郭晓
青岛阜外心血管病医院 心内科
This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1β, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-β/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 2024
OBJECTIVE:Magnetic Resonance Image (MRI) is an important imaging modality for diagnosing heart disease and analyzing heart function. The size and shape of the ventricle are important parameters for judging whether the heart is normal, and the ventricles in the MRI image is effectively segmented It is the key to obtain the ventricle size, shape and other parameters. Accurate segmentation of the entricle is the fundamental guarantee for the evaluation of cardiac function. However, in the heart image, the contrast between the ventricle area and the background area is not obvious, the boundary is blurred, and there is noise in most of the images. The accurate segmentation of the ventricle becomes a challenging problem.METHODS:We performed scanning of short-axis cardiac MR image sequences based on 33 subjects. Each subject has 8 to 15 sequences, each pertaining to a 20-frame sequence. Based on the U-Net neural network structure, the high-resolution information directly transferred from the encoder to the same-height decoder through the connection operation can provide more refined features for segmentation, such as gradients. The MRI left ventricular image segmentation method based on transfer learning and multi-scale discriminant Generative Adversarial Network (TLMDB GAN) solves the problem of insufficient ventricular image data.RESULTS:According to the experimental results of TLMDB GAN and U-Net network on the data set, the Dice coefficients of TLMDB GAN segmentation of the inner cardiac wall and outer cardiac wall of the ventricle are 0.9399 and 0.9697, respectively, which are 0.01 higher than other methods. The Dice coefficients of U-Net segmentation of the inner cardiac wall and outer cardiac wall of the ventricle are 0.8829 and 0.9292, respectively; CONCLUSION: The experimental results show that the TLMDB GAN based on transfer learning and multi-scale discrimination significantly improves the segmentation accuracy when compared with the U-Net segmentation model.
Computer methods and programs in biomedicine 2022
Background:Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.Methods:Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.Results:Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.Conclusion:Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 2022
BACKGROUND:Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated.METHODS:The expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice.RESULTS:MT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice.CONCLUSIONS:MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
BMC cancer 2021
OBJECTIVE:To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population.METHODS:One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Clinical and genetic data were used to evaluate the value of each algorithm by calculating the percentage of patients whose predicted warfarin dose was within 20% of the actual stable therapeutic dose and mean absolute error (MAE).RESULTS:The frequency of patients with CYP2C9*1/*1, CYP2C9*1/*3 and CYP2C9*1/*2 genotype was 92.00%, 7.20%, 0.80%, respectively. That of VKORC1-1639 AA, AG and GG genotype was 82.40%, 15.20%, 2.40%, respectively. CYP4F2*1/*1, *1/*3, *3/*3 genotype was 50.40%, 39.20%, 10.40%, respectively. With the same genotypes for other loci, patients who carried at least one VKORC1-16398G mutant allele had increased warfarin stable daily dose compared with VKORC1-1639AA. Compared with CYP4F2*1/*1, those carrying at least one CYP4F2*3 mutant allele had warfarin stable daily dose increased by 5.9%-13.00%. The percentage of ideal prediction calculated from IWPC model (59.20%), Huang model (57.60%) and Ohno model (52.80%) were higher than others. The MAE were 0.35 (95%CI: 0.11-0.49), 0.15 (95%CI: 0.10-0.32), 0.39 (95%CI: 0.12-0.51), respectively.CONCLUSION:The polymorphisms of CYP2C9, VKORC1 and CYP4F2 genes can influence the stable dose of warfarin in Shandong population. IWPC algorithm is suitable for guiding the use of warfarin in this population.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2020
Heart failure (HF) is one of the most severe heart conditions, which lacks effective therapies. Therefore, it is necessary to develop more efficient drugs for HF. In this study, we investigated the cardioprotective effects of hyperoside against the pathological progression of HF. Thoracic aortic constriction (TAC) was performed to induce HF in rats. Hyperoside treatment improved cardiac function, decreased cardiomyocyte cross-sectional area and heart weight to body weight (HW/BW) ratio in HF rats. Moreover, hyperoside administration repressed apoptosis as evidenced by changing apoptosis-related protein levels, and promoted autophagy in TAC rats and angiotensin II (AngII)-induced H9C2 cells. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated the beneficial effect of hyperoside against apoptosis in H9C2 cells. In summary, these data confirm that hyperoside effectively alleviates HF via suppressing apoptosis and inducing autophagy, which provides evidence that hyperoside may serve as a promising natural drug for treating HF.
Bioscience, biotechnology, and biochemistry 2020
Heart failure (HF) is an end-stage of various serious cardiovascular diseases, which causes liver injury. Hyperoside has been reported to exert protective effect on liver injury and fibrosis. However, the role and related mechanisms of hyperoside in HF-induced liver fibrosis are still unclear. In the current study, we established a model of HF via aortocaval fistula (ACF) in rats in vivo. Hyperoside treatment in ACF rats increased cardiac output, the maximum peak rate of rise/fall in left ventricular pressure (+dP/dt, -dP/dt) and LV ejection fraction (LVEF), decreased LV end-systolic pressure (LVESP), LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV), and reduced heart weight/body weight ratio in a dose-dependent manner. Moreover, hyperoside could attenuate liver fibrosis and injury in ACF rats, as evidenced by reduction of fibrosis area and hydroxyproline content, amelioration of edema and degeneration of liver cell vacuoles, and inhibition of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels. Further, α-smooth-muscle actin (α-SMA), collagen I, profibrotic factor-connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP2) and MMP9 levels were down-regulated in hyperoside-treated ACF rats. Additionally, hyperoside inhibited the activation of TGF-β1/Smad pathway. Finally, we confirmed that hyperoside suppressed TGF-β1-mediated hepatic stellate cell activation in vitro. Collectively, hyperoside showed a suppressive role in HF-induced liver fibrosis and injury.
Acta histochemica 2019
BACKGROUND:Heart failure (HF) with mid-range ejection fraction (EF) (HFmrEF) has attracted increasing attention in recent years. However, the understanding of HFmrEF remains limited, especially among Asian patients. Therefore, analysis of a Chinese HF registry was undertaken to explore the clinical characteristics and prognosis of HFmrEF.METHODS:A total of 755 HF patients from a multi-centre registry were classified into three groups based on EF measured by echocardiogram at recruitment: HF with reduced EF (HFrEF) (n = 211), HFmrEF (n = 201), and HF with preserved EF (HFpEF) (n = 343). Clinical data were carefully collected and analyzed at baseline. The primary endpoint was all-cause mortality and cardiovascular mortality while the secondary endpoints included hospitalization due to HF and major adverse cardiac events (MACE) during 1-year follow-up. Cox regression and Logistic regression were performed to identify the association between the three EF strata and 1-year outcomes.RESULTS:The prevalence of HFmrEF was 26.6% in the observed HF patients. Most of the clinical characteristics of HFmrEF were intermediate between HFrEF and HFpEF. But a significantly higher ratio of prior myocardial infarction (p = 0.002), ischemic heart disease etiology (p = 0.004), antiplatelet drug use (p = 0.009), angioplasty or stent implantation (p = 0.003) were observed in patients with HFmrEF patients than those with HFpEF and HFrEF. Multivariate analysis showed that the HFmrEF group presented a better prognosis than HFrEF in all-cause mortality [p = 0.022, HR (95%CI): 0.473(0.215-0.887)], cardiovascular mortality [p = 0.005, HR (95%CI): 0.270(0.108-0.672)] and MACE [p = 0.034, OR (95%CI): 0.450(0.215-0.941)] at 1 year. However, no significant differences in 1-year outcomes were observed between HFmrEF and HFpEF.CONCLUSION:HFmrEF is a distinctive subgroup of HF. The strikingly prevalence of ischemic history among patients with HFmrEF might indicate a key to profound understanding of HFmrEF. Patients in HFmrEF group presented better 1-year outcomes than HFrEF group. The long-term prognosis and optimal medications for HFmrEF require further investigations.
BMC cardiovascular disorders 2019
OBJECTIVES:Galectin-3 has been shown to be involved in the process of cardiac fibrosis and to predict adverse events in heart failure (HF), but the association of galectin-3 with cause-specific death has not been well established. The purpose of this study was to investigate the prognostic value of baseline galectin-3 for all-cause, cardiovascular (CV), and in-hospital death in patients with HF.METHODS AND RESULTS:From March 2009 to April 2013, we consecutively measured galectin-3 in a large cohort of 1,440 hospitalized patients with HF. Cox proportional hazards regression, discrimination, and reclassification analyses were used to evaluate the association between galectin-3 and death. During a median follow-up of 582 days, 283 deaths were identified, of which 64 were patients who died during hospitalization. Compared with the lowest galectin-3 tertile, the highest 2 tertiles were significantly associated with all-cause, CV, and progressive HF death, but not significant for sudden and in-hospital death when analyzed by multivariable Cox regression. The utility of combining galectin-3 and N-terminal pro-B-type natriuretic peptide was assessed by dichotomizing these 2 biomarkers according to their median values. The highest risk of death due to all-cause, CV, and progressive HF was observed when both biomarkers were elevated after adjustment for established risk factors. Addition of galectin-3 to the prediction model for all-cause and CV death significantly improved discrimination and reclassification.CONCLUSIONS:Galectin-3 independently predicted death and added additional prognostic value beyond established risk factors in hospitalized patients with HF. The utility of galectin-3 alone as a risk predictor was not strong enough to assess sudden or in-hospital death.
Journal of cardiac failure 2015
OBJECTIVE:To explore the predict value of plasma soluble ST2 (sST2) on one-year mortality for hospitalized patients with chronic heart failure (HF).METHODS:A total of 1 244 consecutive hospitalized patients admitted to Heart Failure Center Fuwai Hospital between March 2009 and July 2012 and with HF as their primary diagnosis were included. Plasma sST2 was measured in all patients and patients were followed up for 1 year, and the primary endpoint was defined as all-cause death.RESULTS:There were 193 deaths during follow up. sST2 concentrations at admission were positively correlated with NT-proBNP, NYHA functional class and heart rate, and negatively correlated with left ventricular ejection fraction, blood sodium, total cholesterol and glomerular filtration rate at admission. sST2 concentrations were significantly higher in non-survivors compared with survivors (P < 0.001). Multivariable Cox regression analyses showed that sST2 independently predicted 1-year mortality (per 1 log unit, hazard ratio 1.87, 95% confidence interval: 1.56 to 2.25, P < 0.001). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.776 which was similar to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (AUC = 0.775). The prognostic value was improved when combining these two biomarkers together (AUC = 0.813).CONCLUSIONS:sST2 concentration at admission is correlated with clinical and biochemical indexes and associated with 1-year mortality for hospitalized patients with HF.
Zhonghua xin xue guan bing za zhi 2014
