circWSB1 promotes tumor progression in ccRCC via circWSB1/miR-182-5p/WSB1 axis.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent urological carcinomas with a low overall 5-year survival rate, and its prognosis remains dismal. circular RNAs (circRNAs) has been discovered to be important regulators in ccRCC. However, the specific regulatory mechanisms of circRNAs and their impact on phenotypes require further in-depth research. circRNA microarray sequencing analysis was used in this study to explore the expression pattern of circRNAs in ccRCC. circWSB1 was discovered, and we evaluated its derivation, potential diagnostic efficacy, and prognostic significance in ccRCC tissues. We discovered that circWSB1 is highly expressed in ccRCC. We identified that circWSB1 interacts with miR-182-5p and upregulates the expression of its host gene, WSB1. Through models in vivo and in vitro models, we found that circWSB1 increases WSB1 expression via the circWSB1/miR-182-5p/WSB1 axis, which promotes ccRCC cell proliferation and migration. The high expression of circWSB1 and WSB1 is correlated with poorer clinical prognosis and pathological grading. circWSB1 diminishes the inhibitory impact of miR-182-5p on WSB1 and increases WSB1 expression, thereafter promoting ccRCC development. Our findings provide a promising predictive biomarker and therapeutic target for ccRCC.

Association of Genetic Variants in miR-217 Gene with Risk of Coronary Artery Disease: A Case-Control Study.

OBJECTIVE: To evaluate the associations of genetic variants of the miR-217 gene with coronary artery disease (CAD) risk, as well as plasma level of vascular endothelial growth factor (VEGF). METHODS: A case-control study with 498 CAD patients and 499 frequency-matched healthy controls was conducted to evaluate the associations of four tagSNPs of the miR-217 gene, including rs6724872, rs4999828, rs10206823, and rs41291177, with CAD risk and plasma level of VEGF. RESULTS: SNP rs6724872 and rs4999828 were significantly associated with increased risk of CAD (P value was smaller than 0.05 even after Bonferroni multiple adjustment). Compared with the G allele, C allele of rs6724872 was significantly associated with 1.73-fold increased risk of CAD (95% CI: 1.25-2.39; P = 0.001). While C allele of rs4999828 was significantly associated with 1.75-fold increased risk of CAD, compared with T allele (95% CI: 1.34-2.29; P = 4 × 10-5). Meanwhile, rs6724872 and rs4999828 were also significantly associated with higher level of VEGF (P < 0.001). CONCLUSION: These findings highlighted the important role of genetic variants of the miR-217 gene in the pathogenesis of CAD and potential targets for intervention.

Resveratrol protects H9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis.

Previous studies have demonstrated the cardioprotective role of resveratrol (Res). However, the underlying molecular mechanisms involved in the protective role of Res are still largely unknown. H9c2 cells were distributed into five groups: normal condition (Control), DMSO, 20 mMRes (dissolved with DMSO), hypoxia (Hyp), and Res+Hyp. Cell apoptosis was evaluated using flow cytometry and protein analysis of cleaved caspase 3 (cle-caspase 3). qRT-PCR assay was performed to measure the expression of microRNA-30d-5p (miR-30d-5p). MTT assay was performed to evaluate the cell proliferation. The relationship between miR-30d- 5p and silent information regulator 1 (SIRT1) was confirmed by luciferase reporter, RNA immunoprecipitation (RIP), and western blot assays. Western blot was performed to analyze NF-κB/p65 and I-κBα expressions. Our data showed that hypoxia enhanced apoptosis and NF-κB signaling pathway, which was alleviated by Res treatment. Hypoxia increased the expression of miR-30d-5p while decreased the SIRT1expression, which was also attenuated by Res treatment. Furthermore, miR-30d-5p depletion inhibited the proliferation, reduced apoptosis and decreased the expression of cle-caspase 3 in H9c2 cells with hypoxia treatment. Luciferase reporter, RIP, and western blot assays further confirmed that miR-30d-5p negatively regulated the expression of SIRT1. Interestingly, the rescue-of-function experiments further indicated that knockdown of SIRT1 attenuated the effect of miR-30d-5p depletion on proliferation, apoptosis NF-κB signaling pathway inH9c2 cells with hypoxia treatment. In addition, the suppression of NF-κB signaling pathway increased cell viability while decreased cell apoptosis in hypoxia-mediatedH9c2 cells. Our data suggested Res mayprotectH9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis.

Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes.

Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich enzyme-linked immunosorbent assay (ELISA), and the severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. The results indicated that the median serum TRX levels were significantly (P < 0.0001) higher in stroke patients as compared to normal cases [15.03 ng/mL (interquartile range (IQR), 10.21-32.42) and 8.95 ng/mL (6.79-11.05), respectively]. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r = 0.476, P < 0.0001). After adjusting for all other possible covariates, TRX remained as an independent marker of AIS with an adjusted OR of 1.245 (95 % confidence interval (CI), 1.164-1.352; P < 0.0001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/mL, which yielded a sensitivity of 80.3 % and a specificity of 73.7 %, with the area under the curve at 0.807 (95 % CI, 0.766-0.847). Further, in our study, we found that an increased risk of AIS was associated with serum TRX levels ≥11.0 ng/mL (adjusted OR 6.99; 95 % CI, 2.87-12.87) after adjusting for possible confounders. Our study demonstrated that serum TRX levels at admission were associated with stroke severity and lesion volumes. Elevated levels could be considered as a novel, independent diagnosis marker of AIS in a Chinese sample.

Elevated Serum Mannose-Binding Lectin Levels Are Associated with Poor Outcome After Acute Ischemic Stroke in Patients with Type 2 Diabetes.

The activation of the complement system may be involved in the pathology of stroke and type 2 diabetes (T2DM). We therefore evaluated the long-term prognostic value of early measurement of serum mannose-binding lectin (MBL) levels, an activator of the complement system, in Chinese T2DM with acute ischemic stroke (AIS). Serum MBL levels were determined in T2DM patients with AIS (N = 188). The adjudicated end points were 1-year functional outcomes and mortality. The prognostic value of MBL was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Patients with an unfavorable outcomes and nonsurvivors had significantly increased MBL levels on admission (P < 0.0001 and P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that MBL was an independent predictor of functional outcome (odds ratio (OR) = 8.99, 95% CI 2.21-30.12) and mortality (OR = 13.22, 95% CI 2.05-41.21). The area under the receiver operating characteristic curve of MBL was 0.75 (95% CI 0.68-0.83) for functional outcome and 0.85 (95% CI 0.80-0.90) for mortality. In type 2 diabetic patients with stroke, high levels of MBL predict future functional outcomes and mortality. This indicated that the elevated MBL levels may play a significant role in the pathology of the subsequent damage and that the pathways leading to complement activation warrant further exploration as potential therapeutic targets to improve the prognosis for these patients.