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The human testicular nuclear receptor 4 (TR4) is a critical regulatory gene for the progression of prostate cancer (PCa). Although it has been revealed that TR4 causes chemoresistance in PCa via the activation of octamer-binding transcription factor 4 (OCT4), the detailed mechanism remains unexplored. In the present study, it was revealed that inhibition of TR4 by shRNA in PCa enhanced the sensitivity to docetaxel in vitro and in vivo. TR4 induced the downregulation of miR-145 by directly binding it to the promoter of miR-145, which was confirmed by chromatin immunoprecipitation analysis and luciferase assay. The overexpression of miR-145 suppressed both the chemoresistance and the expression of OCT4 mRNA and protein. Additionally, the TR4 shRNA mediated re-sensitization to docetaxel, along with the downregulated expression of OCT4, were reversed by the concurrent inhibition of miR-145. The luciferase assay revealed that the activity of the wild-type OCT4 3′ untranslated region reporter was suppressed. This suppression diminished when the miR-145 response element mutated. These findings suggest an undescribed regulatory pathway in PCa, by which TR4 directly suppressed the expression of miR-145, thereby inhibiting its direct target OCT4, leading to the promotion of chemoresistance in PCa.

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague–Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.

Purpose The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients. Patients and Methods For the detection of the correlation between GATA3 expression and bladder cancer, we downloaded the mRNA expression data from the Cancer Genome Atlas (TCGA) database and conducted immunohistochemistry staining on formalin-fixed paraffin-embedded (FFPE) sample tissues. Then, bladder cancer cell lines were utilized to investigate the potential functions of GATA3 by cell apoptosis, proliferation and cycle assays. Results The mRNA data from TCGA database and bladder cancer cell lines suggested that GATA3 mRNA expression was significantly higher compared with normal tissues and cells. Conversely, the Western blot assay revealed that the expression of GATA3 was significantly lower in bladder cancer than normal urothelial cell line. Additionally, we found that over-expression of GATA3 was significantly associated with tumor subtype (P = 0.001 in TCGA; P = 0.004 in FFPE tissues), earlier clinical stage (P < 0.001 in TCGA; P < 0.001 in FFPE) and lower grade tumor (P = 0.057 in TCGA; P = 0.002 in FFPE). Kaplan-Meier analysis and multivariate Cox regression analysis indicated that age (P < 0.001 in both cohort), clinical stage (P = 0.028 in TCGA; P = 0.011 in FFPE), recurrence (P < 0.001) and low GATA3 in TCGA cohort (P = 0.035) but high GATA3 in FFPE cohort (P = 0.033) were independent risk factors for overall survival in patients. The assay to detect potential functions of GATA3 indicated that this biomarker could arrest the cell cycle of G2/M and S phase in T24 cells, and inhibit bladder cancer cells proliferation. Conclusion Collectively, our findings identified that GATA3 served as an important prognosis biomarker for bladder cancer patients. However, the mechanism of GATA3 in bladder cancer deserves further studies.

Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our in vitro assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability via cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments.

BACKGROUND This study aimed to perform coexpression analysis of the EZH2 gene using The Cancer Genome Atlas (TCGA) and the Oncomine databases to identify coexpressed genes involved in biological networks in breast cancer, glioblastoma, and prostate cancer, with functional analysis of the EZH2 gene in the C4-2 human prostate cancer cell line in vitro. MATERIAL AND METHODS Data from TCGA and Oncomine databases were analyzed to determine the expression of EZH2 and the top five coexpressed genes in breast cancer, glioblastoma, and prostate cancer and the clinical significance the coexpressed genes. Gene Ontology (GO) analysis was performed to predict the functions and pathways of EZH2 using pathway annotation. The role of EZH2 in the C4-2 human prostate cancer cell line was studied in vitro. RESULTS Analysis of 16 micro-arrays identified 185 genes that were coexpressed with EZH2. The top five coexpressed genes were MCM4, KIAA0101, MKI67, RRM2, and CDC25a. Increased expression of these genes and EZH2 were associated with reduced survival. Coexpressed genes were involved in biological networks associated with the cell cycle, mitosis, and DNA damage. The effects of EZH2 on prostate cancer cell was validated in vitro as knockdown of EZH2 resulted in a G2/M cell cycle arrest, increased DNA damage, and reduced colony number. CONCLUSIONS Coexpression analysis of EZH2 identified its role in the cell cycle, mitosis, and DNA repair. The molecular mechanisms involved in EZH2 gene expression in the cell response to DNA damage requires further study to determine whether EZH2 is a potential human cancer biomarker.

Indwelling ureteral stents represent a very frequently used procedure in urological clinical practice that ensures the drainage of urine from the upper urinary tract. However, the stents could result in many stent-associated complications, such as encrustation and patient discomfort. We developed a new type of biodegradable ureteral stents produced from degradable polyurethane and magnesium alloys. In the present study, we investigated the biocompatibility and the property of degradation of the biodegradable ureteral stents. We evaluated the cytotoxicity of biodegradable ureteral stent by the MTT assay in vitro. The rabbit dorsal muscle embedding test was used to assess the biocompatibility of the degradable stents. Inflammation and fibrosis of muscle tissue were noted to evaluate compatibility at 1, 2, 4, 6 weeks after stents implanted in muscle. The degradation of the biodegradable ureteral stents was assessed by measuring the weight loss of the samples in AUS (artificial urine solution). For validating the degradation property of degradable stents in vivo, we inserted a degradable stent or a conventional biostable stent into Bama pigs. Furthermore, blood studies, liver function tests, renal function tests, urine studies, and computerized tomography (CT) were performed postoperatively. Our study confirms that the degradable polyurethane-based biodegradable ureteral stent has good biocompatibility. Our biodegradable ureteral stents were completely degraded within 4 weeks and provided a better ability of drainage than conventional stents. They hold promise for decreasing the need for a secondary procedure and stent related morbidity, such as infections.

Growing evidence suggests that long non‐coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up‐regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up‐regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR‐515‐5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR‐515‐5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.

Background High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. Methods O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. Results Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. Conclusion We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. Graphical abstract Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.

The aim of this study was to access whether microsurgical subinguinal varicocelectomy (MSV) with testicular delivery has a better therapeutic effect than MSV without testicular delivery, including semen quality, serum testosterone (T) level and International Index of Erectile Function (IIEF)-5 score in infertility male patients with varicocele. In this prospective study, 181 patients were included and they chose the treatment by themselves. A total of 114 patients who received MSV without testicular delivery (TD) and 67 patients who received MSV with TD were followed-up 6 months after the operation. Semen parameters, serum T level and IIEF-5 scores were recorded before and 6 months after the operation. Results showed that MSV with or without TD could improve semen quality, serum T level and IIEF-5 score. For semen quality 6 months after the operation, there was no significant difference between patients received MSV with or without TD. But in patients with varicocele of grade III, MSV without testicular delivery improved the sperm concentration and motility more. And patients received MSV without TD have a higher T level 6 months after the operation, especially in patients ≤27 years. MSV with TD is not superior to that without, but this should be verified in more samples and a better designed randomised controlled study in the future.

The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia.

O-GlcNAcylation (O-GlcNAc) is a posttranslational modification that is mediated by O-GlcNAc-transferase (OGT) and reversed by O-GlcNAcase (OGA). Increasing evidence indicates that protein O-GlcNAcylation is increased in various types of cancer. In the present study, we aimed to evaluate the expression and function of both OGT and OGA in bladder cancer cells in vitro and in vivo. Expression data of OGT and OGA at the mRNA level was obtained from the Oncomine database. Effects of OGT and OGA on cell proliferate, invasive, and migratory abilities were assessed using MTT, wound healing, cell invasive assay, and cell cycle analysis. In vivo assay was also performed in nude mice. The results revealed that the expression of OGT in bladder cancer tissues was higher than that of normal tissues, while the OGA level was found to be lower in cancer tissues. We also found that knockdown of OGT could inhibit cell proliferation, migration, invasion, and induce cell cycle arrest, while these are reversed when OGA is inhibited. We also observed that O-GlcNAcylation could promote tumor formation in vivo, compared with a negative control. In summary, this study describes the oncogenic role of O-GlcNAcylation in bladder cancer cells.

To assess the efficacy and the safety of Greenlight(TM) high-performance system (HPS) 120-W laser photoselective vaporization of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for treatment of benign prostatic hyperplasia (BPH). The related original studies only including randomized controlled trials were searched by databases MEDLINE, EMBASE, Google Scholar, and the Cochrane Controlled Trial Register. The databases were updated till July 2014. The risk ratio, mean difference, and their corresponding 95% confidence intervals were calculated. Risk of bias of the enrolled trials were assessed according to Cochrane Handbook. A total of four trials involving 559 patients were enrolled. Statistical analysis was performed by software Review Manager (V5.3.3). There was no significant difference in International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) between PVP and TURP at 6-, 12-, and 24-month follow-up. Patients in the PVP group were associated with significantly lower risk of capsule perforation (risk ratio (RR) = 0.06, 95% confidence interval (95%CI) = 0.01 to 0.46; p = 0.007), significantly lower transfusion requirements (RR = 0.12, 95%CI = 0.03 to 0.43; p = 0.001), a shorter catheterization time (mean difference (MD) = -41.93, 95%CI = -54.87 to -28.99; p

Ureteral stents are widely used in the department of urology, while the stent could result in many stent-associated complications, such as encrustation, a forgotten stent and patient discomfort. Thus, we developed a novel gradient degradable ureteral stent, which could degrade gradient in vivo, and assessed its effectiveness of the drainage, degradation and biocompatibility in a beagle dog model. In the present study, the degradation time and cytotoxicity were investigated in vitro. And the beagle dogs were inserted with a degradable stent or a biostable stent, and blood studies, liver function tests, renal function tests, urine studies, X-ray, excretory urograms and computerized tomography were performed at immediately, two weeks, four weeks and six weeks postoperative. The results showed that the drainage of the novel stent is similar to the conventional stent, while the biocompatibility and antibacterial ability of the novel stents are better than the conventional stents. The stents we developed provide an alternative for urologists and more assays would be performed in detail to assess the property of the stents.