A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.

Pooled analysis of the efficacy and safety of tibial nerve stimulation versus antimuscarinic agents in the management of overactive bladder syndrome.

OBJECTIVES: The purpose of this meta-analysis was to evaluate the efficacy and safety of tibial nerve stimulation (TNS) versus antimuscarinic agents in the management of overactive bladder (OAB) syndrome. METHODS: The databases MEDLINE, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials from 2000 to May 2021 were searched to identify randomized controlled trials that referred to the use of TNS and antimuscarinic agents for the treatment of OAB syndrome. A systematic review and meta-analysis was conducted. RESULTS: Eight publications involving 420 patients were included in the meta-analysis. In the analysis, we found TNS had a comparable effect with antimuscarinic agents on micturition per day, nocturia, urge incontinence, and voided volume (P = .9; .4; .78; .44, respectively). Scores measured by questionnaires Overactive Bladder Symptom Score and Overactive Bladder questionnaire Short Form items also indicated no statistical difference between 2 groups. TNS group had a significantly less discontinuation rate and adverse events (P = .003; .0001). CONCLUSIONS: TNS is as effective as antimuscarinic agents for the treatment of OAB. Moreover, TNS appears to be more tolerable and safer than antimuscarinic agents.

Systematic review and meta-analysis of the efficacy and safety of vibegron vs antimuscarinic monotherapy for overactive bladder.

BACKGROUND: Vibegron is a new ß3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB. METHODS: Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data. RESULTS: Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups. CONCLUSIONS: The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.

The efficacy and safety of mirabegron on overactive bladder induced by benign prostatic hyperplasia in men receiving tamsulosin therapy: A systematic review and meta-analysis.

BACKGROUND: We conducted a meta-analysis to assess the efficacy and safety of mirabegron on overactive bladder (OAB) induced by benign prostatic hyperplasia (BPH) in men receiving tamsulosin therapy. METHODS: We performed the analysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases including MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were retrieved to get information regarding randomized controlled trials of mirabegron on OAB induced by BPH in men receiving tamsulosin therapy. We also searched the references of included literatures. RESULTS: Three randomized controlled trials containing a total of 1317 BPH patients were included in the analysis. Co-primary efficacy end points: the mean number of micturitions per day [the mean difference (MD) = -0.27, 95% confidence interval (CI): -0.46 to -0.09, P = .004], the urgency episodes per day (the MD = -0.50, 95% CI: -0.77 to -0.22, P = .0004), the total OAB symptom score (the MD = -0.69, 95% CI: -1.00 to -0.38, P < .0001), and mean volume voided (the MD = 10.76, 95% CI: 4.87-16.64, P = .0003) indicated that mirabegron was effective in treating OAB induced by BPH in men receiving tamsulosin therapy. Safety assessments that included treatment-emergent adverse events (odds ratio = 0.88, 95% CI: 0.68-1.13, P = .31) indicated that mirabegron was well tolerated with the exception of post-void residual urine volume (MD = 12.02, 95% CI: 6.01-18.04, P < .0001). CONCLUSIONS: This analysis demonstrates that mirabegron is an effective and safe treatment for OAB symptoms induced by BPH in men receiving tamsulosin therapy with a low occurrence of side effects. Besides, we should be aware that the administration of mirabegron might have the risk of increasing post-void residual urine volume.