Atopic dermatitis (AD) is the most common skin inflammatory disease, affecting up to 3% of adults and 20% of children. Skin barrier impairment is thought to be the primary factor in this disease. Currently, there is no method proposed to monitor non-invasively the different molecular disorders involved in the upper layer of AD skin. Raman microspectroscopy has proved to be a powerful tool to characterize some AD molecular descriptors such as lipid content, global hydration level, filaggrin and its derivatives. Our investigations aimed to extend the use of in vivo Raman microspectroscopy as a rapid and non-invasive diagnostic technique for lipid conformation and organization, protein secondary structure and bound water content analysis in atopic skin. Our approach was based on the analysis of Raman data collected on the stratum corneum (SC) of 11 healthy and 10 mild-to-moderate atopic patients. Atopic skin revealed a modification of lipid organization and conformation in addition to the decrease of the lipid-to-protein ratio. This study also highlighted a reduction of the bound water and an increase in protein organized secondary structure in atopic skin. All these descriptors worsen the barrier function, state and appearance of the skin in AD. This precise and relevant information will allow an in vivo follow-up of the pathology and a better evaluation of the pharmacological activity of therapeutic molecules for the treatment of AD.

The inflammatory context contributes to the morphological, functional and transcriptomic changes observed in AD skin. As a result, this compromised RE model shares some characteristics with those found in AD skin and thus can be used as a relevant tool for screening formulations and drugs for the treatment of AD.

OBJECTIVE: Although xerosis is a common skin disorder among the population, there is no in vivo global study focusing on xerotic skin. Hence, the objective of this study was to characterize xerotic skin from the surface to the molecular scale with in vivo and noninvasive approaches. METHODS: For this purpose, 15 healthy volunteers with normal skin and 19 healthy volunteers with xerotic skin were selected by a dermatologist, thanks to a visual scorage. Firstly, the skin surface was characterized with biometric measurements. Then, the state of skin dryness was assessed by in vivo confocal microscopy. The molecular signature of xerotic skin was then determined by in vivo confocal Raman microspectroscopy. Finally, an identification of stratum corneum (SC) lipids was performed using Normal phase liquid chromatography (NP-LC) coupled to two detectors: Corona and High Resolution/Mass Spectroscopy (HR/MS). RESULTS: Results obtained at the skin surface displayed an increase in the transepidermal water loss (TEWL) and a decrease in the hydration rate in xerotic skin. Confocal microscopy revealed an alteration of the cell shape in xerotic skin. Moreover, confocal Raman microspectroscopy demonstrated directly in vivo and noninvasively the lack of organization and conformation of lipids in this skin. Finally, HPLC analyses revealed that the three ceramide sub-classes (NdS, NS and EOP) significantly decrease in xerosis. Altogether, these results identify parameters for the characterization of xerotic skin compared to normal. CONCLUSION: This study highlighted discriminative parameters from the surface to the molecular level in vivo and non-invasively between xerotic and normal skins. These results will be useful for the development of new cosmetic active ingredients dedicated to xerotic skin.

Objective Although the olfactory receptor OR2AT4 was described as involved in epidermal renewal, there is no data about a cosmetic active ingredient activating this receptor. The aim of this research work was thus to identify a natural molecule binding to this receptor in order to stimulate keratinocyte migration. Methods For this purpose, natural molecules were extracted from Cocos nucifera flour. Then, efficacy of this natural extract was evaluated on keratinocyte migration in vitro. Molecules of the Cocos nucifera flour extract were then identified by UPLC‐MS/MS. Molecular docking was finally conducted to investigate the potential interaction between identified molecules and the olfactory receptor OR2AT4. Results The Cocos nucifera flour extract significantly increased keratinocyte migration and results demonstrated that this effect was mediated by the olfactory receptor OR2AT4. Metabolomic analysis revealed two molecules, nonioside D and butyl 4‐O‐alpha‐D‐glucopyranosyl‐beta‐D‐glucopyranoside, as significantly present in the Cocos nucifera flour extract compared to both Cocos nucifera oil and water. Finally, molecular docking revealed that butyl 4‐O‐alpha‐D‐glucopyranosyl‐beta‐D‐glucopyranoside could interact with the extracellular domain 2 of the OR2AT4. Conclusion This study highlighted for the first time a natural molecule, extracted from Cocos nucifera flour, able to interact with the olfactory receptor OR2AT4 and promote the keratinocyte migration and thus the epithelialization.

Patients with chronic kidney disease are commonly afflicted by pruritus, a condition with no treatment approved in the USA. The etiology of this condition is likely multifactorial, including systemic inflammation and deficiency in the endogenous kappa opioid system. CR845 is a novel and full kappa opioid receptor agonist with no off-target activities, including mu-or delta-opioid receptors. In addition to its unique receptor profile, the peptidic structure of CR845 restricts its entry into the central nervous system. CR845 demonstrated a dosedependent anti-itch activity in mouse models of itch induced by 5-GNTI (a selective kappa opioid receptor antagonist), or by compound 48/80 (a mast cell secretagogue). Additionally, CR845 demonstrated anti-inflammatory properties in rodents and human macrophages. CR845 was not detectable in the central nervous system, therefore CR845 is likely to activate kappa opioid receptors expressed in peripheral neurons and on immune cells. These data are consistent with an 8-week phase II randomized, placebo-controlled study which demonstrated the effectiveness of CR845 at reducing moderate-to-severe pruritus in 174 hemodialysis (HD) patients. CR845 was administered intravenously after each dialysis and the worst itching severity was recorded every 24 h using a 0-10-point numerical rating scale (itch NRS). CR845 was well tolerated at doses ranging from 0.5 to 1.5 mcg/kg. Reduction in itch NRS scores over placebo was observed at all doses, with a change from baseline !3 NRS points by end of Week 8 for 64% of the patients treated with CR845 0.5 mcg/kg vs 29% of the placebo patients (p<0.001). These results suggest that peripheral kappa opioid receptors play an important role in the modulation of itch signals and represent a target for the development of novel antipruritic agents. The profile of CR845 makes this compound a suitable and promising candidate for the treatment of moderate-to-severe pruritus associated with chronic kidney disease.

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Acne vulgaris is a disease of pilosebaceous units associated with increased follicular stratum corneum (SC) thickness and hyperkeratinization, increased sebum secretion, inflammation and impaired skin barrier. We hypothesized that excess unsaturated free fatty acids (UFFAs) in sebum may contribute to these symptoms seen in Acne. Therefore, skin surface lipids in acne and healthy subjects were investigated. In addition, a human epidermal equivalent (HEE) model treated topically with an UFFA was developed mimicking these symptoms seen in Acne. Gene expression profiling of human skin biopsies with and without acne lesions as well as of UFFA-treated HEEs Vs. controls was also performed. Increased levels of UFFAs were observed in skin lipids of human acne subjects. Topical treatment of HEEs with an UFFA resulted in impaired barrier and increased secretion of interleukin-1a (IL-1a), associated with SC thickening and hyperkeratinization, and with increased SC lipid conformational disorder indicating a decrease in barrier integrity. Furthermore, gene expression analysis showed a similar increase in gene expression of inflammatory cytokines and epidermal differentiation both in acne lesions and UFFA-treated HEEs. These data are in agreement with the hypothesis that excess unsaturated free fatty acids (UFFAs) in sebum may contribute to the increased follicular stratum corneum (SC) thickness and hyperkeratinization, inflammation and impaired skin barrier seen in Acne. Taken together, these results suggest that UFFA-treated epidermal tissue induces a phenotypic in vitro model of acne hyperkeratinization which can be useful for the investigation of treatments that modulate acne.

Citation: IFSCC Magazine, 11 (2008) (3) [217][218][219][220][221][222][223] Epidermal differentiation is crucial to guarantee a physiological cornification process. The cornified envelope is the final skin barrier which protects against external aggressions such as UV light and reduces water loss. Skin ageing is associated with decreased functionality of this barrier and reduced epidermal differentiation. We present a new bioactive complex for the stimulation of protein synthesis associated with cornified envelope and markers of epidermal differentiation. Composed of a hydrolyzed oat protein extract and particularly rich in glutamine and glutamic acid combined with ATP and niacinamide, 1% of this complex increases significantly the synthesis of proteins such as filaggrin, late envelope protein and small proline-rich proteins, all markers of epidermal differentiation, in a reconstituted human skin model as measured by DNA array chip analysis, reverse transcription-polymerase chain reaction and immunohistochemistry. When a cream containing 3% of this bioactive complex was applied to the skin of 25 human volunteers, an increase in skin hydration of more than 60% after 14 days of application and a reduction of wrinkles and roughness by more than 50% in 4 weeks were observed compared with a placebo cream. In conclusion, the bioactive complex stimulated synthesis of proteins which are important for epidermal differentiation and skin barrier function and was helpful in fighting skin ageing. Citation: IFSCC Magazine, 11 (2008) (3) 225-229The dermis is considered a highly dynamic structure that determines the biomechanical properties of the skin. It is composed of two dermal compartments separated by a vascular plexus: the papillary dermis and the reticular dermis. In the last few years, several studies have demonstrated the role of the dermal epidermal junction in the cutaneous ageing process. Recently, teams specialized in the study of the dermal matrix have focused their studies on the superior dermis in close contact with the dermal epidermal junction: the papillary dermis. They defined the role of matrix proteins in this area. Collagens XII and XVI, non-fibrillar collagens specific to the papillary dermis, are responsible for skin deformability and extensibility. Oxytalan fibres are related to elastic properties of the skin. Ubiquitous collagens such as collagens I and VI are associated with the cohesion and the resistance of the dermis. As the papillary dermis is the primary site of intrinsic dermal ageing, we studied expression of these molecules in our own in vitro model of intrinsic ageing of the papillary dermis. The results of this innovative approach confirmed that their expression was reduced. Nevertheless, active molecules may exist in nature that are capable of restoring a normal expression profile of these markers for a cosmetic anti-ageing application.