Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury.

PURPOSE: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). MATERIALS AND METHODS: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. RESULTS: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFß1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. CONCLUSIONS: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Circ_0001686 Promotes Prostate Cancer Progression by Up-Regulating SMAD3/TGFBR2 via miR-411-5p.

PURPOSE: As the mechanism of interaction between circular RNAs (circRNAs) and microRNAs (miRNAs) in regulating the development of prostate cancer (PCa) is not clear, this study focuses on investigating these effects. MATERIALS AND METHODS: Sample tissues were collected from the PCa of patients, and microarray analysis of human circRNAs was conducted. The expression of circ_0001686, hsa_miR-411-5p (miR-411-5p) were also detected by qRT-PCR. Circ_0001686 and miR-411-5p mimics were transfected into the PCa cell lines (CWR22RV1and LNCaP) and MTT, colony formation, Transwell, and scratch wound assays were used to analyze the biological behaviors of PCa cells. Si-circ_0001686 and ASO-miR-411-5p were used as negative controls, and dual-luciferase reporter assays were performed to verify the interactions among circ_0001686, miR-411-5p, and SMAD3/TGFBR2. The levels of SMAD3 and TGFBR2 in different treated PCa cells were measured by western blot, and in vivo experiments in a nude mouse model were carried out to strengthen the in vitro findings of miR-411-5p. RESULTS: The expression of circ_0001686 was up-regulated, while the expression of miR-411-5p was down-regulated in PCa cells. Moreover, circ_0001686 promoted cell proliferation, migration, and invasion. Molecular mechanism exploration revealed that circ_0001686 could reduce miR-411-5p, affecting the downstream target genes of SMAD3 and TGFBR2. In vitro and in vivo studies verified that miR-411-5p inhibits PCa progression. CONCLUSIONS: Circ_0001686 can reduce miR-411-5p to increase the expression of SMAD3/TGFBR2, which consequently promotes the proliferation, invasion, and migration of PCa cells.

Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145.

BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. RESULTS: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014). CONCLUSIONS: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.

Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review.

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.

Prognostic significance of urothelial carcinoma with divergent differentiation in upper urinary tract after radical nephroureterectomy without metastatic diseases: A retrospective cohort study.

To evaluate the impact of urothelial carcinoma with divergent differentiation (UCDD) on the prognosis of patients for primary upper urinary tract urothelial carcinoma (UTUC) with pN0/x status treated with radical nephroureterectomy (RNU) and to evaluate the prognostic value of UCDD in different tumor locations (renal pelvis and ureter).Data from a total of 346 patients with UTUC who received RNU between January 2012 and March 2016 in the institution were retrospectively analyzed. Clinicopathological features and prognostic factors age, sex, complaint, height, weight, blood pressure, tumor grade, stage, smoking status, history of adjuvant chemotherapy, tumor location, history of bladder cancer, tumor necrosis, degree of hydronephrosis, tumor size, tumor focality, and preoperative anemia were compared between patients with pure UTUC and patients with UCDD. The endpoints were cancer-specific survival (CSS), overall survival (OS), and intraluminal recurrence-free survival (IRFS).Overall, divergent differentiation was present in 50 patients (14.5%). UCDD was related to different tumor location (P = .01), smoking (P = .04), higher body mass index (P = .02), and advanced tumor grade (P = .01). By Kaplan-Meier analysis, UCDD was found to be significantly correlated with worse IRFS, CSS, and OS (all P < .01). Multivariate analysis demonstrated that UCDD was an independent predictor of IRFS (P < .01), CSS (P = .01), and OS (P = .01). However, 40 patients died for various reasons and the 5-year OS rates were 91.9% in UCDD- group and 68.0% in UCDD+ group, respectively. In patients with ureteral tumors, UCDD was the significant predictor for IRFS, CSS, and OS. However, the prognostic value of UCDD was not observed in pyelocaliceal tumors.The presence of divergent differentiation is associated with inferior survival. UCDD may identify patients at high risks for poor prognosis especially in patients with ureteral tumors. As a result, more attention and follow-up should be given to patients with ureteric urothelial carcinoma.

[Clinicopathological features of primary seminal vesicle adenocarcinoma: A report of 4 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis, and treatment of primary seminal vesicle adenocarcinoma (SVAC). METHODS: We analyzed the clinical data and clinicopathological characteristics of 4 cases of primary SVAC treated in the Department of Urology of the Second Hospital of Tianjin Medical University and reviewed relevant literature. RESULTS: All the 4 patients were treated by open radical resection of the seminal vesicle and prostate and pathologically diagnosed with SVAC. Preoperative prostatic biopsy had shown 1 of the cases to be negative, while preoperative CT and transrectal ultrasound had revealed a huge pelvic cystic neoplasm in another patient. Immunohistochemistry manifested that the 4 cases were all negative for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and cytokeratin 20 (CK20), but positive for cancer antigen 125 (CA125) and CK7. All the patients recovered smoothly after surgery and experienced no recurrence or metastasis during 154, 41, 20, and 12 months of follow-up. CONCLUSIONS: Primary seminal vesicle carcinoma is extremely rare and presents in an advanced stage. Immunohistochemistry plays a valuable role in its differential diagnosis. Various combinations of radical surgery, radiotherapy, androgen-deprivation therapy, and chemotherapy are recommended for the treatment of the disease.