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Ma Y.,Sun Yat Sen University | Chen B.,Peoples Hospital of Guizhou Province | Liu D.,Sun Yat Sen University | Yang Y.,Sun Yat Sen University | And 4 more authors.
Biochemical Pharmacology | Year: 2011

Although MG132, a proteasome inhibitor, is suggested to impede secondary cardiac remodeling after hypertension, the mechanism and optimal duration of treatment remain unknown. This study was designed to investigate the effects and possible mechanism of MG132 on hypertension-induced cardiac remodeling. Male Sprague-Dawley rats subjected to abdominal aortic constriction (AAC) or sham operation received an intraperitoneal injection of MG132 (0.1 mg kg-1 day-1) or vehicle over a 2- or 8-week period. In the end, left ventricular (LV) function was evaluated with echocardiography and pressure tracing. Collagen deposition within the LV myocardium was assessed with Masson's trichrome staining. Ubiquitin-proteasome system (UPS), NF-κB, I-κB, TGFβ1 and Smad2 within the LV tissue were evaluated. In addition, angiotensin II within both plasma and LV tissue was also examined. Compared with the sham groups, the vehicle-treated AAC group exhibited a higher angiotensin II level, LV/body weight ratio, septal and posterior wall thicknesses, and a markedly reduced cardiac function (P < 0.05). Treatment with MG132 for 8 weeks attenuated these cardiac remodeling parameters and improved cardiac function (P < 0.01). 2- and 8-week hypertension led to activation of UPS, which was followed by activation of NF-κB and increased expression of TGFβ1 and Smad2 (P < 0.01). MG132 significantly inhibited NF-κB activity and down-regulate the levels of TGFβ1 and Smad2 expression by 2 and still at 8 weeks (P < 0.01). Short- and long-term treatment with MG132 significantly attenuated hypertension-induced cardiac remodeling and dysfunction, which may be mediated by the NF-κB/TGFβ1 signaling pathway. © 2011 Elsevier Inc. All rights reserved.

Ma Y.,Sun Yat Sen University | Chen Y.,Sun Yat Sen University | Yang Y.,Sun Yat Sen University | Chen B.,Peoples Hospital of Guizhou Province | And 5 more authors.
Biochemical Pharmacology | Year: 2013

Although the role of the ubiquitin-proteasome system (UPS) in cardiac hypertrophy induced by pressure overload has been consistently studied, the fundamental importance of the UPS in cardiac fibrosis has received much less attention. Our previous study found that proteasome inhibitor (MG132) treatment attenuated cardiac fibrosis and heart failure during the early and middle stages of pressure overload. However, the effects of this inhibitor on late-stage pressure overload hearts remain unclear and controversial. The present study was designed to investigate the effects and possible mechanisms of MG132 on cardiac fibrosis and dysfunction during the late stages of pressure overload. Male Sprague Dawley rats with abdominal aortic constriction (AAC) or a sham operation received an intraperitoneal injection of MG132 (0.1 mg kg-1 day -1) or vehicle for 16 weeks. Left ventricular (LV) function, collagen deposition and Ang II levels were evaluated at study termination. Ang II-stimulated adult rat cardiac fibroblasts were utilized to examine the effects of MG132 on collagen synthesis and the relationship between the renin-angiotensin-aldosterone system (RAAS) and the UPS. MG132 treatment attenuated ventricular dysfunction by suppressing cardiac fibrosis rather than inhibiting cardiac hypertrophy during the late-stages of pressure overload. We also found that Ang II activates UPS in the heart and MG132 attenuates Ang II-induced collagen synthesis via suppression of the NF-κB/TGF-β/ Smad2 signaling pathways. Proteasome inhibition therefore could provide a new promising therapeutic strategy to prevent cardiac fibrosis and progression of heart failure even during the late-stages of pressure overload. © 2012 Elsevier Inc.

Zong Z.,University of Sichuan | Zong Z.,State Key Laboratory of Biotherapy | Peng C.,University of Sichuan | Peng C.,Peoples Hospital of Guizhou Province | Lu X.,University of Sichuan
PLoS ONE | Year: 2011

Background: Methicillin-resistant coagulase-negative staphylococci (MR-CoNS) are opportunistic pathogens and serve as a large reservoir of staphylococcal cassette chromosome mec (SCCmec). Characterization of SCCmec in MR-CoNS can generate useful information on the mobilization and evolution of this element. Methodology/Principal Findings: Non-repetitive MR-CoNS clinical isolates (n = 84; 39 S. epidermidis, 19 S. haemolyticus, 9 S. hominis, 6 S. capitis, 4 S. warneri, 2 S. cohnii, 2 S. saprophyticus, 1 S. kloosii, 1 S. simulans and 1 S. massiliensis) were collected. All isolates could grow on plates with 4 mg/L cefoxitin and all had mecA as detected by PCR. Strain typing using RAPD and ERIC-PCR revealed that almost all isolates were of different strains. SCCmec typing was performed using multiplex PCR published previously. For isolates in which SCCmec could not be typed, the mec complex classes were determined by additional PCR and the ccr genes were amplified with published or newly-designed primers and then sequenced. SCCmec types were assigned for 63 isolates by multiplex PCR and were assigned for 14 other isolates by PCR targeting mec and ccr. Among 77 isolates with determined SCCmec types, 54 had a single type, including type III (n = 19), IV (n = 14), V (n = 10), II (n = 2), I (n = 1), VIII (n = 1) and five unnamed types (n = 7), while 23 isolates had two types, III+V (n = 12), II+V (n = 8), II+IV (n = 2) or IV+V (n = 1). The five unnamed types were assigned UT1 (class A mec, ccrA1/ccrB4), UT2 (class C1 mec, ccrA4/ccrB4), UT3 (class A mec, ccrA5/ccrB3), UT4 (class C2 mec, ccrA2/ccrB2 plus ccrC1) and UT5 (class A mec, ccrA1/ccrB1 plus ccrC1). Conclusions/Significance: SCCmec types III, IV and V were prevalent in MR-CoNS and many isolates could harbor more than one type. Several new types of SCCmec were identified, highlighting the great genetic diversity and the need of developing classification schemes for SCCmec in MR-CoNS. © 2011 Zong et al.

Feng X.F.,Peoples Hospital of Guizhou Province
Chinese journal of traumatology = Zhonghua chuang shang za zhi / Chinese Medical Association | Year: 2013

A 34-year-old man admitted to our department with complex blunt pancreaticoduodenal injury after a car accident. The wall of the first, second, and third portions of the duodenum was extensively lacerated, and the pancreas was longitudinally transected along the superior mesenteric vein-portal vein trunk. The pancreatic head and the uncinate process were devitalized and the distal common bile duct and the proximal main pancreatic duct were completely detached from the Vater ampulla. The length of the stump of distal common bile located at the cut surface of remnant pancreas was approximately 0.6 cm. A simplified Kausch-Whipple's procedure was performed after debridement of the devitalized pancreatic head and resection of the damaged duodenum in which the stump of distal common bile duct and the pancreatic remnant were embedded into the jejunal loop. Postoperative wound abscess appeared that eventually recovered by conservative treatment. During 16 months follow-up the patient has been stable and healthy. A simplified pancreaticoduodenectomy is a safe alternative for the Whipple procedure in managing complex pancreaticoduodenal injury in a hemodynamically stable patient.

Yu Z.-Y.,University of Sichuan | Yu Z.-Y.,Peoples Hospital of Guizhou Province | Bai Y.-N.,University of Sichuan | Luo L.I.-X.I.,University of Sichuan | And 2 more authors.
Molecular Medicine Reports | Year: 2013

Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of sinusoidal endothelial cells and hepatocytes during liver regeneration (LR). The present study aimed to screen and validate a microRNA (miRNA) that targets VEGF-A with relative specificity and to elucidate the potential association between hypoxia-inducible factor-1α(HIF-1α) and miRNA expression in the early phase of LR. Changes in the expression of miRNAs, which were predicted to target VEGF-A using online databases, were detected at 12, 24 and 48 h following a 70% partial hepatectomy (PHx) using quantitative PCR (qPCR). An inhibitor of the most downregulated miRNA was transfected into the primary hepatocytes in order to observe changes in the expression of the VEGF-A gene. The expression of HIF-1α protein in the regenerating liver was investigated using western blot analysis. The expression levels of HIF-1α mRNA (messenger RNA), the selected miRNA and VEGF-A mRNA in an anoxic model of hepatocytes was examined with qPCR. Of seven putative miRNAs, the expression of miR-150 exhibited the sharpest downregulation from 12-48 h. The micrOFF™ miR-150 inhibitor significantly elevated the expression levels of VEGF-A mRNA and protein 48 h after transfection. Thus, VEGF-A may be a downstream target of miR-150 during LR. Furthermore, HIF-1α protein expression increased to its highest level 24 h following PHx. miR-150 expression was inhibited and the expression of VEGF-A mRNA increased accordingly in the hypoxia-induced hepatocytes. Our results suggest that miR-150 expression is subject to negative regulation by HIF-1α.

Li Y.,Peoples Hospital of Guizhou Province | Du X.,Huazhong University of Science and Technology
The Journal of Membrane Biology | Year: 2014

Swelling-activated chloride currents (ICl.swell) play an important role in cardiac electrophysiology and arrhythmogenesis. However, the regulation of these currents has not been clarified to date. In this research, we focused on the function of phenylephrine, an α1-adrenoceptor agonist, in the regulation of ICl.swell in human atrial myocytes. We recorded ICl.swell evoked by a hypotonic bath solution with the whole-cell patch-clamp technique. We found that ICl.swell increased over time, and it was difficult to achieve absolute steady state. Phenylephrine potentiated ICl.swell from -1.00 ± 0.51 pA/pF at -90 mV and 2.58 ± 1.17 pA/pF at +40 mV to -1.46 ± 0.70 and 3.84 ± 1.67 pA/pF, respectively (P < 0.05, n = 6), and the upward trend in ICl.swell was slowed after washout. This effect was concentration-dependent, and the α1-adrenoceptor antagonist prazosin shifted the dose-effect curve rightward. Addition of prazosin or the protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM) attenuated the effect of phenylephrine. The PKC activator phorbol 12,13-dibutyrate (PDBu) activated ICl.swell from -1.69 ± 1.67 pA/pF at -90 mV and 5.58 ± 6.36 pA/pF at +40 mV to -2.41 ± 1.95 pA/pF and 7.05 ± 6.99 pA/pF, respectively (P < 0.01 at -90 mV and P < 0.05 at +40 mV; n = 6). In conclusion, the α1-adrenoceptor agonist phenylephrine augmented ICl.swell, a result that differs from previous reports in other animal species. The effect was attenuated by BIM and mimicked by PDBu, which indicates that phenylephrine might modulate ICl,swell in a PKC-dependent manner. © 2014 Springer Science+Business Media New York.

Chen B.L.,Peoples Hospital of Guizhou Province
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To investigate the effects of AICAR on the activity of transcription factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes, and explore the possible role of AMP-activated protein kinase (AMPK) in proteolysis pathways. In vitro cultured neonatal rat cardiac myocytes were treated with AICAR, and Western blotting was used to detect the phosphorylation of FOXO1 and expression of MuRF1 in the cells. AICAR activated AMPK in rat cardiac myocytes. Activated AMPK significantly inhibited the phosphorylation of FOXO1 and increased MuRF1 protein expression. AMPK may regulate proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1 expression.

Peng C.,University of Sichuan | Peng C.,Peoples Hospital of Guizhou Province | Tian C.,University of Sichuan | Zhang Y.,University of Sichuan | And 3 more authors.
American Journal of the Medical Sciences | Year: 2013

Background: Chronic obstructive pulmonary disease (COPD) causes a high rate of morbidity worldwide and predicting a bacterial cause of an exacerbation of COPD is difficult. Methods: In this study, patient serum was obtained and C-reactive protein (CRP) levels were measured using an automated latex-enhanced turbidimetric assay. Sputum samples were obtained and evaluated microscopically. The relationship between CRP and the bacterial colonies in sputum in 81 patients with an exacerbation of COPD was assessed. Receiver operating characteristic (ROC) curves and the respective areas under the curve (AUCs) were calculated. Data from 64 patients with bacterial acute exacerbation of COPD (AECOPD) were compared with those of 37 patients with no documented bacterial AECOPD. Results categorized according to the nature of sputum as mucoid or purulent were also compared. Results: High median CRP levels were observed in bacterial AECOPD compared with nonbacterial AECOPD. The ideal cutoff point for distinguishing patients with bacterial AECOPD from those with nonbacterial AECOPD was 19.65 mg/L (sensitivity, 78.18%; specificity, 84.61%; AUC, 0.832). In patients with mucoid sputum, the cutoff point was 15.21 mg/L and the area under the ROC curve 0.86, with a sensitivity of 81.5% and a specificity of 77.8%. Purulent sputum had a significantly higher CRP level than mucoid sputum, but with an AUC of only 0.617 (95% confidence interval, 0.49-0.74) to diagnosis bacterial AECOPD. Conclusions: In adult patients with symptoms of AECOPD, an elevated serum CRP level of >19.6 mg/L indicates bacterial exacerbation. In patients with AECOPD with mucoid sputum, an elevated CRP level of >15.21 mg/L indicates bacterial infection, which may be a useful clinical marker for therapy of this disease. Copyright © 2013 by the Southern Society for Clinical Investigation.

Peng C.,University of Sichuan | Peng C.,Peoples Hospital of Guizhou Province | Zong Z.,University of Sichuan | Fan H.,University of Sichuan
Clinical Microbiology and Infection | Year: 2012

Acinetobacter baumannii has emerged as an important cause of community-acquired infection. To characterize the microbiological and genotypic features of community-associated Acinetobacter baumannii, 32 isolates associated with community-acquired pneumonia were collected. These isolates were diverse in resistance patterns and had multiple clonal origins. blaOXA-23 was the main acquired oxacillinases-encoding gene detected. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Liu G.-D.,Chongqing Medical University | Liu G.-D.,Peoples Hospital of Guizhou Province | He C.-J.,Peoples Hospital of Guizhou Province
Acta Oto-Laryngologica | Year: 2014

Conclusion: Stellate ganglion block (SGB) is effective for treatment of Bell's palsy in patients with diabetes mellitus. Background: Corticosteroids are widely used for treatment of Bell's palsy in patients with diabetes mellitus but may induce complications like hyperglycemia, which calls for an alternative therapy. This study aimed to ascertain the effect of SGB on Bell's palsy in patients with diabetes mellitus. Methods: This randomized and single-blinded clinical trial involved 96 diabetic patients with Bell's palsy that were randomly divided into a control group (n = 48) and a treatment group (SGB group, n = 48). The House-Brackmann scale and facial disability index (FDI, including FDIP and FDIS) were observed before treatment and at 1 and 3 months after treatment for assessment of the outcome. Results: No statistically significant difference was found between the two groups before treatment as regards the House-Brackmann scale and FDI. There was a statistically significant difference in FDIP score in the two groups after treatment in comparison with before treatment. The FDIS score showed a statistical difference between the two groups after treatment. © 2014 Informa Healthcare.

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