Purpose: Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats.Methods: One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4-mg/kg metformin and/or 1-mg/kg sildenafil.Results: I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats coadministered metformin and sildenafil and those treated with either agent alone.Conclusions: Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.

Objectives: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.Methods: A prospective, randomized, double‐blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health‐Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate‐specific antigen were performed.Results: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health‐Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub‐score of the National Institutes of Health‐Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs.Conclusion: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add‐on treatments in patients with storage symptoms with alpha‐blocker monotherapy.

Lee JY, et al. Investig Clin Urol. 2020 May;61(3):297-303. https://doi.org/10.4111/icu.2020.61.3.297

Purpose: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence.Methods: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed.Results: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered.Conclusions: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery.Trial Registration: The study was registered as a clinical trial (KCT0008369).

Castration-resistant prostate cancer (CRPC) is still a major concern in men’s health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.

Purpose: Overactive bladder (OAB) in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) represents a major therapeutic challenge, as symptoms often persist even after surgical relief of obstruction. The underlying molecular mechanisms, however, remain poorly defined. The aim of this study was to identify differentially expressed proteins in the urothelial tissues of patients with BOO-related OAB using a proteomic approach.Methods: Bladder urothelial tissues were obtained via cold-cup biopsy during transurethral resection of the prostate in patients with BPH. Patients were classified into OAB and non-OAB groups. Proteomic profiling was conducted using liquid chromatography–tandem mass spectrometry, followed by functional annotation and pathway enrichment analyses with the Ingenuity Pathway Analysis and Gene Ontology tools.Results: Proteomic analysis identified 1,510 proteins, of which 133 were differentially expressed proteins in patients with OAB compared with the non-OAB group. Dysregulated pathways included cytoskeletal remodeling, Rho GTPase signaling, serotonergic signaling, and immune responses. Structural proteins such as ACTA2, CFL2, MYLK, and PPP1R12B were markedly downregulated, whereas GNA13 and multiple inflammatory mediators were upregulated. Functional analysis confirmed the enrichment of neurotransmitter catabolic processes, immune responses, and impaired cell-cell contact, suggesting structural disorganization and aberrant epithelial signaling in the OAB group.Conclusions: BOO-related OAB is associated with distinct molecular disturbances in cytoskeletal organization, neurotransmitter pathways, and immune responses. These proteomic findings provide novel insights into disease pathophysiology and highlight potential molecular targets for biomarker discovery and therapeutic interventions.