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Objective·To investigate the effects of trimethylamine oxide (TMAO) on cardiac function in mice with hypertrophic cardiomyopathy (HCM) and its potential molecular mechanism.Methods·Mice with myosin heavy chain 6 (Myh6) c.1211G>A (p.R404Q+/-) point mutation were used as the animal model. According to dietary supplementation of TMAO and TMAO inhibitor iodomethylcholine (IMC), the wild type (WT) mice and HCM mice were divided into WT group, HCM group (HCM-1 group, HCM-2 group), WT+TMAO group, HCM+TMAO group and HCM+IMC group, respectively. Left ventricular fraction shortening (FS) and left ventricular posterior wall thickness (LVPW) were assessed by echocardiography in all mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum TMAO concentration of mice in the HCM-1 group and WT group. The regularity of myocardial cell arrangement of mice was evaluated by hematoxylin and eosin staining (HE staining). The proportion of myocardial fibrosis was evaluated by Masson staining. The activity of protein kinase A (PKA) in mouse myocardial tissue was detected by PKA kit. The expression of ryanodine receptor 2 (RyR2) and p-RyR2(S2808) in mouse myocardial tissue was detected by Western blotting.Results·The results of echocardiography showed that at 12 months of age, the FS of mice in the WT+TMAO group and HCM+TMAO group were lower than those in the corresponding WT group and HCM-1 group, respectively (P

objective*To screen new potential pathogenic genes in the course of esophageal squamous cell carcinoma. Methods*The data of miRNA chips GSE122497 and GSE164174 were obtained by GEO database. The differential mirnas of esophageal cancer patients and healthy people were screened by GEO2R, and the intersection was obtained by Venn Diagram Webtool. Target Scan tool and DIANATOOLS tool were used to predict the target genes of differential miRNA, and the intersection of predicted target genes of the two tools was used for gene function analysis. The protein interactions of target genes were analyzed by using STRING tool and Hub genes were selected. Results*(1) A total of 108 differential miRNAs were detected in the chip. (2) After taking the intersection of Target Scan tool and DIANATOOLS tool, there were 1 354 different target genes. (3) Gene Ontology (GO) analysis showed that gene functions of differential target genes were significantly enriched in biological processes such as DNA template transcriptional regulation and RNA polymerase II promoter transcriptional regulation, as well as RNA polymerase II core promoter proximal sequence specific DNA binding, protein binding, metal ion binding and other molecular functions. It mainly existed in nucleus, cytoplasm, cytoplasm and other cellular components. In descending order of the number of enriched genes, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the above genes were significantly enriched in tumor pathway, MAPK signaling pathway, stem cell pluripotency regulation signaling pathway, etc. (4) There were 1 326 nodes and 2 300 edges in the protein interaction network, and the average node connectivity was 3.47. The selected Hub genes were SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), β-transducin repeat containing E3 ubiquitin protein ligase (BTRC), SMAD specific E3 ubiquitin protein ligase 1 (SMURF 1), ubiquitin conjugating enzyme E2 D1 (UBE2D1), and cullin 2 (CUL2). Previous studies have shown that the above genes are related to ubiquitination. Conclusion*SMURF2, BTRC, SMURF1, UBE2D1 and CUL2 genes screened from GEO database may be involved in the disease process of esophageal squamous cell carcinoma through the ubiquitin of targeted regulatory proteins. [ABSTRACT FROM AUTHOR]