Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study.

Background: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression. Material and methods: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Results: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation. Conclusion: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

CLC-3 regulates TGF-ß/smad signaling pathway to inhibit the process of fibrosis in hypertrophic scar.

Objective: To study the role and mechanism of chloride channel-3 (ClC-3) in the formation of hypertrophic scar by constructing ClC-3 interference vectors and examining their effects on human hypertrophic scar fibroblasts (HSFB). Methods: Human HSFB and human normal skin fibroblasts (NSFB) were used in this study, and ClC-3 interference vectors were constructed to transfect cells. ClC-3 inhibitors NPPB and Tamoxifen were used to treat cells. Cell migration and the expression of TGF-ß/Smad, CollagenⅠ,CollagenⅢ were examined to explore the role of ClC-3 in the formation of hypertrophic scar. Results: Compared with the normal skin tissue, the positive expression of ClC-3 and TGF-ß in the scar tissue was significantly increased. The relative expression of ClC-3 and TGF-ß1 in HSFB cells was higher than that in NSFB cells. Interfering with the expression of CLC-3 can inhibit the migration of HSFB cells and the expression of TGF- ß/Smad, CollagenⅠ/Ⅲ. The experiment of HSFB cells treated by CLC-3 inhibitors can also obtain similar results. Conclusion: Inhibiting CLC-3 can reduce the formation of hypertrophic scars.