Background: Cutaneous melanoma (CM) of the skin stands as the leading cause of mortality among skin cancer-related deaths. Despite the successes achieved with novel therapies such as immunotherapy and targeted therapy, their efficacy remains limited, necessitating further exploration of new treatment modalities. The gut microbiota and CM may be linked, as indicated by a growing body of preclinical and observational research. Nevertheless, the exact correlation between the intestinal microbiota and CM remains to be determined. Therefore, this study aims to assess the potential causal relationship between the gut microbiota and CM.Methods: The study utilized exposure data obtained from the MiBioGen consortium’s microbiome GWAS, which included a total of 18,340 samples gathered from 24 population-based cohorts. Data at the summary level for CM were acquired from the UK Biobank investigation. The main analytical strategy utilized in this research was the inverse variance weighted (IVW) technique, supported by quality assurance measures like the weighted median model, MR-Egger, simple model, and weighted model approaches. The Cochran’s Q test was used to evaluate heterogeneity. To ascertain potential pleiotropy, we employed both the MR-Egger regression and the MR-PRESSO test. Sensitivity analysis was conducted using the leave-one-out method.Results: The study found that the class Bacteroidia (OR = 0.997, 95% CI: 0.995–0.999, p = 0.027), genus Parabacteroides (OR = 0.997, 95% CI: 0.994–0.999, p = 0.037), order Bacteroidales (OR = 0.997, 95% CI: 0.995–0.999, p = 0.027), and genus Veillonella (OR = 0.998, 95% CI: 0.996–0.999, p = 0.046) have protective effects on CM. On the order hand, the genus Blautia (OR = 1.003, 95% CI: 1–1.006, p = 0.001) and phylum Cyanobacteria (OR = 1.002, 95% CI: 1–1.004, p = 0.04) are identified as risk factors for CM.Conclusion: We comprehensively assessed the potential causal relationship between the gut microbiota and CM and identified associations between six gut microbiota and CM. Among these, four gut microbiota were identified as protective factors for CM, while two gut microbiota were identified as risk factors for CM. This study effectively established a causal relationship between the gut microbiota and CM, thereby providing valuable insights into the mechanistic pathways through which the microbiota impacts the progression of CM.

Background: Keloid is a common fibroproliferative disorder, often manifesting symptoms such as itching and pain. Given the unique characteristics of keloids, their occurrence is primarily limited to humans, posing difficulties for spontaneous keloid development in animals. Consequently, the creation of animal models has somewhat impeded the comprehensive investigation of keloids.Aims: The aim is to develop a keloid mouse model that mimics the formation process of human keloids, enabling researchers to gain a deeper understanding of their pathophysiological mechanisms and to explore effective therapeutic approaches.Methods: Human keloid fibroblasts were isolated, cultured, and subcutaneously injected with Matrigel into nude mice at four concentrations (1 × 10⁶, 3 × 10⁶, 5 × 10⁶, and 7 × 10⁶ cells). Subcutaneous nodules were transplanted into additional mice to validate stability. Histological and immunohistochemical analyses were performed to assess morphological and molecular features.Results: Keloid‐like nodules formed in a cell density‐dependent manner, with the highest concentration group (7 × 10⁶ cells) achieving nodule formation in 39.6 ± 3.2 days, significantly faster than lower concentrations (p < 0.001). The transplantation success rate reached 80%, with nodules exhibiting dense collagen deposition (72.7% ± 3.8%), CD34‐positive microvessels (23.1 ± 2.2 vessels/field), and α‐SMA expression (11.29% ± 3.7%), closely mirroring human keloid histopathology.Conclusion: The combination of human keloid fibroblasts and Matrigel provides a simple and rational approach for constructing a nude mouse model, offering a reliable animal model for experimental and clinical research on the pathogenesis and treatment strategies of keloids.

Keloids are fibroproliferative lesions resulting from abnormal wound healing, characterized by the excessive growth and metabolic reprogramming of keloid fibroblasts (KFs). The underlying mechanisms responsible for these metabolic abnormalities remain under debate. This research employed comprehensive bioinformatics techniques to pinpoint ACSS3 (Acetyl-CoA Synthetase Short-Chain Family Member 3) and the Wnt/β-Catenin pathway as pivotal contributors to keloid pathogenesis. ACSS3, a mitochondrial protein involved in metabolic regulation, is downregulated in keloid. Lentiviral transfection-induced overexpression of ACSS3 suppressed KFs activity, normalized glycolytic flux, and reduced the levels of critical glycolytic enzymes. Conversely, ACSS3 knockdown elicited opposite effects, which were reversed by ICG-001. Single-cell analysis demonstrates that fibroblasts are the primary cell type involved in the fibrotic process. An ACSS3 regulatory network was developed. Additionally, Molecular docking and dynamics simulations were conducted to identify potential drugs targeting ACSS3. In summary, this study demonstrates that ACSS3 modulates aerobic glycolysis and the activity of KFs via the Wnt/β-Catenin pathway, positioning ACSS3 as a promising therapeutic target for keloid treatment.