Thioredoxin-interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease.

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-1ß, 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-1ß. 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.

[Identification of a novel FBN1 variant in a pedigree affected with Marfan syndrome].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Marfan syndrome (MFS). METHODS: Clinical data of the patients was collected. With genomic DNA extracted from peripheral blood samples, potential mutation was detected by targeted exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: Targeted exome sequencing and Sanger sequencing revealed a missense c.649T to C(p.Trp217Arg) variant in the exon 7 of FBN1 gene, which was unreported previously. Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1. CONCLUSION: A novel missense variant of the FBN1 gene was identified, which probably underlies the autosomal dominant MFS in this pedigree.

CircRNA ZNF609 in peripheral blood leukocytes acts as a protective factor and a potential biomarker for coronary artery disease.

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.

The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for patients with urological cancers: A meta-analysis.

BACKGROUND: The lymphocyte to monocyte ratio (LMR), a novel systematic biomarker of inflammation, has been reported to be associated with the progression and prognosis of many malignant cancers. However, the relationship between LMR and survival outcome of urological cancers (UCs) remains controversial. Herein, we conducted a meta-analysis to identify the prognostic value of pretreatment LMR in patients with UCs. METHODS: A literature search was performed in PubMed, Web of Science, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials, Scopus, and CINAHL databases up to July 2018. The pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association of LMR with survival outcome and clinicopathological characteristics in UCs. RESULTS: A total of 17 articles containing 5552 patients were included in our study. The synthesized analysis showed that elevated pretreatment LMR level could predict favorable overall survival (OS) of UCs patients (pooled HR = 0.82, 95%CI: 0.77-0.87). Additionally, the decreased LMR level was correlated with tumor stage (OR = 1.72, 95%CI: 1.15-2.55), lymph node metastasis (OR = 1.46, 95%CI:1.06-1.99), grade (OR = 1.79, 95%CI:1.41-2.27), tumor size (OR = 2.21, 95%CI:1.81-2.68) and necrosis (OR = 1.71, 95%CI:1.36-2.16). CONCLUSION: The high pretreatment LMR was associated with favorable prognosis, and could be a potential prognostic biomarker in patients with UCs.

Distinct prognostic roles of S100 mRNA expression in gastric cancer.

BACKGROUND: The S100 protein family is implicated in tumor invasion and metastasis, but its prognostic roles in gastric cancer (GC) has not been elucidated. MATERIALS AND METHODS: In the current study, Kaplan-Meier plotter (KM plotter) database integrated the expression data and survival information of 1065 GC patients were downloaded from the Gene Expression Omnibus (GEO) (GSE22377, GSE14210 and GSE51105) that published by the three major cancer centers (Berlin, Bethesda and Melbourne). Then this database was used to explore the prognostic values of mRNA expression of each individual S100 in GC patients. We further assessed the prognostic value of S100 in different Lauren classifications, clinicopathological features and clinical treatment of gastric cancer. RESULTS: Expression of 12 members of the S100 family correlated with overall survival (OS) for all GC patients. Increased expression of S100A3, S100A5, S100A7, S100A7A, S100A11, S100A13, S100Z and S100 G were found to be strongly associated with worse survival, while S100A8, S100A9, S100B and S100 P were correlated with better prognosis in all GC patients. Further assessment of prognostic values of S100 in gastric cancer with different clinical features indicated that different S100 members may interact with different signaling pathways and exerted different functions in gastric cancer development. CONCLUSIONS: Although the results should be further testified in clinical studies, our findings offer new insights into the contribution of S100 members to GC progression and might promote development of S100 targeted reagents for treating GC.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value.

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.