Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms ar...Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.展开更多
Background Acute coronary syndrome （ACS） is a leading cause of mortality and morbidity worldwide, which comprises unstable angina （UA） and acute myocardial infarction （AMI）, and the investigation of bio- logical...Background Acute coronary syndrome （ACS） is a leading cause of mortality and morbidity worldwide, which comprises unstable angina （UA） and acute myocardial infarction （AMI）, and the investigation of bio- logical markers to assess those most at risk of recurrent cardiovascular events is necessary. Methods Sixty-six healthy control people and 67 cases of UA patients were enrolled in Guangdong general hospital. Enzyme linked immunosorbent assay （ELISA） was used to detect the level of plasma ACTG2. The receiver operating characteristic curve （ROC） was used to analyze the prediction value of ACTG2 for UA. According to the aver- age level of plasma ACTG2 in UA patients, UA patients were divided into the low ACTG2 group （ 〈 average level） and the high ACTG2 group （≥ average level）, and the differences in clinical characteristics between the two groups were investigated. Results The ELISA result showed that the level of plasma ACTG2 was 67.823 ± 58.479 pg/mL in healthy people, while the plasma ACTG2 was 94.514 ± 65.453 pg/mL in UA pa- tients, with a significant difference （P 〈 0.05）. ROC analysis result showed that the Area under curve（AUC） for the prediction of UA was 0.653 （95% CI 0.559-0.747）, with a high statistical significance, indicating that circulating ACTG2 may possess high prediction value for UA. In addition, among the 67 UA patients, 39 were allocated to the low ACTG2 group and 28 to the high ACTG2 group. Comparison of the baseline charac- teristics between the two groups showed that patients in the high ACTG2 group were older than those in the low ACTG2 group. In addition, levels of Lipoprotein （a）（Lpa）, Total bilirubin（TBIL） and Pro-Brain Natri- uretic Peptide （ProBNP） in the high ACTG2 group were also higher than those in the low ACTG2 group. Conclusions Circulating ACTG2 could significantly increase in UA patients, which may be used as a biomarker for the prediction of UA.展开更多
Background Bone marrow mesenchymal stem cells （BMSCs） can be isolated and cultured to many passages However, Stem cells including BMSCs quickly undergo senescence in culture. The cell senescence and multidirectional...Background Bone marrow mesenchymal stem cells （BMSCs） can be isolated and cultured to many passages However, Stem cells including BMSCs quickly undergo senescence in culture. The cell senescence and multidirectional differentiation have hampered producing BMSCs in quantity with their undifferentiated state. In this study we report a natural compound, vitamin C （Vc）, maintains BMSCs stem property. Methods Human BMSCs were isolated from bone marrow and purified by 1.073 g/mL density gradient centrifugation. 50 ng/mL Vc were added to BMSCs for different time point. Flowcytometry was used to detect cell surface markers of BMSCs with or without Vc treatment. BMSCs proliferation was analyzed by MTF assay. PCR（polymerase chain reaction） and real-time PCR were used for detecting c-kit, nanog, and Oct-4 genes expression levels. DNA methyltransferase （Dnmt） 1 and Dnmt3b levels were also detected by real-time PCR. Results Flowcytometry showed that after Vc treatment for 6 h, the surface markers of BMSCs were almost unchanged. Vc increased the proliferation activity of BMSCs from 6h to 24 h. PCR showed the expression of c-kit, nanog, and oct-4 genes were obviously increased c-kit, nanog, and oct-4 in Vc treated group than control group at 12 h. Real-time PCR showed that the level of genes were unregulated from 6h to 12h compared with control group. Vc also increased Dnmt3b but not Dnmtl gene expression. Conclusions Our results showed Vc acts at least accelerates BMSCs proliferation and maintains stem cell property. In our study BMSCs generation and provided additional insights into the we highlighted a method of improving the speed of mechanistic basis of preventing BMSCs senescence展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30772142, 81070103, 81070102）, the National Key Basic Research Program （NKBRP） of China （No. 2006CB503806） and the Natural Science Foundation of Guangdong Province （No. 8251008004000001 and 9451008002003467）.
文摘Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.
基金supported by the National Natural Science Foundation of China(No.81270222/81470439)the Natural Science Foundation of the Guangdong Province(No.S2011020005911/S2015010009453)
文摘Background Acute coronary syndrome （ACS） is a leading cause of mortality and morbidity worldwide, which comprises unstable angina （UA） and acute myocardial infarction （AMI）, and the investigation of bio- logical markers to assess those most at risk of recurrent cardiovascular events is necessary. Methods Sixty-six healthy control people and 67 cases of UA patients were enrolled in Guangdong general hospital. Enzyme linked immunosorbent assay （ELISA） was used to detect the level of plasma ACTG2. The receiver operating characteristic curve （ROC） was used to analyze the prediction value of ACTG2 for UA. According to the aver- age level of plasma ACTG2 in UA patients, UA patients were divided into the low ACTG2 group （ 〈 average level） and the high ACTG2 group （≥ average level）, and the differences in clinical characteristics between the two groups were investigated. Results The ELISA result showed that the level of plasma ACTG2 was 67.823 ± 58.479 pg/mL in healthy people, while the plasma ACTG2 was 94.514 ± 65.453 pg/mL in UA pa- tients, with a significant difference （P 〈 0.05）. ROC analysis result showed that the Area under curve（AUC） for the prediction of UA was 0.653 （95% CI 0.559-0.747）, with a high statistical significance, indicating that circulating ACTG2 may possess high prediction value for UA. In addition, among the 67 UA patients, 39 were allocated to the low ACTG2 group and 28 to the high ACTG2 group. Comparison of the baseline charac- teristics between the two groups showed that patients in the high ACTG2 group were older than those in the low ACTG2 group. In addition, levels of Lipoprotein （a）（Lpa）, Total bilirubin（TBIL） and Pro-Brain Natri- uretic Peptide （ProBNP） in the high ACTG2 group were also higher than those in the low ACTG2 group. Conclusions Circulating ACTG2 could significantly increase in UA patients, which may be used as a biomarker for the prediction of UA.
基金supported by grants from National Natural Science of Foundation China (Nos. 30900610, 30672077)the National Key Basic Research Program (NKBRP) of China (No.2006CB503806)Guangdong Provincial Natural Science Foundation (Nos. 9451008002003467, 8251008004000001, 06020831,06020821)
文摘Background Bone marrow mesenchymal stem cells （BMSCs） can be isolated and cultured to many passages However, Stem cells including BMSCs quickly undergo senescence in culture. The cell senescence and multidirectional differentiation have hampered producing BMSCs in quantity with their undifferentiated state. In this study we report a natural compound, vitamin C （Vc）, maintains BMSCs stem property. Methods Human BMSCs were isolated from bone marrow and purified by 1.073 g/mL density gradient centrifugation. 50 ng/mL Vc were added to BMSCs for different time point. Flowcytometry was used to detect cell surface markers of BMSCs with or without Vc treatment. BMSCs proliferation was analyzed by MTF assay. PCR（polymerase chain reaction） and real-time PCR were used for detecting c-kit, nanog, and Oct-4 genes expression levels. DNA methyltransferase （Dnmt） 1 and Dnmt3b levels were also detected by real-time PCR. Results Flowcytometry showed that after Vc treatment for 6 h, the surface markers of BMSCs were almost unchanged. Vc increased the proliferation activity of BMSCs from 6h to 24 h. PCR showed the expression of c-kit, nanog, and oct-4 genes were obviously increased c-kit, nanog, and oct-4 in Vc treated group than control group at 12 h. Real-time PCR showed that the level of genes were unregulated from 6h to 12h compared with control group. Vc also increased Dnmt3b but not Dnmtl gene expression. Conclusions Our results showed Vc acts at least accelerates BMSCs proliferation and maintains stem cell property. In our study BMSCs generation and provided additional insights into the we highlighted a method of improving the speed of mechanistic basis of preventing BMSCs senescence
