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Feng H.,Luzhou Medical College | Gu J.,Fifth Peoples Hospital of Chongqing | Gou F.,Luzhou Medical College | Huang W.,Luzhou Medical College | And 9 more authors.
Journal of Diabetes Research | Year: 2016

While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-Acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-Acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy. © 2016 Hong Feng et al. Source

Li Q.,Fifth Peoples Hospital of Chongqing | Jia Y.,Zhengzhou University | Zhang J.,Chongqing Medical University | Yang J.,Chongqing Medical University
BioMed Research International | Year: 2015

Objective. Even though there is a therapeutic potential to treat Alzheimer's disease (AD) with neural cell replenishment and replacement, immunological rejections of stem cell transplantation remain a challenging risk. Autologous stem cells from AD patients however may prove to be a promising candidate. Therefore, we studied the neuronal differentiation efficiency of bone marrow mesenchymal stem cells (MSCs) from APP695 transgenic mice, which share features of human AD. Method. Cultured MSCs from APP695 transgenic mice are used; neuronal differentiation was assessed by immunocytochemistry and Western blot. Correlation with Notch signaling was examined. Autophage flux was assessed by western blot analysis. Results. MSCs from APP695 mice have higher neuronal differentiation efficiency than MSCs from wild type mice (WT MSCs). The expression of Notch-1 signaling decreased during the differentiation process. However, autophagy flux, which is essential for neuronal cell survival and neuronal function, was impaired in the neuronally differentiated counterparts of APP695 MSCs (APP695 MSCs-n). Conclusion. These results suggested autologous MSCs of APP690 mice may not be a good candidate for cell transplantation. Copyright © 2015 Qian Li et al. Source

Ling Z.,Chongqing Medical University | Liu Z.,Chongqing Medical University | Su L.,Chongqing Medical University | Wu J.,Chongqing Medical University | And 11 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2014

Background-The purpose of this study was to compare the efficacy of radiofrequency catheter ablation (RFCA) versus antiarrhythmic drugs (AADs) for treatment of patients with frequent ventricular premature beats (VPBs) originating from the right ventricular outflow tract (RVOT). Methods and Results-A total of 330 eligible patients were included in the study and were randomly assigned to RFCA or AADs group. The absolute number and the burden of VPBs on 12-lead Holter monitors were measured at baseline and at 1st, 3rd, 6th, and 12th months after randomization. Left ventricular eject fraction was evaluated by transthoracic echocardiogram at baseline and at 3 and 6 months after randomization. During the 1-year follow-up period, VPB recurrence was significantly lower in patients randomized to RFCA group (32 patients, 19.4%) versus AADs group (146 patients, 88.6%; P<0.001, log-rank test). In a Poisson generalized estimating equations (GEE) regression model, RFCA was associated with a greater decrease in the burden of VPBs (incidence rate ratio 0.105; 95% confidence intervals [0.104-0.105]; P<0.001) compared with AADs. In a liner GEE model, the left ventricular eject fraction had a tendency to increase after the treatment in both groups (coefficient, 0.584; 95% confidence intervals [0.467-0.702]; P<0.001). In a Cox proportional model, the QS morphology in lead I was the only predictor of VPB recurrence free for catheter ablation (hazards ratio, 0.154; 95% confidence intervals [0.044-0.543]; P=0.004). Conclusions-Catheter ablation is more efficacious than AADs for preventing VPB recurrence in patients with frequent VPBs originating from the RVOT. QS morphology in lead I was associated with better outcome after ablation. © 2014 American Heart Association, Inc. Source

Zhang Y.,Chongqing Medical University | Shen J.,Fourth Peoples Hospital of Chongqing | Li Z.,Chongqing Medical University | Zhu A.,Fifth Peoples Hospital of Chongqing | And 6 more authors.
International Journal of Cardiology | Year: 2013

Background The persistence of polymer may be related to late and very late stent thrombosis. Recently, biodegradable polymer (BD) and polymer-free (PF) stents have become a focus for prevention of detrimental clinical events. However, the long-term efficacy of these types of stent compared to that of permanent polymer (PP) stents is unclear. Methods and results A total of 989 consecutive coronary heart disease (CHD) patients from five centres who required the implantation of drug-eluting stents (DES) were randomly divided into the PP (n = 321), PF (n = 327) and BD groups (n = 341). The primary endpoint was major adverse cardiac events (MACE). The secondary endpoints were stent thrombosis events, all-cause death and rehospitalisation. The study was designed to test the noninferiority of the PF and BD stents compared with that of the PP stent with respect to two-year MACE, using a noninferiority margin of 0.05. After clinical follow-up for 26.96 ± 12.99 months, the 2-year MACE rates were 6.17% in the PF group, 6.58% in the BD group and 7.24% in the PP group. The noninferiority testing produced lower limits of the one-sided 95% confidence interval of - 0.0435 (P = 0.024) for the PF group and - 0.0401 (P = 0.017) for the BD group. There were no significant differences in stent thrombosis events, all-cause death and rehospitalisation among the three groups (all P > 0.05). Conclusion In this multicentre, randomised, controlled clinical trial, PF paclitaxel-eluting stents and BD rapamycin-eluting stents were shown to be noninferior to PP rapamycin-eluting stents in two-year clinical outcomes for the treatment for CHD. © 2013 Elsevier Ireland Ltd. All rights reserved. Source

Zhou D.-Y.,Fifth Peoples Hospital of Chongqing | Su Y.,Fifth Peoples Hospital of Chongqing | Gao P.,Southwest University | Yang Q.-H.,Southwest University | And 2 more authors.
Life Sciences | Year: 2015

Aims To investigate the effects of resveratrol on high glucose (HG)-induced vascular injury, and to establish the mechanism(s) underlying these effects. Main methods Human umbilical vein endothelial cells (HUVECs) were treated with glucose, and then incubated with resveratrol in the presence or absence of Compound C, an AMP-activated protein kinase (AMPK) inhibitor. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) method. Reactive oxygen species, malondialdehyde, and superoxide dismutase were detected by flow cytometry, thiobarbituric acid reaction, and the nitroblue tetrazolium method, respectively. Protein levels of total and phosphorylated AMPKα and acetyl-CoA carboxylase were detected by immunoblotting. Key findings Resveratrol significantly ameliorated HG-induced decreases in cell viability and superoxide dismutase levels and increases in reactive oxygen species and MDA levels. Moreover, resveratrol significantly reversed HG-induced dephosphorylation of AMPKα and acetyl-CoA carboxylase. However, treatment with Compound C curtailed the beneficial effects of resveratrol on HG-treated HUVECs. Significance Resveratrol ameliorates HG-induced injury in HUVECs by activation of AMPKα, leading to increased cellular reductive reactions and decreased oxidative stress. These results provide further evidence for resveratrol-mediated activation of AMPKα. © 2015 Elsevier Inc. All rights reserved. Source

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