The specific regulatory mechanism of bladder urothelial barrier dysfunction after infection with uropathogenic Escherichia coli (UPEC) is still unclear. The cross talk between bladder urothelial cells and mast cells may play an important role during UPEC infection. In this study, the pyroptosis of urothelial cells was investigated after UPEC infection both in vivo and in vitro. The levels of IL-1β and IL-18 in exosomes derived from bladder urothelial cells after UPEC infection were detected. The role of these processes in the recruitment and activation of mast cells was measured. The mechanism of mast cell-induced disruption of bladder epithelial barrier function was also assessed. We found that UPEC infection induced pyroptosis of bladder urothelial cells and led to the release of IL-1β and IL-18 in the form of exosomes, which promoted the migration of mast cells. Tryptase secreted by mast cells aggravated the damage to the barrier function of the bladder urothelium by acting on protease-activated receptor 2 (PAR2). Inhibition of pyroptosis or the tryptase-PAR2 axis reduced the disruption of bladder urothelial barrier function and decreased the bacterial burden. The present study supports a novel mechanism by which pyroptosis-dependent release of exosomes from bladder urothelial cells activates mast cells and regulates bladder urothelial barrier function during UPEC infection.

Background Bladder cancer (BC) is the most common cancer of the urinary tract and invariably predicts a poor prognosis. In this study, we found a reliable gene signature and potential biomarker for predicting clinical prognosis. Methods The gene expression profiles were obtained from the GEO database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found. Three different microarray datasets were integrated in order to more precisely identify up-expression genes. Functional analysis revealed that these genes were mainly involved in cell cycle, DNA replication and metabolic pathways. Results Based on protein-protein interactome (PPI) networks that were identified in the current study and previous studies, we focused on KIF15 for further study. The results showed that KIF15 promotes BC cell proliferation via the MEK -ERK pathway, and Kaplan‐Meier survival analysis revealed that KIF15 expression was an independent prognostic risk factor in BC patients. Conclusion KIF15 may represent a promising prognostic biomarker and a potential therapeutic option for BC.

Purpose: Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo. Methods: Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH-133 (1 mg/kg, intraperitoneally), CB2 antagonist AM-630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3-methyladenine (3-MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated in these mice. Bladders were collected, weighed, and processed for real-time polymerase chain reaction, immunoblotting analysis, histological and immunohistochemical analysis.Results: Twenty-four hours after IP injection of CYP, the bladder of CYP-treated mice showed histological evidence of inflammation. The expression of CB2 in bladder was significantly increased in CYP-treated mice. Mechanical sensitivity was significantly increased in CYP-treated mice and CB2 agonist JWH-133 attenuated this effect (P < .05). The number of urine spots was significantly increased after CYP treatment and it was decreased in JWH-133 treated mice (P < .05). Activating CB2 with JWH-133 significantly alleviated bladder tissue inflammatory responses and oxidative stress induced by CYP. Activation of CB2 by JWH-133 increased the expression of LC3-II/LC3-I ratio, and decreased the expression of SQSTM1/p62 in the bladder of cystitis mice, whereas AM-630 induced inverse effects. Further study indicated that JWH-133 could promote autophagy and blocking autophagy by 3-MA dismissed the effort of CB2 in alleviating bladder tissue inflammatory responses and oxidative stress injury. Furthermore, treatment with 3-MA decreased the expression of p-AMPK and induced the phosphorylation of mTOR in the presence of JWH-133 stimulation in cystitis model.

This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.

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Relationship between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the type 2 diabetes mellitus (T2DM) susceptibility is still conflicting at present. This meta-analysis was conducted to assess the association between VDR BsmI gene polymorphism and the risk of T2DM. The association studies were identified from PubMed, and Cochrane Library on 1 January 2014, and eligible investigations were included and synthesized using meta-analysis method. Eleven reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T2DM susceptibility. In overall populations, B allele, BB genotype and bb genotype were not associated with T2DM risk. VDR BsmI gene polymorphism was also not associated with the T2DM risk in Asians and Caucasians. In conclusion, VDR BsmI gene polymorphism was also not associated with T2DM risk in overall populations, Asians and Caucasians. However, more studies should be conducted to confirm it.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.

The association of transforming growth factor-β1 (TGFβ1) is an important signaling pathway factor involving extracellular matrix regulation, and its gene polymorphisms with the risk of rheumatoid arthritis (RA) is currently still fiercely debated. Therefore, this meta-analysis was performed to determine if TGFβ1 T869C, G915C, and C509T gene polymorphisms correlate with the risk of developing RA. Association reports were identified from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 May 2013, and eligible studies were recruited and synthesized to identifying patterns among study results. T869C TT genotype in the overall population was associated with increased RA risk (OR = 1.28, 95% CI: 1.02-1.60, p = 0.03). In the sub-group analysis, T869C TT genotype was shown to be a risk factor for RA, and T869C C allele or CC genotype a protective factor against RA disease in Asians, but these associations were not found in Caucasians. Furthermore, TGFβ1 C509T TT genotype was distinctly associated with RA susceptibility, but the T allele and CC genotype were not. TGFβ1 G915C gene polymorphism was not associated with RA susceptibility. In conclusion, the TT genotype of TGFβ1 T869C was associated with RA risk in the overall population and Asians. Furthermore, CC genotype or C allele was determined to be protective factors with respect to the RA risk in the overall population and Asians. Nonetheless, additional studies are required to firmly establish a correlation between the aforementioned polymorphisms and RA risk.