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AIM:From the perspective of regulating mitochondrial complex I activity by DJ-1 protein,this study aims to explore the mechanism of DJ-1-mediated resveratrol(RES)preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion(I/R)in rats.METHODS:After intramyocardial injection of lentivirus carrying DJ-1 shRNA(sh-DJ-1)or negative control(NC)shRNA,the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery.Sprague-Dawley(SD)rats were randomly divided in-to 6 groups:sham group,I/R group,RES+I/R group,NC+RES+I/R group,sh-DJ-1+RES+I/R group,and IACS-010759(mitochondrial complex I inhibitor)+RES+I/R group,with 10 rats in each group.The rats in RES treatment groups were given RES(20 mg/kg)via gavage for 7 d prior to the myocardial I/R modeling,once daily.Moreover,the rats in sham and I/R groups received an equivalent volume of normal saline via gavage.Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography,respectively.The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species(ROS)in the myocardium.The levels of malondialdehyde(MDA),superoxide dis-mutase(SOD)and lactate dehydrogenase(LDH)in the serum were detected using kits.Western blot and co-immunopre-cipitation assays were used to observe the interaction between DJ-1 and the two subunits,ND-1 and NDUFA4,of the mito-chondrial complex I.RESULTS:Compared with I/R group,RES pretreatment significantly reduced the myocardial in-farction area,mitochondrial ROS levels,serum LDH activity,and serum MDA content(P＜0.01).It also elevated left ventricular ejection fraction,left ventricular fractional shortening and serum SOD activity(P＜0.01).Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1(P＜0.01),promoted the interaction between DJ-1 and ND-1/NDUFA4,which in turn protected the activity of mitochondrial complex I(P＜0.01).However,when the ex-pression of DJ-1 was suppressed,the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group(P＜0.05 or P＜0.01).CONCLUSION:Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1,and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I,thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxida-tive stress damage.
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Objective To analyze the drug resistance phenotype and genetic background of New Delhi metallo-β-lactamase (NDM)-producing bacterial strains in Lishui area of Zhejiang province.Methods The imipenem-resistant Enterobacteriaceae strains were isolated from January 2012 to December 2016 in Lishui Municipal Central Hospital of Zhejiang Province.Mrieux Vitek 2 Compact system was used to identified strains and PCR was used to screen for blaNDMgene.Susceptibility was detected by K-B method and MICs were obtained by Vitek 2 with GN13 cards.Plasmids typing was carried out by DNA sequencing of the replication initiator with the transconjugates as templates.The blaNDMgenetic contexts were detected by PCR and complete genome sequencing.Results A total of 102 strains of carbapenem-resistant enterobacteria (CRE), mainly Escherichia coli and Enterobacter cloacae, were isolated, of which 15 were positive for blaNDMwith a positive detection rate of 14.7%.The resistance rate to β-lactam antibiotics was 100%, and the resistance rates to aztreonam, compound sulfamethoxazole , tobramycin and gentamicin were all ＞80%;and the resistance rate to quinolones was ＞50%.Among the 15 NDM-producing strains , 12 strains were positive for Hodge test, and 2 strains of Enterobacter cloacae and 1 strain of Escherichia coli were negative. There were 11 strains of blaNDM-1and 4 strains of blaNDM-1.A variety of plasmid types such as IncX 3, IncFIIγ and IncA/C were detected, and 4 blaNDM-5genes were located in the IncX3 plasmid.Four blaNDMsurrounding gene structures were found, of which 8 blaNDM-1genes were located in ISAb125-hyp-blaNDM-1-bleMBL-TrpF-DsbC-IS26, while blaNDM-5was located in IS3000-IS5-blaNDM-5-bleMBL-TrpF-DsbC-IS26 structure, and the former was reported for the first time in China.Conclusion NDM-producing bacterial strains in Lishui area are prevalent at a low level and have high sensitivity to fosfomycin and polymyxin .The blaNDMgene may have multiple sources, but IncX3 plasmid is still the main source for gene transfer.Some new types of blaNDM-1 gene structure have been also found in this study.
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Objective To observe the effect of febuxostat on IL-1β, TNF-αand COX-2 in gout patients.Methods 82 patients with gout in our hospital from August 2015 to August 2016 were divided into the groups of 40 mg/day of febuxostat and 80 mg/day of febuxostat randomly, 41 cases respectively.Select the same period in our hospital health examination of 41 cases.The levels of serum uric acid were measured before and after one week, two weeks and four weeks after treatment.Serum levels of IL-1β, TNF-αand IL-1βin serum were measured by enzyme-linked immunosorbent assay (ELISA) COX-2 levels.Results The levels of serum uric acid in the group of 40 mg/day vs 80 mg/day of febuxostat were (570.4 ±70.5) μmol/L and (572.8 ±71.2) μmol/L, significantly higher than the normal group (296.5 ±9.7) μmol/L (P<0.05), serum uric acid level decreased gradually with the time of administration, and the serum uric acid levels of the two dosages of fosobutamol at one,two,four weeks were significantly lower than before treatment (P<0.05), but not to below the normal level.The IL-1βof 40 mg/day and 80 mg/day of febuxostat was (40.5 ±6.8) pg/mL and (41.7 ±7.2) pg/mL, COX-2 were (15.5 ±1.7) pg/mL and (15.8 ±1.8) pg/mL respectively, significantly higher than the normal group (8.8 ± 1.7) pg/mL (P<0.05), The expression of IL-1βwas significantly decreased at the second week of IL-1βdecreasing as the time of IL-1βdecreased gradually (P<0.05); TNF-αin 40 mg/day group and 80 mg/day group was significantly lower than that before treatrment (P<0.05), but not to below the normal level.Conclusion Febuxostat can significantly reduce serum uric acid levels in patients with gout, and may reduce IL-1β, TNF-αand COX-2 and other cytokine levels.
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Objective To investigate correlations of hyperuricemia and matrix metalloproteinase -9 level with left ventricular remodeling in patients with type 2 diabetes and the clinical effect of intervention for hyperuricemia.Methods 100 type 2 diabetic patients with hyperuricemia in our hospital from June 2011 to June 2012 were selected as hyperuricemia group,50 type 2 diabetic cases with normal uric acid were considered as DM group.Levels of blood glucose,blood lipids,glycosylated hemoglobin and matrix metalloproteinase-9 were detected.All patients underwent echocardiography.Patients in hyperuricemia group were randomly divided into treatment group (receiving allopurinol and alkaline urine-alkalify therapy added to hypoglycemic treatment,n=50) and control group (receiving hypoglycemic treatment,n=50).After 6 months of treatment,levels of blood glucose,blood lipids,glycosylated hemoglobin,matrix metalloproteinase-9 and echocardiography were rechecked.Results The levels of triglyceride (TG),blood uric acid,MMP-9,left ventricular posterior wall thickness (LVPWT),interventricular septal thickness (IVST) and left ventricular mass index (LVMI) were increased in hyperuricemia group versus DM group[(2.3±0.5) mmol/L vs.(1.6±0.30) mmol/L,(498.9±32.5) μmol/L vs.(322.8±35.6) μmol/L,(765±38) g/L vs.(420±26) pg/L,(11.0±1.1) mm vs.(9.2±0.8) mm,(11.5±1.6) mm vs.(10.1±1.1) mm,(138.7±35.6) g/m2 vs.(115.0±10.4)g/m2,t=4.945,5.124,4.895,3.985,3.965,3.989,respectively,all P＜0.05].Levels of TG,blood uric acid,MMP,LVPWT,IVST were decreased in treatment group after treatment versus before treatment [(1.6±0.5) mmol/L vs.(2.3±0.6) mmol/L,(323.0±30.5) μmol/L vs.(496.6±32.6) μmol/L,(766±34) pg/L vs.(410±25)pg/L,(9.1±0.8) mm vs.(11.0±1.1) mm,(9.2±1.1) mm vs.(11.6±1.5) mm,(116±10.5)g/m2 vs.(138.8±35.2) g/m2,t=3.386,4.525,4.865,3.256,3.895,3.985,all P＜0.05].Correlation analysis showed that LVMI had positive correlations with levels of blood uric acid,TG,MMP-9 (r=0.435,0.348,0.356,respectively).Conclusions Hyperuricemia involves in left ventricular remodeling,and therapeutic intervention on the hyperuricemia can reverse this remodeling.
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Sixty cases of type 2 diabetes with diabetic peripheral neuropathy (DPN), 46 cases of type 2 diabetes without DPN and 50 healthy persons were recruited. Plasma homocysteine (Hcy), serum folic acid, vitamin B 12 levels and the mutations of Hcy metabolism related enzyme-methyhenetetrahydrofolate reductase (MTHFR) were assayed in individuals in this study. The results showed that high Hcy, low folic acid and vitamin B 12 levels are related with DPN in the patients with type 2 diabetes. The mutation of MTHFR C677T is associated with diabetes, but not with DPN.