Immunological profile of lactylation-related genes in Crohn's disease: a comprehensive analysis based on bulk and single-cell RNA sequencing data.

BACKGROUND: Crohn's disease (CD) is a disease characterized by intestinal immune dysfunction, often accompanied by metabolic abnormalities. Disturbances in lactate metabolism have been found in the intestine of patients with CD, but studies on the role of lactate and related Lactylation in the pathogenesis of CD are still unknown. METHODS: We identified the core genes associated with Lactylation by downloading and merging three CD-related datasets (GSE16879, GSE75214, and GSE112366) from the GEO database, and analyzed the functions associated with the hub genes and the correlation between their expression levels and immune infiltration through comprehensive analysis. We explored the Lactylation levels of different immune cells using single-cell data and further analyzed the differences in Lactylation levels between inflammatory and non-inflammatory sites. RESULTS: We identified six Lactylation-related hub genes that are highly associated with CD. Further analysis revealed that these six hub genes were highly correlated with the level of immune cell infiltration. To further clarify the effect of Lactylation on immune cells, we analyzed single-cell sequencing data of immune cells from inflammatory and non-inflammatory sites in CD patients and found that there were significant differences in the levels of Lactylation between different types of immune cells, and that the levels of Lactylation were significantly higher in immune cells from inflammatory sites. CONCLUSIONS: These results suggest that Lactylation-related genes and their functions are closely associated with changes in inflammatory cells in CD patients.

Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Background: Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two. Methods: The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01). Conclusion: Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.

miR-1307-3p overexpression inhibits cell proliferation and promotes cell apoptosis by targeting ISM1 in colon cancer.

BACKGROUND: colon adenocarcinoma (COAD) is the most common malignant tumor of gastrointestinal tract. Our study attempts to explore the effect of miR-1307-3p on biological function of COAD cells and its connection with isthmin 1 (ISM1). METHODS: The miRNA dataset and clinical information of patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. The survival prognosis was analyzed by GGSURV package from R. MicroRNA (miR)-1307-3p was identified by identifying overlapping miRNAs that target ISM1, across two databases (miRDB and Targetscan). Dual luciferase reporter assay was employed to scrutinize the relationship between miR-1307-3p and ISM1. RT-PCR was used to quantify miR-1307-3p and ISM1 expression of colon cancer tissues and cell lines. Western blot was performed to quantify related protein expression. Flow Cytometry, CCK8 and colony formation assays were performed to evaluate the apoptosis, cell cycle, cell viability and proliferation of COAD cells. RESULTS: miR-1307-3p mRNA level decreased in both COAD tissues and cell lines. Overexpression of miR-1307-3p suppressed the proliferation, promoted apoptosis and arrested cell cycle at G1 phase, meanwhile, downregulation of ISM1 accelerated the proliferation, inhibited apoptosis and promote cell cycleprogression. The result of dual luciferase reporter assay indicated that miR-1307-3p targeted ISM1 directly and inhibited its expression. The functions of miR-1307-3p regulating cleaved caspase-3, cyclinD1, Ki67 protein levels and activation of Wnt3a/ß-catenin signaling pathway were reversed by ISM1. CONCLUSIONS: miR-1307-3p inhibited activation of Wnt3a/ß-catenin signaling through targeting downregulation of ISM1, thereby inhibited proliferation and promote apoptosis of COAD cells.