Background: Circular RNAs (circRNAs) have been reported to aberrantly express in coronary artery disease (CAD). Due to their special structures, circRNAs have the potential to be specific and stable markers.We conducted this study to explore circZNF609's function in atherosclerosis and to evaluate its predictive values for CAD.Methods: About 330 CAD patients and 209 controls were enrolled and the expression of circZNF609 in peripheral blood leukocytes (PBLs) was detected by quantitative real time polymerase chain reaction (RT-PCR). Spearman correlation, multivariate regression, multivariate logistic regression and receiver operating characteristic curve (ROC) were performed. Moreover, circZNF609 was overexpressed in mice macrophage RAW264.7 to investigate its influence on inflammatory cytokines. Finally, bioinformatics analysis was executed to excavate the potential downstream pathway of circZNF609.Results: The expression level of circZNF609 in PBLs of CAD patients was significantly decreased compared with the controls (the fold changes of 0.4133, P<0.0001). The logistic regression analysis showed that decreased circZNF609 expressions were independently associated with increased risks of CAD. The area under the ROC curve was 0.761 (95% CI: 0.721-0.800, P<0.0001). Furthermore, the circZNF609 expression level was correlated with C-reactive protein (r=−0.138, P=0.026) and lymphocyte counts (r=0.16, P=0.01). After overexpression of circZNF609 in RAW264.7 cells, the expression level of IL-6 (P<0.001) and TNF-α (P<0.01) were significantly decreased and IL-10 was significantly increased (P<0.001). Bioinformatics analysis suggested that the abnormal expression of circZNF609 might probably sponge miRNA to modulate the inflammation cytokines.Conclusions: CircRNA ZNF609 played an anti-inflammatory role and was an independent protective factor for CAD. It represented a moderate diagnostic value and might provide a new therapeutic target for CAD.
Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA–miRNA–mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.
Numerous studies have demonstrated that thioredoxin‐interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL‐1β, IL‐18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP‐1 and macrophages/foam cells. Furthermore, Transwell assay and co‐cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP‐1 or the adhesion of THP‐1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP‐1 cells and expressions of NLRP3, IL‐18 and IL‐1β. Oppositely, knock‐down TXNIP inhibited the migration and adhesion of THP‐1 and expressions of NLRP3, IL‐18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.
Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application. Methods : The effective components and its targets of XFZYD were predicted and screened based on the TCMSP database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using DAVID database. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Differentially expressed genes in GSE71226 were identified using GEO2R. Finally, molecular docking was performed by Schrodinger software. Results: A total of 108 effective compounds and 137 candidate therapeutic targets were screened. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanism of XFZYD for ASCVD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Moreover, the expression profile in GSE71226 supported our findings, while molecular simulation docking results also demonstrated the reliability of the predicted results. Conclusions: This study demonstrates the therapeutic potential of XFZYD for the treatment of ASCVD based on systemic pharmacology, which could provide a guiding principle for its clinical application as well as valuable insights for further drug discovery. Key words: Systematic pharmacology; atherosclerosis; Xuefu Zhuyu decoration; ASCVD
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