Daily Cosmetic Research Analysis

Obesity is a complex metabolic disorder characterized by excessive fat accumulation and chronic, low-grade inflammation, contributing to a range of associated diseases. Conventional treatments are often limited by poor targeting, low efficacy, and undesirable side effects. Natural compounds with anti-inflammatory and metabolic regulatory properties have attracted considerable attention due to their safety and multitarget mechanisms. Herein, we propose an effective antiobesity strategy involving the construction of a carrier-free nanodrug (CG NPs) via the self-assembly of two natural compounds, curcumin (Cur) and glycyrrhetinic acid (GA), both of which exhibit multiple antiobesity effects. To achieve efficient and targeted delivery, CG NPs are incorporated into a dissolvable microneedle coated with black phosphorus nanosheets (CG@BP/MN), forming a biocompatible transdermal platform. When combined with mild photothermal therapy, CG@BP/MN enables transdermal drug delivery to modulate subcutaneous fat, efficiently promoting white adipose tissue browning, enhancing lipolysis, and modulating macrophage polarization. Cur and GA act synergistically to regulate lipid metabolism, attenuate inflammation, and improve insulin sensitivity. In a diet-induced obesity mouse model, this therapeutic plan significantly reduces body weight, elevates energy expenditure, and prevents weight regain following treatment cessation. Overall, this therapeutic platform represents a safe, effective, and clinically promising approach to the long-term management of obesity.

The cosmetic application of arbutin (AR) has recently been challenged due to concerns regarding the skin toxicity associated with its metabolite, hydroquinone (HQ). While the derivatization of AR provides a strategy to promote stability, the multistep and complicated chemical synthesis restricts its industrial production. The present study reported a naturally derived AR derivative, 6'-O-caffeoylarbutin (CA), which is hypothesized to resist hydrolysis to HQ owing to the conjugation effect and steric hindrance, resulting in better stability. To verify this hypothesis, the degradation of CA and AR was investigated using high-performance liquid chromatography with diode-array detection. The skin-lightening substances, AR and caffeic acid, were found in the degradation products of CA under acidic conditions, which also contained lower quantities of HQ compared to that generated by AR. However, CA was not degraded under enzymatic conditions, exhibiting better stability, which might contribute to its prolonged efficacy and reduced toxicity. The long-lasting skin-lightening efficacy of CA was further verified in a zebrafish drug-withdrawal model. Notably, Mechanistic investigations revealed that CA disrupts melanosome maturation and trafficking by modulating the melanocyte-inducing transcription factor-regulated pathway, providing molecular insights into its skin-lightening efficacy.

The cellular and molecular complexity of acne pathogenesis has hindered progress toward effective targeted therapies. While keratinocytes are known to influence skin inflammation, their precise transcriptional programs and regulatory circuitry in acne remain unclear. We developed an integrative computational framework that combines single-cell RNA sequencing (scRNA-seq), gene co-expression network analysis (WGCNA), and two complementary machine learning algorithms (SVM-RFE, LASSO) to identify disease-relevant biomarkers. We mapped acne lesion cellular composition, reconstructed keratinocyte differentiation trajectories, and integrated miRNA-transcription factor-drug interaction networks to link molecular signatures to potential interventions. We uncovered marked keratinocyte heterogeneity and enriched late-stage pro-inflammatory states in acne lesions, accompanied by increased macrophage/monocyte and T cell infiltration. Six keratinocyte-associated biomarkers (PYGL, C10orf99, C12orf75, S100A2, PI3, CARD18) were identified, achieving high diagnostic accuracy (AUC > 0.85). Functional enrichment connected these genes to cytokine and chemokine signaling, while regulatory analysis revealed upstream modulators (hsa-let-7b-5p, FOXC1). Drug-gene network mapping suggested repurposing potential for cyclosporin A and valproic acid. In conclusion, our study delineates a keratinocyte-centered molecular signature that shapes acne pathogenesis and provides potential therapeutic biomarkers.