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Introduction: Xerosis cutis is characterized by a decreased stratum corneum (SC) hydration and an impaired skin barrier function. Urea, the most prevalent natural moisturizing factor (NMF), is currently considered the gold standard. Its efficacy can further be increased by combining urea with other NMF and skin barrier lipids (SBLs). Objective: We set out to evaluate physiological effects of a novel functional moisturizer containing 10% urea, additional NMF components, and a combination of SBLs on skin hydration and skin barrier integrity on a cellular and phenotypic level in female volunteers suffering from xerosis. Methods: Two double-blind, vehicle-controlled clinical studies were conducted. In the first study, 44 female subjects having very dry body skin applied the moisturizer or its vehicle twice daily to their volar forearms. Twenty-four hours after a single product application as well as 24 h after 2 weeks of treatment, SC hydration was measured by corneometry. Skin barrier function was assessed by transepidermal water loss 24 h and 48 h after 2 weeks of regular use. Twenty-four hours after 2 weeks of application, skin tape stripping was performed, and urea content was determined in the 3rd strip by means of high-performance liquid chromatography/tandem mass spectrometry. In the second study, 22 women with self-reported very dry skin applied the moisturizer or vehicle twice daily to their volar forearms for 2 weeks. Then, suction blister samples were obtained for gene expression analysis using RT-PCR. Results: Application of the actives led to significantly improved skin hydration and barrier function at all points in time. Compared to the vehicle, application of the moisturizer for 2 weeks resulted in a significant increase in SC urea content. Relative gene expression data revealed significant upregulation of genes associated with skin barrier function, hydration, differentiation, and lipid metabolism compared to the vehicle-treated area. Conclusions: Overall, our data demonstrate that the functional moisturizer provides an adequate bioavailability of urea and a beneficial biophysical impact on xerotic skin. Topical treatment with a combination of urea and additional NMF as well as SBL can modify mRNA expression of important epidermal genes stimulating cellular processes and functions. The well-tolerated novel functional moisturizer stimulates molecular mechanisms involved in skin hydration and barrier function and is a profoundly effective treatment option for xerosis cutis.

Background Perioral dermatitis is a clinically distinctive reaction pattern of facial dermatitis, including redness, dryness, burning, pruritus and skin tightness. A gold standard treatment remains unclear. Objectives Our study evaluates the clinical value of a skin care cream with the transient receptor potential vanilloid type 1 inhibitor 4‐t‐butylcyclohexanol in POD patients over 8 weeks. Methods This open, unblinded 8‐week clinical trial included 48 patients. A skin care cream containing 4‐t‐butylcyclohexanol was applied over a period of 8 weeks. Standardized questionnaires were used at baseline, 4 and 8 weeks, for history documentation, objective and subjective severity scores, and quality of life assessments. Six different skin physiology parameters were assessed at all timepoints. Results The perioral dermatitis severity score decreased significantly during the treatment period. This was mirrored by significantly lower patients’ subjective numerical rating score and an improved quality of life score. Transepidermal water loss, stratum corneum hydration and skin erythema improved significantly during the treatment period. Conclusion This transient receptor potential vanilloid type 1 inhibitor‐based skin care cream improved subjective and objective parameters of perioral dermatitis. Decreased transepidermal water loss values and increased stratum corneum hydration demonstrate a restored skin barrier function. Consequently, the topical inhibition of these receptors is a promising management option for POD.

Post-inflammatory hyperpigmentation (PIH) is a major cosmetic concern especially in individuals with darker skin complexion. Unfortunately, treatment with anti-inflammatory ingredients alone does not prevent the development of hyperpigmented spots. Recently, isobutylamido-thiazolyl-resorcinol (Thiamidol) was described as a very potent inhibitor of human tyrosinase. The objective of this research was to investigate the potential of this compound to prevent PIH induced by epidermal wounding (suction blister) and related to acne.Suction blister-induced PIH was treated with a formulation containing Thiamidol or a vehicle for 3 months, and the changes in hyperpigmentation were monitored by spectroscopic measurements. The effect of skin care formulations containing Thiamidol on acne-related PIH was investigated in two studies, a vehicle-controlled, double-blinded, randomized clinical study and a clinical observational study. Both studies had a duration of 3 months and included assessments such as clinical photography, clinical grading and melanin index measurements.Already after 2 weeks of treatment, suction blister sites treated with Thiamidol were significantly lighter than control sites and improved throughout the treatment period. Subjects´ self-grading demonstrated that Thiamidol significantly improved the visibility of acne-induced hyperpigmentation compared to the vehicle treatment. A skin care regimen with Thiamidol significantly improved acne-related PIH over 12 weeks shown by Mexameter measurements, expert grading, self-grading and clinical photography.Thiamidol represents a safe and effective ingredient for cosmetic products against post-inflammatory hyperpigmentation.L’hyperpigmentation post-inflammatoire (Post-Inflammatory Hyperpigmentation, PIH) est une préoccupation d’ordre esthétique majeure, en particulier chez les personnes dont le teint est plus foncé. Malheureusement, un traitement par des ingrédients anti-inflammatoires seuls n’empêche pas le développement de taches hyperpigmentées. Récemment, l’isobutylamido-thiazolyl-résorcinol (Thiamidol) a été décrit comme un inhibiteur très puissant de la tyrosinase humaine. L’objectif de cette investigation était d’étudier le potentiel de ce composé pour prévenir la PIH induite par une plaie épidermique (bulle de succion) et liée à l’acné. MÉTHODES: La PIH induite par la bulle de succion a été traitée avec une formulation contenant du Thiamidol ou un véhicule pendant 3 mois et les changements dans l’hyperpigmentation ont été surveillés par le biais de mesures spectroscopiques. L’effet des formulations pour soins de la peau contenant du Thiamidol visant à traiter la PIH liée à l’acné a été étudié au cours de deux études : une étude clinique randomisée, en double aveugle, contrôlée par véhicule et une étude clinique observationnelle. Les deux études avaient une durée de 3 mois et comportaient des évaluations telles que la photographie médicale, l’évaluation par les médecins et les mesures de l’indice de mélanine. RÉSULTATS: Après 2 semaines de traitement seulement, les sites de bulles de succion traités par du Thiamidol étaient significativement plus clairs que les sites-témoins et avaient montré une amélioration tout au long de la période de traitement. L’auto-évaluation des sujets a démontré que le Thiamidol améliorait significativement la visibilité de l’hyperpigmentation induite par l’acné par rapport au traitement par véhicule. Un programme de soins de la peau contenant du Thiamidol a significativement amélioré la PIH liée à l’acné sur 12 semaines, comme l’ont démontré les mesures de Mexameter, l’évaluation par des experts, l’auto-évaluation des sujets et la photographie médicale.Le Thiamidol représente un ingrédient sûr et efficace pour les produits cosmétiques contre l’hyperpigmentation post-inflammatoire.

CXCL5 has recently been identified as a mediator of UVB-induced pain in rodents. To compare and to extend previous knowledge of cutaneous CXCL5 regulation, we performed a comprehensive study on the effects of UV radiation on CXCL5 regulation in human skin. Our results show a dose-dependent increase in CXCL5 protein in human skin after UV radiation. CXCL5 can be released by different cell types in the skin. We presumed that, in addition to immune cells, non-immune skin cells also contribute to UV-induced increase in CXCL5 protein. Analysis of monocultured dermal fibroblasts and keratinocytes revealed that only fibroblasts but not keratinocytes displayed up regulated CXCL5 levels after UV stimulation. Whereas UV treatment of human skin equivalents, induced epidermal CXCL5 mRNA and protein expression. Up regulation of epidermal CXCL5 was independent of keratinocyte differentiation and keratinocyte-keratinocyte interactions in epidermal layers. Our findings provide first evidence on the release of CXCL5 in UV-radiated human skin and the essential role of fibroblast-keratinocyte interaction in the regulation of epidermal CXCL5.

The retrochalcone licochalcone A (LicA) has previously been shown to possess antimicrobial and anti-inflammatory properties. In this study, we focused on pathways responsible for the antioxidative properties of LicA. In vitro, LicA protected from oxidative stress mediated by reactive oxygen species (ROS) by activating the expression of cytoprotective phase II enzymes. LicA induced nuclear translocation of NF-E2-related factor 2 (Nrf2) in primary human fibroblasts and elevated the expression of the cytoprotective and anti-inflammatory enzymes heme oxygenase 1 and glutamate-cysteine ligase modifier subunit. LicA-treated cells displayed a higher ratio of reduced to oxidized glutathione and decreased concentrations of ROS in UVA-irradiated human dermal fibroblasts, as well as in activated neutrophils. In vivo, ultraweak photon emission analysis of skin treated with LicA-rich licorice extract revealed a significantly lowered UVA-induced luminescence, indicative for a decrease in oxidative processes. We conclude from these data that topical application of licorice extract is a promising approach to induce Nrf2-dependent cytoprotection in human skin.

The neuropeptide hormone oxytocin (OXT) mediates a wide spectrum of tissue-specific actions, ranging from cell growth, cell differentiation, sodium excretion to stress responses, reproduction and complex social behaviour. Recently, OXT expression was detected in keratinocytes, but expression of its receptor and function are still unexplored in human skin. Here, we showed that both OXT and its receptor are expressed in primary human dermal fibroblasts and keratinocytes. OXT-induced dose-dependent calcium fluxes in both cell types demonstrating that the OXT receptor (OXTR) is functionally expressed. We also showed that OXT decreases proliferation of dermal fibroblasts and keratinocytes in a dose-dependent manner. In order to further investigate OXT-mediated functions in skin cells, we performed OXTR knockdown experiments. OXTR knockdown in dermal fibroblasts and keratinocytes led to elevated levels of reactive oxygen species and reduced levels of glutathione (GSH). Moreover, OXTR-depleted keratinocytes exhibited an increased release of the pro-inflammatory cytokines IL6, CCL5 and CXCL10. Our data indicate that the OXT system modulates key processes which are dysregulated in atopic dermatitis (AD) such as proliferation, inflammation and oxidative stress responses. Furthermore, we detected a downregulation of the OXT system in peri-lesional and lesional atopic skin. Taken together, these data suggest that the OXT system is a novel neuroendocrine mediator in human skin homoeostasis and clinically relevant to stressed skin conditions like AD.

Skin of patients suffering from atopic eczema displays a higher epidermal nerve fiber density, associated with neurogenic inflammation and pruritus. Using an in vitro coculture system, allowing a spatially compartmented culture of somata from porcine dorsal root ganglion neurons and human primary skin cells, we investigated the influence of dermal fibroblasts and keratinocytes on neurite outgrowth. In comparison with dermal fibroblasts, keratinocytes induced more branched and less calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers. By adding neutralizing antibodies, we showed that nerve growth factor (NGF) and glial cell-line-derived neurotrophic factor (GDNF) are pivotal neurotrophic factors of skin cell–induced neurite outgrowth. Keratinocytes and dermal fibroblasts secreted different ratios of neurotrophic factors, influencing morphology and CGRP immunoreactivity of neurites. To investigate changes of the peripheral nervous system in the pathogenesis of atopic eczema in vitro, we analyzed neurite outgrowth mediated by atopic skin cells. Atopic keratinocytes produced elevated levels of NGF and mediated an increased outgrowth of CGRP-positive sensory fibers. Our results demonstrate the impact of dermal fibroblasts and keratinocytes on skin innervation and emphasize the role of keratinocytes as key players of hyperinnervation in atopic eczema.

SummarySensitization of the capsaicin receptor TRPV1 is central to the initiation of pathological forms of pain, and multiple signaling cascades are known to enhance TRPV1 activity under inflammatory conditions. How might detrimental escalation of TRPV1 activity be counteracted? Using a genetic-proteomic approach, we identify the GABAB1 receptor subunit as bona fide inhibitor of TRPV1 sensitization in the context of diverse inflammatory settings. We find that the endogenous GABAB agonist, GABA, is released from nociceptive nerve terminals, suggesting an autocrine feedback mechanism limiting TRPV1 sensitization. The effect of GABAB on TRPV1 is independent of canonical G protein signaling and rather relies on close juxtaposition of the GABAB1 receptor subunit and TRPV1. Activating the GABAB1 receptor subunit does not attenuate normal functioning of the capsaicin receptor but exclusively reverts its sensitized state. Thus, harnessing this mechanism for anti-pain therapy may prevent adverse effects associated with currently available TRPV1 blockers.