. It modulates gene expression in skin cells and cell metabolism, notably decreasing ATP production.