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

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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Bioactive Components of Chinese Herbal Medicines in the Treatment of Glucose and Lipid Metabolism Disorders:Evidence and Potential Mechanisms

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Engineering 2023年第10期29卷 73-82页

作者： Ying Zhang Jiaming Ju Lei Jiao Baofeng Yang Department of Pharmacology&State–Province key Laboratories of Biomedicine-Pharmaceutics of China&key laboratory of cardiovascular Medicine Research Ministry of EducationCollege of PharmacyHarbin Medical UniversityHarbin 150081China Department of Pharmacology and Therapeutics Melbourne School of Biomedical SciencesFaculty of MedicineDentistry and Health SciencesUniversity of MelbourneMelbourneVIC 3010Australia Research Unit of Noninfectious Chronic diseases in frigid zone Chinese Academy of Medical SciencesHarbin 150081China

Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and *** increasing number of studies have shown that excessive body fat accumulation is associated with type 2 diabetes or insulin resistance in a vicious *** vicious cycle promotes the occurrence and development of the aforementioned ***,stabilizing the blood lipids and blood glucose of patients is the predominant strategy for improving the symptoms of patients with cardiovascular,cerebrovascular,and central nervous system *** Chinese medicine,mainly Chinese herbal medicine(CHM),has a history of more than 2000 years in China,which has established a unique theory and accumulated a great wealth of clinical ***,CHM has been widely used in China and other countries for the treatment of cardiovascular and cerebrovascular diseases,with the advantages of preventing and curing hyperlipidemia,diabetes,hypertension,and other ***,the use of CHM in Western countries remains rather limited,partly because of the incomplete understanding of multiple complex components and uncertain pharmacological ***,we review and discuss the benefits,molecular mechanisms,and clinical research progress of bioactive components of CHM and their preparations as therapeutics for hyperlipidemia and hyperglycemia.

关键词： Chinese herbal medicines Hyperlipidemia Hyperglycemia cardiovascular and cerebrovascular diseases

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I prostanoid receptor activation attenuates pressure overload-induced cardiac hypertrophy by enhancing glucose oxidation

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4448-4451页

作者： Qian Liu Guizhu Liu Yujuan Zhuo Shihong Chen Yinghong Zheng Kai Zhang Song Xiang Jiangping Song Liming Yang Ying Yu Department of Pharmacology Tianjin Key Laboratory of Inflammatory BiologyCenter for Cardiovascular DiseasesHaihe Laboratory of Cell EcosystemKey Laboratory of Immune Microenvironment and Disease(Ministry of Education)The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsSchool of Basic Medical SciencesTianjin Medical UniversityTianjinChina School of Medicine Jiangnan UniversityWuxiJiangsuChina Department of Pathophysiology Key Laboratory of Cardiovascular PathophysiologyHarbin Medical UniversityHarbinHeilongjiangChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesTianjin Medical UniversityTianjinChina State key laboratory of cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Pathophysiology School of Basic Medical SciencesHarbin Medical University-DaqingDaqingHeilongjiangChina State key laboratory of frigid zone cardiovascular diseases(SKLFZCD) Harbin Medical UniversityHarbinHeilongjiangChina

Heart failure(HF)is one of the leading causes of mortality and morbidity *** current treatments can improve cardiac dysfunction in HF patients,the overall mortality rate remains high,indicating more effective therapeu... 详细信息

关键词： mortality cardiac hypertrophy

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Xinfuli Granule improves post-myocardial infarction ventricular remodelingand myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway

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Journal of Geriatric Cardiology 2017年第5期14卷 301-307页

作者： Jie MA Zhi-Yuan LI Xiao-Peng LIANG Cai-Xia GUO Pei-Pei LU Li-Hong MA Department of Traditional Chinese Medicine State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College Beij'ing China

Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI).MethodsSprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western *** LVIDS (P key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence furth

关键词： Acute myocardial infarction Myocardial fibrosis TGF-β/Smads signaling pathway Ventricular remodeling Wnt/β-cateninsignaling pathway Xinfuli Granule

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LncDACH1 promotes mitochondrial oxidative stress of cardiomyocytes by interacting with sirtuin3 and aggravates diabetic cardiomyopathy

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Science China(Life Sciences) 2022年第6期65卷 1198-1212页

作者： Qi Zhang Danyang Li Xue Dong Xiaowen Zhang Junwu Liu Lili Peng Bo Meng Qi Hua Xinyu Pei Lu Zhao Xiaoxi Hu Yang Zhang Zhenwei Pan Yanjie Lu Baofeng Yang Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular Medicine ResearchMinistry of EducationCollege of PharmacyHarbin Medical UniversityHarbin 150081China College of Pharmacy Qiqihar Medical UniversityQiqihar 161006China Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China Research Unit of Noninfectious Chronic diseases in frigid zone(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China

Diabetic cardiomyopathy(DCM)is a common complication in diabetic *** molecular mechanisms of DCM remain to be fully *** intronic long noncoding RNA of DACH1(lnc DACH1)has been demonstrated to be closely associated with heart failure and cardiac *** this study,we investigated the role of lnc DACH1 in DCM and the underlying molecular *** expression of lnc DACH1 was increased in DCM hearts and in high glucose-treated *** of lnc DACH1 reduced mitochondrial oxidative stress,cell apoptosis,cardiac fibrosis and hypertrophy,and improved cardiac function in DCM *** of lnc DACH1 exacerbated mitochondria-derived reactive oxygen species(ROS)level and apoptosis,decreased activity of manganese superoxide dismutase(Mn-SOD);while silencing of lnc DACH1 attenuated ROS production,mitochondrial dysfunction,cell apoptosis,and increased the activity of Mn-SOD in cardiomyocytes treated with high *** DACH1 directly bound to sirtuin3(SIRT3)and facilitated its degradation by ubiquitination,therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse *** addition,SIRT3 silencing abrogated the protective effects of lnc DACH1 deficiency in *** summary,lnc DACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse *** of lnc DACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy.

关键词： diabetic cardiomyopathy apoptosis oxidative stress lncRNA SIRT3

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Mettl13 protects against cardiac contractile dysfunction by negatively regulating C-Cbl-mediated ubiquitination of SERCA2a in ischemic heart failure

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Science China(Life Sciences) 2023年第12期66卷 2786-2804页

作者： Shuting Yu ZhiYong Sun Xiuzhu Wang Tiantian Ju Changhao Wang Yingqi Liu Zhezhe Qu KuiWu Liu Zhongting Mei Na Li Meixi Lu Fan Wu Min Huang Xiaochen Pang Yingqiong Jia Ying Li Yaozhi Zhang Shunkang Dou Jianhao Jiang Xin Li Baofeng Yang Weijie Du Department of Pharmacology(The State-Province key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Northern Translational Medicine Research and Cooperation Center Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China Research Unit of Noninfectious Chronic diseases in frigid zone Chinese Academy of Medical Sciences2019RU070Harbin 150081China Traditional Chinese Medicine School Beijing University of Chinese MedicineBeijing 100029China

Ischemic heart failure(HF)remains a leading cause of morbidity and *** homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF ***-like protein 13(Mettl13)has been shown to regulate protein translation efficiency by acting as a protein lysine methyltransferase,but its role in cardiac pathology remains *** study aims to characterize the roles and mechanisms of Mettl13 in cardiac contractile function and *** found that Mettl13 was downregulated in the failing hearts of mice post-myocardial infarction(MI)and in a cellular model of oxidative ***-specific overexpression of Mettl13 mediated by AAV9-Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to MI,while silencing of Mettl13 impaired cardiac function in normal ***,Mettl13 overexpression abrogated the reduction in cell shortening,Ca^(2+)transient amplitude and SERCA2a protein levels in the cardiomyocytes of adult mice with ***,knockdown of Mettl13 impaired the contractility of cardiomyocytes,and decreased Ca^(2+)transient amplitude and SERCA2a protein expression in vivo and in ***,Mettl13 impaired the stability of c-Cbl by inducing lysine methylation of c-Cbl,which in turn inhibited ubiquitination-dependent degradation of ***,the inhibitory effects of knocking down Mettl13 on SERCA2a protein expression and Ca^(2+)transients were partially rescued by silencing c-Cbl in H_(2)O_(2)-treated *** conclusion,our study uncovers a novel mechanism that involves the Mettl13/c-Cbl/SERCA2a axis in regulating cardiac contractile function and remodeling,and identifies Mettl13 as a novel therapeutic target for ischemic HF.

关键词： heart failure Mettl13 SERCA2a c-Cbl ubiquitination

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FAM210A:Implications in mitochondrial dynamics and metabolic health

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frigid zone Medicine 2023年第4期3卷 196-198页

作者： Han Lou Henghui Xu Yong Zhang Department of Pharmacology College of Pharmacyand Department of Cardiologythe Second Affiliated HospitalHarbin Medical UniversityHarbin 150081China The State key laboratory of frigid zone cardiovascular diseases(SKLFZCD) and the Key Laboratory of CardiovascularMedicine ResearchMinistry of EducationHarbin 150081China Research Unit of Noninfectious Chronic diseases in frigid zone Chinese Academy of Medical Sciences2019RU070Harbin 150081China

Brown adipose tissue(BAT),crucial for mammalian thermoregulation and energy metabolism,boasts a dense concentration of *** a vital cellular organelle,mitochondria undergo substantial remodeling in cold environments,pl... 详细信息

关键词： metabolism environments dynamics

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Acute cold exposure triggers thermogenic memory in brown adipose tissue

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frigid zone Medicine 2023年第4期3卷 199-201页

作者： Tong Zhao Xin Liu Department of Pharmacology the State-Province key Laboratories of Biomedicine-Pharmaceutics of China College of PharmacyHarbin Medical UniversityHarbin 150081China The State key laboratory of frigid zone cardiovascular diseases(SKLFZCD) and the Key Laboratory of Cardiovascular Medicine ResearchMinistry of EducationHarbin 150081China

1 Introduction Infants are born with a substantial amount of brown adipose tissue(BAT),primarily clustered around their upper back,shoulders,and upper chest[1].As age progresses,the primary BAT gradually diminishes,and concomitantly,de novo lipogenesis(DNL)continues to occur in subcutaneous adipose tissue throughout the *** abundance of BAT in young children enhances their thermogenic capacity,making weight gain challenging and increasing resistance to cold *** adults.

关键词： continue brown primarily

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Blue LED promotes the chemosensitivity of human hepatoma to Sorafenib by inducing DNA damage

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BIOCELL 2023年第8期47卷 1811-1820页

作者： TONG WANG JINHUAN HONG JIAJIE XIE QIAN LIU JINRUI YUE XUTING HE SHIYU GE TAO LI GUOXIN LIU BENZHI CAI LINQIANG LI YE YUAN Department of Pharmacy(The University key laboratory of Drug Research Heilongjiang Province)The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina Department of General Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinChina national key laboratory of frigid cardiovascular Disease HarbinChina Department of Pharmacology(The State-Province key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbinChina Department of Clinical Pharmacology College of PharmacyHarbin Medical UniversityHarbinChina

Background:Phototherapies based on sunlight,infrared,ultraviolet,visible,and laser-based treatments present advantages like high curative effects,small invasion,and negligible adverse reactions in cancer *** aimed to explore the potential therapeutic effects of blue light emitting diode(LED)in human hepatoma cells and decipher the underlying cellular and molecular ***:Wound healing and transwell assays were employed to probe the inhibition of the invasion and migration of hepatocellular carcinoma cells in the presence of blue *** sphere-forming test was used to evaluate the effect of LED blue light irradiation on cancer stem cell *** and western blotting were used to detect the changes inγ-*** Cell Counting Kit-8 assay,5-ethynyl-2′-deoxyuridine staining,and colony formation assay were used to detect the combined effect of blue LED and sorafenib on cell proliferation ***:We demonstrated that the irradiation of blue LED light in hepatoma cells could lead to cell proliferation reduction along with the increase of cell ***,blue LED irradiation also markedly suppressed the migration and invasion ability of human hepatoma *** formation analysis further revealed the decreased cancer stemness of hepatoma cells upon blue LED ***,blue LED irradiation significantly promoted the expression of the phosphorylation of the core histone protein H2AX(γ-H2AX),a sensitive molecular marker of DNA *** addition,we found that the combined treatment of blue LED irradiation and sorafenib increased cancer cell sensitivity to ***:Collectively,we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer cells by inducing DNA damage and could enhance chemosensitivity of cancer cells,which represents a potential approach for human hepatoma treatment.

关键词： Blue LED Irradiation Liver cancer DNA damage Chemotherapy resistance

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Unveiling metabolic flux changes during acute cold exposure

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frigid zone Medicine 2023年第4期3卷 193-195页

作者： Pingping Tang Henghui Xu Yong Zhang 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 State key laboratory of frigid zone cardiovascular diseases(SKLFZCD) Harbin 150081China Research Unit of Noninfectious Chronic diseases in frigid zone Chinese Academy of Medical Sciences2019RU070Harbin 150081China Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbin 150081China

Controlling energy expenditure during acute cold exposure is a fundamental aspect of metabolic dynamics in ***,prior studies on cold-induced thermogenesis faced limitations,primarily focusing on brown adipose tissue(BAT)and lacking precise in vivo flux *** editorial aims to highlight the recent research by Bornstein et *** a comprehensive and quantitative insight into the intricate alterations in metabolic flux that drive this phenomenon[1].

关键词： precise primarily limitations

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