Multi-omics approach to understand the impact of sun exposure on an in vitro skin ecosystem and evaluate a new broad-spectrum sunscreen.

A reconstructed human epidermal model (RHE) colonized with human microbiota and sebum was developed to reproduce the complexity of the skin ecosystem in vitro. The RHE model was exposed to simulated solar radiation (SSR) with or without SPF50+ sunscreen (with UVB, UVA, long-UVA, and visible light protection). Structural identification of discriminant metabolites was acquired by nuclear magnetic resonance and metabolomic fingerprints were identified using reverse phase-ultra high-performance liquid chromatography-high resolution mass spectrometry, followed by pathway enrichment analysis. Over 50 metabolites were significantly altered by SSR (p < 0.05, log2 values), showing high skin oxidative stress (glutathione and purine pathways, urea cycle) and altered skin microbiota (branched-chain amino acid cycle and tryptophan pathway). 16S and internal transcribed spacer rRNA sequencing showed the relative abundance of various bacteria and fungi altered by SSR. This study identified highly accurate metabolomic fingerprints and metagenomic modifications of sun-exposed skin to help elucidate the interactions between the skin and its microbiota. Application of SPF50+ sunscreen protected the skin ecosystem model from the deleterious effects of SSR and preserved the physiological interactions within the skin ecosystem. These innovative technologies could thus be used to evaluate the effectiveness of sunscreen.

Broad-spectrum sunscreens containing the TriAsorB™ filter: In vitro photoprotection and clinical evaluation of blue light-induced skin pigmentation.

BACKGROUND: Blue light (BL), particularly high-energy visible (HEV) light (400-450 nm), can cause skin damage and pigmentation. Therefore, effective sunscreens should offer photoprotection beyond ultraviolet (UV) radiation to also prevent or limit BL-induced cutaneous effects. OBJECTIVES: To evaluate the in vitro BL photostability and photoprotection properties of nine sunscreens containing the broad-spectrum UV/BL phenylene bis-diphenyltriazine (PBDT or TriAsorB™) filter, together with three other organic UV filters, and to assess the in vivo photoprotection level provided by two of these products against BL-induced skin pigmentation. METHODS: In vitro BL photostability and photoprotection factors, comprising the percentage of BL radiation stopped by the product (%BL) and the critical wavelength extended to BL (BL-CW), were determined by spectrophotometry. The in vivo photoprotection provided by two representative sunscreens (i.e. similar formulations, one non-tinted and one tinted) was assessed in two open randomized studies (20 and 16 women, respectively) after exposure of two test areas (with and without sunscreen) on the back of each subject to a 412-nm irradiation dose at 50 J/cm2 , using instrumental and clinical measurements of skin pigmentation. The percentage sunscreen photoprotective effectiveness (%PPE) was calculated by comparing intrasubject post-exposure pigmentation changes between the with and without sunscreen test areas. RESULTS: In vitro, the nine PBDT-containing products were highly photostable and had a BL-CW ≥385 nm and a %BL ≥30% (range: 30%-50%), thus allowing effective BL photoprotection. In vivo, both representative sunscreens prevented BL-induced immediate skin pigmentation (1 and 24 h post-exposure) with %PPE values ranging from 50.7% to 75.5% for colorimetric assessments (p < 0.001) and from 31.2% to 72.7% for visual scores (p ≤ 0.001). CONCLUSIONS: All PBDT-containing sunscreens were considered effective at absorbing BL radiation in vitro. The two representative broad-spectrum sunscreens tested in subjects significantly reduced BL-induced immediate skin pigmentation following single exposure to monochromatic BL radiation.

Randomized, double-blind, placebo-controlled study of F17464, a preferential D3 antagonist, in the treatment of acute exacerbation of schizophrenia.

F17464, a highly potent preferential D3 antagonist, is a novel compound in development for schizophrenia treatment. This phase II, double-blind, randomized, placebo-controlled, parallel-group study in five European countries evaluated the efficacy and safety of F17464, 20 mg twice daily, versus placebo over 6 weeks in patients with acute exacerbation of schizophrenia. Change from baseline to Day 43 of the Positive and Negative Syndrome Scale (PANSS) total score was the primary outcome. The data from 134 randomized patients (67 per group) were analyzed (efficacy/safety). Using analysis of covariance (ANCOVA) after last observation carried forward (LOCF) imputation (primary analysis), the PANSS total score reduction was statistically significantly greater for F17464 than placebo treated subjects at endpoint (p = 0.014); using ANCOVA with Multiple Imputation (MI) method, the between-group difference was in favor of F17464 but did not reach statistical significance. Differences in PANSS positive and general psychopathology subscale score, Marder positive factor score, PANSS response, and PANSS resolution criteria were also statistically significant in favor of F17464 (p values < 0.05) using the LOCF method, with similar results as for the primary analysis using the MI method. Treatment-related adverse events (AEs) were reported in 49.3% and 46.3% of patients on F17464 and placebo, respectively. The most common AEs in F17464 group: insomnia, agitation, and increased triglycerides; worsening of schizophrenia/drug ineffective was less frequent in F17464. Interestingly, no weight gain, no extrapyramidal disorder except rare akathisia were observed under F17464. This 6-week trial demonstrated therapeutic efficacy of 40 mg/day F17464 in improving symptoms of acute exacerbation of schizophrenia with a favorable safety profile.