Daily Cosmetic Research Analysis

Vitiligo is an acquired depigmenting disorder characterized by progressive melanocyte loss, yet its cellular mechanisms remain incompletely understood. Here, we identify a melanocyte dedifferentiation-like shift as a potentially reversible pathogenic mechanism. In healthy skin, melanocytes reside within a basement membrane niche defined by dystroglycan-laminin-211 adhesion. In vitiligo, extracellular matrix remodeling with reduced laminin-211 and increased laminin-332 is associated with a shift toward integrin α3β1-laminin-332 interactions. This alteration correlates with melanocyte dedifferentiation-like changes, together with Rho-F-actin remodeling, and coordinated alterations in Hippo, MAPK, and c-Jun signaling. Affected melanocytes exhibit reduced pigmentation and features of neural crest-like states, including multilineage potential. Importantly, these changes are partially reversible. Pharmacological modulation restored melanocyte differentiation and pigmentation in mouse models and ex vivo human skin, with JAK inhibition also promoting redifferentiation. These findings identify a microenvironment-driven mechanism in vitiligo and suggest potential therapeutic strategies.

The development of new approach methodologies using machine learning offers promising alternatives to animal testing for toxicity assessment. However, to be suitable for regulatory use, machine learning models must ensure transparency and interpretability. In this study, we developed the explainable machine learning model for skin sensitization risk assessment (ExSERA), a regression model designed to predict murine Local Lymph Node Assay (LLNA) EC3 values, quantitative indicators of skin sensitization potency. Using XGBoost, we trained the model on 154 substances from OECD TG 497 and externally validated it with 38 substances from the Expansion of the Cosmetics Europe Skin Sensitization Database. The model incorporated 21 variables, including results from three in vitro assays (DPRA, KeratinoSens™, and h-CLAT), molecular descriptors, and structural alerts. Within the applicability domain, 80% of internal validation and 65% of external validation predictions fell within a five-fold range of the measured LLNA EC3 values. Variable contribution analysis using Shapley Additive exPlanations showed that all three in vitro assays were the most influential contributors, with higher toxic activity correlating with stronger predicted sensitization. This interpretable model, grounded in the mechanistic understanding of skin sensitization, demonstrates potential for regulatory application as a defined approach.

INTRODUCTION: Total alar reconstruction is challenging because it requires recreating a unique, multilayered anatomy with dynamic characteristics. Conventional techniques are often multistage and require additional donor sites for internal lining and cartilage grafting, thereby increasing donor-site morbidity. Secondary thinning procedures are often required, and long-term alar stability outcomes remain variable. We present the Integrated Lining Nasolabial Flap, a single-stage technique in which the internal lining is derived from dermal and epidermal layers of the flap itself, thereby eliminating additional donor-site morbidity. We report functional and aesthetic outcomes and assess postoperative alar stability, focusing on the potential role of sustained nasal dilator use as a non-cartilage-based supportive strategy. PATIENTS AND METHODS: Twenty patients who underwent single-stage total alar reconstruction with the Integrated Lining Nasolabial Flap were retrospectively reviewed. Patients with at least 6 months of follow-up were included in the analysis. Early and late postoperative complications were recorded. Postoperative alar collapse was assessed and analyzed in relation to nasal dilator compliance. Cosmetic outcomes were evaluated using a visual analog scale and the FACE-Q "Satisfaction with Nostrils" module, and the association with patient age was examined. RESULTS: Twenty patients (mean age, 60.2 ± 7.9 years) underwent single-stage reconstruction with this technique and were included in the analysis, with a median follow-up of 12.5 months (range, 6-32 months). Early complications occurred in 2 patients (10%) and were limited to superficial wound dehiscence, which was managed conservatively. No flap loss, vascular compromise, or internal lining necrosis was observed. Late complications were observed in 8 patients (40%), including alar retraction in 2 (10%), isolated alar collapse in 1 (5%), combined alar collapse with retraction in 2 (10%), and alar asymmetry in 3 (15%). No patient required a secondary thinning procedure. Alar collapse (isolated or combined) occurred in three patients (15%), all of whom were noncompliant with nasal dilator use; no collapse was observed among compliant patients (P = 0.004). The median cosmetic VAS score was 60 (range, 50-90), and the median FACE-Q "Satisfaction with Nostrils" score was 72 (range, 44-91). No significant correlation was found between age and aesthetic outcomes. CONCLUSION: The Integrated Lining Nasolabial Flap allows single-stage total alar reconstruction by creating the internal lining from the flap itself, avoiding additional donor sites and secondary thinning procedures. In this Level IV study, sustained postoperative nasal dilator use was significantly associated with improved alar stability. CLINICAL RELEVANCE STATEMENT: This technique offers a single-stage solution for total alar reconstruction by integrating the internal lining into the nasolabial flap design, potentially reducing surgical complexity and donor-site morbidity. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .