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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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Prevention and control measures of the major cold-region diseases (hypertension) in China

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frigid zone Medicine 2021年第1期1卷 3-8页

作者： Zhenwei Pan Yong Zhang Tengfei Pan Haihai Liang Baofeng Yang Department of Pharmacology(The Key Laboratory of Cardiovascular research Ministry of Education)at College of PharmacyHarbin Medical UniversityHarbin 150086China research unit of noninfectious chronic diseases in frigid zone Chinese Academy of Medical SciencesChina2019RU070

Hypertension is the most common cardiovascular condition in clinical practice and a major risk factor for stroke and cardiovascular *** are more than 270 million hypertension patients in China,and the prevalence of hypertension in the high-latitude cold areas is significantly higher than in the low-latitude warm *** unique epidemiological characteristics and risk factors of hypertension in the cold regions of China urge for establishment of the prevention and control system for targeted and more effective management of the condition.

关键词： hypertension cold region prevention cure

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Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1

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Acta Pharmaceutica Sinica B 2020年第5期10卷 812-824页

作者： Xin Liu Yunwei Wei Xue Bai Mingqi Li Huimin Li Lei Wang Shuqian Zhang Xia Li Tong Zhao Yang Liu Rui Geng Hao Cui Hui Chen Ranchen Xu Heng Liu Yong Zhang Baofeng Yang 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 Department of Oncological and Laparoscopic Surgery the First Affiliated Hospital of Harbin Medical UniversityHarbin 150001China Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbin 150086China Department of Pharmacology and Therapeutics Melbourne School of Biomedical SciencesFaculty of MedicineDentistry and HealthSciences University of MelbourneMelbourne VIC 3010Australia research unit of noninfectious chronic diseases in frigid zone Chinese Academy of Medical Sciences2019 Research Unit 070Harbin 150081China

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical *** at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary *** we studied the preventive effects of different approaches of berberine treatment for primary adhesion,and its effects on adhesion reformation compared to *** found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery(pre-berberine)or direct addition into injured cecum immediately after the surgery(inter-berberine).Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary *** dysregulated TIMP-1/MMP balance was observed in patients after surgery,as well as adhesion tissues from primary adhesion or adhesion reformation ***-berberine treatment had a better effect for adhesion reformation prevention than *** promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core,which was reversed by TIMP-1 overexpression in *** conclusion,this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

关键词： Peritoneal adhesion Berberine Adhesion reformation TIMP-1

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Development status of novel spectral imaging techniques and application to traditional Chinese medicine

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Journal of Pharmaceutical Analysis 2023年第11期13卷 1269-1280页

作者： Qi Wang Yong Zhang Baofeng Yang Department of Medicinal Chemistry and Natural Medicinal Chemistry College of PharmacyHarbin Medical UniversityHarbin150081China Department of Pharmacology(The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin150081China research unit of noninfectious chronic diseases in frigid zone Chinese Academy of Medical SciencesHarbin150081China Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbin150086China Department of Pharmacology and Therapeutics Melbourne School of Biomedical SciencesFaculty of MedicineDentistry and Health Sciences University of MelbourneMelbourneVIC3010Australia

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical *** spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of *** spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation *** this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are *** advantages and disadvantages of each technology are also ***,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are ***,the evaluation of the efficacy of TCM in vivo is *** future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

关键词： Chinese medicine Spectral imaging Fluorescence spectroscopy Photoacoustic imaging

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Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

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Engineering 2024年第7期38卷 133-143页

作者： Shuang Yang Yixiu Zhao Xiaoling Cheng Tingting Zhan Jiaying Tian Xue Liu Chunyue Ma Zhiqi Wang Luying Jin Qian Liu Yanli Wang Jian Huang Jinhui Wang Yan Zhang Baofeng Yang Department of Pharmacology&Key Laboratory of Cardiovascular Medicine research Ministry of Education of the People’s Republic of ChinaCollege of PharmacyHarbin Medical UniversityHarbin 150081China National Key Laboratory of frigid zone Cardiovascular diseases(NKLFZCD) Harbin Medical UniversityHarbin 150081China Department of Medicinal Chemistry and Natural Medicine Chemistry College of PharmacyHarbin Medical UniversityHarbin 150081China research unit of noninfectious chronic diseases in frigid zones Chinese Academy of Medical SciencesHarbin 150081China

Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main *** Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ***,the underlying mechanism of BXTY is still *** this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the *** was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of *** results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma *** addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent *** effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT ***,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of *** expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with *** 2028,ODQ,or KT 5823 also reversed this effect of *** conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

关键词： Myocardial ischemia Vasomotion Soluble guanylate cyclase Buxu Tongyu Granule

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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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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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Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure

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Signal Transduction and Targeted Therapy 2023年第4期8卷 2007-2021页

作者： Ye Yuan Zhongting Mei Zhezhe Qu Guanghui Li Shuting Yu Yingqi Liu Kuiwu Liu Zhihua Shen Jiaying Pu Yanquan Wang Changhao Wang Zhiyong Sun Qian Liu Xiaochen Pang Ao Wang Zijing Ren Tong Wang Ying Liu Jinhuan Hong Jiajie Xie Xin Li Zhonghua Wang Weijie Du Baofeng Yang 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 Pharmacy(The University Key Laboratory of Drug research Heilongjiang Province)The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina research unit of noninfectious chronic diseases in frigid zone Chinese Academy of Medical Sciences2019RU070 HarbinChina Department of Clinical Pharmacology College of PharmacyHarbin Medical UniversityHarbinChina Department of Cardiology The First Affiliated Hospital of Harbin Medical UniversityHarbinChina Translational Medicine research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinChina

Heart failure(HF)patients in general have a higher risk of developing *** animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease *** ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human *** critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine ***,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been ***,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft ***-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis *** expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as *** of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in ***-enriched miR-22-3p was packaged in exosomes and transferred into tumor *** of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ***4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor *** together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from ***

关键词： Exosomes enriched prevailing

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Peroxisome proliferator-activated receptors gama ameliorates liver fibrosis in non-alcoholic fatty liver disease by inhibiting TGF-β/Smad signaling activation

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frigid zone Medicine 2024年第1期4卷 12-22页

作者： Qingwei Zhang Wenjie Zhao Zeqi Sun Xinxin Dong Liwei Zhu Zhen Zhang Ximing Chen Yingying Hu Menghan Du Jiamin Li Yong Zhang Department of Pharmacology College of Pharmacyand Department of Cardiologythe Second Affiliated HospitalHarbin Medical UniversityHarbin 150081China Department of Pharmacology 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 research unit of noninfectious chronic diseases in frigid zone Chinese Academy of Medical Sciences2019RU070Harbin 150081China

Background:Nonalcoholic fatty liver disease(NAFLD)is a chronic condition characterized by a progressive decline in liver function,leading to disruptions in liver integrity and metabolic function,resulting in lipid deposition and excessive accumulation of extracellular matrix(ECM).The pathogenesis of NAFLD is complex and not yet fully understood,contributing to the absence of specific therapeutic *** proliferator-activated receptor gamma(PPARγ)is a ligand-activated transcription factor pivotal in regulating lipid and glucose ***,the impacts of PPARγon NAFLD remains insufficiently ***,this study aimed to investigate the role of PPARγin NAFLD and its underlying molecular ***:Chemical detection kits were utilized to quantify collagen content,alanine aminotransferase(ALT),and aspartate aminotransferase(AST)level *** real-time polymerase chain reaction(qRT-PCR)was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells,while western blotting was conducted to analyze the levels of both PPARγand the TGF-β/Smad signaling ***:Our findings unveiled significantly reduced PPARγexpression in a rat model of NAFLD,leading to subsequent activation of the TGF-β/Smad signaling ***,PPARγactivation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen *** a cellular level,PPARγactivation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9),along with inflammatory response genes interleukin(IL)-1βand ***,PPARγactivation led to a significant decrease in the levels of ALT and *** the molecular level,PPARγnotably down-regulated the TGF-β/Smad signaling pathway,which is known to promote liver ***:These groundbre

关键词： NAFLD PPARγ TGF-β/Smad liver fibrosis

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