Patients with advanced prostate cancer (PCa) have poor prognosis. Circular RNAs (circRNAs) regulate biological processes in a variety of cancers, but the precise roles of circRNAs in PCa are poorly understood. Herein, we identified a novel circRNA, termed circMBOAT2 (has_circ_0007334), which was significantly overexpressed in PCa tissues and cell lines. Overexpression of circMBOAT2 was associated with high Gleason score, advanced pathological T stage, and poor prognosis. Overexpression of circMBOAT2 promoted proliferation, migration, and invasion of PCa cells in vitro , and enhanced tumorigenesis and metastasis in vivo . Mechanistically, circMBOAT2 overexpression upregulated the expression of mTOR by acting as a decoy for miR-1271-5p, resulting in the activation of the PI3K/Akt pathway, ultimately promoting the progression of PCa. Importantly, application of an inhibitor of mTOR significantly antagonized circMBOAT2-mediated PCa tumorigenesis in vivo . circMBOAT2 promotes proliferation and metastasis of PCa through miR-1271-5p/mTOR axis-mediated activation of the PI3K/Akt pathway. In summary, our findings uncover a molecular mechanism in the progression of PCa and indicate that circMBOAT2 may be a useful prognostic biomarker and therapeutic target in PCa.
High level of detrimental factors including reactive oxygen species (ROS) and inflammatory cytokines accumulated in the infarct core and their erosion to salvageable penumbra are key pathological cascades of ischemia-reperfusion injury in stroke. Few neuroprotectants can remodel the hostile microenvironment of the infarct core for the failure to interfere with dead or biofunctionally inactive dying cells. Even ischemia-reperfusion injury is temporarily attenuated in the penumbra by medications; insults of detrimental factors from the core still erode the penumbra continuously along with drug metabolism and clearance. Herein, a strategy named "nanobuffer" is proposed to neutralize detrimental factors and buffer destructive erosion to the penumbra. Inspired by neutrophils' tropism to the infarct core and affinity to inflammatory cytokines, poly(lactic-co-glycolic acid) (PLGA) nanoparticles are coated with neutrophil membrane to target the infarct core and absorb inflammatory cytokines; α-lipoic acid is decorated on the surface and cannabidiol is loaded for ROS scavenging and neuroprotection, respectively, to construct the basic unit of the nanobuffer. Such a nanobuffer exerts a comprehensive effect on the infarct area via detrimental factor neutralization and cannabidiol-induced neuroprotection. Besides, the nanobuffer can possibly be enhanced by dynamic ROP (ring-opening-polymerization)-induced membrane cross-fusion among closely adjacent units in vivo. Systematic evaluations show significant decrease of detrimental factors in the core and the penumbra, reduced infarct volume, and improved neurological recovery compared to the untreated group of stroke rats.
The efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie's disease (PD) has been controversial for a very long time. We aimed to evaluate the efficiency of ESWT for PD and provide possible evidence on the basis of a meta-analysis of existing comparative studies. All controlled studies, including randomized controlled trials (RCTs), cohort studies and case-control studies, that focused on the efficiency of ESWT for PD, were prospectively identified through comprehensive searches of PubMed, the Cochrane Library and Embase databases. We conducted a meta-analysis of these studies. Six studies including 443 patients were selected for the meta-analysis. Pooling data of these studies showed that ESWT could significantly increase the percentage of men with lessening of penile plaques (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.11-3.85, P=0.02), relief of pain (OR 4.46, 95% CI 2.29-8.68, P<0.0001) and complete remission of pain (OR 5.86, 95% CI 2.66-12.92, P<0.0001). However, insignificant differences were found in improvement of penile curvature (OR 1.88, 95% CI 0.97-3.65, P=0.06) and sexual function (OR 2.22, 95% CI 0.69-7.11, P=0.18) between ESWT and placebo groups. Further, similar results were shown for sensitivity and publication bias analysis when only RCTs were included. However, sporadic complications caused by ESWT were reported, but no patient needed additional treatment aside from conservative observation. ESWT may be an effective and safe treatment for lessening of penile plaques and relieving pain for men with PD, but not for improving of penile curvature and sexual function.
In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users.
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