1.Research advance in role of ROS in cardioprotection offered by preconditioning or postconditioning
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):229-232
Reactive oxygen species(ROS)play an important role in the cardiac ischemic and reperfusion injury.However,accumulating evidences have demonstrated that ROS are pivotal components of redox signaling cascade relevant to cardioprotection induced by either preconditioning or postconditioning. In this review,the definition, source and detection methods of ROS are introduced.Besides,the role of ROS in the cardioprotection offered by preconditioning or postconditioning and the effects of either preconditioning or postconditioning on ROS are summarized.
2.Canonical Wnt pathway and schizophrenia
Xuemei WANG ; Donghong CUI ; Zeping XIAO
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):225-228
Schizophrenia is one of the most severe psychiatric disorders.Although the etiology is unknown,schizophrenia appears to be a polygenic disorder associated with environmental factors.There are evidences that intracellular signaling plays an important role in the pathogenesis of schizophrenia.Canonical Wnt pathway,which is closely related to the development and function maintenance of central nervous system,have drawn wide attention.Evidences for potential disturbances of Wnt signaling pathways in schizophrenia have accumulated,which are in favour of the hypothesis that Wnt signaling alterations may be important in the pathogenesis of schizophrenia.The research advances in the relationship between canonical Wnt signaling pathway and schizophrenia are reviewed in this paper.
3.Study of obstructive sleep apnea-hypopnea syndrome and metabolic syndrome in females
Guanhua MA ; Min LI ; Ling CHEN ; Liang YE ; Kun YANG ; Huanying WAN
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):218-221
Objective To analyse the changes of metabolic parameters and condition of metabolic syndrome(MS)in females with obstructive sleep apnea-hypopnea syndrome(OSAHS),and explore the interaction between OSAHS and MS.Methods Sixty females undergoing polysomnography were included,and were divided into simple snorer group(n=19),mild OSAHS group(n=21)and moderate to severe OSAHS group(n=20).Epworth sleepiness scale(ESS)scores and metabolic parameters were compared among groups.Forty-one patients with OSAHS were subdivided into group with MS(MS group,n=15)and group without MS(non-MS group,n=26).ESS scores,apnea hypopnea index(AHI),oxygen desaturation index(ODI)and lowest pulse oxygen saturation(LSpO_2)were compared between MS group and non-MS group.Results There was no significant difference in age,body mass index(BMI),total cholesterol(TC),triglyceride(TG),low density cholesterol(LDL),high density cholesterol(HDL),apolipoprotein A-I(apoA-I)and apolipoprotein B(apoB) among simple snorer group,mild OSAHS group and moderate to severe OSAHS group(P>0.05).Correlation analysis revealed ESS was positively related to AHI(r=0.327,P=0.011).ESS scores and proportions of hypertension,fasting plasma glucose(FPG)and MS were significantly higher in moderate to severe OSAHS group than those in simple snorer group(P<0.05).BMI,FPG,TG,proportion of hypertension,ODI and ESS score in MS group were significantly higher than those in non-MS group(P<0.05),while there was no significant difference in AHI and LspO_2 between these two groups(P>0.05). Conclusion ESS score may reflect the severity of OSAHS in females.Females with OSAHS matched for age and BMI have no difference in blood fat.With the increase of severity of OSAHS,glycometabolism can be impaired,the prevalences of hypertension and MS increase.MS can exacerbate the severity of OSAHS,indicating that MS and OSAHS interact with each other.
4.Expression of CD133 mRNA in tissues of gastric cancer and its relationship with clinicopathological features
Peng ZHANG ; Jugang WU ; Hongbiao WU ; Shiting WANG ; Jiwei YU ; Bojian JIANG
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):213-217
Objective To investigate the expression of CD133 mRNA in tissues of gastric cancer,and explore its relationship with clinicopathological features. Methods The tissues of gastric cancer and normal tissues adjacent to gastric cancer were obtained from 31 patients.The expression of CD133 mRNA was detected by semi-quantitative RT-PCR,and its relationship with clinicopathological features such as sex,age,tumor diameter,infiltration depth,TNM staging,tumor differentiation,lymph node metastasis and Ki-67 proliferation index was analysed. Results The relative gray scale values of CD133 mRNA in tissues of gastric cancer and normal tissues adjacent to gastric cancer were 0.378 3±0.141 1 and 0.038 1 ±0.091 9,respectively(P=0.000).The relative gray scale values of CD133 mRNA in tissues of gastric cancer with tumor diameter>5 cm were significantly higher than those with tumor diameter≤5 cm[(0.439 3±0.148 4)vs(0.334 3±0.121 2)](P=0.041),and those in tissues with lymph node metastasis were significantly higher than those without lymph node metastasis[(0.426 6±0.132 0)vs(0.239 5±0.030 9)](P=0.004).The rate of lymph node metastasis and the number of metastatic lymph nodes were positively related to relative gray scale values of CD133 mRNA(r=0.466,P=0.008;r=0.464,P=0.009).The relative gray scale values of CD133 mRNA in those with low expression of Ki-67 were significantly higher than those with high expression of Ki-67[(0.436 4±0.139 8)vs(0.316 4±0.117 4)](P=0.02),and expression of Ki-67 were negatively related to relative gray scale values of CD133 mRNA(r=-0.461,P=0.009).Conclusion The expression of CD133 mRNA in tissues of gastric cancer was associated with the rate of lymph node metastasis,number of metastatic lymph nodes and expression of Ki-67,which reflect the status of lymph node metastasis and proliferation of gastric cancer.
5.Value of GPC3 and PEG10 mRNA in peripheral blood in diagnosis of metastasis in hepatocellular carcinoma
Jie ZHANG ; Zhiqing WANG ; Jiaping YU ; Jiqiang LI ; Hailiang GE
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):208-212
Objective To explore the value of glypican-3(GPC-3)mRNA and paternally expressed 10(PEG10)mRNA in peripheral blood in diagnosis of metastasis in hepatocellular carcinoma(HCC). Methods With SYBR Green I as fluorescence signal,real-time fluorescent quantitative reverse transcription-polymerase chain reaction was employed to detect the expression of GPC-3 mRNA and PEG10 mRNA in peripheral blood from patients with HCC with metastasis(n=8),HCC without metastasis(n=12)and hepatic cirrhosis(n=11),and receiver operator characteristics curve(ROC)and specific parameters were adopted to analyse their value in predictive and exclusive diagnosis. Results The expression of GPC-3 mRNA and PEG10 mRNA in HCC with metastasis was significantly higher than that in HCC without metastasis and in hepatic cirrhosis(P<0.05),while there was no significant difference in the expression of GPC-3 mRNA and PEG10 mRNA between HCC without metastasis and hepatic cirrhosis.In single test,the sensitivities in the differential diagnosis between HCC with metastasis and HCC without metastasis were 66.7%for GPC-3 mRNA and 72.2%for PEG10 mRNA,and the specificities were 91.7%and 91.7%.respectively.The areas under ROC were 0.748 for GPC-3 mRNA and 0.812 for PEG10 mRNA.With two markers in parallel test,the sensitivity,specificity,negative likelihood and diagnostic accuracy were 90.7%,84.O%,0.11 and 83.3%,respectively.In serial test,the sensitivity,specificity,positive likelihood and diagnostic accuracy were 60.5%,98.7%,45.5 and 73.3%,respectively. Conclusion Detection of GPC-3 mRNA and PEG10 mRNA in peripheral blood may help to predict blood metastasis and extrahepatic metastasis of HCC,and PEG10 mRNA works better than GPC-3 mRNA.The serial test of GPC-3 mRNA and PEG10 mRNA is helpful to the predictive diagnosis of peripheral blood metastasis of HCC.
6.Preliminary study on AmpC β-lactamase and related drug-resistant mechanism of pathogenic bacteria in blood stream
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):204-207
Objective To investigate the characteristics of strains of AmpC β-lactamase(AmpC enzyme)production in Dathogenic bacteria in blood stream and clinical presentations of the cases, and study the related ampC and ampD genes.Methods One hundred and eighty-one strains of gram negative bacillus in blood stream were collected,Cefoxitin screening test and three-dimensional test were performed for screening of strains of AmpC enzyme,production and those of AmpC enzyme hyperproduction retrospective analysis was condected in the strains with positive results.ampC and ampD gene PCR ampliftcation, sequencing and sequence analysis of positive strains were performed, and gene homology of ampC positive strains was analysed bv Rep-PCR. Results Among 181 strains in blood stream,strains of AmpC enzyme production were detected in 39 isolates by Cefoxitin screening test,with the detection rate of 21.5%(39/181).The detection rate of strains of AmpC enzyme hyperproduction by three-dimensional test was 43.6%(17/39).PCR revealed that the positive rates for ampC and ampD genes were 41%(16/39)and 56.4%(22/39),respectively.The ampC gene sequencing of 16 positive strains indicated that the homology was 98%to 100%by comparison with the GenBank,while the ampD gene sequencing of 2 strains of Enterobacter cloacae demonstrated that the suspected gene mutations existed in the carboxy-terminal of ampD gene. Conclusion The prevalence of drug-resistant pathogenic bacteria in blood stream in this study is due to nosocomial infection.The mutation of ampC gene is rare in the pathogenic bacteria in blood stream with production of AmpC enzyme,while the rate of gene mutation in Enterobacter cloacae is higher, and the deletion and amino acid substitutions in the carboxy-terminal of ampD is highly relevant to the depressed expression of AmpC enzyme.
7.Long-term effect of ketamine on learning and memory function of postnatal rats
Boxiong SHEN ; Xingqian QU ; Zhijun CHENG
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):196-199
Objective To investigate the effect of ketamine on learning and memory function of adult rats after injection of ketamine at early development stage. Methods Twelve rats born in a week were randomly divided into ketamine anesthesia group(Ket group)and normal saline control group(Ns group).Rats in Ket group were intraperitoneally injected with 50 mg/kg ketamine,and those in Ns group were administrated with same amount of normal saline.After eight weeks,Morris water maze test was adopted to explore the latency in place navigation and spatial probe ability.The sections of hippocampus were obtained,and immunohistochemical staining was employed to detect the expression of Bax and Bcl-2.Results In Morris water maze test,the latency in place navigation of Ket group Was significantly longer than that of Ns group(P<0.05),and the spatial probe ability significantly decreased(P<0.05).It Was revealed by immunohistochemical staining that the expression of Bax in Ket group was significantly higher than that in Ns group,while there was no significant difference in the expression of Bcl-2 between these two groups. Conclusion Application of ketamine in neonatal rats may result in learning and memory impairment in adulthood,and the underlying mechanism may correlate to the apoptosis of neuron in hippocampus region.
8.Role of calcitonin gene-related peptide and IP3 pathway in ischemic preconditioning in isolated perfused hearts of rats with type 1 diabetes mellitus
Shiting WANG ; Zhuying GUO ; Manghua XU ; Fenghou GAO
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):191-195
Objective To investigate the role of calcitonin gene-related peptide(CGRP)and IP3 signal pathway in ischemic preconditioning(IPC)in the isolated perfused hearts of rats with type 1 diabetes mellitus. Methods Type 1 diabetes mellitus rat models were established in 80 SD rats,and were randomly divided into 4 week(D-4w)group and 8 week (D-8w)group.These two groups were randomly subdivided into model control(D-Cont)group,type 1 diabetes mellitus ischemia-reperfusion(IR)group,IPC group,CGRP(IPC+CGRP)group and IP3 inhibitor wortmanin(IPC+WMN) group.Another 16 rats were served as normal control(N-Cont)group.In vitro perfusion models of isolated hearts were established by Langendorff methods,and CGRP or wortmanin(WMN)were administered during perfusion.The left ventricle function of isolated heart in each group was monitored by multichannel biosignal analysis system,and coronary artery flow was recorded.The serum CGRP levels were detected by ELISA.The activity of lactate dehydrogenase(LDH)and creatine kinase(CK)in effluent of coronary artery was detected by biochemical method.The size of myocardial infarction was determined by NBT staining,and apoptosis of cadiocytes was detected by TUNEL method. Results Compared with N- Cont group,the CGRP level in serum of rats with type 1 diabetes mellitus decreased with time,the basic left ventricle function decreased,while the activity of LDH and CK in effluent of coronary artery,size of myocardial infarction and cardiomyocyte apoptosis index increased(P<0.05).Compared with N-Cont group,the left ventricle function was significantly lower in IR group,and more severe myocardial damage was observed.IPC improved myocardial damage of D-4w IR group,while had no protection on D-8w IR group.Compared with IPC group,the left ventricle function was significantly improved in IPC+CGRP group.IPC+WMN blocked the myocardial protection of D-4w group from IPC.Conclusion CGRP and IP3 signal pathway are involved in the protection provided by IPC in isolated hearts of rats with type 1 diabetes mellitus.
9.Identification of cardiomyocytes differentiated from mesenchymal stem cells and study on expression of Nesprin protein
Wengang YANG ; Song XUE ; Zheng WANG ; Feng LIAN ; Genxing XU ; Sha LIU ; Jinhui LI ; Yuanyuan WANG ; Ritai HUANG ; Hongsheng ZHU
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):180-185
Objective To induce and identify the differentiation of rat bone marrow mesenchymal stem cells(MSCs)into cardiomyocytes in vitro,and observe the expression of Nesprin protein during the differentiation. Methods Rat MSCs were isolated and purified by Ficoll density gradient centrifugation,and adhered for serial subcultivation.Surface-associated antigens of MSCs of the second passage were dedected by flow cytometry.MSCs of the second passage were induced by 10μmol/L 5-azacytidine(5-Aza)to differentiate into cardiomyocytes,and the morphological changes were observed.The expression of Desmin,α-sarcomeric actin and cardiac Troponin I(cTnI) mRNA and protein was detected by RT-PCR,immunocytochemistIv and immunofluorescence staining, and the expression of Nesprin protein was detected by Western blotting. Results The morphology of MSCs induced by 5-Aza was bigger and longer,and the nuclei became bigger,exhibiting more consistent patterns.The expression of Desmin,α-sarcomeric actin and cTnI mRNA and protein of MSCs was positive.Immunofluorescence staining revealed that Nesprin protein positioned in the nuclear membrane,and Western blotting detection demonstrated that the expression of Nesprin protein significantly increased after differentiation(P<0.05).Conclusion MSCs may be successfully induced to differentiate into cardiomyocytes.The expression of Nesprin protein in the differentiated MSCs may significantly increase,indicating Nesprin may play a role in the differentiation from MSCs to cardiomyocytes.
10.Long-term effects of oxypurinol on oxidative modification of actin and myocardial contractility in mice with heart failure
Zhen TAN ; Zhi ZHANG ; Qinyan DAI ; Jianjun ZHANG ; Weidong GAO
Journal of Shanghai Jiaotong University(medical Science) 2010;30(2):174-179
Objective To investigate the long-term effects of xanthine oxidase inhibitor,oxypurinol on myocardial contractility of post-ischemic heart failure in mice,and explore the underlying mechanism. Methods One hundred and twenty SV120 mice were randomly assigned into myocardial infarction control group,sham operation group and Oxy treatment group.Post-ischemic heart failure were induced by left anterior descending coronary artery ligation in myocardial infarction control group and Oxy treatment group,and mice in Oxy treatment group and sham operation group were orally administered with 0.5 mmol/L Oxy each day.Nine to eleven months after treatment,echocardiography was performed in all groups.Trabeculae from the right ventricle of mice were dissected for assessment of changes in excitation-contraction coupling.Sarcomere length was measured by laser diffraction.Intracellular free Ca~(2+) concentration([Ca~(2+)]_I)was detected with fluorescent dye Fura-2,which was microinjected iontophoretically into cells. Steady-state force-[Ca~(2+)]_I was achieved by addition of ryanodine and increasing the stimulus frequency to induce tetanization,and the relationship between myocardial contractility and intracellular Ca~(2+) transients was analysed.Besides,Western blotting was performed to determine the oxidation of myofilament proteins. Results Long-term oral administration of oxypurinol significantly improved myocardial contraction function and reduced ventricular wall thickness.Programming of excitation-contraction coupling was significantly improved,and maximal Ca~(2+) activated force(F_(max))in steady-state wag also significantly increased.Western blotting revealed the oxidative modification of actin in mice of Oxy treatment group was significantly inhibited compared with that of myocardial infarction control group. Conclusion Long-term treatment with Oxy improves the cardiac contraction function and boosts the cardiac force dramatically in post-ischemia heart failure.The increase in contraction is the result of increased myofilament Ca~(2+) responsiveness.Thus,antioxidant oxypurinol,by preventing oxidative damage to contractile proteins,can augment contraction with little changes in[Ca~(2+)]_I,represents new class of inotropic agents with advantages of reducing Ca~(2+) overload,and offers new promises in management of heart failure in the future.