Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.

BackgroundHepatitis B virus (HBV) infection is a blood borne infectious disease that affects the liver. Human bone marrow mesenchymal stem cells (BMSCs) may serve as a cell source for adult stem cell transplantation in liver repair. However, the susceptibility of human BMSCs to HBV infection is poorly understood. The aim of this study was to investigate the infection and replication of HBV in cultures of human BMSCs.ResultsHuman BMSCs were confirmed using flow cytometry. Intracellular HBV DNA was detected at d 2 after infection and maintained at relatively high levels from d 6 to d 12. The maximal level of intracellular HBV DNA was 9.37 × 105 copies/mL. The extracellular HBV DNA was observed from d 3 to d 15, and the levels ranged from 3.792 × 102 copies/mL to 4.067 × 105 copies/mL. HBsAg in the culture medium was detected from d 2 to d 16. HBeAg secretion was positive from d 5 to d 13. HBcAg constantly showed positive signals in approximately 7%-20% of BMSCs from 2 days after exposure. Intracellular HBV covalently closed circular DNA (cccDNA) could be detected as early as 2 days postinfection, and strong signals were obtained with increasing time.ConclusionHBV can infect and replicate in human BMSCs. Human BMSCs may be a useful tool for investigating HBV life-cycle and the mechanism of initial virus-cell interactions.

Background: No consensus has been reached on the definite associations among prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Hence, this meta-analysis was conducted to explore their triadic relation by summarizing epidemiological evidence.Methods: Systematical and comprehensive retrieval of online databases PubMed, PMC, EMBASE and Web of Science was performed to acquire eligible studies, up to April 1st, 2019. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify their correlations.Results: A total of 42 studies were enrolled in the quality assessment and 35 were finally included in the meta-analyses. Among them, 27 studies were included to describe the association between prostatitis and PCa (OR=1.72, 95% CI=1.44-2.06, I2=90.1%, P<0.001). 21 studies presented significant evidence about the relation between BPH and PCa (OR=2.16, 95% CI=1.75-2.88, I²=97.1%, P<0.001). Due to the huge heterogeneity among studies, those with obvious outliers were excluded based on the Galbraith plots. Ultimately, 17 studies were screened out to assess the association between prostatitis and PCa (OR=1.59, 95% CI=1.48-1.70, I²=29.4%, P=0.123). Meanwhile, 8 studies were retained to evaluate the association between BPH and PCa (OR=3.10, 95% CI=2.87-3.35, I²=8.4%, P=0.365). As for the relation between prostatitis and BPH, a case-control study and a cohort study both supported that prostatitis could enhance the risk of BPH.Conclusions: Significant correlations were revealed among prostatitis, BPH and PCa. Prostatitis or BPH could lead to escalating risks of PCa. Meanwhile, people with a history of prostatitis might be more vulnerable to BPH.

Accumulated evidence indicates that miR-455-5p functions as tumor suppressor in the progression of various cancers. However, the mechanism through which miR-455-5p influences the tumorigenesis of human prostate cancer (PCa) remains undetermined. In this study, reanalysis of data obtained from the Memorial Sloan Kettering Cancer Center showed that miR-455-5p can be used as biomarker for PCa diagnosis and predictor of poor prognosis. Functional assays indicated that miR-455-5p overexpression could suppress cellular proliferation, inhibit tumor growth, and trigger apoptosis by activating and cleaving caspase 3. We experimentally verified that miR-455-5p negatively regulated the C–C motif chemokine receptor 5 (CCR5). Overall, our data demonstrate that miR-455-5p suppressed PCa cellular proliferation and induced cell apoptosis by downregulating CCR5. Thus, miR-455-5p may be considered a new therapeutic strategy for PCa.