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1.
Front Genet ; 15: 1447139, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119581

RESUMEN

Background: Renal cell carcinoma (RCC) is the most prevalent type of malignant kidney tumor in adults, with clear cell renal cell carcinoma (ccRCC) comprising about 75% of all cases. The SETD2 gene, which is involved in the modification of histone proteins, is often found to have alterations in ccRCC. Yet, our understanding of how these SETD2 mutations affect ccRCC characteristics and behavior within the tumor microenvironment is still not fully understood. Methods: We conducted a detailed analysis of single-cell RNA sequencing (scRNA-seq) data from ccRCC. First, the data was preprocessed using the Python package, "scanpy." High variability genes were pinpointed through Pearson's correlation coefficient. Dimensionality reduction and clustering identification were performed using Principal Component Analysis (PCA) and the Leiden algorithm. Malignant cell identification was conducted with the "InferCNV" R package, while cell trajectories and intercellular communication were depicted using the Python packages "VIA" and "cellphoneDB." We then employed the R package "Deseq2" to determine differentially expressed genes (DEGs) between groups. Using high-dimensional weighted gene correlation network analysis (hdWGCNA), co-expression modules were identified. We intersected these modules with DEGs to establish prognostic models through univariate Cox and the least absolute shrinkage and selection operator (LASSO) method. Results: We identified 69 and 53 distinctive cell clusters, respectively. These were classified further into 12 unique cell types. This analysis highlighted the presence of an abnormal tumor sub-cluster (MT + group), identified by high mitochondrial-encoded protein gene expression and an indication of unfavorable prognosis. Investigation of cellular interactions spotlighted significant interactions between the MT + group and endothelial cells, macrophaes. In addition, we developed a prognostic model based on six characteristic genes. Notably, risk scores derived from these genes correlated significantly with various clinical features. Finally, a nomogram model was established to facilitate more accurate outcome prediction, incorporating four independent risk factors. Conclusion: Our findings provide insight into the crucial transcriptomic characteristics of ccRCC associated with SETD2 mutation. We discovered that this mutation-induced subcluster could stimulate M2 polarization in macrophages, suggesting a heightened propensity for metastasis. Moreover, our prognostic model demonstrated effectiveness in forecasting overall survival for ccRCC patients, thus presenting a valuable clinical tool.

2.
Front Nutr ; 11: 1394618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812937

RESUMEN

Background: Dietary strategies play a crucial role in the prevention of kidney stones. While milk is known for its rich nutritional content, its impact on kidney stone formation remains unclear. This study aimed to examine the relationship between milk consumption and the risk of kidney stones among U.S. adults. Methods: We included 24,620 participants aged 20 and older from the National Health and Nutrition Examination Survey (2007-2018). Milk consumption was defined based on each participant's response to the questionnaire item on "Past 30 day milk product consumption." Kidney stones history was self-reported by participants. The analysis employed weighted multivariate logistic regression models, followed by subgroup analyses for result validation, and explored the age-related dynamics of milk consumption's effect on kidney stone risk using a restricted cubic spline model. Results: Adjusted findings revealed that higher milk intake was associated with a decreased risk of kidney stones (odds ratio [OR] = 0.90, 95% confidence interval [CI] 0.85-0.96), notably among women (OR = 0.86, 95% CI 0.80-0.92) but not significantly in men (OR = 0.94, 95% CI 0.86-1.02). Smoothed curves across all ages showed that women consuming milk had a lower incidence of kidney stones than those who did not, particularly with regular consumption. Conclusion: This study uncovered that across all age groups, higher frequency of milk consumption in women is associated with a reduced risk of kidney stones. However, further prospective cohort studies are needed to confirm this finding.

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