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Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

Journal of Geriatric cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN Tianjin Key laboratory of Ionic-molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this *** A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent *** Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + *** In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept c

关键词： remodeling cardiac inhibited

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Protein C deficiency with venous and arterial thromboembolic events

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World Journal of Clinical Cases 2024年第12期12卷 2000-2003页

作者： Nan Zhang Dong-Kun Sun Xu Tian Xin-Yu Zheng Tong Liu Department of cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China

Protein C(PC)is a key component of the vitamin K-dependent coagulation *** exerts anticoagulant effects by inactivating factors V and *** or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous ***,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic *** editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

关键词： Protein C deficiency Venous thromboembolism Myocardial infarction Editorial Arterial thromboembolism

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with muscle Loss

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research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network research Center Sungkyunkwan University School of MedicineSuwonKorea research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

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Journal of Genetics and Genomics 2024年第8期51卷 844-854页

作者： Yi Hu Huaming Cao Jie Sheng Yizhuo Sun Yuping Zhu Qin Lin Na Yi Siyu He Luying Peng Li Li State Key laboratory of cardiology and Medical Innovation Center Shanghai East HospitalTongji University School of MedicineShanghai 200120China Shanghai Arrhythmias research Center Shanghai East HospitalTongji University School of MedicineShanghai 200120China laboratory of molecular Genetics and Stem Cell Differentiation Tongji University School of MedicineShanghai 200120China Department of cardiology Shanghai Shibei HospitalShanghai 200435China research Units of Origin and Regulation of Heart Rhythm Chinese Academy of Medical SciencesShanghai 200120China

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure,with noncoding RNAs exerting regulatory ***,the molecular function of circular RNAs(circRNAs)in the progression from cardiac hypertrophy to heart failure remains *** uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure,we construct a global triple network(microRNA,circRNA,and mRNA)based on the competitive endogenous RNA(ceRNA)*** observe that cardiac hypertrophy-related circRNA(circRNA CHRC),within the ceRNA network,is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse *** circRNA CHRC increases cross-sectional cell area,atrial natriuretic peptide,andβ-myosin heavy chain levels in primary mouse *** screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in *** with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p,while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC *** summary,circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

关键词： circRNA CHRC Heart failure CeRNA miR-431-4p KIf15

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Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease:current knowledge and new insights

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Frontiers of Medicine 2024年第1期18卷 31-45页

作者： Yaonan Song Haoran Wei Zhitong Zhou Huiqing Wang Weijian Hang Junfang Wu Dao Wen Wang Division of cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key laboratory of Genetics and molecular Mechanisms of Cardiological Disorders Wuhan430030China

Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid *** are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular *** this review,we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of *** summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases,such as heart failure,coronary heart disease/atherosclerosis,and cardiac *** underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic ***,other possible mechanisms such as inflammatory response and oxidative stress could also be induced by ***,since PAGln is produced across different organs including the intestine,liver,and kidney,the cross-talk among multiple organs focused on the function of this uremic toxic ***,the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

关键词： PAGln cardiovascular disease gut microbiota uremic metabolite biomarker

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Advance on Chinese Medicine for Hypertensive Renal Damage:Focus on the Complex molecular Mechanisms

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Chinese Journal of Integrative Medicine 2024年第10期30卷 938-948页

作者： LU Yan XIE Xue-na XIN Qi-qi YUAN Rong MIAO Yu CONG Wei-hong CHEN Ke-ji laboratory of Cardiovascular Diseases Xiyuan Hospital of China Academy of Chinese Medical Sciences School of Pharmacy Macau University of Science and Technology National Clinical research Center for Chinese Medicine cardiology

Hypertensive renal damage(HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine(CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

关键词： Chinese medicine hypertensive renal damage molecular mechanisms research progress

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Bile acids and coronavirus disease 2019

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1939-1950页

作者： Xiaoru Huang Xuening Liu Zijian Li Department of Pharmacy Peking University Third HospitalBeijing 100191China Department of Pharmaceutical Management and Clinical Pharmacy College of PharmacyPeking UniversityBeijing 100191China Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalBeijing Key Laboratory of Cardiovascular Receptors ResearchKey Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesMinistry of HealthState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has been significantly ***,long-term health effects and prevention strategy remain ***,it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 *** research indicates a link between COVID-19 and bile acids,traditionally known for facilitating dietary fat *** bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor,a bile acid nuclear *** activation of G-protein-coupled bile acid receptor,another membrane receptor for bile acids,has also been found to regulate the expression of angiotensin-converting enzyme 2,the receptor through which the virus enters human ***,we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2,and reveal their complicated pathophysiological mechanisms.

关键词： Bile acids COVID-19 Farnesoid X receptor G-protein-coupled bile acid receptor SARS-CoV-2 Angiotensin-converting enzyme 2 Ursodeoxycholic acid Chenodeoxycholic acid

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Cardiovascular disease burden in patients with urological cancers:The new discipline of uro-cardio-oncology

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Cancer Innovation 2024年第2期3卷 28-44页

作者： Yi Zheng Ying Liu Ziliang Chen Yunpeng Zhang Zuo Qi Ning Wu Zhiqiang Zhao Gary Tse Yong Wang Hailong Hu Yuanjie Niu Tong Liu Tianjin Key laboratory of Ionic-molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina School of Nursing and Health Studies Hong Kong Metropolitan UniversityHong KongChina

Cancer remains a major cause of mortality worldwide,and urological cancers are the most common cancers among *** therapeutic agents have been used to treat urological cancer,leading to improved survival for ***,this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medica***,we propose the novel discipline of uro-cardio-oncology,an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological *** this comprehensive review,we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers,including androgen deprivation therapy,vascular endothelial growth factor receptor tyrosine kinase inhibitors,immune checkpoint inhibitors,and *** addition,we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance,diagnosis,and effective management of cardiovascular compli***,we provide an analysis of future perspectives in this emerging specialty,identifying areas in need of further research.

关键词： anticancer therapy cardiovascular toxicity mechanism multidisciplinary management urological cancer

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In-situ forming ultra-mechanically sensitive materials for high-sensitivity stretchable fiber strain sensors

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National Science Review 2024年第6期11卷 254-263页

作者： Rouhui Yu Changxian Wang Xiangheng Du Xiaowen Bai Yongzhong Tong Huifang Chen Xuemei Sun Jing Yang Naoji Matsuhisa Huisheng Peng Meifang Zhu Shaowu Pan State Key laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and Engineering Donghua University MOE Key Lab of Disaster Forecast and Control in Engineering School of Mechanics and Construction Engineering Jinan University State Key laboratory of molecular Engineering of Polymers Department of Macromolecular Science and Institute of Fiber Materials and Devices Fudan University Department of cardiology Shanghai Xuhui Central HospitalZhongshan-Xuhui Hospital Fudan University research Center for Advanced Science and Technology and Institute of Industrial Science The University of Tokyo

Fiber electronics with flexible and weavable features can be easily integrated into textiles for wearable applications. However, due to small sizes and curved surfaces of fiber materials, it remains challenging to load robust active layers, thus hindering production of high-sensitivity fiber strain sensors. Herein, functional sensing materials are firmly anchored on the fiber surface in-situ through a hydrolytic condensation *** anchoring sensing layer with robust interfacial adhesion is ultra-mechanically sensitive, which significantly improves the sensitivity of strain sensors due to the easy generation of microcracks during stretching. The resulting stretchable fiber sensors simultaneously possess an ultra-low strain detection limit of 0.05%, a high stretchability of 100%, and a high gauge factor of 433.6, giving 254-folds enhancement in sensitivity. Additionally, these fiber sensors are soft and lightweight, enabling them to be attached onto skin or woven into clothes for recording physiological signals, e.g. pulse wave velocity has been effectively obtained by them. As a demonstration, a fiber sensor-based wearable smart healthcare system is designed to monitor and transmit health status for timely intervention. This work presents an effective strategy for developing high-performance fiber strain sensors as well as other stretchable electronic devices.

关键词： fiber strain sensor stretchable wearable healthcare

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Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ

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Frontiers of Medicine 2024年第3期18卷 465-483页

作者： Fei Xu Han Chen Changyi Zhou Tongtong Zang Rui Wang Shutong Shen Chaofu Li Yue Yu Zhiqiang Pei Li Shen Juying Qian Junbo Ge Department of cardiology and laboratory of Heart Valve Disease West China HospitalSichuan UniversityChengdu610041China Department of cardiology Zhongshan HospitalFudan UniversityResearch Unit of Cardiovascular Techniques and DevicesChinese Academy of Medical SciencesShanghai200032China Shanghai Institute of Cardiovascular Diseases Shanghai200032China National Clinical research Center for Interventional Medicine&Shanghai Clinical research Center for Interventional Medicine(19MC1910300) Shanghai200032China

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular *** smooth muscle cells(VSMCs),the main components of atherosclerotic plaque,switch from contractile to synthetic phenotypes during *** is crucial in regulating VSMC phenotypes in atherosclerosis,and it can be reversely regulated by ***,the specific effects of deubiquitinases on atherosclerosis have not been thoroughly *** this study,RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases,which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype *** in vivo studies using Apoe−/−mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque ***,VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in *** RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation,adhesion,and *** spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ***,we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβwith its catalytic triad,thereby reducing the K48-linked ubiquitylation of PDGFRβ.Inhibiting OTUB1 in VSMCs could promote PDGFRβdegradation via the ubiquitin–proteasome pathway,so it was beneficial in preventing VSMCs’phenotype *** findings revealed that knocking down OTUB1 ameliorated VSMCs’phenotype switch and atherosclerosis progression,indicating that OTUB1 could be a valuable translational therapeutic target in the future.

关键词： atherosclerosis vascular smooth muscle cell ubiquitylation deubiquitinase OTUB1 PDGFRβ

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