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Objective:To investigate the role of KLF4 in lipopolysaccharide induced cardiomyocyte injury.Methods:Primary rat cardiomyocytes were isolated and cultured, and randomly divided into 5 groups: control group, negative control (NC), LPS group, KLF4 overexpression group, KLF4 overexpression+LPS group. MTT method was used to detect cell activity, ROS, SOD 2, GPX and MDA were detected by kit, TNFa, IL-1 β and IL-6 were detected by ELISA. TUNEL staining was used to detect apoptosis. The protein levels of TLR4 and Nrf2 were detected by Western blot.Results:The expression of KLF4 in cardiomyocytes was significantly higher than that in the NC group ( P<0.001). The cell activity of LPS group was significantly lower than that of NC group ( P < 0.001), and that of KLF4 overexpression +LPS group was higher than that of LPS group ( P<0.001). The levels of TNFa, IL-1 β and IL-6 in LPS group were significantly higher than those in the NC group ( P<0.0001), and the levels of TNFa, IL-1 β and IL-6 in KLF4 overexpression +LPS group were lower than those in LPS group ( P<0.0001). The levels of ROS and MDA in LPS group were significantly higher than those in the control group, while the activities of SOD2 and GPX were lower than those in the NC group ( P<0.0001); the levels of ROS and MDA in KLF4 overexpression +LPS group were lower than those in LPS group, while the activities of SOD2 and GPX were higher than those in LPS group ( P<0.0001). The number of apoptosis in LPS group was significantly higher than that in the NC group, and that in KLF4 overexpression +LPS group was lower than that in LPS group ( P< 0.001). The level of TLR4 wan higher and Nrf2 protein in the nucleus of LPS group was lower than that of the NC group. The level of TLR4 was lower and Nrf2 protein in the nucleus of KLF4 overexpression+LPS group was significantly higher than that of LPS group ( P < 0.001). Conclusions:KLF4 can alleviate LPS induced cardiomyocyte injury by regulating TLR4 and NRF2 signals.
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Objective@#To investigate the role of piperine on the transformation of endothelial cells into fibroblasts.@*Methods@#Cultured human umbilical vein endothelial cells (HUVECs, 4-6 passage) were used for the main experiments. The transformation models of endothelial cells into fibroblasts were induced by transforming growth factor β (TGF-β) stimulation. HUVECs were divided into 6 groups: control group, TGF-β group and 4 groups treated with various concentrations of piperine (1, 5, 10, 20 μmol/L). CKK-8 was used to detect cell proliferation. The CD31/α-smooth muscle actin (α-SMA) expression level was detected by fluorescent staining. The vascular endothelial cadherin (VE-cadherin)/vimentin expression was detected by immunofluorescence staining. RT-PCR was used detect the mRNA expressions of transformation markers. Western blot was used to detect the protein expression of snail and twist.@*Results@#TGF-β increased HUVECs proliferation (P<0.05), which could be significantly inhibited by 10 and 20 μmol/L of piperine, but not by 1 and 5 μmol/L of piperine. Immunofluorescence results demonstrated that TGF-β increased HUVECs transformation to fibroblasts as shown by downregulated expression of endothelial markers CD31, VE-cadherin, and upregulated expression of α-SMA and vimentin, again, these effects could be attenuated by 10 and 20 μmol/L piperine. The expression levels of collagen type Ⅰ and type Ⅲ were significantly higher in TGF-β group than in control group (P<0.05), significantly lower in TGF-β+10 μmol/L piperine group and TGF-β+20 μmol/L piperine group than in TGF-β group (P<0.05).In addition, RT-PCR results showed that TGF-β increased mRNA expression of transformation markers (snail1, snail2, twist1, twist2), while 10 and 20 μmol/L of piperine could significantly downregulated the mRNA expressions of these markers. The protein expression levels of snail and twist were significantly higher in TGF-β group than in control group (both P<0.05), which was significantly lower in TGF-β+20 μmol/L piperine group than in TGF-β group (both P<0.05).@*Conclusions@#Piperine can inhibit the transformation of endothelial cells into fibroblasts. This effect might be viewed as one of the potential mechanisms of reduced myocardial fibrosis post piperine treatment.
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Objective To investigate the efficacy and safety of levosimendan on patients with acutely decompensated heart failure (ADHF).Methods A prospective randomized and controlled study was carried out from June 2013 to June 2014.Patients were randomly divided into levosimendan group and dobutamine group,with 60 patients in each group.All patients received an intravenous infusion of levosimendan or dobutamine for 24 hours.Brain natriuretic peptide (BNP),stroke volume (SV) and left ventricular ejection fraction (LVEF) were measured.The cardiovascular mortality,rehospitalization rate,the composite endpoint differences and the incidence of adverse events were compared between two groups in 1,3,6 months after treatment.Comparisons between two groups were made using Student t-test or one-way ANOVA.Statistical analysis was performed using SPSS 17.0 software and a P value of ＜ 0.05 was considered statistically significant.Results There was no significant difference in the basic characteristics between two groups.Compared with baseline level,the plasma BNP levels,SV and LVEF were improved at 24 h in both groups (P ＜ 0.05).The cardiac function indexes were better in levosimendan group than in dobutamine group at 24 h [BNP (1147±407) pg/mL vs.(1 502±501) pg/mL,SV (60.9±9.6) mL vs.(57.3±10.3) mL,LVEF (31.6±6.0)％ vs.(28.8±5.1)％,P＜0.05].One month later,the cardiac function indexes were still better in levosimendan group than baseline [BNP (796 ± 296) pg/mL vs.(1 951 ±692) pg/mL,SV (64.6±9.5) mL vs.(52.2±9.1) mL,LVEF (33.4 ±5.8)％ vs.(25.7 ± 6.1) ％,P ＜ 0.05].After l months of treatment,the composite endpoint in levosimendan group was significantly lower than dobutamine group (5％ vs.16.3％,P =0.043).There was a downward trend of mortality and rehospitalization rate in levosimendan group in six months follow-up (P ＞ 0.05).The incidence of side effects was no statistically significant between groups (both were 13.3％).Conclusions Levosimendan is superior to that of dobutamine in improving the hemodynamic status and prognosis in ADHF patients,and the adverse reaction of levosimendan is less.
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Objective:To explore the therapeutic effect of intra-aortic balloon counterpulsation (IABP)on acute my-ocardial infarction (AMI)complicated pump failure.Methods:Clinical data of 82 AMI patients complicated pump failure,which received emergency percutaneous coronary intervention (PCI)in our hospital from Jan 2010 to Oct 2013,were retrospectively analyzed.The patients were divided into IABP group (n=42,received PCI with auxiliary IABP)and routine PCI group (n=40,only received routine PCI therapy).Success rate of treatment,mortality,he-modynamic conditions [systolic blood pressure (SBP),diastolic blood pressure (DBP)and heart rate (HR)]stable to PCI time,length of hospital stay and complications were compared between two groups.Results:Compared with routine PCI group after treatment,there were significant rise in blood pressure [SBP: (80.3± 16.2)mmHg vs. (88.4±12.5)mmHg,DBP:(55.4±10.2)mmHg vs.(60.0±10.5)mmHg]and urine volume [(30.2±8.3)ml/h vs.(40.3±9.4)ml/h],and significant reduction in HR [(92.4±26.1)times/min vs.(80.5±18.5)times/min] in IABP group,P 0.05).Conclusion:IABP adjuvant treatment helps to raise success rate of PCI,improve hemodynamic condition and increase urine volume,shorten length of hospital stay in patients with AMI complicated pump failure.
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Objective To discuss prognosis and relevant factors of the advanced age patients ( over 75 years old) with acute coronary syndrome two years after treated by percutaneous coronary intervene ( PCI ) and conservative treatment .Methods divided 134 cases of advanced age inpatients with acute coronary syndrome were into the obser -vation group and control group in accordance with the different therapies .To 71 inpatients in the observation group treated with standard PCI therapies and treated 63 inpatients in the control group with conservative treatment .Compare the clinical data and their cardiovascular event occurrence rate , case fatality rate and influencing factor of the two groups two years after they left the hospital .Results During the hospitalization ,there were 2 patients in the observa-tion group died,the case fatality rate was 2.82%(2/71),during 24 months follow-up visit,the cardiovascular event occurrence rate was 16.90%(12/71),and cardiac mortality was 5.63%(4/71).Well,in control group,there were 3 patients died,the case fatality rate was 4.76%(3/63),during 24 months follow-up visit,the cardiovascular event occurrence rate was 36.51%(23/63),and cardiac mortality was 11.11%(7/63).The fatality rate of the two groups during the hospitalization had no significant difference (χ2 =0.352,P=0.553),the cardiovascular event occurrence rate and cardiac mortality of the patients in the observation group was superior to that of the control group 24 months after they left hospital,the difference between the two groups was significant (χ2 =6.650,P=0.010).Conclusion PCI treatment to advanced age patients with ACS could reduce their myocardial infarction risk and case fatality rate and improve the symptom obviously ,effectively reduce the patients ’ cardiovascular event and cardiac death occurrence rate in two years .
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The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts. Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups. The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1, 1.0, 10.0, and 100.0 nmol/L, respectively). Myocardial ischemia was induced by globally stopping the perfusion flow. Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min. The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detection (HPLC-EC). Following acute ischemia, testosterone (1.0, 10.0 and 100.0 nmol/L) significantly reduced norepinephrine release (P0.05). Electrical stimulation of the ventricle evoked norepinepherine release, and this was diminished by the perfusion with testosterone at the concentrations of 1.0, 10.0 and 100.0 nmol/L (P<0.01). It is suggested that testosterone suppresses ischemia- and electrical stimulation-induced norepinepherine release in the isolated rat hearts.
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Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.
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Positive selection and differential selective pressure analyses were carried out to study Haemagglutinin (HA) genes of H9N2 influenza viruses from different hosts in this paper. Results showed that, although most positions in HAs were under neutral or purifying evolution, a few positions located in the antigenic regions and receptor binding sites were subject to positive selection and some of them were even positively selected at the population level. In addition, there were always some positions differentially selected for viruses from different hosts. Both selection pressure working on HA codons and positions differentially selected might account for the extension of the host range and adaptations to different hosts of H9N2 influenza viruses.
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Objective Brain natriuretic peptide(BNP) is released from the cardiac ventricles in response to increased wall tension. The prognostic significance of blood brain natriuretic peptide in Chinese patients with cardiovascular disease has not been established. The purpose of this study was to investigate the value of brain natriuretic peptide for predictin g cardiac death within 1 month in Chinese patients with cardiovascular disease. Methods One hundred and seven inpatients with cardiovascular disease, whose blood brain natriuretic peptide concentration were measured within 1 - 3 days of admission, using triage BNP test, were divided into 2 groups: the survival and the non-survival, according to the results of 1was positively correlated with heart rate, left ventricular end-diastolic dimension, history of heart failure and old myocardial infarction (r=0.28, P=0. 000 4; r=0.49, P＜0. 000 5; r=0.39, P＜0. 000 5; r=Area under the curve of the receiver-operating-characteristic(ROC) of brain natriuretic peptide to predict cardiac death at 1 month in patients with cardiovascular disease was 0.89%, 95% confidence interval 0.79-0. 98, P＜0. 000 5; stepwise logistic regression analysis indicated that brain natriuretic peptide (≥755pg/mL) was the only independent predictor of cardiac death at 1 month in patients with cardiovascular disease (OR= 17.6, 95 % confidence interval, 8.7- 66.5, P＜0. 000 5 ). Conclusion Brain natriuretic peptide might predict cardiac death at 1 month in patients with cardiovascular disease.