Multi-Omics Characterization of Circular RNA-Encoded Novel Proteins Associated With Bladder Outlet Obstruction

Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.

Preliminary results of a randomized crossover clinical trial comparing a new electromagnetic and vibrating device and alpha-blocker agents in patients affected by bladder outlet obstruction secondary to benign prostatic hyperplasia

To the Editor, Benign Prostatic Hyperplasia (BPH) is one of the main causes of patients seeking urological counselling in Western countries. It has been estimated that nearly 70 percent of United States men between the ages of 60 and 69 years, and nearly 80 percent of men ≥ 70 years, have some degree of BPH [...].

Improved bladder contractility after transplantation of human mesenchymal stem cells overexpressing hepatocyte growth factor into underactive bladder from bladder outlet obstruction models of rats

Introduction An underactive bladder can lead to difficulty in voiding that causes incomplete emptying of the bladder, suggesting the need for a new strategy to increase bladder contractility in such patients. This study was performed to investigate whether human mesenchymal stem cells (hMSCs) were capable of restoring bladder contractility in rats with underactive bladder due to bladder outlet obstruction (BOO) and enhancing their effects by overexpressing hepatocyte growth factor (HGF) in hMSCs. Materials and methods The hMSCs were transplanted into the bladder wall of rats. Fifty female Sprague-Dawley rats at six weeks of age were divided into five groups: group 1: control; group 2: sham intervention; group 3: eight-week BOO; group 4: BOO rats transplanted with hMSCs; and group 5: BOO rats transplanted with hMSCs overexpressing HGF. Two weeks after the onset of BOO in groups 4 and 5, hMSCs were injected into the bladder wall. Cystometry evaluation was followed by Masson’s trichrome staining of bladder tissues. Realtime PCR and immunohistochemical staining were performed to determine for hypoxia, apoptosis, and angiogenesis. Results Collagen deposition of bladder increased in BOO but decreased after transplantation of hMSCs. The increased inter-contraction interval and residual urine volume after BOO was reversed after hMSCs transplantation. The decreased maximal voiding pressure after BOO was restored by hMSCs treatment. The mRNA expression of bladder collagen1 and TGF-β1 increased in BOO but decreased after hMSCs transplantation. The decrease in vWF-positive cells in the bladder following BOO was increased after hMSCs transplantation. Caspase 3 and TUNEL-positive apoptosis of bladder cells increased in BOO but decreased after transplantation of hMSCs. These effects were enhanced by overexpressing HGF in hMSCs. Conclusion Transplantation of hMSCs into bladder wall increased the number of micro-vessels, decreased collagen deposition and apoptosis of detrusor muscle, and improved bladder underactivity. The effects were enhanced by overexpressing HGF in hMSCs. Our findings suggest that the restoration of underactive bladder using hMSCs may be used to rectify micturition disorders in patients following resolution of BOO. Further studies are needed before hMSCs can be used in clinical applications.

Bladder Sonomorphological Tests in Diagnosing Bladder Outlet Obstruction in Patients with Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis

<b><i>Aims:</i></b> We aimed to investigate the accuracy of bladder sonomorphological parameters including detrusor wall thickness (DWT) and ultrasound-estimated bladder weight (UEBW) for diagnosing bladder outlet obstruction (BOO) in patients with lower urinary tract symptoms (LUTS). <b><i>Methods:</i></b> A comprehensive search was conducted through databases including PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, China Knowledge Network (CNKI), China Biomedical Literature Database, Wanfang Database, the Chongqing VIP Chinese Science, and Technology Periodical Database (VIP) to select studies assessing the diagnostic accuracy of DWT and UEBW to diagnose BOO in adults with LUTS. Databases were searched from inception to 2020 without restriction. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and measures of accuracy were calculated using random-effects model. <b><i>Results:</i></b> The initial search included 84 publications, of which 78 publications were screened, and 16 studies with 1,847 patients finally contained diagnostic data. The results from 10 out of 16 studies assessing DWT showed a pooled sensitivity (SSY) of 0.68 (95% CI, 0.56–0.78) and specificity (SPY) of 0.91 (95% CI, 0.82–0.96) with <i>I</i>² values of 93%, while 6 studies evaluating UEBW were analyzed with a SSY of 0.88 (95% CI, 0.78–0.93) and SPY of 0.81 (95% CI, 0.67–0.90) with <i>I</i>² values of 83%. <b><i>Conclusions:</i></b> DWT shows high SPY, and UEBW performs high SSY of diagnosing BOO. Further well-designed studies are needed to evaluate the utilization of DWT and UEBW for the diagnosis of BOO.

Differentially Expressed Genes Correlated with Fibrosis in a Rat Model of Chronic Partial Bladder Outlet Obstruction

Chronic partial bladder outlet obstruction (PBOO) is a prevalent clinical problem that may result from multiple etiologies. PBOO may be a secondary condition to various anatomical and functional abnormalities. Bladder fibrosis is the worst outcome of PBOO. However, gene alterations and the mechanism of fibrosis development after PBOO onset are not clear. Therefore, we aimed to investigate gene expression alterations during chronic PBOO. A rat model of PBOO was established and validated by a significant increase in rat bladder weight. The bladder samples were further analyzed by microarray, and differentially expressed genes (DEGs) that are more related to PBOO compared with the control genes were selected. The data showed that 16 significantly upregulated mRNAs and 3 significantly downregulated mRNAs are involved in fibrosis. Moreover, 13 significantly upregulated mRNAs and 12 significantly downregulated mRNAs are related to TGFB signaling. Twenty-two significantly upregulated mRNAs and nine significantly downregulated mRNAs are related to the extracellular matrix. The genes with differential expressions greater than four-fold included Grem1, Thbs1, Col8a1, Itga5, Tnc, Lox, Timp1, Col4a1, Col4a2, Bhlhe40, Itga1, Tgfb3, and Gadd45b. The gene with a differential expression less than a quarter-fold was Thbs2. These findings show the potential roles of these genes in the physiology of PBOO.

Modified bladder outlet obstruction index for powerful efficacy prediction of transurethral resection of prostate with benign prostatic hyperplasia

Background The correlation between modified bladder outlet obstruction index (MBOOI) and surgical efficacy still remains unknown. The purpose of the study was to investigate the clinical value of the MBOOI and its use in predicting surgical efficacy in men receiving transurethral resection of the prostate (TURP). Methods A total of 403 patients with benign prostate hyperplasia (BPH) were included in this study. The International Prostate Symptom Score (IPSS), quality of life (QoL) index, transrectal ultrasonography, and pressure flow study were conducted for all patients. The bladder outlet obstruction index (BOOI) (PdetQmax–2Qmax) and MBOOI (Pves–2Qmax) were calculated. All patients underwent TURP, and surgical efficacy was accessed by the improvements in IPSS, QoL, and Qmax 6 months after surgery. The association between surgical efficacy and baseline factors was statistically analyzed. Results A comparison of effective and ineffective groups based on the overall efficacy showed that significant differences were observed in PSA, Pves, PdetQmax, Pabd, BOOI, MBOOI, TZV, TZI, IPSS-t, IPSS-v, IPSS-s, Qmax, and PVR at baseline (p < 0.05). Binary logistic regression analysis suggested that MBOOI was the only baseline parameter correlated with the improvements in IPSS, QoL, Qmax, and the overall efficacy. Additionally, the ROC analysis further verified that MBOOI was more optimal than BOOI, TZV and TZI in predicting the surgical efficacy. Conclusion Although both MBOOI and BOOI can predict the clinical symptoms and surgical efficacy of BPH patients to a certain extent, however, compared to BOOI, MBOOI may be a more useful factor that can be used to predict the surgical efficacy of TURP. Trial registration retrospectively registered.

Identifying occult bladder outlet obstruction in women with detrusor-underactivity-like urodynamic profiles

Voiding dysfunction can result from detrusor underactivity (DU), bladder outlet obstruction (BOO), or both. Conceptually, women with high-pressure low-flow urodynamic profiles are diagnosed with BOO without DU. However, the possibility of BOO is often neglected in women with DU-like (low-pressure low-flow) urodynamic (UDS) profiles. By reviewing the videourodynamic studies (VUDS) of 1678 women, our study identified the key factors suggesting urodynamic BOO (determined by radiographic evidence of obstruction) in women with DU-like UDS profiles (Pdet.Qmax < 20 cmH2O and Qmax < 15 mL/s). In 355 women with DU-like UDS profiles, there were 70 (19.7%) with BOO and 285 (80.3%) without BOO. The BOO group had predominantly obstructive symptoms. The BOO group showed significantly decreased bladder sensation, lower detrusor pressure (Pdet.Qmax), lower flow rate (Qmax), smaller voided volume, and larger post-voiding residual (PVR) compared to the non-BOO group. In multivariate analysis, volume at first sensation, Qmax, PVR, and detrusor overactivity (DO) remained independent factors for BOO. The receiver operating characteristic (ROC) areas for the parameters were largest for PVR (area = 0.786) and Qmax (area = 0.742). The best cut-off points were 220 mL for PVR and 4 mL/s for Qmax. Our findings provide simple indicators for BOO in women with DU.

A Brunn’s cyst as a cause of bladder outlet obstruction: a case report

A Brunn’s cyst in the proximity of the bladder neck is a rare cause of bladder outlet obstruction. This case study concerns a 45-year-old male presenting with bladder outlet obstruction secondary to a Brunn’s cyst. A provisional diagnosis of Brunn’s cyst was based on ultrasonography, CT scan and cystoscopic examination which indicated a cystic lesion at the bladder neck. Transurethral resection of the cyst was performed with successful resolution of the obstructive voiding symptoms. The final diagnosis of this case based on the pathology is a Brunn’s cyst.