Sunscreens can preserve human skin microbiome upon erythemal UV exposure.

OBJECTIVE: Ultraviolet radiation (UVR) is a known environmental key factor for premature skin ageing. Only few scientific evidence is available to support the effects of UVR on the skin microbiome. This in vivo pilot study aimed to evaluate the impact on the skin microbiome upon erythemal UV exposure and the protection of UV-exposed skin microbiome by UV filters. METHODS: Ten female volunteers were treated with an sun protection factor (SPF) 20 sunscreen and placebo formulation (without UV filters) on their upper middle backs and irradiated with an erythemal dose (2 MED) by a solar simulator. Skin swabbing samples from four zones (i.e., unexposed, exposed, sunscreen- and placebo-treated on exposed skin) were collected for the microbiome analysis before and 2 h after UV exposure, respectively, and processed via shallow 16S rRNA Amplicon and Shotgun metagenomic sequencing. An in vitro UV method was developed to confirm the protection of isolated bacterial strains by single UV filters and combinations. RESULTS: Alpha diversity was impacted by significant inter-individual differences and by treatment rather than by irradiation. Cutibacterium acnes was found to be the most abundant and a confounding factor for diversity. On a species level, Lactobacillus crispatus was negatively associated with UVR and placebo treatment, whereas there was a positive association with sunscreen treatment. The sunscreen treatment also favoured an interaction network with central Micrococcus genus. The in vitro results showed that both single UV filters and combinations had specific effects on the survival rates of L. crispatus, C. acnes, and Staphylococcus epidermidis. CONCLUSION: We identified potential microorganisms and bacterial interactions that were associated with an SPF 20 sunscreen treatment. The specific protection of L. crispatus as a key player in the UV-exposed skin microbiome and reduction of C. acnes population by UV filters might lead to new cosmetic concepts for photoprotection.

OBJECTIF: Le rayonnement ultraviolet (RUV) est un facteur environnemental clé connu du vieillissement prématuré de la peau. Peu de preuves scientifiques sont disponibles pour étayer les effets des RUV sur le microbiome cutané. Cette étude pilote in vivo visait à évaluer l'impact sur le microbiome cutané d'une exposition érythèmateuse aux UV et la protection du microbiome cutané exposé aux UV par des filtres UV. MÉTHODES: Dix volontaires de sexe féminin ont été traitées avec une crème solaire SPF 20 et une formulation placebo (sans filtres UV) sur la partie supérieure du centre du dos et irradiées avec une dose érythémateuse (2 MED) par un simulateur solaire. Des échantillons de peau prélevés par écouvillonnage dans quatre zones (c.-à-d., zone non exposée, zone exposée, zone traitée avec un écran solaire et zone traitée avec un placebo sur la peau exposée) ont été prélevés pour l'analyse du microbiome avant et 2 heures après l'exposition aux UV, respectivement, et traités par séquençage superficiel d'amplicon de l'ARN 16S et métagénomique shotgun. Une méthode UV in vitro a été développée pour confirmer la protection des souches bactériennes isolées par des filtres UV individuels et des combinaisons de filtres. RÉSULTATS: La diversité alpha a été affectée par des différences interindividuelles significatives et par le traitement plutôt que par l'irradiation. Le cutibacterium acnes s'est avéré être le facteur le plus abondant et confondant pour la diversité. Au niveau de l'espèce, le Lactobacillus crispatus était négativement associé au traitement par RUV et placebo, tandis qu'on observait une association positive avec le traitement par écran solaire. Le traitement par crème solaire favorisait également un réseau d'interactions avec le genre Micrococcus central. Les résultats in vitro ont montré que les filtres UV individuels et les associations de filtres avaient des effets spécifiques sur les taux de survie de L. crispatus, C. acnes, et S. epidermidis. CONCLUSION: Nous avons identifié des micro-organismes et des interactions bactériennes potentiels qui étaient associés à un traitement par crème solaire SPF 20. La protection spécifique de L. crispatus en tant qu'acteur clé dans le microbiome cutané exposé aux UV et la réduction de la population de C. acnes par des filtres UV pourraient conduire à de nouveaux concepts cosmétiques de photoprotection.

Preliminary clinical pharmacokinetic evaluation of bemotrizinol - A new sunscreen active ingredient being considered for inclusion under FDA's over-the-counter (OTC) sunscreen monograph.

Protection against sunburn, skin damage and the carcinogenic effects of ultraviolet light are the primary health benefits associated with UV filters used in topical sunscreen drug products. Countries such as Europe have 30+ UV filters approved for sunscreen products while the US has about 10, greatly reducing the options to provide diverse, effective sun protection products. Bemotrizinol (BEMT) is the first new sunscreen active ingredient to be evaluated for inclusion in the Over-The-Counter (OTC) sunscreen monograph using FDA's new Generally Recognized as Safe and Effective (GRASE) testing guidelines. An in vitro skin permeation test (IVPT) and clinical pilot pharmacokinetic Maximum Usage Trial (MUsT) were completed to support the GRASE determination for 6% BEMT. IVPT results indicated an oil +10% ethanol as the model sunscreen intervention for the pilot MUsT. The open-label trial revealed: BEMT concentrations rarely exceeded FDA's defined threshold (0.5 ng/mL) in plasma; no evidence for BEMT accumulation or steady-state concentrations above threshold; only one moderate and few mild treatment emergent adverse events (TEAEs). Therefore, maximal topical applications of 6% BEMT in a model sunscreen formulation did not contribute to meaningful systemic exposure. These results support the safety of BEMT 6% for human sunscreen use.

Defining early recurrence in patients with resected primary colorectal carcinoma and its respective risk factors.

PURPOSE: There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors. METHODS: A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery. Patient data were retrieved from a prospectively maintained institutional database. Included patients underwent resection for primary, non-metastatic colorectal carcinomas with curative intent between 1995 and 2010. Aims of the study were (1) to define the optimal cut-off point of recurrence-free survival based on overall survival using a minimum p value approach and (2) to identify patterns of initial recurrence and putative risk factors for early recurrence using regression models. RESULTS: Recurrence was diagnosed in 412 of 1893 patients. Statistical analysis suggested that a recurrence-free survival of 16 months could be used to distinguish between early and late recurrence based on overall survival (p < 0.001). Independent risk factors for early recurrence included advanced pT categories (pT3,4/ypT3,4) and positive lymph node status (pN+/ypN+). Early recurrence was independent of site of recurrence and was associated with worse prognosis. CONCLUSIONS: Recurrence of colorectal carcinoma within 16 months after primary treatment should be labeled as "early." Tumor categories pT3,4/ypT3,4 and positive lymph node status pN+/ypN+ are predictive of early recurrence.

Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties.

One of the first lines of cutaneous defense against photoaging is a) the synthesis of melanin and b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair. Thus, making the activation of MC1R an attractive strategy for modulating skin pigmentation and oxidative stress. In this context, we designed and synthesized pentapeptides that act as MC1R agonists. These peptides bound, with high potency, to MC1R and activated cAMP synthesis in CHO cells expressing human MC1R. Using one lead pentapeptide, we could show that this activation of MC1R was specific as testing the activation of other G-protein coupled receptors, including the MC-receptor family, was negative. In vitro efficacy on mouse melanoma cells showed similar potency as for the synthetic MC1R agonist alpha-melanocyte stimulating hormone (NDP-alpha-MSH). Moreover, we could reproduce this activity in human skin tissue culture. The lead pentapeptide was able to induce ex-vivo protein expression of key melanogenesis markers melanocyte inducing transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP-1). Concerning oxidative stress response, we found that the pentapeptide enhanced the activation of Nrf2 after UVA-irradiation. Our results make this pentapeptide an ideal candidate as a skin pigmentation enhancer that mimics alpha-MSH and may also have anti-photoaging effects on the skin.