Epidermal barrier function in dry, flaky and sensitive skin: A narrative review.

The stratum corneum (SC)-the outermost layer of the epidermis-is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin's microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment.

Predictors of female age, health and attractiveness perception from skin feature analysis of digital portraits in five ethnic groups.

OBJECTIVE: Research indicates the impact of skin colour, tone evenness and surface topography on ratings of age, health and attractiveness in women. In addition to subjective assessments, these effects have been quantified with objective measures derived from skin image analysis. Signs of skin ageing may manifest differently across ethnic groups. However, comparisons have been limited to research with two ethnic groups, preventing conclusions about an ethnicity-specific ranking of skin ageing signs. METHODS: We report results from a multi-ethnic and multi-centre study in which faces of women (n = 180; aged 20-69 years) from five ethnic groups were imaged. Facial images were rated for age, health and attractiveness by members of the same ethnic group (each n = 120). Digital image analysis was used to quantify skin colour, gloss, tone evenness and wrinkling/sagging. We assessed associations between face ratings and skin image measurements in the total sample (i.e. all ethnic groups) and separately by ethnicity. RESULTS: Skin image analysis revealed differences between ethnic groups, including skin colour, gloss, tone evenness, wrinkling and sagging. Differences in the relative predictive utility of individual skin features in accounting for ratings of age, health and attractiveness also were observed between ethnic groups. Facial wrinkling and sagging were the best predictors of face ratings in each ethnic group, with some differences in the type (or predictive magnitude) of skin features. CONCLUSION: The current findings corroborate previous reports of differences between ethnic groups in female facial skin and indicate differential effects of skin features on ratings of age, health and attractiveness, within and between ethnic groups. Facial wrinkling and sagging were the best predictors of age and attractiveness ratings, and skin tone evenness and gloss had an additional role in ratings of health.

OBJECTIF: La présente étude montre l'impact de la couleur de la peau, de l'uniformité du teint, et de la texture cutanée sur l'évaluation de l'âge, de la santé et de l'attractivité chez les femmes. En plus d'évaluations subjectives, ces aspects ont été quantifiés à l'aide de mesures objectives provenant d'analyse d'image de la peau. Les signes de vieillissement de la peau peuvent se manifester différemment selon les groupes ethniques. Cependant, les précédentes recherches se limitent à des comparaisons entre deux groupes ethniques, empêchant ainsi de conclure sur un classement des signes de vieillissement cutané par ethnie. MÉTHODE: Nous présentons les résultats d'une étude multiethnique et multicentrique dans laquelle des visages de femmes (n = 180 ; âgées de 20 à 69 ans) de cinq groupes ethniques ont été imagés. Les images des visages ont été évaluées en termes d'âge, de santé et d'attractivité par des membres du même groupe ethnique (n = 120 par groupe). Des algorithmes d'analyse d'image ont été utilisés pour quantifier la couleur de la peau, la brillance, l'uniformité du teint et les rides/affaissement de la peau. Nous avons analysé les corrélations entre l'évaluation des visages et les mesures quantitatives issues de l'analyse d'image sur la totalité de l'échantillon (c'est-à-dire tous les groupes ethniques) et séparément par ethnie. RÉSULTATS: L'analyse d'image a révélé des différences entre les groupes ethniques, notamment en ce qui concerne la couleur de la peau, la brillance, l'uniformité du teint, les rides et le relâchement cutané. Des différences dans la valeur prédictive relative des différentes caractéristiques cutanées dans l'évaluation de l'âge, de la santé et de l'attractivité ont également été observées entre les groupes ethniques. Les rides et l'affaissement du visage ressortent comme les meilleurs prédicteurs de l'évaluation pour tous les groupes ethniques, avec quelques différences dans le type (ou l'ampleur de la prédiction) des différentes caractéristiques cutanées. CONCLUSION: Les résultats actuels corroborent les rapports précédents sur les différences entre les groupes ethniques concernant la peau du visage des femmes. Ils montrent également des effets différentiels des caractéristiques cutanées sur l'évaluation de l'âge, de la santé et de l'attractivité, au sein des groupes ethniques et entre eux. Les rides et l'affaissement du visage ressortent comme les meilleurs prédicteurs de l'âge et de l'attractivité, tandis que l'uniformité et la brillance du teint jouent un rôle supplémentaire dans l'évaluation de la santé.

Moisturizing at a molecular level - The basis of Corneocare.

This review covers the last 20 years of research we and our collaborators have conducted on ethnic differences in facial skin moisturization placed in historical context with previous research. We have focussed particularly on the biochemical and cellular gradients of the stratum corneum (SC) with the aim of discovering new skin moisturization and SC maturation mechanisms, identifying new technologies and/or providing conceptual innovations for ingredients that will improve our understanding and treatment of dry skin. Specifically, we discuss gradients for corneodesmosomes and proteases, corneocyte phenotype-inducing enzymes, filaggrin and natural moisturizing factor (NMF), and barrier lipids. These gradients are interdependent and influence greatly corneocyte maturation. The interrelationship between corneodesmolysis and the covalent attachment of ω-hydroxy ceramides and ω-hydroxy fatty acids to the corneocyte protein envelope forming the corneocyte lipid envelope is especially relevant in our new understanding of mechanisms leading to dry skin. This process is initiated by a linoleoyl-ω-acyl ceramide transforming enzyme cascade including 12R lipoxygenase (12R-LOX), epidermal lipoxygenase-3 (eLOX3), epoxide hydrolase 3 (EPHX3), short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), ceramidase and transglutaminase 1. Our research has opened the opportunity of using novel treatment systems for dry skin based on lipids, humectants, niacinamide and inhibitors of the plasminogen system. It is clear that skin moisturization is a more complex mechanism than simple skin hydration.

Cette revue couvre 20 années de recherche que nous avons menées avec nos collaborateurs sur les différences ethniques d'hydratation de la peau du visage, en regard du contexte historique de recherches antérieures. Nous avons en particulier focalisé sur les gradients biochimiques et cellulaires du stratum corneum (SC) dans le but de découvrir de nouveaux mécanismes d'hydratation et de maturation du SC, et avons identifié de de nouvelles technologies et/ou apporté des concepts innovants pour le développement d'ingrédients, permettant d'améliorer notre compréhension et le traitement de la peau sèche. Nous discutons spécifiquement les gradients de cornéodesmosomes et de protéases, d'enzymes cornéocytaires inductrices de phénotype, de filaggrine et du facteur naturel d'hydratation (NMF), et des lipides de la barrière. Ces gradients sont inter-dépendants et influencent de façon majeure la maturation des cornéocytes. L'interrelation entre la lyse des cornéodesmosomes et la fixation covalente des céramides ω-hydroxy et des acides gras ω-hydroxy à l'enveloppe protéique des cornéocytes, formant l'enveloppe lipidique, est particulièrement pertinente pour la compréhension des mécanismes menant à une peau sèche. Ce process est initié par une cascade enzymatique de transformation du céramide linoleoyl-ω-acyl incluant la lipoxygénase 12R (12R-LOX), la lipoxygénase-3 épidermique (eLOX3), l'hydrolase d'époxyde 3 (EPHX3), le membre 7 de la famille des déshydrogénase/ réductases à courte chaine 9C (SDR9C7), la céramidase et la transglutaminase 1. Nos recherches ont permis d'utiliser de nouveaux systèmes traitants à destination de la peau sèche à base de lipides, d'humectants, de niacinamide et d'inhibiteurs du système plasminogénique. Il est clair que l'hydratation de la peau est un mécanisme plus complexe qu'une simple teneur en eau.

A comprehensive comparison of facial skin hydration based on capacitance and conductance measurements in Chinese women.

OBJECTIVES: The aim of this study was to compare the data of conductance and capacitance measurements of facial skin hydration and to evaluate and discuss the advantages and disadvantages of the different approaches. METHODS: We measured skin capacitance (Corneometer® CM 825) and skin conductance (Skicon-200EX®) on 30 pre-defined facial sites of 125 Chinese women, resulting in 3750 readings per device. The data were analysed and compared, and continuous colour maps were generated on a 3D avatar for capacitance, conductance, relative difference (Δ%) and correlation (R-value) by interpolating between the individual readings and converting the values to colours. This visualization allows a better interpretation of the results. RESULTS: The complexity of facial skin hydration is revealed by this approach. The similarities and discrepancies in the facial hydration maps are clearly apparent. Due to the superiority of the Skicon in measuring high hydration levels, differences in skin hydration were evident on the forehead compared with the Corneometer maps, which may be related to the more superficial measurement of the Skicon within the stratum corneum. Conversely, a greater understanding of the complexity of facial skin hydration in the nasolabial fold was obvious when using the Corneometer. The best congruence between the instruments was found at two specific but separated facial areas, one around the inner eye region and the other one on a line between the nasolabial sulcus and the oblique, lateral jaw. Interestingly, the data were not normally distributed for both instruments and they had opposite skews. All facial clusters were statistically different from each other (p < 0.001), except the cheek and jaw for the Skicon. Larger than expected percentage coefficients of variance were found for the Corneometer on some facial sites that might be explainable by differences in stratum corneum physiology and biochemistry. Corneometer values of 48 AU and Skicon values of 132 µS were taken as the cutoff for normally hydrated facial skin. CONCLUSIONS: Both devices have their advantages and disadvantages suggesting that bio-instrumental measurement of skin hydration is actually more complicated than commonly thought and that the different facial zones and the use of multiple instrumentation have not been adequately considered.

OBJECTIFS: L'objectif de cette étude était de comparer des données issues de mesures d'hydratation de la peau du visage par conductance et capacité électrique, et d'évaluer et discuter les avantages et désavantages de ces différentes approches. METHODES: La capacité électrique de la peau (Corneometer® CM 825) et saconductance (Skicon-200EX®) ont été mesurées en 30 points pré-définis du visage de 125 femmes chinoises, menant ainsi à 3750 mesures par appareil. Les données ont été analysées et comparées, puis transposées visuellement sur avatar 3D via la création de cartographies continues de couleur par conversion de chaque valeur en une coordonnée de couleur et interpolation colorielle entre les différents points. Des cartographies de capacité électrique, de conductance ainsi que celle de la différence relative (Δ%) et de corrélation (R-value) ont été générées, ces visualisations permettant de mieux interpréter les résultats. RESULTS: Cette étude a mis en lumière la complexité de l'hydratation de la peau du visage. Les similarités et différences entre les cartographies d'hydratation faciale apparaissent clairement. Du fait de la supériorité du Skicon pour la mesure de hauts taux d'hydratation, des différences sont clairement visualisées entre les cartographies d'hydratation des deux appareils au niveau du front, et pourraient être dues à une mesure plus superficielle au sein du stratum corneum avec le Skicon. A l'inverse, l'utilisation du Corneometer permet une bien meilleure compréhension de la complexité de l'hydratation de la peau au niveau du sillon nasogénien. Les appareils montrent les résultats les plus similaires au niveau de deux zones spécifiques et séparées du visage, une au niveau du coin interne de l'œil et l'autre sur une ligne séparant le sillon nasolabial et l'oblique latéral de la machoire. Il est intéressant de noter que les distributions des données ne suivent pas une loi normale, pour aucun des deux appareils, et présentent des biais de distribution opposés. Tous les résultats obtenus au niveau des clusters faciaux étudiés montrent des différences statistiquement significatives entre eux (p⟨0.001), à l'exception de la joue et de la mâchoire, avec le Skicon. Des pourcentages de coefficients de variation plus élevés qu'attendus ont été obtenus avec le Corneometer en certaines zones du visage, qui pourraient être expliqués par des différences physiologiques et biochimiques du stratum corneum. Des valeurs de 48 UA avec le Corneometer et de 132 µS avec le Skicon ont été retenues comme valeurs seuil d'une peau du visage normalement hydratée. CONCLUSIONS: Les deux appareils montrent des avantages et désavantages, suggérant que la mesure bio-instrumentale de l'hydratation cutanée du visage est en réalité plus compliquée que communément admise et qu'une approche multiinstrumentale n'a pas été suffisamment considérée à ce jour pour appréhender les différentes zones du visages.

Changes in levels of omega-O-acylceramides and related processing enzymes of sun-exposed and sun-protected facial stratum corneum in differently pigmented ethnic groups.

INTRODUCTION: We report on the differences in ceramide composition and levels of omega-O-acylceramide processing enzymes of sun-exposed and sun-protected facialstratum corneum (SC) among Albino African, Black African and Caucasian women living in South Africa. METHODS: Tape strippings were taken from the sun-exposed cheek and the sunprotected postauricular site (PA). In two subsets proteomic (n = 18) and lipidomic (n = 24) analysis were performed using mass-spectrometry-based shotgun platforms. RESULTS: No significant differences in total ceramide levels or ceramide subtypes were found between the Black African and Caucasian women in either the cheek or PA samples. Compared to the other two groups the levels of total ceramide as well as selected omega-O-acylceramide species were increased in Albino Africans. On the cheek, ceramide (CER) EOS, EOH along with CER AS were increased relative to the Caucasian women, while CER EOP and EOdS were elevated relative to the Black African women. Moreover, on the PA site CER EOP and EOdS were elevated compared with the Black African women and CER EOdS in Caucasians. Decreasesin masslevels of 12R-LOX and eLOX3 were observed on cheeks compared with the PA sites in all ethnic groups. On the PA sites 12R-LOX was particularly lower in the Albino Africans compared with the Black African and Caucasian women. On the cheeks mass levels of SDR9C7 was also lower in the Albino Africans. CONCLUSION: The mass levels of the ceramides were similar between Black African and Caucasian women. However, elevated total ceramides and excessively elevated selected omega-O-acylceramides were apparent in the Albino African women. The findings in the Albino African women were unexpected as these participants suffer from impaired skin barrier function. However, the elevated levels omega-O-acylceramides can contribute to barrier insufficiency by directly impacting SC lipid phase behaviour and/or secondly elevated omegaO-acylceramide levels may indicate a reduced attachment of ceramides to the corneocyte lipid envelope and reduced corneocyte maturation that can also impair the barrier. Indeed, differences in the mass levels of omega-O-acylceramide processing enzymes were observed for 12R-LOX and SDR9C7 for the Albino Africans. This indicates a corneocyte lipid scaffold disorder in this population.

INTRODUCTION: Nous décrivons les différences de composition en céramides et de niveaux des enzymes du métabolisme des oméga-O-acylcéramides du stratum corneum facial (SC) photo-exposé et photo-protégé chez des femmes Albinos Africaines, Noires Africaines et Caucasiennes vivant en Afrique du Sud. MÉTHODES: Les prélèvements ont été effectués sur la joue photo-exposée et sur le site post-auriculaire (PA) photo-protégé à l'aide de disques adhésifs. Dans deux sous-groupes, des analyses protéomiques (n = 18) et lipidomiques (n = 24) ont été réalisées à l'aide de plateformes de spectrométrie de masse non-ciblées. RÉSULTATS: Aucune différence significative de quantité globale de céramides ou dans les différentes classes de céramides n'a été observée entre les femmes Noires Africaines et les femmes Caucasiennes, quels que soient les échantillons (Joue ou de PA). Comparativement aux deux autres groupes, les quantités de céramides totales, ainsi que certaines espèces d'oméga-O-acylcéramides, étaient plus élevés chez les femmes Albinos Africaines. Sur la joue, les céramides (CER) EOS, EOH et CER AS étaient plus élevés que chez les femmes Caucasiennes, tandis que les CER EOP et EOdS étaient plus élevés que chez les femmes Noires Africaines. De plus, sur le site PA, les CER EOP et EOdS étaient plus élevés que chez les femmes Noires Africaines et les CER EOdS chez les Caucasiennes. Des diminutions des niveaux d'enzymes 12R-LOX et eLOX3 ont été observées sur les joues par rapport aux sites PA dans tous les groupes ethniques. Sur les sites PA, le niveau de 12RLOX était notablement plus faible chez les femmes Albinos Africaines comparativement aux femmes Noires Africaines et Caucasiennes. Sur les joues, le niveau de SDR9C7 était également plus faible chez les Albinos Africaines. CONCLUSION: La masse des céramides totaux était similaire entre les femmes Noires Africaines et Caucasiennes. Cependant, des niveaux élevés de céramides totaux et excessivement élevés des oméga-O-acylcéramides sélectionnés, ont été observés chez les femmes Albinos Africaines. Les résultats obtenus chez les femmes Albinos Africaines étaient surprenants car ces participantes souffrent d'une altération de la fonction de la barrière cutanée. Néanmoins, les niveaux élevés d'oméga-O-acylcéramides peuvent en premier lieu contribuer à l'insuffisance de la barrière en ayant un impact direct sur le comportement de la phase lipidique du SC et/ou, deuxièmement, peuvent indiquer une fixation réduite des céramides à l'enveloppe lipidique des cornéocytes et une maturation réduite des cornéocytes pouvant aussi altérer la barrière. En outre, des différences dans les niveaux d'expression des enzymes de transformation de l'oméga-O-acylcéramide ont été observées pour 12R-LOX et SDR9C7 chez les femmes Albinos Africaines. Ceci indique une désorganisation de l'échafaudage lipidique des cornéocytes dans cette population.

Characterizing the nanomechanical properties of microcomedones after treatment with sodium salicylate ex vivo using atomic force microscopy.

OBJECTIVE: The treatment of acne presents a major clinical and dermatological challenge. Investigating the nanomechanical properties of the microcomedone precursor lesions using atomic force microscopy (AFM) may prove beneficial in understanding their softening, dissolution and prevention. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution. METHODS: Therefore, to support this exploration, sodium salicylate (NaSal), a common ingredient employed in skin care products, is applied ex vivo to microcomedones,collected by nose strip adhesive tape, and their nanomechanical properties are assessed using AFM. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution. RESULTS: Herein, our findings demonstrate that when microcomedones are treated with 2% NaSal, samples appeared significantly more compliant ('softer') ((1.3 ± 0.62) MPa) when compared to their pre-treated measurements ((7.2 ± 3.6) MPa; p = 0.038). Furthermore, elastic modulus maps showed that after 2% NaSal treatment, areas in the microcomedone appeared softer and swollen in some, but not in all areas, further proving the valuable impact of 2% NaSal solution in altering the biomechanical properties and morphologies in microcomedones. CONCLUSION: Our results are the first of their kind to provide qualitative and quantitative mechanobiological evidence that 2% NaSal decreases the elastic modulus of microcomedones. Therefore, this study provides evidence that NaSal can be beneficial as an active ingredient in topical treatments aimed at targeting microcomedones.

OBJECTIF: Le traitement de l'acné présente un défi clinique et dermatologique majeur. L'étude des propriétés nanomécaniques des lésions précurseurs en tant que microcomédons à l'aide de la microscopie à force atomique (AFM) peut s'avérer bénéfique pour comprendre leur ramollissement, leur dissolution et leur prévention. MÉTHODES: Par conséquent, pour soutenir cette exploration, le salicylate de sodium (NaSal), un ingrédient couramment utilisé dans les produits de soins de la peau, est appliqué ex vivo aux microcomédons et leurs propriétés nanomécaniques sont évaluées à l'aide de l'AFM. Bien que le mécanisme biochimique exact du NaSal sur les microcomédons ne soit pas entièrement compris à l'heure actuelle, il semble présenter un effet exfoliant significatif sur la peau via la dissolution des cornéodesmosomes. RÉSULTATS: Ici, nos résultats démontrent que lorsque les microcomédons sont traités avec 2% de NaSal, les échantillons semblaient significativement plus conformes ("plus doux") ((1.3 ± 0.62) MPa) par rapport à leurs mesures pré-traitées ((7.2 ± 3.6) MPa ; P = 0,03826). De plus, les cartes du module d'élasticité ont montré qu'après un traitement à 2 % de NaSal, les zones du microcomédon semblaient plus molles et gonflées dans certaines zones, mais pas dans toutes, prouvant ainsi l'impact précieux d'une solution de NaSal à 2 % dans la modification des propriétés biomécaniques et de la morphologie des microcomédons. CONCLUSION: Nos résultats sont les premiers du genre à fournir des preuves mécanobiologiques qualitatives et quantitatives que 2% de NaSal diminue le module d'élasticité des microcomédons. Par conséquent, cette étude fournit des preuves que NaSal peut être bénéfique en tant qu'ingrédient actif dans les traitements topiques visant à cibler les microcomédons.

Effect of regioisomers of hydroxystearic acids as peroxisomal proliferator-activated receptor agonists to boost the anti-ageing potential of retinoids.

INTRODUCTION: We report on the in vitro and ex vivo effects of chiral (R)-10-hydroxystearic acid (10-HSA) compared with other mono-hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol. METHODS: Following treatment with hydroxystearic acids peroxisomal proliferator-activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast collagen proteome was studied by mass-spectrometry-based proteomics and collagen type III was assessed by immunohistochemistry on human ex vivo skin. RESULTS: 10-HSA was the most effective PPARα agonist (15.7× induction; p < 0.001), followed by 9-HSA (10.1× induction) and then 12-HSA (4.9× induction) with 17-HSA (1.7× induction) being similar to the effects of stearic acid (1.8× induction). Collagen type I levels were increased in primary human fibroblasts by 2.12× and 1.56× for 10-HSA and 9-HSA, respectively, in vitro with the10-HSA being significant (p < 0.05), whereas 12-HSA and SA had no statistical effect over the untreated control. 10-HSA and 12-HSA modified the intracellular fibroblast collagen proteome slightly with significant increases in collagen alpha-1 (VI) and alpha-3 (VI) proteins but only 10-HSA increased levels of collagen alpha-2 (V), alpha-1 (III), alpha-1 (I) and alpha-2 (I) (all p < 0.05) with the increases being significantly different between 10-HSA and 12-HSA for collagen alpha-1 (I), collagen-3 (VI) and collagen alpha-2 (I) (p < 0.01). Collagen type III in ex vivo skin was increased +47% (p < 0.05) by 0.05% (1.7 mM) retinol, +70% (p < 0.01) by 0.01% (0.33 mM) 10-HSA and the combination increased levels by +240% (p < 0.01 for either ingredient). CONCLUSION: Chiral (R)-10-HSA has been shown to be superior to 9, 12 and 17-HSA as a PPARα agonist. Moreover, 10-HSA stimulated collagen synthesis in monolayer fibroblast culture as assessed by proteomics and immunohistochemically. Furthermore, we also show the synergistic effects of 10-HSA with retinol on collagen III synthesis in skin explants. These results further highlight the efficacy of 10-HSA as a cosmetically acceptable PPARα agonist and anti-ageing ingredient.

INTRODUCTION: Nous rapportons les effets in vitro et ex vivo de l'acide chiral (R)-10-hydroxystéarique (10-HSA) par rapport à d'autres régioisomères d'acide mono-hydroxystéarique et à l'acide stéarique (SA) ainsi que ses avantages lorsqu'il est associé au rétinol. MÉTHODES: Après un traitement avec des acides hydroxystéariques, l'activité du récepteur alpha activé par les proliférateurs peroxysomaux (PPARα) a été déterminée dans un test du gène rapporteur de la luciférase, le collagène de type I a été évalué dans les fibroblastes dermiques humains primaires par immunohistochimie, la modification du protéome du collagène des fibroblastes intracellulaires a été étudiée par spectrométrie de masse. La protéomique et le collagène de type III ont été évalués par immunohistochimie sur la peau humaine ex vivo. RÉSULTATS: la 10-HSA était l'agoniste PPARα le plus efficace (induction 15,7X ; p<0,001), suivi de la 9-HSA (induction 10,1X) puis de la 12-HSA (induction 4,9X) avec la 17-HSA (induction 1,7X) étant similaire aux effets de l'acide stéarique (induction 1,8X). Les niveaux de collagène de type I ont été augmentés dans les fibroblastes humains primaires de 2,12X et 1,56X pour la 10-HSA et la 9-HSA respectivement in vitro, la 10-HSA étant significative (p<0,05) : alors que la 12-HSA et la SA n'ont eu aucun effet statistique sur le témoin non traité. La 10-HSA et la 12-HSA ont légèrement modifié le protéome du collagène des fibroblastes intracellulaires avec des augmentations significatives des protéines de collagène alpha-1 (VI) et alpha-3 (VI), mais seule la 10-HSA a augmenté les niveaux de collagène alpha-2 (V), alpha -1 (III), alpha-1 (I) et alpha-2 (I) (tous p<0,05) avec des augmentations significativement différentes entre 10-HSA et 12-HSA pour le collagène alpha-1 (I), le collagène- 3 (VI) et Collagène alpha-2 (I) (p<0,01). Le collagène de type III dans la peau ex vivo a augmenté de +47 % (p<0,05) de 0,05 % (1,7 mM) de rétinol, de +70 % (p<0,01) de 0,01 % (0,33 mM) de 10-HSA et la combinaison a augmenté les niveaux de +240 % (p<0,01 pour chaque ingrédient). CONCLUSION: La chiral (R)-10-HSA s'est avérée supérieure à 9, 12 et 17-HSA en tant qu'agoniste de PPARα. De plus, la 10-HSA a stimulé la synthèse de collagène dans la culture de fibroblastes monocouche telle qu'évaluée par protéomique et immunohistochimique. De plus, nous montrons également les effets synergiques de la 10-HSA avec le rétinol sur la synthèse du collagène III dans les explants de peau. Ces résultats soulignent en outre l'efficacité de la 10-HSA en tant qu'agoniste de PPARα et ingrédient anti-âge cosmétiquement acceptable.

Differences between perceived age and chronological age in women: A multi-ethnic and multi-centre study.

OBJECTIVE: Accuracy in assessing age from facial cues is important in social perception given reports of strong negative correlations between perceived age and assessments of health and attractiveness. In a multi-ethnic and multi-centre study, we previously documented similar patterns of female facial age assessments across ethnicities, influenced by gender and ethnicity of assessors. METHODS: Here we extend these findings by examining differences between estimated age from digital portraits and chronological age (Δ age) for 180 women from three age groups (20-34, 35-49, 50-66 years) and five ethnicities (36 images of each ethnicity, assessed for age on a continuous scale by 120 female and male raters of each ethnicity). RESULTS: Across ethnicities, Δ age was smallest in French assessors and largest in South African assessors. Numerically, French women were judged oldest and Chinese women youngest relative to chronological age. In younger women, Δ age was larger than in middle-aged and older women. This effect was particularly evident when considering the interaction of women's age with assessor gender and ethnicity, independently and together, on Δ age. CONCLUSION: Collectively, our findings suggest that accuracy in assessments of female age from digital portraits depends on the chronological age and ethnicity of the photographed women and the ethnicity and gender of the assessor. We discuss the findings concerning ethnic variation in skin pigmentation and visible signs of ageing and comment on implications for cosmetic science.

OBJECTIF: La capacité à évaluer l'âge d'un visage avec exactitude en fonction de ses caractéristiques est important dans sa perception sociale. En effet, des corrélations négatives fortes ont été rapportées entre l'âge perçu d'un visage d'une part, et sa santé et attractivité d'autre part. Dans le cadre d'une étude multi-ethnique et multicentrique, nous avons déjà documenté, dans une démarche similaire, comment la perception de l'âge de visages féminins entre différentes populations, est influencée par le genre et l'origine des évaluateurs. METHODES: Ici nous approfondissons ces premiers résultats par l'étude des différences entre l'âge estimé sur portraits numériques de 180 femmes issues de 3 groupes d'âges (20-34, 35-49, 50-66 ans) et de 5 populations d'origine différente (36 images de chaque population) et leur âge réel (Δ âge), et ce par 120 évaluatrices et évaluateurs de chaque population évaluant l'âge des visages en utilisant une échelle continue. RESULTATS: Au sein des différentes populations d'évaluateurs, le Δ âge le plus faible a été trouvé chez les évaluateurs français et le plus élevé chez les évaluateurs sud-africains. Sur portraits numériques, les femmes françaises ont été perçues comme étant les plus âgées et les femmes chinoises les plus jeunes, par rapport à leur âge réel. Chez les femmes les plus jeunes, le Δ âge a été plus élevé que chez les femmes d'âge moyen et les plus âgées. Ceci a particulièrement été le cas lorsque l'on considère les interactions entre l'âge des femmes évaluées, et le genre et l'origine des évaluateurs, de façon indépendante ou liée, avec le Δ âge. CONCLUSION: Aux travers des différentes analyses, nos résultats suggèrent que l'exactitude avec laquelle l'âge des femmes est évalué sur images numériques de leur visage, dépend de l'âge réel et de l'origine de ces femmes photographiées, ainsi que de l'origine est du genre de l'évaluateur. Nous discutons ces résultats en regard des variations de pigmentation cutanée et de signes visibles de l'âge entre les différentes populations et commentons les implications possibles pour les sciences cosmétiques.

Cross-cultural perception of female facial appearance: A multi-ethnic and multi-centre study.

Humans extract and use information from the face in assessments of physical appearance. Previous research indicates high agreement about facial attractiveness within and between cultures. However, the use of a narrow age range for facial stimuli, limitations due to unidirectional cross-cultural comparisons, and technical challenges have prevented definitive conclusions about the universality of face perception. In the present study, we imaged the faces of women aged 20 to 69 years in five locations (China, France, India, Japan, and South Africa) and secured age, attractiveness, and health assessments on continuous scales (0-100) from female and male raters (20-66 years) within and across ethnicity. In total, 180 images (36 of each ethnicity) were assessed by 600 raters (120 of each ethnicity), recruited in study centres in the five locations. Linear mixed model analysis revealed main and interaction effects of assessor ethnicity, assessor gender, and photographed participant ("face") ethnicity on age, attractiveness, and health assessments. Thus, differences in judgments of female facial appearance depend on the ethnicity of the photographed person, the ethnicity of the assessor, and whether the assessor is female or male. Facial age assessments correlated negatively with attractiveness and health assessments. Collectively, these findings provide evidence of cross-cultural variation in assessments of age, and even more of attractiveness, and health, indicating plasticity in perception of female facial appearance across cultures, although the decline in attractiveness and health assessments with age is universally found.

A series of in vitro and human studies of a novel lip cream formulation for protecting against environmental triggers of recurrent herpes labialis.

PURPOSE: These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers. SUBJECTS AND METHODS: In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial that assessed the lip cream in healthy subjects with dry lips were conducted. In the clinical trial, subjects applied the lip cream or were untreated and evaluated using transepidermal water loss (TEWL), corneometry, visual assessments of lip dryness, expert photographic evaluations, and subject-rated outcomes. RESULTS: The lip cream's in vitro water vapor transmission rate (84.1 g/(m2 h)) indicated moderate occlusivity. The lip cream, but not placebo or control (water), reduced ultraviolet A (UVA)- and UVB-induced DNA damage, and tumor necrosis factor-α (EpiDermFT) and pros-taglandin E2 release (EpiDermFT and EpiGingival™). The lip cream's in vivo sun protection factor (SPF) was 12.2 (lower confidence limit, 11.3) and SPF/UVA protection factor ratio was 0.9. The characterization of dry vs normal lips identified differences in moisturization. In the clinical trial, the lip cream significantly decreased TEWL (difference: -7.19 [95% CI: -11.41, -2.98]; P<0.01), increased corneometry (difference: 4.62 [95% CI: 1.05, 8.19]; P<0.05), and reduced visual dryness (difference: -1.48 [95% CI: 2.24, -0.71]; P<0.001) compared to untreated subjects. Significant benefits were also observed on expert photographic assessments of scaling (difference: -0.89 [95% CI: -1.75, -0.03]; P< 0.05), cupping (difference: -1.50 [95% CI: -2.30, -0.70]; P<0.001), and healthy appearance (difference: -1.44 [95% CI: -2.29, -0.58]; P<0.01); differences in overall healthy appearance were not significant (P=0.51). Subject-rated assessments indicated improvements in cracking, dryness, and flaking in the lip cream group but worsening in untreated subjects. CONCLUSION: These studies indicate that this novel, daily-use lip cream protects against UV radiation, drying, and chapping, which are established environmental RHL triggers.

Appearance of aging signs in differently pigmented facial skin by a novel imaging system.

BACKGROUND: Facial wrinkles, pores, and uneven skin tone are major beauty concerns. There is differential manifestation of aging signs in different ethnic groups. In this regard, studies on Black Africans from the African continent are scarce. OBJECTIVE: To investigate facial wrinkles, pores, and skin tone in Black African women from Mauritius Island and elucidate the differences to Caucasian women from France. METHODS: Facial images were taken using the imaging system ColorFace® . Wrinkles and pores were measured by their length, depth, surface, volume, and number; for skin tone, we measured L*a*b* and calculated ITA, IWANewtone , and color homogeneity. RESULTS: We found good correlations of wrinkle and pore scores with expert ranking done on ColorFace® images for Caucasians (Spearman's rho = 0.78 and 0.72) and Black Africans (Spearman's rho = 0.86 and 0.65). Caucasians showed more advanced facial signs of aging than Black Africans. Exceptions were vertical lines on upper lip and the depth of pores which were greatest for the Black African subjects. Black Africans had higher heterogeneity scores indicative for uneven skin tone. Luminance (L*) was significantly higher in Caucasians but a* and b* values were significantly higher in the Black African subjects. ITA and IWANewtone were significantly higher for Caucasians. CONCLUSIONS: The high correlation between expert ranking and wrinkle and pore measurements prove ColorFace® a valid imaging system to study skin aging. Our results show that Africans from the African continent show delayed signs of aging compared to Caucasians. Some exceptions suggest that ethnic differences in facial aging are a complex phenomenon.

Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology.

BACKGROUND: The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography. OBJECTIVE: To explore this phenomenon in allergic contact dermatitis. METHODS: Patch testing was performed on patients with previously positive patch test reactions to potassium dichromate (Cr), nickel sulfate (Ni), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), or p-phenylenediamine. Moreover, a control (pet.) patch and an irritant (SLS) patch were applied. After 3 days, the stratum corneum from tested sites was collected, and NMF levels and corneocyte morphology, expressed as the amount of circular nanosize objects, quantified according to the Dermal Texture Index (DTI), were determined. RESULTS: Among allergens, only MCI/MI reduced NMF levels significantly, as did SLS. Furthermore, only MCI/MI caused remarkable changes at the microscopic level; the corneocytes were hexagonal-shaped with pronounced cell borders and a smoother surface. The DTI was increased after SLS exposure but not after allergen exposure. CONCLUSIONS: MCI/MI significantly decreased NMF levels, similarly to SLS. The altered corneocyte morphology suggests that skin barrier damage plays a role in the pathogenesis of MCI/MI contact allergy. The DTI seems to differentiate reactions to SLS from those to the allergens tested, as SLS was the only agent that caused a DTI increase.

Topical ceramides neither enhance UVB-induced apoptosis in normal human keratinocytes nor affect viability in UVB-irradiated reconstructed human epidermis.

Ceramides are the major lipid of lamellar sheets present in intercellular spaces of the stratum corneum contributing to epidermal barrier properties. Therefore, ceramides and their analogues have been studied for barrier enhancing and water-holding properties for decades. In vitro studies have indicated cytotoxic potential for cell-permeable ceramides thereby raising the question whether topical ceramide application might contribute to UVB-induced apoptosis. Phytosphingosine, N-hexanoyl-phytosphingosine and N-stearoylphytosphingosine (ceramide III) in concentrations ≤5 µm have been used for co-stimulation with low (160 J/m(2) ) or high (600 J/m(2) ) UVB doses in subconfluent basal and confluent differentiating keratinocytes. Significantly, increased caspase-3 activity was observed in basal keratinocytes irradiated with 600 J/m(2) UVB and in differentiating keratinocytes with both UVB doses. Co-stimulation with the named ceramides did not further increase (i) caspase-3 activity and (ii) nucleosomal fragmentation in differentiating keratinocytes. Moreover, co-stimulation with 1-mm ceramides did not further affect viability/lactate dehydrogenase release in UVB-irradiated reconstructed human epidermis corroborating the safety of these ceramides.

The effect of a vitamin A palmitate and antioxidant-containing oil-based moisturizer on photodamaged skin of several body sites.

BACKGROUND: Cumulative lifetime sun exposure is accepted as having a very important role to play in the expression of the signs of photoaging, which is then superimposed on the intrinsic processes involved in the chronological aging of skin. Many groups have evaluated the effects of emulsion-based products, mostly although not exclusively, on the face using a variety of actives including retinoids and antioxidants. Nevertheless, the effect of a topical anhydrous product on photodamaged skin has not been reported in the literature. AIMS: The objective of this study was to clinically evaluate the effect of a vitamin A palmitate and antioxidant-containing oil-based moisturizer on facial, neck, decolletage, arms, and lower leg body sites. METHODS: In a randomized, controlled and efficacy grader-blinded clinical study conducted over 12 weeks, while at the same time recording the changes in skin condition for a no-treatment group over the same time period, live clinical expert grading of all body sites and also grading of photographs for the face and neck assessed changes in the signs of photodamage was performed for the treatment and no-treatment groups. RESULTS: Compared to the no-treatment group, and to baseline, the oil improved fine lines, coarse wrinkles, mottled pigmentation, uneven skin tone, roughness, firmness, and clarity of the skin on the face and neck and was also shown to improve crepey skin texture, dryness, scaling and roughness on the decolletage, arms and lower legs at the primary end point at 12 weeks (P < 0.001). Moreover, improvements in a variety of parameters were observed as quickly as 2 weeks. In general, the degree of improvement was greatest in the order legs > arms > decolletage > face > neck. CONCLUSIONS: Collectively, these results show the cumulative improvements in the signs of photoaging compared to a no-treatment control group for the oil-based antiaging moisturizer for the first time. The differences in the efficacy of the vitamin A palmiate and antioxidant oil-based moisturizer on different body sites probably reflect the differences in likely photodamage.

Stratum corneum proteases and dry skin conditions.

This paper reviews the role of stratum corneum (SC) proteases and their inhibitors in normal and xerotic skin conditions. The importance of the corneodesmosome for SC integrity is also discussed, and the effect of proteases on its disassembly. The relevance of each enzyme class is outlined, as well as their potential inhibitors. It is becoming much clearer, however, that the LEKTI family of inhibitors are critical for SC enzyme control. Delayed desquamation is the accumulation of corneocytes on the surface of the SC that leads ultimately to the cosmetic condition commonly termed as "dry skin". The reductions of serine protease activity are a consistent theme in dry skin, and non-eczematous atopic dermatitis otherwise known as atopic xerosis leading to retention hyperkeratosis. Flaky skin is normally seen on the body whereas a rough skin is observed on the face. Increased protease activity occurs in most, if not all, inflammatory dermatoses, ranging from the genetic disorders, psoriasis and eczematous atopic dermatitis to sub-clinical barrier abnormalities induced by surfactants or by environmental influences as a result of premature desquamation. In some of these conditions a thinner SC is apparent, e.g., eczematous atopic skin or on photodamaged facial skin. A better understanding of the proteolytic events and of the regulatory mechanisms involved in desquamation should enable the design of new treatments for skin disorders associated with faulty desquamation. This new knowledge will be an important basis for new developments in 'corneotherapy' and 'corneocare'.

Effect of cosmetic ingredients as anticellulite agents: synergistic action of actives with in vitro and in vivo efficacy.

BACKGROUND: The pathophysiology of cellulite involves changes in the subcutaneous adipose layer and the extracellular matrix (ECM) that supports it together with overlying dermal layer. Cellular mechanisms governing cellulite are not fully understood. However, it is accepted that changes include enhanced lipogenesis, decreased lipolysis, and increased lipid storage within the adipocytes as well as changes in the dermal architecture. AIM: In our studies the ability of cosmetic agents Furcellaria lumbricalis, Fucus vesiculosus, retinoid, conjugated linoleic acid (CLA), and a glaucine mixture to stimulate in vitro 1) lipolysis in human adipocytes and 2) production of pro-collagen I by fibroblasts was investigated in vitro. The ability of these ingredients to improve cellulite condition in vivo was also determined. PATIENTS/METHODS: Mature adipocytes and 'aged' fibroblasts were used for in vitro studies. The assessment of cellulite in vivo was performed by dermatological grading and ultrasound measurements. RESULTS: Mature adipocytes treated with combined actives resulted in a significant synergistic increase in free glycerol release. On "aged" fibroblasts, combined treatment of F. vesiculosus and F. lumbricalis stimulated pro-collagen I production. CLA increased pro-collagen I production, but the glaucine mixture had no effect. The clinical study demonstrated a significant improvement in cellulite grading by a dermatologist after 8 and 12 weeks vs. vehicle, and ultrasound imaging showed a significant decrease in fat thickness compared with placebo after 12 weeks. CONCLUSIONS: Our studies revealed a potent cocktail of ingredients that when combined together can act in vitro to markedly improve lipolysis mechanisms and by way of stimulating pro-collagen I can also have an effect on the surrounding extracellular matrix. The in vitro actions of the ingredients were translated in vivo, where a clinical improvement of cellulite condition was observed.

Facial skin-lightening benefits of the tetrapeptide Pro-Lys-Glu-Lys on subjects with skin types V-VI living in South Africa.

BACKGROUND: Irregular skin pigmentation may be a substantial contributor to the signs of aging and to a person's lack of psychological well-being. Although a large number of skin-lightening agents are available, the opportunity exists to identify more efficacious agents, agents that target alternative biological mechanisms. AIMS: To provide clinical evidence of the skin-lightening effect of the tetrapeptide, Pro-Lys-Glu-Lys (PKEK), on subjects with skin types V-VI living in South Africa. METHODS: Pro-Lys-Glu-Lys was evaluated in a double-blind and vehicle-controlled clinical study using expert grading of digital images by comparing its effects in subjects with skin types V-VI suffering from facial melasma and postinflammatory hyperpigmentation. RESULTS: This study demonstrated the efficacy of PKEK on subjects with skin types V-VI. On comparing the two treatments, the skin-lightening peptide-containing formulation was significantly superior to the vehicle at 12 weeks on overall appearance (P < 0.05) and evenness of skin tone (P < 0.01). CONCLUSIONS: The tetrapeptide, PKEK, has proven skin-lightening benefits on skin discoloration from melasma and postinflammatory hyperpigmentation. These studies have been conducted on subjects with skin types V-VI living in South Africa, but we believe this technology to be suitable for all racial groups.

Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin.

BACKGROUND: Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin. AIMS: To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits. METHODS: The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study. RESULTS: In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo. CONCLUSION: Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.