The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.

Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids' biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.

CTLA-4 rs5742909 polymorphism and cervical cancer risk: A meta-analysis.

BACKGROUND: Number of studies have been performed to evaluate the relationship between the cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) gene variant rs5742909 polymorphism and cervical cancer risk, but the sample size was small and the results were conflicting. This meta-analysis was conducted to comprehensively evaluate the overall association. METHODS: PubMed, Web of Science, Embase, China Biology Medical Literature database, China National Knowledge Infrastructure, WanFang, and Weipu databases were searched before July 31, 2018. The strength of associations was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). All of the statistical analyses were conducted using Review Manager 5.3 and Stata 14.0. RESULTS: Eleven studies involved 3899 cases and 4608 controls. Overall, significant association was observed between the CTLA-4 gene variant rs5742909 polymorphism and cervical cancer (T vs C: OR = 1.40, 95% CI = 1.12-1.76; TT vs CC: OR = 2.22, 95% CI = 1.13-4.37; TT vs CT+CC: OR = 1.96, 95% CI = 1.03-3.74; TT+CT vs CC: OR = 1.47, 95% CI = 1.14-1.90). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (T vs C: OR = 1.56, 95% CI = 1.22-1.99), but not in Caucasians (T vs C: OR = 1.19, 95% CI = 0.87-1.62). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. CONCLUSION: our meta-analysis supports that the CTLA-4 gene variant rs5742909 polymorphism might contribute to individual susceptibility to cervical cancer in Asians.