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OBJECTIVE@#To explore the correlation of plasma N-acetyl-neuraminic acid level with Thrombolysis In Myocardial Infarction (TIMI) risk score and clinical outcomes of patients with acute coronary syndrome (ACS).@*METHODS@#We consecutively enrolled 708 consecutive patients (401 male and 307 female, mean age 63.6±10.6 years) undergoing coronary angiography in our hospital between October, 2018 and July, 2019, including 597 patients with ACS and 111 without ACS (control group). The patients with ACS group were divided into high (=104), moderate (=425) and low (=68) risk groups according to their TIMI risk scores. All the participants were examined for plasma Neu5Ac level using liquid chromatography-tandem mass spectrometry and underwent coronary angiography with their Gensini scores calculated. The patients with ACS were followed up after discharge for a mean of 15 months for the occurrence of major adverse cardiac events (Mace). Binary logistic regression analysis was performed to identify the risk factors of Mace in these patients.@*RESULTS@#Plasma Neu5Ac levels were significantly higher in ACS group than in the control group ( < 0.05). ROC curve analysis showed that plasma Neu5Ac level could assist in the diagnosis of ACS (0.648 [0.597-0.699]) with a sensitivity of 39.2% and a specificity of 86.5% at the cutoff value of 288.50 ng/mL. In the ACS patients, plasma Neu5Ac level was significantly higher in the high-risk group than in the moderate-risk and low-risk groups ( < 0.05) and could assist in the diagnosis of a high risk (0.645 [0.588-0.703]) with a sensitivity of 42.3% and a specificity of 80.1% at the cutoff value of 327.50 ng/ mL. Plasma Neu5Ac was positively correlated with age, serum uric acid, creatinine, lipoprotein a, Ddimer, C-reactive protein, MB isoform of creatine kinase and Gensini score and negatively correlated with high-density lipoprotein level. During the followup, 80 ACS patients experienced Mace, who had significantly higher plasma Neu5Ac level than those without Mace (=517). Logistic regression analysis showed that plasma Neu5Ac level and a history of previous stroke were independent risk factors for the occurrence of Mace.@*CONCLUSIONS@#Plasma Neu5Ac level can provide assistance in the diagnosis and risk stratification of ACS and is an independent risk factor for prognosis of ACS patients.
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OBJECTIVE@#To investigate whether autophagy mediates the effects of aldehyde dehydrogenase 2 (ALDH2) on the proliferation of neonatal rat cardiac fibroblasts cultured in high glucose.@*METHODS@#Cardiac fibroblasts were isolated from neonatal (within 3 days) SD rats and subcultured. The fibroblasts of the third passage, after identification with immunofluorescence staining for vimentin, were treated with 5.5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), or 30 mmol/L glucose in the presence of Alda-1 (an ALDH2 agonist), daidzin (an ALDH2 2 inhibitor), or both. Western blotting was employed to detect ALDH2, microtubule-associated protein 1 light chain 3B subunit (LC3B) and Beclin-1 in the cells, and a hydroxyproline detection kit was used for determining hydroxyproline content in cell culture medium; CCK- 8 kit was used for assessing the proliferation ability of the cardiac fibroblasts after the treatments.@*RESULTS@#Compared with the control cells, the cells exposed to high glucose exhibited obviously decreased expressions of ALDH2, Beclin-1 and LC3B and increased cell number and hydroxyproline content in the culture medium. Treatment of the high glucose-exposed cells with Alda-1 significantly increased Beclin-1, LC3B, and ALDH2 protein expressions and lowered the cell number and intracellular hydroxyproline content, whereas the application of daidzin resulted in reverse changes in the expressions of ALDH2, Beclin-1 and LC3B, viable cell number and intracellular hydroxyproline content in high glucose-exposed cells.@*CONCLUSIONS@#Mitochondrial ALDH2 inhibits the proliferation of neonatal rat cardiac fibroblasts induced by high glucose, and the effect is possibly mediated by the up-regulation of autophagy-related proteins Beclin-1 and LC3B.
Subject(s)
Animals , Rats , Aldehyde Dehydrogenase , Aldehyde Dehydrogenase, Mitochondrial , Metabolism , Animals, Newborn , Autophagy , Beclin-1 , Physiology , Fibroblasts , Glucose , Microtubule-Associated Proteins , Mitochondrial Proteins , Rats, Sprague-DawleyABSTRACT
To investigate the effect of activating aldehyde dehydrogenase 2 (ALDH2) on TASK-1 two-pore potassium channel in myocardial injury of diabetic rats. Methods: Diabetic rats were induced by intraperitoneal injection of streptozotocin (55 mg/kg). The diabetic rats were divided into 4 groups: normal group, diabetes at 4th week (DM4W) group, diabetes at 8th week (DM8W) group, and diabetes at 8th week+low concentration of ethanol intervention (DM8W+EtOH) group. The cardiac function of rats was determined by cardiac ultrasonography. The content of hydroxyproline was detected by ELISA. The appearance of myocardial morphous and positive material were observed by HE and PAS staining. The protein expression of TASK-1 was detected by Western blot. Whole-cell patch clamp technique was used to record the action potential duration at 30% and 90% repolarization (APD30, APD90) and two-pore potassium channel TASK-1 current in rat ventricular myocytes. Meanwhile, according to the sensitive electrophysiological characteristics of the potassium channel to acid and base, whether it is two-port potassium channel TASK-1current can be determined. Results: Compared with the N group, end-diastole left ventricular diameter (LVIDd), end-systolic left ventricular diameter (LVIDs), hydroxyproline content, TASK-1 protein expression increased, APD30 and APD90 extend, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF), and TASK-1 current decreased (all P<0.01) in the DM4W group and the DM8W group. HE staining showed that myocardial cell and fiber arrangement disorder, myocyte hypertrophy, myocardial widened and PAS staining reveals that positive material increased in the DM4W group and the DM8W group. Compared with the DM4W group, these changs are more obvious in DM8W rats (P<0.01 or P<0.05). Compared with the DM8W group, in the DM8W+EtOH group, the left ventricular function was restored, the hydroxyproline content and expression of TASK-1 protein were decreased, the TASK-1 current was increased, and APD30 and APD90 were shortened (all P<0.01). HE staining showed that myocardial cell injury was ameliorate and PAS staining showed decreased deposition of positive substances in the DM8W+EtOH group. Conclusion: Activation of aldehyde dehydrogenase 2 by low concentration of ethanol can reduce myocardial injury and fibrosis caused by diabetes, and its mechanism may be related to the changes of the two-por potassium channel TASK-1.
Subject(s)
Animals , Rats , Aldehyde Dehydrogenase, Mitochondrial , Diabetes Mellitus, Experimental , Heart Diseases , Metabolism , Myocardium , Potassium , Potassium Channels, Tandem Pore Domain , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes of the two- pore K channel TASK-1 in diabetic rats with myocardial injury.</p><p><b>METHODS</b>Thirty-six SD rats were divided into normal group (N), diabetes at 4 weeks (DM 4W) group, and diabetes at 8 weeks (DM 8W) group. The cardiac functions of the rats were determined using cardiac ultrasonography, and the body weight and heart weight of the rats at different time points were measured to calculate the heart/body weight ratio (HW/BW). Myocardial fibrosis in the rats was assessed using Masson's staining. The protein expression of TASK-1 in the myocardium was detected using Western blotting. Whole- cell patch clamp technique was used to record the action potential duration (APD) and twopore domain potassium channel TASK- 1 current in acutely isolated rat ventricular myocytes. meanwhile, The inhibition of TASK-1 current was observed by the TASK-1 specific inhibitor ML-365.</p><p><b>RESULTS</b>Compared with the normal group, the diabetic rats showed significantly increased HW/BW ( < 0.05), end- diastole left ventricular diameter (LVIDd), end- systolic left ventricular diameter (LVIDs), and TASK-1 protein expression, with obviously decreased left ventricular diameter shortening rate (FS) and ejection fraction (EF) ( < 0.01). Masson staining showed that in diabetic rats, the collagen fibers were thickened, interwoven into a network with uneven arrangement and increased deposition. Compared with DM 4W group, the rats in DM 8W group exhibited progressive increases in LVIDd, LVIDs, HW/BW, and TASK-1 expression ( < 0.01 or 0.05); FS and EF were further decreased ( < 0.01). Masson staining showed worsened morphological changes of the myocardium with increased deposition. Compared with that in the normal group, the current of TASK- 1 in diabetic rats at 8 weeks was significantly reduced ( < 0.01) and the duration of action potential was extended ( < 0.05). The TASK-1 current was successfully inhibited by ML-365.</p><p><b>CONCLUSIONS</b>Diabetes can induce myocardial fibrosis and aggravate myocardial injury possibly in relation to changes in the protein expression and current of the two-port potassium channel TASK-1.</p>
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Objective To assess the relationship of CYP2C19 gene polymorphism with clopidogrel respon-siveness and the level of EETs in patients with ACS. Methods A total of 123 patients with ACS receiving aspirin combined with clopidogrel dual antiplatelet were enrolled. According to the results of CYP2C19 genotype,patients were divided into three groups:fast metabolic type ,medium metabolic type ,and slow metabolism type. The concentration of EETs and PAIR were compared between three groups. Logistic analysis was used to analyze the risk factors of LCR. Results There were differences statistically in level of EETs and PAIR among the three groups(P<0.05). Logistic analysis showed that the slow metabolism of CYP2C19 gene and lower EETs level were risk factors for LCR. The area under the ROC curve was 0.893(P < 0.05)by EETs level to predict the CYP2C19 genotype. Conclusion The slow metabolism of CYP2C19 gene was an independent risk factor for LCR,while the increase of plasma EETs level was a protective factor.
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Objective: To explore the relationship between blood levels of cyclophilin A (CyPA) and chronic heart failure (CHF). Methods: A total of 166 CHF patients were enrolled as CHF group, according to NYHA classiifcation, it was further divided into 4 sub-groups: Class I,n=37, Class II,n=39, Class III,n=46 and Class IV,n=44. In addition, there was a Normal control group,n=52. Blood levels of CyPA, B-type natriuretic peptide (BNP) and high sensitivity C-reactive protein (hs-CRP) were examined and compared among different groups. Results: Compared with Normal control group, CHF group had elevated CyPA (5.11 ± 2.43) ng/ml vs (2.28 ± 0.61) ng/ml, BNP (385.65 ± 184.06) pg/ml vs (90.37 ± 18.44) pg/ml and hs-CRP (11.74 ± 5.44) mg/L vs (5.99 ± 1.14) mg/L, all P0.05. Pearson correlation analysis indicated that blood levels of CyPA were positively related to BNP and hs-CRP in CHF patients (r=0.838,P Conclusion: Blood levels of CyPA were elevated in CHF patients and it’s obviously related to NYHA classiifcation, which might have certain effects on CHF diagnosis and evaluation.
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Objective To assess the diet quality of pregnant women during the second trimester using the dietary inflammatory index ( DII) and to explore the correlation between the DII in second trimester of preg-nancy and preterm delivery.Methods A total of 253 women with singleton pregnancy in 16-20 gestational weeks who had received routine prenatal care between August 2014 and April 2015 at the First Affiliated Hospi-tal of Anhui Medical University were enrolled with cluster random sampling.The included women were asked to recall daily dietary intake in the 3 days prior to the survey.All dietary data were analyzed for energy and nutri-ents intake with a nutritional analysis software, followed by calculation of DII according to previous reports. Based on quartiles of the DII scores, the participants were divided into three groups, namely the anti-inflam-matory group (DII-2.55).The participants were followed up until delivery and the pregnancy outcomes were recorded. The relationship between the DII in second trimester of pregnancy and preterm delivery were analyzed. Results DII scores of the 253 pregnant women during the second trimester of pregnancy ranged from -7.913 to 3.872.The risks of preterm birth in the anti-inflammatory diet group, the intermediate group, and the pro-inflammatory diet group were 0, 1.6%, and 6.3%, respectively, with statistically significant differences among the groups (P=0.034).The higher DII scores (pro-inflammatory) were associated with higher inci-dence of preterm birth ( P<0.05 ) .Conclusion DII may be used to assess diet quality of pregnant women during the second trimester and to predict the risk of preterm birth.
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<p><b>OBJECTIVE</b>To compare the DNA methylation-related alteration induced by trichloroethylene (TCE) in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the role of SET on the mechanisms in TCE-induced epigenetic pathway.</p><p><b>METHODS</b>The L-02 cells and pre-established SET deficient cells were treated with different TCE concentrations, and the changes of total cell viability, DNA methylation level and DNA methyltransferases (DNMTs) activity were measured, respectively. In addition, the TCE-induced alteration in the protein expression of DNMT1, DNMT3a and DNMT3b were analyzed by Western blotting.</p><p><b>RESULTS</b>After treatment with TCE for 24 h, the cell proliferation level was significantly decreased in both cell lines. When concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, the proliferation levels of L-02 cells were 100.00±2.70, 83.34±2.38, 75.56±4.51, 71.67±2.77 and 66.67±1.63, respectively (F = 58.29, P < 0.001); the cell proliferation levels of SET deficient cells were 101.12±1.67, 85.01±2.33, 79.44±1.67, 78.337±3.89 and 76.11±3.33, respectively (F = 42.41, P < 0.001). When concentration of TCE reached 4.0 mmol/L, the difference of cell proliferation level between two groups was statistically significant (t = -3.51; P = 0.013). After treated by TCE for 24 h, the global DNA methylation significantly decreased in both cell lines (F value was 212.87 and 79.32, respectively, P < 0.001). The difference between two groups was not statistically significant. After treated by TCE for 24 h, the methyltransferases activities were significantly decreased in both cell cells (F values were 77.92 and 113.80, respectively, P-0.001). The SET deficiency could inhibit the decrease of methyltransferases activity under TCE treatment. When the concentration of TCE reached 8.0 mmol/L, the enzymatic activity of L-02 cells and SET deficient cells decreased to 67.61%±2.85% and 72.97%± 1.94%, respectively. The difference between two groups was statistically significant (t = -3.94, P = 0.008). After treated with TCE for 24 h, concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, and the relative protein levels of DNMT1 in normal L-02 cells increased significantly to 1.00±0.03, 1.28±0.04, 1.20±0.04, 1.62±0.05, 1.43±0.04 (F = 103.00, P < 0.001); In SET deficient cells, the expressions of DNMT1 were 1.00±0.04, 0.96±0.02, 1.19±0.05, 0.85±0.03, 0.83±0.03, which was significantly down-regulated under TCE treatment (F = 44.18, P < 0.001).</p><p><b>CONCLUSION</b>SET deficiency can significantly attenuate the TCE-induced decreases of cell viability and DNMTs activity, as well as alteration of protein expression of DNMT1 in L-02 cells, which indicated that SET was involved in the mechanism of TCE-induced cytotoxicity and epigenetic pathway in L-02 cells.</p>
Subject(s)
Humans , Cell Line , Cell Survival , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases , DNA Methylation , Liver , TrichloroethyleneABSTRACT
Objective: To explore the endothelial microparticle (EMP) level in elderly patients with acute coronary syndrome (ACS) combining diabetic mellitus (DM)) and to study the relationship between EMP level and ACS combining DM in elder patients. Methods: A total of 208 patients≥65 years with coronary angiography in our hospital were summarized including 124 male with the age of (71.9 ± 5.2) years. The patients were divided into 3 groups, Control group, n=51 normal subjects, ACS without DM group, n=83 and ACS+DM group, n=74. Plasma EMP levels were measured by FACSCalibur lfow cytometry as CD31+/CD42b-EMPS and the vascular stenosis degree was quantitatively calculated with Gensini score. Results: The CD31+/CD42b-EMPs level in ACS + DM group >ACS without DM group > Control group, all P Conclusion: Plasma CD31+/CD42b-EMPs level increased in elderly ACS patients and the elevation level related to vascular lesion degree/combining with DM, which indicated the endothelial dysfunction in such patients.
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<p><b>OBJECTIVE</b>To investigate the correlation of G487A polymorphism of aldehyde dehydrogenase-2 (ALDH2) gene with hypertension in patients with coronary heart disease complicated by type 2 diabetes.</p><p><b>METHODS</b>This study was conducted among 167 patients with coronary heart disease complicated by diabetes mellitus. The polymorphisms of gene G487A ALDH2 were determined using polymerase chain reaction-restricted fragments length polymorphism technique (PCR-RFLP). According to the genotypes, the patients were divided into GG group (n=105) and GA/AA group (n=62), and the incidence of hypertension, risk factors of hypertension, systolic and diastolic pressures, and pulse pressure indexes were compared between the two groups. Multivariate logistic regression analysis was performed to adjust the effects of the confounding factors.</p><p><b>RESULTS</b>The incidence of hypertension in GA/AA group was significantly higher than that in GG group (P<0.05), and the former group showed a significantly greater differences between systolic and pulse pressure; the diastolic pressure was comparable between the two groups. Multivariate logistic regression analysis showed that GA/AA was associated with an increased risk of hypertension in synergy with high insulin level and insulin resistance.</p><p><b>CONCLUSION</b>ALDH2 gene G487A polymorphism may be associated with hypertension in patients with coronary heart disease complicated by type 2 diabetes, and the patients with an A allele have a greater risk of developing hypertension.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Alcohol Dehydrogenase , Genetics , Coronary Disease , Genetics , Diabetes Mellitus, Type 2 , Genetics , Hypertension , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Objective To examine the influence of 3R intensive nursing on working memory dysfunction of patients with early Parkinson's disease. Methods 30 patients with early Parkinson's disease were assessed by Working Memory Test Battery,and acceped 3R- nursing. The condition of working memory dysfunction was compared before and after nursing intervention. Results The patients with early Parkinson's disease had evident difference than the normal controls, especially the visualspatial working memory. After 3R- nursing, the subtest scores and dimensions were improved apparently. Conclusions The clinical effect of 3R- nursing method in patients with early Parkinson's disease has significant predominance ,so it is worth popularizing.
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<p><b>OBJECTIVE</b>To establish the animal model of atherosclerotic erectile dysfunction induced by high-cholesterol diet and explore the mechanisms of atherosclerotic erectile dysfunction.</p><p><b>METHODS</b>Thirty male rabbits were divided into two groups randomly: normal diet (ND) group (n = 10) and high-cholesterol (HCH) group fed with 1.5% cholesterol diet (n = 20). Serum total cholesterol, plaque areas of the ascending aorta, the ratio of intima/media thickness and level of vascular cell adhesion molecule 1 (VCAM-1) mRNA expression of internal pudendal artery were determined after twelve weeks.</p><p><b>RESULTS</b>After twelve weeks, all rabbits of the HCH group got hyperlipemia, 9 of which presented typical atherosclerosis (ATH). The rate of atherosclerosis induced by high-cholesterol diet was 52.9%. Serum total cholesterol levels of the ATH and HCH groups were higher than that of the ND group (P<0.01). The penile erection times and rate in the ATH and HCH groups decreased significantly, compared with the ND group (P<0.01). Both the ratio of intima/media thickness and the level of VCAM-1 mRNA expression of internal pudendal artery in the ATH group were higher than those in the HCH and ND groups (P<0.01).</p><p><b>CONCLUSION</b>It is easy, prectuable and reliable to establish the animal model of atherosclerotic erectile dysfunction induced by high-cholesterol diet. And one of the main causes of atherosclerotic erectile dysfunction is hypercholesterolemia, which through VCAM-1 may induce the structural and functional modifications of the endothelium of the internal pudendal artery and make the corpus cavernosum ischemia.</p>
Subject(s)
Animals , Male , Rabbits , Atherosclerosis , Diet, Atherogenic , Disease Models, Animal , Hypercholesterolemia , Impotence, Vasculogenic , RNA, Messenger , Random Allocation , Vascular Cell Adhesion Molecule-1 , GeneticsABSTRACT
AIM: To study the effect of cocaine on caspase-3 in myocardiac cells of male rats in different age. METHODS: Three-week-old( n= 16), six-week-old( n= 16) and twelve-week-old( n= 16)male Sprague Dawley rats were all divided into control groups and experiment groups randomly, each group had eight animals, experiment groups were given cocaine hydrochloride (15 mg?kg -1 body weight) subcutaneously daily for four weeks.The ratio of heart weight to body weight (HW/BW,mg/g) were measured. DNA fragmentation of myocardia cells was determined by gel electrophoresis, and caspase-3 activity in myocardia cells was tested by flow cytometry (FCM). RESULTS: In three experiment groups, the DNA isolated from myocardial cells displayed clear ladder pattern. The HW/BW and the caspase-3 activity were increased significantly than those of control groups ( P