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Abstract Background MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are indicated to play essential roles in spermatogenesis. However, little is known about the expression patterns or function of miRNAs in human testes involved in infertility. Methods In this study, the miRNA expression profiles of testes of patients with non-obstructive azoospermia (NOA) and normal controls were performed by using microarray technologies. Results Altered microRNA expression in NOA patients was found, with 154 differentially down-regulated and 19 up-regulated miRNAs. These findings have been confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assays on select miRNAs, including miR-302a, miR-491-3p, miR-520d-3p and miR-383. Several down-regulated miRNA clusters in patients with NOA were identified, such as the oncogenic potential of the mir-17-92 cluster and mir-371,2,3 cluster. Conclusion This is the first report that the expression of miRNAs is altered in testicular tissues of patients with NOA, suggesting a role of miRNAs in regulating spermatogenesis in human males.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men. Previous studies demonstrated that the immune mediators, including interleukin (IL)-1β, IL-6, interferon-γ, tumor necrosis factor-α, and immunoglobulins, are elevated in the expressed prostate secretions and seminal fluid of CP/CPPS men. The memory T, T helper 1 (Th1), Th17, and Th22 cells increase in the peripheral blood of CP/CPPS men. Additionally, prostate antigens specific-autoreactive T cells are identified in CP/CPPS patients. After generally reviewing and comparing the inflammatory responses in autoimmune diseases and CP/CPPS, we presumed that CP/CPPS is more likely to be defined as an autoimmune disease. Thus, a better understanding of autoimmune diseases would contribute to a deeper understanding of the CP/CPPS and provide new inspirations for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Prostatic calculi (PCal) are commonly present with prostate disease; we aim to map the incidence and associated clinical risk factors of PCal in Han Chinese. We retrospectively selected men who sought a medical check-up in 2018. Basic clinical items, including age, weight, height, prostate specific antigen (PSA), uric acid (UA), fasting blood glucose (FBG), urinalysis results, and transabdominal prostate ultrasound, were recorded. Univariate and logistic regression analyses were performed to evaluate whether these factors were associated with the presence of PCal. We recorded the parameters of laboratory tests and clinical information from 14,427 men; men with PCal comprised 51.65% of the total group and 76.61% of the subgroup of benign prostate hyperplasia (BPH) patients. All the enrolled parameters showed meaningful differences, but the logistic regression analysis only indicated significant effects related to age (OR = 1.044, 95% CI = 1.040–1.047, and p <.001), body mass index (BMI) (OR = 1.035, 95% CI = 1.022–1.048, and p <.001), UA (OR = 0.999, 95% CI = 0.999–1.000, and p =.029), BPH (OR = 2.923, 95% CI = 2.678–3.191, and p <.001), and prostate cysts (OR = 0.609, 95% CI = 0.471–0.788, and p <.001). The odds ratio of the predicted combined model is 1.068. PCal was detected in 51.65% of men among healthy Han Chinese and in 76.61% of BPH patients. Age, BMI, UA, BPH, and prostate cysts were independent risk factors for the presence of PCal. [ABSTRACT FROM AUTHOR]

Objectives: Patients with autosomal dominant polycystic kidney disease (ADPKD) showed relatively high incidence of urinary stones. Enlarged kidneys occupied by cysts could make the stone-removal surgery relatively difficult. This study aimed to compare the efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU), flexible ureteroscopic lithotripsy (FURL) and percutaneous nephrolithotomy (PCNL) in the ADPKD patients with upper urinary stones. Methods: In this study, 45 patients with ADPKD who underwent RPLU, FURL and PCNL procedures were evaluated. Demographic and serum parameters, stone features, outcomes and complications were analyzed. Results: 45 patients were included in the present study, 13 received RPLU, 21 received FURL, and 11 received PCNL. There were no significant differences in demographic and serum parameters between the three groups. Stone-free rates of the three approaches are 100%, 85.7% and 90.9%, respectively. Patients who underwent FURL had shorter mean operative time and postoperative hospital stay. Compared to RPLU and PCNL, FURL resulted in fewer complications, but the difference is statistically non-significant. Conclusions: RPLU, FURL and PCNL are commonly used surgical methods to solve upper urinary calculi in ADPKD patients and could achieve satisfactory stone clearance. Among them, FURL showed a relative high safety and faster recovery. [ABSTRACT FROM AUTHOR]

E3 ubiquitin ligase gene, WWP2, is associated with acute kidney injury (AKI). This research was conducted to explore the role of WWP2 in AKI. AKI cell model was produced in human renal proximal tubular epithelial cell line (HK‐2) by ischemia‐reperfusion (IR) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR‐induced HK‐2 cells. Quantitative real‐time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down‐regulated and p53 was up‐regulated in IR‐induced HK‐2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR‐induced HK‐2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI, showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment. Significance of the study: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects and mechanisms of baicalin against prostate cancer cell growth and cell cycle progression. A human prostate cancer cell line LNCaP was engrafted into nude mice, and the oncogenicity of LNCaP cells was analyzed. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure LNCaP and PC3 proliferation capability. CDK6 mRNA level was detected using qRT-PCR. Western blotting was performed to assess the levels of cell cycle-associated proteins. In addition, cell cycle and apoptosis were analyzed using flow cytometry. Baicalin significantly decreased the expression of cell cycle-associated proteins. Furthermore, baicalin showed an observable effect on proliferation, cell cycle progression and apoptosis in LNCaP and PC3 cells. Upregulation of CDK6 and FOXM1 reversed the effect of baicalin. CDK6- and FOXM1-mediated cell growth attenuated the protective effect of baicalin in prostate cancer. This study presented an understanding of the role and mechanism of baicalin in prostate cancer cells, providing a new target and therapies for the prevention and treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the regulatory mechanism of cancer‐associated fibroblasts (CAFs) exosome in bladder cancer (BC) cell proliferation and invasion. CAFs and normal fibroblasts (NFs) were isolated from tumor tissues and adjacent normal tissues of BC patients, and examined by immunocytochemistry for the expression of fibroblast activation protein alpha (FAP) and α‐smooth muscle actin (α‐SMA). Exosomes were extracted from CAFs and NFs and observed under a transmission electron microscope, and expression of the exosome markers CD9 and CD63 was confirmed by western blotting. The distribution and intensity of fluorescence were observed by confocal laser microscopy to analyze exosomes uptake by BC cell lines T24 or 5367. BC cell proliferation and invasion were detected by MTT and Transwell assays, respectively. LINC00355 levels in CAFs, NFs, CAFs exosome, NFs exosome, and BC cells were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Results showed that CAFs exosome significantly promoted BC cell proliferation and invasion relative to NFs exosome. LINC00355 expression was significantly elevated in CAFs exosome when compared with that in NFs‐exosome. Up‐regulated LINC00355 expression was observed both in T24 and 5367 cells co‐incubated with CAFs exosome. Exosomes derived from LINC00355 siRNA‐transfected CAFs observably repressed BC cell proliferation and invasion when compared with control siRNA‐CAFs exosome. In conclusion, CAFs exosome–mediated transfer of LINC00355 regulates BC cell proliferation and invasion. Significance of the study. In this study, our data suggest that the exosomes released from CAFs promote BC cell proliferation and invasion. The mechanism of this effect is, at least in part, related to the increased LINC00355. Regulation of LINC00355 expression in exosomes released from CAFs might be a putative therapeutic strategy against the pathogenesis of BC. [ABSTRACT FROM AUTHOR]

Objective: Levels of urinary prostatic exosomal protein (PSEP) were detected to evaluate the clinical potential of PSEP as a diagnostic marker of chronic prostatitis (CP). Materials and methods: The level of urinary PSEP was measured in 412 cases by an enzyme-linked immunosorbent assay kit, including 202 controls and 210 CP cases. Of the CP patients, 116 cases met the definition of the USA National Institutes of Health category III (NIH-III), with 60 cases of NIH-IIIA and 56 cases of NIH-IIIB. The ages, body mass indexes (BMI), white blood cell (WBC) levels in expressed prostatic secretions (EPS), lecithin body counts in EPS, urine PSEP levels both before and after prostate massage obtained from the CP patients and NIH-CPSI scores were analyzed. Results: In the diagnosis of CP, the PSEP contents in the urine samples before and after prostate massage manifested a sensitivity of 86.93% vs. 61.06%, and a total coincidence rate of 85.24% vs. 61.06%, respectively. The area under the ROC curve was 0.926 vs. 0.709 for the before and after massage PSEP contents, respectively. Besides, during the follow-up of patients with CP, the improvement in symptoms was not correlated with the level changes of PSEP. Conclusion: Measurement of PSEP levels for the clinical diagnosis of CP is objective and painless. It could be a novel, simple, and noninvasive method for the diagnosis of CP. However, differences in fluid intake may result in a concentration or dilution of urine, which would ultimately affect the judgment of PSEP results. [ABSTRACT FROM AUTHOR]

Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) commonly experience learning and memory decline and the underlying pathogenesis remains unclear. Therefore, we aimed to study the effects of CP/CPPS on cognitive function by using a mouse model of experimental autoimmune prostatitis (EAP). Non-obese diabetic mice were immunized subcutaneously by prostate antigen and adjuvant twice and tested for cognitive performance by Morris water maze and novel object recognition test after the EAP induction. Then, dendritic complexity and spine densities were measured by using the Golgi-Cox procedure. Transmission electron microscopy was used to observe the synaptic morphology. In addition, activation of microglia and its association with synapses were also investigated by immunofluorescence staining. Our results showed that EAP induced a notable decrease in the learning and memory ability of mice, simultaneously causing a reduction in dendritic complexity detected by Sholl analysis. Likewise, the spine densities and synaptic proteins including synaptophysin and postsynaptic density protein 95 (PSD95) were significantly decreased in the EAP group. These observations were also accompanied by structural changes in synaptic plasticity. Additionally, EAP mice showed microglial activation in the hippocampus, and these activated microglia further increased contact with synaptic terminals. Taken together, our data are the first to indicate that EAP induces cognitive declines and structural neuroplastic changes in mice, accompanied by microglial activation and microglia-synapse contacts. [ABSTRACT FROM AUTHOR]

Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund's adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-γ was increased, and TGF-β was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-β and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo. Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP. [ABSTRACT FROM AUTHOR]

Objective: To present our experience of combining transperitoneal robot-assisted laparoscopic pyeloplasty (RALP) and concomitant flexible cystoscope lithotomy for ureteropelvic junction obstruction (UPJO) complicated by renal caliceal stones in the same session. Patients and methods: Between October 2014 and November 2017, RALP combined with flexible cystoscope lithotomy was performed in 16 patients with UPJO and ipsilateral renal caliceal stones. Stone location and size were preoperatively assessed. After pyelotomy with appropriate length (about 8–15 mm), a 16F flexible cystoscope through the assistant trocar or robotic trocar was introduced directly into the renal pelvis under laparoscopic vision. Holmium laser lithotripsy and pressure irrigation via a pump were used for caliceal stone removal. Subsequently, robot-assisted laparoscopic pyeloplasty was undergone in a standard fashion. Results: The calculi sizes ranged from 5 to 34 mm (mean 18.6 mm) and an average of 3.4 stones per patient was removed (range 1–8 stones). Complete stone clearance confirmed by postoperative imaging was achieved in all patients. Mean operative time was 204.6 min and estimated blood loss was 55.6 mL. Mean hospital stay was 6.7 days (3–17). The stent was removed after 8 weeks. No major intraoperative or postoperative complications were noted during a mean follow-up of 10.4 months (range 6–27 months). Conclusions: RALP combined with flexible cystoscope lithotomy is safe and effective alternatives for the simultaneous management of UPJO complicated by renal caliceal stones. [ABSTRACT FROM AUTHOR]