Cutaneous Melanoma and 486 Human Blood Metabolites: A Mendelian Randomization Study.

BACKGROUND: Cutaneous melanoma (CM) has long been recognized as a lethal form of cancer. Despite persistent research endeavors, the precise underlying pathological mechanisms remain largely unclear, and the optimal treatment for this patient population remains undetermined. OBJECTIVES: This study aims to examine the causal associations between CM and 486 metabolites. METHODS: A two-sample Mendelian randomization (MR) analysis was conducted to ascertain the causal relationship between blood metabolites and CM. The causality analysis involved the inverse variance weighted (IVW) method, followed by the MR-Egger and weighted median (WM) methods. To increase the robustness of our findings, several sensitivity analyses, including the MR-Egger intercept, Cochran's Q test, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were performed. The robustness of our results was further validated in independent outcome samples followed by a meta-analysis. Additionally, a metabolic pathway analysis was carried out. RESULTS: The two-sample MR analysis yielded a total of 27 metabolites as potential causal metabolites. After incorporating the outcomes of the sensitivity analyses, seven causal metabolites remained. Palmitoylcarnitine (OR 0.9903 95% CI 0.9848-0.9958, p = 0.0005) emerged as the sole metabolite with a significant causality after Bonferroni correction. Furthermore, the reverse MR analysis provided no evidence of reverse causality from CM to the identified metabolites. CONCLUSIONS: This study suggested a causal relationship between seven human blood metabolites and the development of CM, thereby offering novel insights into the underlying mechanisms involved. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Beverage consumption and facial skin aging: Evidence from Mendelian randomization analysis.

BACKGROUND: Observational studies have linked coffee, alcohol, tea, and sugar-sweetened beverage (SSB) consumption to facial skin aging. However, confounding factors may influence these studies. The present two-sample Mendelian randomization (MR) investigated the potential causal association between beverage consumption and facial skin aging. METHODS: The single-nucleotide polymorphisms (SNPs) associated with coffee, alcohol, and tea intake were derived from the IEU project. The SSB-associated SNPs were selected from a genome-wide association study (GWAS). Data on facial skin aging were derived from the largest GWAS involving 16 677 European individuals. The inverse variance-weighted (IVW) was the main MR analysis method, supplemented by other methods (MR-Egger, weighted median, simple mode, and weighted mode). The MR-Egger intercept analysis was used for sensitivity analysis. Moreover, we conducted a replication analysis using data from another GWAS dataset on coffee consumption to validate our findings. RESULTS: Four instrumental variables (IVs) sets were used to examine the causal association between beverage consumption (coffee, alcohol, tea, SSB) and facial skin aging. Our results revealed that genetically predicted higher coffee consumption reduced the risk of facial skin aging (OR: 0.852; 95% CI: 0.753-0.964; p = 0.011, IVW method). The sensitivity analysis confirmed the robustness of the findings, with no evidence of pleiotropy or heterogeneity. The results of replicated MR analysis on coffee consumption were consistent with the initial analysis (OR = 0.997; 95% CI = 0.996-0.999; p = 0.003, IVW method). CONCLUSIONS: This study manifests that higher coffee consumption is significantly associated with a reduced risk of facial skin aging. These findings can offer novel strategies for identifying the underlying etiology of facial skin aging.

Injectable Cartilage Microtissue Regenerated by Autologous Chondrocytes for Nasal Augmentation: A 5-Year Follow-Up Study.

BACKGROUND: A lack of ideal filling materials is a critical limitation in current rhinoplasty. Cartilage sheet regeneration by autologous chondrocytes is expected to provide an ideal source of material. However, the inability to perform minimally invasive transplantation of cartilage sheets has greatly limited the clinical application of this material. In this article, the authors propose the concept of injectable cartilage microtissue (ICM) based on cartilage sheet technology, with the aim of achieving minimally invasive augmentation rhinoplasty in clinical practice. METHODS: Approximately 1.0 cm2 of posterior auricular cartilage was collected from 28 patients. Isolated chondrocytes were expanded, then used to construct autologous cartilage sheets by high-density seeding and in vitro culture in chondrogenic medium with cytokines (eg, transforming growth factor beta-1 and insulin-like growth factor-1) for 3 weeks. Next, ICM was prepared by granulation of the cartilage sheets; it was then injected into a subcutaneous pocket for rhinoplasty. RESULTS: ICM was successfully prepared in all patients, and its implantation efficiently raised the nasal dorsum. Magnetic resonance imaging confirmed that regenerative tissue was present at the injection site; histologic examinations demonstrated mature cartilage formation with typical cartilage lacunae and abundant cartilage-specific deposition of extracellular matrix. Excellent or good postoperative patient satisfaction results were achieved in 83.3% of patients over 5 years of follow-up. Obvious absorption of grafts occurred in only two patients (8.3%). CONCLUSIONS: These results demonstrated that ICM could facilitate stable cartilage regeneration and long-term maintenance in the human body; the implantation of ICM enabled natural augmentation of the depressed nasal dorsum. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.