MicroRNA-488 inhibits progression of colorectal cancer via inhibition of the mitogen-activated protein kinase pathway by targeting claudin-2.

Colorectal cancer (CRC) affects people globally, and lymph node metastasis (LNM) is an important indicator of poor clinical outcome in CRC. The current study aims to evaluate the role of microRNA-448 (miR-488) and claudin-2 (CLDN2) in epithelial-mesenchymal transition (EMT) and LNM of CRC through the MAPK signaling pathway. First, microarray analysis indicated that miR-488 was poorly expressed in CRC, whereas CLDN2 was highly expressed. Additionally, the bioinformatics website MicroRNA.org and the dual luciferase reporter gene assay found that CLDN2 was a target gene of miR-488. Next, the results for the correlations between expression of miR-488 and clinicopathological characteristics of CRC indicated that the expression of miR-488 was closely associated with differentiation degree, LNM, and Dukes stages in CRC patients. Moreover, overexpression of miR-488 inhibited the activation of the MAPK signal transduction pathway. Notably, loss- and gain-of-function experiments demonstrated that upregulation of miR-488 suppressed SW480 cell viability, invasion, and migration and promoted apoptosis in SW480 cells. Finally, overexpression of miR-488 inhibited LNM, microlymphatic vessel density, and tumor growth in nude mice. We conclude that overexpression of miR-488 could suppress the cell proliferation, EMT, and LNM of CRC cells via inhibition of the CLDN2-mediated MAPK signaling pathway, which could be a new molecular therapy target for CRC.

Vitamin E consumption and the risk of bladder cancer.

Background: Vitamin E has anti-cancer properties, which was demonstrated mainly due to its antioxidant effect. Several epidemiological studies have investigated the association between vitamin E consumption and the risk of bladder cancer. However, the results were inconsistent. The meta-analysis study aimed to evaluate the association of vitamin E consumption and the risk of bladder cancer. METHODS: We conducted a systematic literature search in the electronic databases, which included MEDLINE, EMBASE and the Cochrane Library till 1 January 2016. The pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were calculated depending on the heterogeneity among studies. Subgroup analysis and sensitivity analysis were also performed. Publication bias was assessed using Begg's test and Egger's test. RESULTS: A total of 11 prospective studies (3 randomized clinical trials and 8 cohort studies) including 575601 participants were identified to be eligible for our present meta-analysis. The pooled RRs with 95% CI for highest versus lowest vitamin E consumption was 0.89 (0.78-1.00). An inverse linear association between vitamin E consumption and bladder cancer risk was detected in the dose response analysis. The results were also stable in the subgroup analysis and sensitivity analysis. Meanwhile, no obvious publication bias was observed. CONCLUSIONS: Our study indicates that vitamin E consumption was inversely associated with the risk of bladder cancer.

HOXA11-AS promotes the growth and invasion of renal cancer by sponging miR-146b-5p to upregulate MMP16 expression.

Recently, increasing studies showed that long noncoding RNAs (lncRNAs) play critical roles in tumor progression. However, the function and underlying mechanism of HOMEOBOX A11 antisense RNA (HOXA11-AS) on renal cancer remain unclear. In the current study, our data showed that the expression of HOXA11-AS was significantly upregulated in clear cell renal cell carcinoma (ccRCC) tissues and cell lines. High HOXA11-AS expression was associated with the advanced clinical stage, tumor stage, and lymph node metastasis. Function assays showed that HOXA11-AS inhibition significantly suppressed renal cancer cells growth, invasion, and ETM phenotype. In addition, underlying mechanism revealed that HOXA11-AS could act as a competing endogenous RNA (ceRNA) that repressed miR-146b-5p expression, which regulated its downstream target MMP16 in renal cancer. Taken together, our findings suggested that HOXA11-AS could promote renal cancer cells growth and invasion by modulating miR-146b-5p-MMP16 axis. Thus, our findings suggested that HOXA11-AS could serve as potential therapeutic target for the treatment of renal cancer.

MicroRNA-184 inhibits proliferation and promotes apoptosis of human colon cancer SW480 and HCT116 cells by downregulating C-MYC and BCL-2.

This study aimed to investigate the effects of microRNA-184 (miR-184) on the proliferation and apoptosis of human colon cancer cells through the regulation of C-MYC and BCL-2. Human colon cancer tissues were selected as case group, and adjacent normal tissues were as control group. Human colon cancer SW480 and HCT116 cells were allocated into blank, miR-184 mimic negative control (mimic-NC), miR-184 inhibitor NC (inhibitor-NC), miR-184 mimic, and miR-184 inhibitor groups. Flow cytometry, Annexin V/PI and MTT assay were used to examine the cell cycle, apoptosis and viability. The expressions of C-MYC, BCL-2 and miR-184 were detected via immunohistochemistry, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR). C-MYC and BCL-2 were direct targets to miR-184. The growth of colon cancer cells in the miR-184 mimic group was inhibited and exhibited an increase in apoptosis. Cell growth in the miR-184 mimic group was increased in addition to the inhibition of apoptosis. Compared with miR-184 mimic group, the expressions of C-MYC and BCL-2 in miR-184 inhibitor group were increased. The expressions of C-MYC and BCL-2 in colon cancer tissues exhibited high levels of expression, while miR-184 displayed relatively low levels in comparison to the adjacent normal tissues. An association was detected regarding the expressions of miR-184, C-MYC and BCL-2 with the differentiation, invasion depth and lymph node metastasis. MiR-184 expression was negatively related to C-MYC and BCL-2 expressions. Our study suggested that miR-184 could inhibit proliferation and promote apoptosis of colon cancer cells by down-regulating expressions of C-MYC and BCL-2.

Decreased expression of BRAF-activated long non-coding RNA is associated with the proliferation of clear cell renal cell carcinoma.

BACKGROUND: BRAF-activated long non-coding RNA (BANCR) has been associated with various types of cancer. Nevertheless, the role of BANCR in clear cell renal cell carcinoma (ccRCC) is still not fully understood. This study aims to investigate the relationship between ccRCC and BANCR. METHODS: Expression of BANCR in TCGA renal cancer data sets was analyzed. The expression pattern of BANCR in Immortalized normal human proximal tubule epithelial cell line HK-2 and ccRCC cell lines (ACHN, CAKI-1, A498 and 786-O) was detected by real-time quantitative RT-PCR (qRT-PCR). ccRCC tissues with adjacent normal renal tissues diagnosed by pathological methods from 62 patients were used to detect the expression of BANCR, and its correlation with prognosis of ccRCC patients was assessed by Kaplan-Meier method. The LV-BANCR vector was used to examine the influence of BANCR on the proliferation, migration, invasion, apoptosis and cell cycle distribution of ccRCC cells in vitro. RESULTS: BANCR was downregulated in renal cancer according to TCGA data sets. Compared with adjacent normal renal tissues and normal human proximal tubule epithelial cell line HK-2, BANCR expression was significantly decreased in ccRCC tissues and ccRCC cell lines, and its low expression was associated with poor prognosis. Moreover, in the condition of BANCR overexpression by LV-BANCR vector, the proliferation, migration, invasion capacity of ccRCC cells was inhibited, while the apoptosis was increased and the G1 cell cycle arrest was induced in vitro. CONCLUSIONS: BANCR is downregulated in ccRCC tissues and cell lines, and is associated with ccRCC progression. Thus, BANCR may represent a novel prognostic biomarker and a potential therapeutic target for ccRCC patients.

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer.

P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control. A growing number of studies have demonstrated that several piRNA and PIWI proteins are aberrantly expressed in various kinds of cancers and may probably serve as a novel biomarker and therapeutic target for cancer treatment. Nevertheless, their specific mechanisms and functions need further investigation. In this review, we discuss about the biogenesis, functions and the emerging role of piRNAs and PIWI proteins in cancer, providing novel insights into the possible applications of piRNAs and PIWI proteins in cancer diagnosis and clinical treatment.

Anti-proliferative potential of Glucosamine in renal cancer cells via inducing cell cycle arrest at G0/G1 phase.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common types of cancer in urological system worldwide. Recently, the anticancer role of Glucosamine has been studied in many types of cancer. The aim of this study was to investigate the effects of Glucosamine on RCC. METHODS: The effects of Glucosamine on RCC cell proliferation and apoptosis were investigated by MTT assay and Annexin V-FITC Apoptosis assay, respectively in vitro. Cell cycle was detected by flow cytometry after treatment with Glucosamine. Protein levels of several cell cycle associated markers were examined by Western Blot. RESULTS: Our data showed that Glucosamine significantly inhibited the proliferation of renal cancer 786-O and Caki-1 cells in a dose-dependent manner. Besides, Glucosamine treatment resulted in cell cycle arrest at G0/G1 phase in both cell lines. Meanwhile, the expression of several regulators that contribute to G1/S phased transition, such as Cyclin D1, CDK4 and CDK6, were significantly down-regulated with the up-regulation of cell cycle inhibitors, p21 and p53, after treatment with glucosamine. However, the apoptosis rate of RCC cells was down-regulated when treatment with Glucosamine at 1 mM and 5 mM, while up-regulated at 10 mM. CONCLUSIONS: Our findings indicated that Glucosamine inhibited the proliferation of RCC cells by promoting cell cycle arrest at G0/G1 phase, but not promoting apoptosis. The present results suggested that Glucosamine might be a potential therapeutic agent in RCC treatment in the future.

Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma.

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

Up-regulation of flotillin-2 is associated with renal cell carcinoma progression.

Flotillin-2 (FLOT2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathway. FLOT2 has recently been identified to be involved in tumorigenesis of several cancers such as breast cancer, melanoma, and gastric cancer. However, the role of FLOT2 in renal cell carcinoma (RCC) remains unclear. The expression levels of FLOT2 in RCC patients and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. FLOT2 protein expression was also analyzed in archived paraffin-embedded RCC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Small-interfering RNA (siRNA) was used to suppress FLOT2 expression in RCC cell lines. In vitro assays were performed to further explore its role in tumor progression. The expression level of FLOT2 was higher in RCC tissues and cell lines than in corresponding adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2. IHC analysis revealed high expression levels of FLOT2 in RCC specimens. The RCC patients with higher FLOT2 expression had an advanced clinical stage and poorer prognosis than those with lower FLOT2 expression. FLOT2 expression was an independent prognostic marker of overall RCC patient survival in a multivariate analysis. In vitro assays indicated that knockdown of FLOT2 reduced cell proliferation, migration, and invasion. Our data suggest that FLOT2 is a novel molecule involved in RCC progression, which provide a potential prognostic biomarker and therapeutic target.

Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials.

AIM: Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 12 (two randomized controlled trials, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSION: The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

Preventive effect of phosphodiesterase 5 inhibitor tadalafil on experimental post-pyelonephritic renal injury in rats.

BACKGROUND: To evaluate the effects of Tadalafil, a phosphodiesterase 5 enzyme inhibitor, on Escherichia coli-induced renal damage in an acute pyelonephritis (PN) rat model. METHODS: Experimental PN was induced in 32 Wistar rats, and four groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (Tadalafil), and group 4 (antibiotic + Tadalafil). Antibiotic was given on days 3 to 8, and Tadalafil was administered between days 0 and 28 of bacterial inoculation. Half of the rats were killed on the ninth day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the sixth week of the study and evaluated for histopathological parameters and renal fibrosis markers. RESULTS: Inflammatory activity was significantly milder in rats treated with antibiotic + Tadalafil versus no treatment group both in the early and late periods. In the late period, interstitial fibrosis or tubular atrophy was lower in the antibiotic + Tadalafil group versus the no treatment and antibiotic groups, and in Tadalafil versus antibiotic group. Tadalafil administration significantly reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. In addition, circulating tumor necrosis factor α, interleukin 1ß was greatly reduced in Tadalafil group versus the no treatment group. CONCLUSIONS: We have provided the first evidence that phosphodiesterase 5 enzyme inhibitor Tadalafil ameliorates circulating inflammatory cytokines, reverses oxidant/antioxidant dysfunction and eventually possesses an overall protective effect on renal tissue from Escherichia coli-induced PN-related kidney injury. Phophodieterase 5 inhibitor might be a novel therapeutic target for PN.

Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis.

BACKGROUND: The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis. METHODS: Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration. RESULTS: Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P < 0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P < 0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761). CONCLUSION: Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required.

VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α.

Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.

[Safety and efficacy of L-carnitine and tadalafil for late-onset hypogonadism with ED: a randomized controlled multicenter clinical trial].

OBJECTIVE: To evaluate the safety and effect of L-carnitine combined with tadalafil in the treatment of late-onset hypogonadism (LOH) with erectile dysfunction (ED). METHODS: We randomly divided 140 cases of LOH with ED aged 40 -70 years into a treatment and a control group to receive L-carnitine + tadalafil and testosterone undecanoate + tadalafil, respectively. After 8 weeks of treatment, we obtained the scores on IIEF-5 and Aging Male Symptoms (AMS), observed changes in the levels of sex hormones, analyzed the results of the routine blood test and PSA level, and evaluated the safety of medication. RESULTS: Finally, 110 cases were included, 60 in the treatment group and 50 in the control. After 8 weeks of medication, the IIEF-5 and AMS scores were significantly improved as compared with the baseline both in the treatment group (17.7 +/- 3.5 vs 10.2 +/- 2.7 and 36.2 +/- 6.5 vs 48.8 +/- 5.8) and in the control group (16.7 +/- 2.6 vs 9.3 +/- 2.4 and 35.8 +/- 6.6 vs 50.7 +/- 5.0) (both P < 0.05), with no significant differences between the two groups (P > 0.05). As for the safety of medication, there were no significant differences between the two groups before and after treatment (P > 0.05). Two patients in the control group showed a PSA level > 4 microg/L, which was confirmed to be caused by prostatitis during follow-up. CONCLUSION: L-carnitine combined with tadalafil is safe and effective for the treatment of LOH with ED.

Statin use and risk of bladder cancer: a meta-analysis.

PURPOSE: Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on bladder cancer is conflicting. To quantify the association between statin use and risk of bladder cancer, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: A literature search was carried out using MEDLINE, EMBASE, and OVID databases between January 1966 and October 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed- and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95 % confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. RESULTS: A total of 13 (three RCTs, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies, but no publication bias. Pooled results indicated a nonsignificant increase in total bladder cancer risk among all statin users [RR = 1.07, 95 % CI (0.95, 1.21)]. Long-term statin use did not significantly affect the risk of total bladder cancer [RR = 1.21, 95 % CI (0.92, 1.59)]. In our subgroup analyses, the results were not substantially affected by study design, region, and confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSIONS: The findings of this meta-analysis suggested that there was no association between statin use and risk of bladder cancer. More studies, especially RCTs, are needed to confirm this association.

A comparative study of thulium laser resection of the prostate and bipolar transurethral plasmakinetic prostatectomy for treating benign prostatic hyperplasia.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown. We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume. OBJECTIVE: To compare the safety and short-term efficacy of thulium laser resection of the prostate (TMLRP) and bipolar transurethral plasmakinetic prostatectomy (TUPKP) for the treatment of patients with benign prostatic hyperplasia (BPH). METHODS: A total of 100 patients diagnosed with BPH were randomly divided into two groups, treated with either TMLRP (50, group 1) or TUPKP (50, group 2). There was no significant difference in preoperative variables such as age, prostate volume, prostate-specific antigen (PSA) level, International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ) and postvoid residual urine volume (PVR) between the two groups. The perioperative parameters and therapeutic effects were recorded and compared between the two groups. RESULTS: There were significant differences in the following parameters between the two groups (TMLRP vs TUPKP [mean ± SD]): operation duration, 61.2 ± 24.2 vs 30.14 ± 15.9 min; catheterization time, 1.8 ± 0.4 vs 3.2 ± 0.6 d; postoperative hospital stay, 3.3 ± 0.8 vs 4.1 ± 1.3 d. The volume of blood loss and postoperative bladder irrigation were significantly lower in TMLRP group than in the TUPKP group. At 1 month after the operation, there were four cases of urethral stricture in the TUPKP group. At 3 months after the operation, IPSS, quality of life (QoL), Qmax and PVR were significantly improved, with no significant difference between the two groups. CONCLUSIONS: TMLRP is superior to TUPKP in terms of safety, blood loss, recovery time and complication rate, and is as efficacious as TUPKP for treating BPH. Operation duration was significantly longer in the TMLRP group than in the TUPKP group.

Epigallocatechin gallate attenuates interstitial cystitis in human bladder urothelium cells by modulating purinergic receptors.

BACKGROUND: Epigallocatechin gallate (EGCG) has exhibited antitumor properties against bladder cancer. However, its effects in interstitial cystitis (IC) have not been investigated. METHODS: Here, we performed repeated cystoscopy and re-biopsy of bladder mucosa before and after intravesical irrigation of EGCG in eight patients diagnosed with IC based on clinical and histopathologic assessments. Six normal bladder tissue samples were obtained from age-, race-, and sex-matched asymptomatic control subjects. IC symptom index was used to compare the therapeutic effect in IC patients. Patient-derived bladder epithelial cells were cultured and cell stretch experiments and ATP assays were performed. The expression of purinergic receptors X1, X2, and X3, and Y1, Y2, and Y11, in biopsied samples was detected by Western blotting and real-time polymerase chain reaction, respectively. Moreover, the expression of inducible NO synthase, phosphorylated Akt, and phosphorylated NF-κB was also assessed. RESULTS: All EGCG-treated patients demonstrated different extents of remission of symptoms. We found a significant upregulation in P2X1, P2X2, and P2X3 receptor proteins and P2Y1, P2Y2, and P2Y11 receptor transcripts in IC patients. However, EGCG therapy attenuated the expression of all purinergic receptors. In addition, EGCG demonstrated prominent antioxidative and antiinflammatory effects via inhibition of the upregulation of iNOS and phosphorylated NF-κB. Furthermore, the stretch-activated release of ATP in cultured bladder urothelial cells was greater in cells derived from IC patients, compared with those from the control patients, but EGCG, at all concentrations tested, effectively abolished the increase in ATP release from stretched IC patient-derived cells. CONCLUSIONS: Our study suggests that inhibition of the expression of purinergic receptors and ATP release in urothelial cells by EGCG supports further development of EGCG as a novel therapeutic option for IC.

Novel evidence demonstrates that epithelial-mesenchymal transition contributes to nephrolithiasis-induced renal fibrosis.

PURPOSE: To investigate fibrotic lesions in renal tissues obtained from patients with large calculi, and to selectively evaluate the expression and clinical significance of Twist and E-cadherin in nephrolithiasis patients. METHODS: We recruited 50 patients with kidney stone and 32 matched healthy controls. We determined plasma creatinine (Cr) and corrected Cr clearance (CCr). For the 50 patients, we detected daily urine protein excretion. At the end of percutaneous nephroscopic lithotomy, we performed puncture biopsy to acquire kidney tissue. We obtained normal control kidney tissues from non-nephrolithiasis patients who received a surgical biopsy during open surgery. We determined the expression of Twist and E-cadherin by immunohistochemical staining and scored it with clinical parameters. In addition, we analyzed the degree of expression of Twist and its correlation with long-term renal survival. RESULTS: Overall, the renal function of patients significantly decreased, as indicated by Cr and reduced CCr compared with healthy controls. Activated Twist was strongly expressed in tubular epithelial cells from kidneys of nephrolithiasis patients, whereas we found little positive staining of Twist in normal kidneys. Meanwhile, the expression of E-cadherin was significantly suppressed in kidneys of nephrolithiasis patients. Twist expression was inversely correlated with E-cadherin expression; using multivariate analysis, data showed that the factors influencing renal survival in patients were CCr (relative ratio, 4.39; 95% confidence interval, 1.34-14.38; P = 0.013) and the extent of Twist expression (relative ratio, 3.45; 95% confidence interval, 1.10-10.68; P = 0.033). CONCLUSIONS: Our data suggest that the possible novel EMT marker molecule Twist and Twist staining might be a valuable index predicting renal fibrosis progression in human nephrolithiasis.

Effect of free radical scavenger on c-jun activation in rats with crush syndrome.

OBJECTIVES: To evaluate the relationship between reactive oxygen species (ROS)-mediated kidney injuries and Jun N-terminal kinase (JNK) activity and the therapeutic effects of tempol in crush syndrome (CS) model rats. METHODS: Male Wister rats were randomly divided into sham operation group (SOG), CS groups (CS6G, CS12G and CS24G) and tempol treatment group (TG, a ROS scavenger). CS model rats were established by crushing the hind limbs of rats with 15 kg pressure for 6 hours, and inferior caval vein blood and kidney samples were harvested at 6, 12, 24 hours after removing crush pressure. In TG, 100 mg/kg tempol was intraperitoneally injected into CS model rats after withdraw of crush pressure. In SOG, rats were fixed on the board without any crush pressure. The activation of c-jun was determined by western blotting. Serological parameters and the content of malondialdehyde (MDA) in kidney tissues were determined by standard methods. RESULTS: Acute kidney injury reached the peak at 12 hours after the crush pressure. Compared with SOG, the content of phosphorylated c-jun was significantly higher in CSG and TG (p < 0.05), and the content of phosphorylated c-jun in the CSG was significantly higher than that in TG (p < 0.05). Interestingly, the changes of the MDA content in the kidney tissues of the 3 groups were similar to the changes of phosphorylated c-jun content. CONCLUSION: ROS-mediated phosphorylation of c-jun may play important roles in the acute kidney injury of CS rats. Tempol can inhibit the phosphorylation of c-jun and alleviate the acute kidney injury.

Improvement of erectile function in patients with benign prostatic hyperplasia undergoing transurethral plasmakinetic resection of the prostate.

OBJECTIVE: Although transurethral resection of the prostate remains the gold standard surgical treatment for benign prostatic hyperplasia, transurethral plasmakinetic resection of the prostate has become a popular alternative. This study investigated the effects of plasmakinetic resection of the prostate on erectile function. METHODS: A total of 400 patients that underwent plasmakinetic resection of the prostate or transurethral resection of the prostate were prospectively enrolled in this study. Of these, 384 patients met the inclusion criteria. One experienced surgeon carried out all the procedures. The International Prostate Symptom Score, International Index of Erectile Function-5, maximum flow rate and ultrasound postvoid residual volume were determined, and evaluated preoperatively and at 12 months postoperatively. Prostate-specific antigen, age and prostate volume of each patient were recorded. RESULTS: The median International Index of Erectile Function-5 score of plasmakinetic resection of the prostate patients significantly increased from 8.0 (interquartile range 7.0-9.0) preoperatively to 21.0 (19.0-22.0) at 12 months postoperatively (P < 0.05). The score of plasmakinetic resection of the prostate patients was significantly higher than that of the transurethral resection of the prostate group (P < 0.05); however, the International Prostate Symptom Score of the plasmakinetic resection of the prostate group was not significantly different from that of the transurethral resection of the prostate group (P > 0.05). CONCLUSIONS: A significant improvement in erectile function can be observed at 12 months in patients undergoing plasmakinetic resection of the prostate. Despite these encouraging findings, the effects of plasma kinetic resection of the prostate on erectile function remain to be further studied.