SUMMARYExcessive production of reactive oxygen species (ROS) by an overactive nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system in penile tissue is an important mechanism of erectile dysfunction (ED). S-allyl cysteine (SAC), a bioactive component derived from garlic, was recently reported to exert versatile antioxidant properties. We hypothesized that SAC would be able to resolve diabetes-related ED by reducing ROS generation, and designed this study to investigate this possibility as well as to determine the related underlying mechanisms. A streptozotocin-induced diabetes rat model was established and used for comparative analysis of 4-week treatment regimens with insulin or SAC. The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to determine erectile function. Differential levels of ROS, NADPH oxidase subunits, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling pathway, and apoptosis were evaluated in cavernous tissues. Max ICP/MAP was found to be markedly decreased in untreated diabetic rats; SAC, but not insulin, treatment restored the ratio to baseline (in non-diabetic untreated controls). The corpus cavernosum of untreated diabetic rats showed increased p47 phox and p67 phox expression, ROS production and penile apoptotic index, and decreased phospho-endothelial nitric oxide synthase (phospho-eNOS, Ser1177) expression, cGMP concentration, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio and smooth muscle cell number. SAC treatment normalized all the diabetes-induced effects, whereas insulin treatment partially normalized the alterations, but produced no effects on P47 phox expression, penile ROS level, apoptotic index, Bcl-2/Bax ratio and smooth muscle cell number. Collectively, these data indicate that SAC treatment can restore erectile function in diabetic rats by preventing ROS formation through modulation of NADPH oxidase subunit expression. Furthermore, the poor efficacy of conventional insulin treatment for diabetic ED may be associated with an elevated level of ROS in penile tissue.
Adipose-derived stem cells (ADSCs) have recently been considered as a promising therapy for erectile dysfunction (ED). However, the mechanism of ADSC-based therapy is unclear. Insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed in vitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment with labeled ADSCs or PBS. Eight additional 5-month-old rats were used as a young rat group. At 2 weeks post-transplantation, all rats were analyzed for erectile function, cavernous IGF-1, bFGF and VEGF levels, and penile histology. Conditioned medium and co-culture systems were used in cell experiments to detect how growth factors act on corpus cavernosum smooth muscle cells (CCSMCs) under oxidative stress conditions via crystal violet staining and immunofluorescence staining. We found that ADSCs secreted significantly higher IGF-1, bFGF, and VEGF levels in culture medium compared with basal medium. Compared with young rats, untreated aged rats had significantly lower Max ICP/MAP and ADSC treatment significantly increased the ratio. Immunofluorescence staining demonstrated a small number of labeled ADSCs in the corpus cavernosum. The untreated aged rats showed significantly decreased cavernous IGF-1, bFGF, and VEGF levels and significantly decreased contents of cavernous smooth muscle and endothelium compared with young rats. ADSC treatment partially normalized these alterations. In cell experiments, the groups receiving growth factor neutralizing antibody separately or combined had significantly decreased numbers of CCSMCs compared with control groups. These results indicated that ADSC treatment may improve aging-related ED partially through the secretion of IGF-1, bFGF, and VEGF.
The aim of the present study was to evaluate the diagnostic value of the ImmunoCyt test compared with urine cytology in detecting bladder cancer. A systematic literature search was performed to locate all publications reporting on the diagnostic accuracy of the ImmunoCyt test for bladder cancer. Data were extracted from 2×2 tables or calculated from reported accuracy data. Collected data were meta-analyzed for sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and summary receiver operator characteristic (sROC) curve analysis. We applied the Meta-DiSc 1.4 and STATA 13.0 software to the meta-analysis. Seven separate studies consisting of 1,602 patients with bladder cancer were considered in the meta-analysis. We found that the ImmunoCyt test had a higher sensitivity than the urine cytology test [0.725, 95% confidence interval (CI) 0.683–0.765 vs. 0.566, 95% CI, 0.521–0.611], but the specificity, positive LR, negative LR, DOR, area under the curve (AUC) and Q index of the ImmunoCyt test were lower compared with the urine cytology test. In addition, the pooled sensitivity, specificity, positive LR, negative LR, DOR, AUC, and Q index of the combined method (combination of ImmunoCyt and cytology) were 0.833, 0.644, 2.804, 0.228, 13.50, 0.8554 and 0.7863, respectively. The results of the Eggers test showed no publication bias (P>0.05). In conclusion, specificity, positive LR, negative LR, DOR, the AUC, and the Q index of the urine cytology test may be superior to the ImmunoCyt test, but the ImmunoCyt test has greater sensitivity than the urine cytology test. Use of ImmunoCyt and cytology in combination has the potential to improve the sensitivity and promises to be an alternative in the detection of bladder cancer.
BackgroundThis study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism.MethodsFirst, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells.ResultsWound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells.ConclusionERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5423-9) contains supplementary material, which is available to authorized users.
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