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lncRNA Gm20257 alleviates pathological cardiac hypertrophy by modulating the PGC-1α-mitochondrial complex IV axis

FRONTIERS OF MEDICINE 2024年第4期18卷 664-677页

作者： Yu, Tong Gao, Qiang Zhang, Guofang Li, Tianyu Liu, Xiaoshan Li, Chao Zheng, Lan Sun, Xiang Wu, Jianbo Cao, Huiying Bi, Fangfang Wang, Ruifeng Liang, Haihai Li, Xuelian Zhou, Yuhong Lv, Lifang shan, hongli shanghai Univ Engn Sci Inst Frontier Med Technol Shanghai Frontiers Sci Res Ctr Druggabil Cardiovas Shanghai 201620 Peoples R China Harbin Med Univ Sch Basic Med Dept Physiol Harbin 150081 Peoples R China Harbin Med Univ Ctr Funct Expt Teaching Sch Basic Med Harbin 150081 Peoples R China Harbin Med Univ Coll Pharm Dept Pharmacol State Key Lab Frigid Zone Cardiovasc DisState Pro Harbin 150081 Peoples R China

Pathological cardiac hypertrophy, a major contributor to heart failure, is closely linked to mitochondrial function. The roles of long noncoding RNAs (lncRNAs), which regulate mitochondrial function, remain largely unexplored in this context. Herein, a previously unknown lncRNA, Gm20257, was identified. It markedly increased under hypertrophic stress in vivo and in vitro. The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy. Conversely, the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensin II-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively, thus restoring cardiac function. Importantly, Gm20257 restored mitochondrial complex IV level and enhanced mitochondrial function. Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator-activated receptor coactivator-1 (PGC-1 alpha), which could increase mitochondrial complex IV. Subsequently, Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1 alpha. Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1 alpha was a direct downstream target of Gm20257. This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP. These findings suggest that Gm20257 improves mitochondrial function through the PGC-1 alpha-mitochondrial complex IV axis, offering a novel approach for attenuating pathological cardiac hypertrophy.

关键词： lncRNA Gm20257 cardiac hypertrophy PGC-1 alpha mitochondrial complex IV ATP LONG NONCODING RNA HEART-FAILURE CARDIOMYOPATHY REGULATOR

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Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

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Frigid Zone Medicine 2024年第1期4卷 41-50页

作者： Tongzhu Jin Zhen Ye Ruonan Fang Yue Li Wei Su Qianqian Wang Tianyu Li hongli shan Yanjie Lu Haihai Liang Laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Department of Pharmacy Suqian First HospitalSuqian 223800China Research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac *** Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt *** objective of this study was to explore the role and mechanism of Notum in cardiac ***:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction *** protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction *** cell necrosis and infiltration were confirmed through H&E and Masson *** expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast ***:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ***,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac ***,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin *** preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in ***:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast

关键词： cardiac fibrosis Notum Wnt/β-catenin senescence myocardial infarction

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Establishment and Application of Prevention and Control Techniques of New Sugarcane White Leaf Disease

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Agricultural Biotechnology 2024年第4期13卷 18-20,27页

作者： Xiaoyan WANG Ruonan QIU Hong XU Yulong JIANG Rongyue ZHANG Fengyun ZHANG Ming GONG Jinxue LEI hongli shan Jie LI Yingkun HUANG Key Laboratory on Genetic Improvement of Sugarcane in Yunnan Province Sugarcane Research InstituteYunnan Academy of Agricultural SciencesKaiyuan 661699China Economic Crop Workstation Lancang Lahu Autonomous CountyLancang 665600China Yunnan Zichen Agricultural Development Co. Ltd.Xiangyun 672100China

Aiming at the basic and key technical problems in prevention and control of sugarcane white leaf disease(SCWL),this study systematically overcame key technical bottleneck of prevention and control of new SCWL after 10 years of collaborative research,and achieved several innovative *** phytoplasmas newly recorded in China and the new subgroup of SCWL phytoplasmas(16SrXI-D)were discovered for the first time in Yunnan,and the whole genome analysis of the epidemic subgroup was *** main transmission source of SCWL pathogens has been identified as infected seed canes,and Tettigoniella viridis and Clovia conifer were newly discovered as vectors for virus *** disease resistance of 25 main varieties was identified,and 10 control varieties were *** prevention and control strategy of"emphasizing early warning,strictly carrying out quarantine,blocking the vectors and controlling residual plants"was put forward,and a comprehensive prevention technique was established through integration of various techniques,and standardized technical regulations were formulated for demonstration *** promotion and application of these achievements have realized scientific prevention and control of SCWL,effectively curbed the spread of SCWL,and ensured the safety of sugarcane producing areas in China,achieving great economic,social and ecological benefits and providing technical support for high-quality development,loss reduction and efficiency improvement of China's sugar industry.

关键词： Sugarcane white leaf disease Comprehensive prevention and control Application

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YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

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Frigid Zone Medicine 2024年第1期4卷 51-64页

作者： Fangfang Bi Miao Cao Yuquan Wang Qingming Pan Zehong Jing Danyang Bing Lifang Lyu Tong Yu Tianyu Li Xuelian Li Haihai Liang hongli shan Yuhong Zhou Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA Institute for Frontier Medical TechnologyShanghai University of Engineering ScienceShanghai 201620China Department of Basic Medicine Xiamen Medical CollegeXiamen 361023China

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold ***1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein *** YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely ***:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)*** protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride *** vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic *** to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac *** of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac *** hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite *** of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing *** hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT ***:YBX1 protected the heart

关键词： YBX1 PI3K/AKT apoptosis mitochondrial function myocardial infarction

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MicroRNAs in idiopathic pulmonary fibrosis: involvement in pathogenesis and potential use in diagnosis and therapeutics

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Acta Pharmaceutica Sinica B 2016年第6期6卷 531-539页

作者： Huimin Li Xiaoguang Zhao hongli shan Haihai Liang Department of Pharmacology College of Pharmacy Harbin Medical University

MicroRNAs (miRNAs) are a class of phylogenetically conserved, non-coding short RNAs, 19-22 nt in length which suppress protein expression through base-pairing with the 3'-untranslated region of target mRNAs. miRNAs have been found to participate in cell proliferation, differentiation and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high lethality fibrotic lung disease for which currently there is no effective treatment. Some miRNAs have been reported to be involved in the pathogenesis of pulmonary fibrosis. In this review, we discuss the role of miRNAs in the pathogenesis, diagnosis and treatment of IPF. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND

关键词： Idiopathic pulmonary fibrosis MicroPNA Pathogenesis Early diagnosis Therapeutic target lncRNA

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尿沉渣评分对急性肾损伤诊断的临床应用研究

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中华检验医学杂志 2024年第5期47卷 548-553页

作者：张慧续薇曲林琳赵春贺单洪丽张勤高洪臣孙文瑞朱丽娜张月闫欣杨笑权王婉宁张东付尧赵旭何亮吉林大学第一医院检验科长春130021 北华大学医学技术学院吉林132013 吉林大学第一医院肾病内科长春130021 吉林大学第一医院重症医学科长春130021 吉林大学第一医院肝胆胰内科长春130021 吉林大学第一医院普通外科中心胃结直肠外科长春130021

目的:评估尿沉渣评分(USS)在急性肾损伤(AKI)的早期诊断、病因鉴别、分期及预后判断中的临床应用,探讨独立的USS及其联合血尿素氮(Bun)、血清肌酐(sCr)和尿酸(UA)对AKI的诊断效能。方法:收集2023年8月23日至9月28日期间吉林大学第一医... 详细信息

目的:评估尿沉渣评分(USS)在急性肾损伤(AKI)的早期诊断、病因鉴别、分期及预后判断中的临床应用,探讨独立的USS及其联合血尿素氮(Bun)、血清肌酐(sCr)和尿酸(UA)对AKI的诊断效能。方法:收集2023年8月23日至9月28日期间吉林大学第一医院住院患者9020份晨尿标本,经Sysmex UF5000检测,筛出小而圆形上皮细胞(SRC)>1/μl和/或管型(CAST)>1/μl 3226份进行尿沉渣镜检,选取肾小管上皮细胞和/或CAST阳性的404例入组,其中男218例,女186例,年龄59.5(49.0,71.0)岁。404例分组方法:依据镜检结果的USS分为USS AKI组(345例)和USS非AKI组(59例);依据改善全球肾脏病预后组织(KDIGO)标准,分为KDIGO标准AKI组(63例)和KDIGO标准非AKI组(341例);依据病历记载的临床诊断,分为临床诊断AKI组(29例)和临床诊断非AKI组(375例);通过查阅病历,对KDIGO标准AKI组按病因分为肾性AKI组(33例)和非肾性AKI组(30例)。采用χ^(2)检验或Fisher精确检验比较不同AKI病因、分期的USS。采用Logistic回归法计算发生肾性AKI及3期AKI的优势比。应用受试者工作特征曲线下面积评价USS、sCr、UA、Bun单独及联合诊断AKI的敏感度、特异度并计算诊断AKI的最佳截断值、敏感度与特异度。结果:以USS对KDIGO标准AKI组进行病因鉴别,肾性与非肾性AKI的USS比较差异有统计学意义(χ^(2)=11.070,P<0.001)。与USS=1相比,当USS≥2分时肾性AKI的优势比为8.125(95%CI 2.208~29.901)。以USS进行AKI分期研究,各期USS的组间比较差异有统计学意义(χ^(2)=15.724,P<0.05)。与USS=1分相比,当USS≥2分时发生3期AKI优势比为9.714(95%CI 1.145~82.390)。独立的USS诊断AKI的AUC为0.687(95%CI 0.618~0.757,P<0.001),特异度65.7%,敏感度61.9%;USS联合Bun、sCr、UA诊断AKI的AUC为0.794(95%CI 0.608~0.980,P<0.05),特异度82.4%,敏感度88.9%。结论:USS≥2分提示发生肾性AKI或3期AKI的可能性增加,USS联合Bun、sCr、UA可提高AKI诊断效能。

关键词：尿尿沉渣评分急性肾损伤尿沉渣镜检检验临床应用

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MicroRNAs Control Cardiac Fibrosis

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中国药理通讯 2013年第3期30卷 46-47页

作者： hongli shan Haihai Liang Yanjie Lu Baofeng Yang Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) Harbin 15008 China

Cardiac fibrosis is characterized by aberrant proliferation of cardiac fibroblasts and exaggerated deposition of extracellular matrix (ECM) in the myocardial interstitial, and eventually leads to heart failure. Therefore, reveal the mechanism of cardiac fibrosis is of great value for clinical therapy, microRNAs (miRNAs) are a class of endogenous, non-coding small RNAs,

关键词：骨髓间充质干细胞心肌细胞^K+ 心律失常心脏疾病

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lncRNA PFAR Promotes Lung Fibroblast Activation and Fibrosis by Targeting miR-138 to Regulate the YAP1-Twist Axis

lncRNA PFAR Promotes Lung Fibroblast Activation and Fibrosis...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Xiaoguang Zhao Haihai Liang hongli shan Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)Harbin Medical University

Long non-coding RNAs(lncRNAs) have been reported to be involved in various pathophysiological processes in many ***,the role and mechanism of lncRNAs in idiopathic pulmonary fibrosis(IPF) have not been explicitly *** the present study,we reported that lncRNA NONMMUT065582,designated pulmonary fibrosis-associated RNA(PFAR),was up-regulated in the lungs of mice with lung fibrosis as well as in fibrotic lung *** of PFAR promoted fibrogenesis through modulation of miR-138,whereas knockdown of PFAR attenuated TGF-β1-induced fibrogenesis in lung *** addition,knockdown of miR-138 promoted fibrogenesis by targeting regulation of yes-associated protein 1(YAP1),whereas enhanced expression of miR-138 attenuated fibrogenesis in lung ***,PFAR acted as competing endogenous RNA(ceRNA) of miR-138:forced expression of PFAR reduced the expression and activity of miR-138 to activate YAP1 and promote fibrogenesis in lung fibroblasts,whereas loss of YAP1 abrogated the pro-fibrotic effect of *** importantly,PFAR silencing alleviated BLM-induced lung fibrosis in *** together,the results of our study identified lncRNA PFAR as a new pro-fibrotic molecule that acts as a ceRNA of miR-138 during lung fibrosis and demonstrated PFAR as a potential novel therapeutic target for the prevention and treatment of lung fibrosis.

关键词： lncRNA PFAR Promotes Lung Fibroblast Activation and Fibrosis by Targeting miR-138 to Regulate the YAP1-Twist Axis Twist miR

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Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

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Frontiers of Medicine 2015年第4期9卷 444-456页

作者： Samuel Chege Gitau Xuelian Li Dandan Zhao Zhenfeng Guo Haihai Liang Ming Qian Lifang Lv Tianshi Li Bozhi Xu Zhiguo Wang Yong Zhang Chaoqian Xu Yanjie Lu Zhiming Du hongli shan Baofeng Yang Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) Harbin Medical University Harbin 150081 China Institute of Cardiovascular Research Harbin Medical University Harbin 150081 China Department of Pharmacy and Complementary Medicine School of Health Sciences Kenyatta University PO. BOX 43844-00100 Nairobi Kenya Institute of Clinical Pharmacy the Second Affiliated Hospital Harbin Medieal University Harbin 150081 China

Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid （aspirin） provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction （TAC） or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin （10 mg·kg^-1· d^-1）; the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II （10 nmol· L^-1） was treated with the human equivalent of low （10 or 100μmol·L^-1） and high （1000μmol·L^-1） aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, p-myosin heavy chain （IS-MHC）, atrial natriuretic peptide （ANP）, and b-type natriuretic peptide （BNP）. Aspirin efficiently reversed the upregulation of β-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3~. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of β-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin.

关键词： aspirin Akt cardiac hypertrophy GSK-3β Wnt/β-catenin

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甘蔗黑穗病研究状况文献计量分析

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中国糖料 2024年第3期46卷 80-90页

作者：王长秘罗志明单红丽李银煳张荣跃李婕王晓燕尹炯云南省农业科学院甘蔗研究所/云南省甘蔗遗传改良重点实验室/云南省蔗糖产业工程研究中心云南开远661699

本文以甘蔗黑穗病和Sugarcane smut为主题词分别在CNKI和SCI-E数据库中进行检索,并应用文献计量分析方法对文献发文趋势、期刊、机构、基金和被引用文献进行了统计分析。共检索到中文文献284篇和外文文献495篇。其中甘蔗黑穗病的中文文... 详细信息

本文以甘蔗黑穗病和Sugarcane smut为主题词分别在CNKI和SCI-E数据库中进行检索,并应用文献计量分析方法对文献发文趋势、期刊、机构、基金和被引用文献进行了统计分析。共检索到中文文献284篇和外文文献495篇。其中甘蔗黑穗病的中文文献占中英文总文献的35.54%,我国甘蔗黑穗病相关研究文献占甘蔗主要病害文献的48.97%。近年来国内外甘蔗黑穗病研究的发文量逐渐增加,这些文献主要来自于糖业和病理学领域的机构、作者和期刊。国内期刊主要发表关于甘蔗黑穗病防治、发生规律以及抗黑穗病相关研究的文献,而国外期刊则侧重于甘蔗黑穗病的致病机理和病原菌与甘蔗互作的研究。本文通过统计分析甘蔗黑穗病研究领域的文献发文概况,旨在了解甘蔗黑穗病研究的基本情况和趋势,并结合当前的研究热点方向,为下一步的甘蔗黑穗病研究提供参考。

关键词：甘蔗黑穗病文献计量 CNKI Web of science

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