陈现杰
阜外华中心血管病医院 心血管外科
Objective:Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI.Methods:Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships.Results:SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia.Conclusions:Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.
Cardiovascular therapeutics 2022
BACKGROUND AND OBJECTIVE:The incidence of atrial fibrillation is increasing annually. We develop an automatic detection system, which is of great significance for the early detection and treatment of atrial fibrillation. This can lead to the reduction of the incidence of critical illnesses and mortality.METHODS:We propose an atrial fibrillation detection algorithm based on multi-feature extraction and convolutional neural network of atrial activity via electrocardiograph signals, and compare its detection based on cluster analysis, one-versus-one rule and support vector machine, using accuracy, specificity, sensitivity and true positive rate as evaluation criteria.RESULTS:The atrial fibrillation detection algorithm proposed in this paper has an accuracy rate of 98.92%, a specificity of 97.04%, a sensitivity of 97.19%, and a true positive rate of 96.47%. The average accuracy of the algorithms we compared is 80.26%, and the accuracy of our algorithm is 23.25% higher than this average pertaining to the other algorithms.CONCLUSION:We implemented an atrial fibrillation detection algorithm that meets the requirements of high accuracy, robustness and generalization ability. It has important clinical and social significance for early detection of atrial fibrillation, improvement of patient treatment plans and improvement of medical diagnosis.
Computer methods and programs in biomedicine 2021
PURPOSE:Coronary artery disease (CAD) is known to have high prevalence, high disability and mortality. The incidence and mortality of cardiovascular disease are also gradually increasing worldwide. Therefore, our paper proposes to use a more efficient image processing method to extract accurate vascular structures from vascular images by combining computer vision and deep learning.METHOD:Our proposed segmentation of coronary angiography images based on PSPNet network was compared with FCN, and analyzed and discussed the experimental results using three evaluation indicators of precision, recall and Fl-score. Aiming at the complex and changeable structure of coronary angiography images and over-fitting or parameter structure destruction, we implemented the parallel multi-scale convolutional neural network model using PSPNet, using small sample transfer learning that limits parameter learning method.RESULTS:The accuracy of our technique proposed in this paper is 0.957. The accuracy of PSPNet is 26.75% higher than the traditional algorithm and 4.59% higher than U-Net. The average segmentation accuracy of the PSPNet model using transfer learning on the test set increased from 0.926 to 0.936, the sensitivity increased from 0.846 to 0.865, and the specificity increased from 0.921 to 0.949. The segmentation effect in this paper is closest to the segmentation result of the human expert, and is smoother than that of U-Net segmentation.CONCLUSION:The PSPNet network reduces manual interaction in diagnosis, reduces dependence on medical personnel, improves the efficiency of disease diagnosis, and provides auxiliary strategies for subsequent medical diagnosis systems based on cardiac coronary angiography.
Computer methods and programs in biomedicine 2021
Cyanotic congenital heart disease (CCHD) is the main cause of death in infants worldwide. Long noncoding RNAs (lncRNAs) have been pointed to exert crucial roles in development of CHD. The current research is designed to illuminate the impact and potential mechanism of lncRNA SNHG14 in CCHD in vitro. The embryonic rat ventricular myocardial cells (H9c2 cells) were exposed to hypoxia to establish the model of CCHD in vitro. Quantitative real-time polymerase chain reaction was conducted to examine relative expressions of SNHG14, miR-25-3p, and KLF4. Cell viability was determined by the MTT assay. Lactate dehydrogenase (LDH) was measured by an LDH assay kit. Apoptosis-related proteins (Bax and Bcl-2) and KLF4 were detected by Western Blot. The targets of SNHG14 and miR-25-3p were verified by the dual-luciferase reporter assay. SNHG14 and KLF4 were upregulated, whereas miR-25-3p was downregulated in hypoxia-induced H9c2 cells and cardiac tissues of patients with CCHD compared with their controls. Knockdown of SNHG14 or overexpression of miR-25-3p facilitated cell viability, while depressing cell apoptosis and release of LDH in hypoxia-induced H9c2 cells. MiR-25-3p was a target of SNHG14 and inversely modulated by SNHG14. MiR-25-3p could directly target KLF4 and negatively regulate expression of KLF4. Repression of miR-25-3p or overexpression of KLF4 reversed the suppression impacts of sh-SNHG14 on cell apoptosis and release of LDH as well as the promotion impact of sh-SNHG14 on cell viability in hypoxia-induced H9c2 cells. Sh-SNHG14 protected H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro.
Journal of cardiovascular pharmacology 2021
BACKGROUND:Hypoxia/reoxygenation (H/R)-mediated apoptosis and inflammation are major causes of tissue injury in acute myocardial infarction (AMI). Exploring the underlying mechanisms of cardiomyocyte injury induced by H/R is important for AMI treatment. Circular RNAs have been demonstrated to paly vital roles in the pathogenesis of AMI. Our study aimed to explore the function of circular RNA UBXN7 (circUBXN7) in regulating H/R-induced cardiomyocyte injury.METHODS:H/R-treated H9c2 cells and a mouse model of AMI were used to investigate the function of circUBXN7 in H/R damage and AMI. The expressions of circUNXN7, miR-622 and MCL1 were analyzed by RT-qPCR. CCK-8 was used for examining cell viability. Cell apoptosis was evaluated with caspase 3 activity and Annexin V/PI staining. MCL1, Bax, Bcl-2 and cleaved-caspase 3 were examined with western blot. ELISA was used to examine the secretion of IL-6, TNF-α and IL-1β.RESULTS:CircUBXN7 was downregulated in patients and mice with AMI, as well as in H/R-treated cells. Overexpression of circUBXN7 mitigated H/R-mediated apoptosis and secretion of inflammatory factors including IL-6, TNF-α and IL-1β. CircUBXN7 suppressed cell apoptosis and inflammatory reaction induced by H/R via targeting miR-622. MiR-622 targeted MCL1 to restrain its expression in H9c2 cells. Knockdown of MCL1 abrogated circUBXN7-mediated alleviation of apoptosis and inflammation after H/R treatment.CONCLUSION:CircUBXN7 mitigates cardiomyocyte apoptosis and inflammatory reaction in H/R injury by targeting miR-622 and maintaining MCL1 expression. Our study provides novel potential therapeutic targets for AMI treatment.
American journal of translational research 2021
microRNAs are an emerging class of molecules that regulate pathogenesis of cardiovascular diseases. Here we aim to elucidate the effects and mechanism of miR-135a, a previously reported regulator of ischemia-reperfusion (I/R) injury, in myocardial I/R injury. Quantitative real-time polymerase chain reaction analysis revealed that the expression level of miR-135a was significantly decreased both in the rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation. Overexpression of miR-135a in vivo markedly decreased the infarct size and inhibited the I/R-induced cardiomyocyte apoptosis. Overexpression of miR-135a in H9c2 also exerted antiapoptosis effects. Furthermore, bioinformatics analysis, luciferase activity, and the Western blot assay indicated that protein tyrosine phosphatase 1B (PTP1B) is a direct target of miR-135a. In addition, the expression of proapoptotic-related genes, such as p53, Bax, and cleaved caspase3, were decreased in association with the downregulation of PTP1B. In summary, this study demonstrates that miR-135a exerts protective effects against myocardial I/R injury by targeting PTP1B.
Journal of cellular biochemistry 2019
Previous studies have shown that phosphatase and tensin homolog (PTEN) are key regulators of the development of many malignant tumors and other diseases. However, its regulatory effect on coronary heart disease (CHD) has rarely been reported. Therefore, the regulatory effect of PTEN on the survival and cell death of vascular smooth muscle cells (VSMCs) in CHD mice was elucidated in this study. It was found that the protein and messenger RNA expressions of PTEN in VSMCs of 10 CHD mice were lower than those of normal mice. Then PTEN was overexpressed in VSMCs. It was suggested that the upregulation of PTEN was not conducive to the proliferation and survival of VSMCs in the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay. The flow cytometry (Annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide) and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to detect the apoptotic rate of overexpressing PTEN cells. Some data showed that the expression of PTEN could lead to increased apoptotic rate. It was shown that antiapoptotic Bcl-2 levels were decreased, but cleaved caspase-3 and proapoptotic Bax levels were promoted by SIRT6 overexpression in Western blot analysis. Moreover, PI3K/Akt expression and phosphorylation were significantly decreased in cells expressing PTEN. Recovery of PI3K expression inhibited the suppressive influence of PTEN on VSMC survival, as evidenced by the activated PI3K/Akt pathway, increased cell proliferative rate, reduced the apoptotic level, and reversed expression patterns of Bcl-2 and Bax. Therefore, the findings in this study provide a new idea on the occurrence and development mechanism of CHD and may promote the discovery of innovative therapies.
Journal of cellular biochemistry 2019
