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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

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Science china(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-ming Li Ya-Ting Chen Meng-Jie Deng yan Li Yue-ming Peng jian-Jun gao zhi-Wei Mo Jia-Guo Zhou zhi-Jun Ou Jing-Song Ou Division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(Sun Yat-sen university) Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China Division of Vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Division of Hypertension and Vascular Diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

Increase of PCSK9 expression in diabetes promotes VEGFR2ubiquitination to inhibit endothelial function and skin wound healing

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Science china Life Sciences 2024年

作者： jian-Jun gao Fang-Yuan Wu Yu-Jia liu Le Li Yi-Jun Lin Yue-Ting Kang Yue-ming Peng Yi-Fang liu Chen Wang Zhen-Sheng Ma yang Cao Hong-Yu Cao zhi-Wei Mo yan Li Jing-Song Ou zhi-Jun Ou Division of Cardiac Surgery Cardiovascular Diseases Institute The First Affiliated Hospital Sun Yat-sen University National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University) Key Laboratory of Assisted Circulation and Vascular Diseases Chinese Academy of Medical Sciences Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Division of Hypertension and Vascular Diseases Department of Cardiology Heart Center The First Affiliated Hospital Sun Yat-sen University Division of Vascular Surgery The First Affiliated Hospital Sun Yat-sen University Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-sen University

Diabetic foot ulcers（DFUs） are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9（PCSK9） regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells（ECs） increased significantly under high glucose（HG）stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2（VEGFR2）, which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase（eNOS）, and ERK1/2, leading to decreased nitric oxide（NO） production and increased superoxide anion(O2·-) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2·-production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/***, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

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Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications

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World Journal of Diabetes 2024年第10期15卷 2041-2057页

作者： ming-Wei Fan Jin-Lan Tian Tan Chen Can Zhang Xin-Ru liu Zi-jian zhao Shu-hui Zhang yan Chen department of Gastroenterology Binzhou Medical University HospitalBinzhou 256600Shandong ProvinceChina

Diabetes mellitus(DM)is one of the major causes of mortality worldwide,with inflammation being an important factor in its onset and *** review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway in mediating inflammatory ***,it compre-hensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM,diabetic gastroenteropathy,diabetic cardiomyopathy,non-alcoholic fatty liver disease,and other ***,the role of cGAS-STING in autonomic dysfunction and intes-tinal dysregulation,which can lead to digestive complications,has been ***,this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.

关键词： Cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes Diabetes mellitus Inflammation Glycolipid metabolism Diabetes gastroenteropathy Nonalcoholic fatty liver disease Diabetes cardiovascular disease Diabetes nephropathy

DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2774-2790页

作者： mingjing yan Junpeng gao ming Lan Que Wang Yuan Cao Yuxuan Zheng Yao yang Wenlin Li Xiaoxue Yu Xiuqing Huang Lin Dou Bing liu Junmeng liu Hongqiang Cheng Kunfu Ouyang Kun Xu Shenghui Sun Jin liu Weiqing Tang Xiyue Zhang Yong Man Liang Sun jianping Cai Qing He Fuchou Tang jian Li Tao Shen The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Peking university Fifth School of Clinical Medicine Beijing 100730China department of Laboratory Medicine Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Biomedical Pioneering Innovation Center School of Life SciencesPeking UniversityBeijing 100871China Emergency Center Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Cardiology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Graduate School of Peking Union medical College Beijing 100730China department of Health Care Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China department of Pathology and Pathophysiology and department of Cardiology at Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310058China department of cardiovascular Surgery Peking University Shenzhen HospitalShenzhen 518036China Experimental Technology Center for Life Sciences at Beijing Normal university Beijing 100875China

DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor *** DDX17 is abundantly expressed in the myocardium,its role in heart is not fully *** generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte ***-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart *** of DDX17 expression in cardiomyocytes protects cardiac function under pathological *** studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart *** also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart *** findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

关键词： DDX17 homeostasis cardiac

Continuous age-and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease

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World Journal of Pediatrics 2024年第9期20卷 949-956页

作者： zhao-Yuan Wu Si-Wei Chi liu-jian Ouyang Xiao-Qin Xu Jing-Nan Chen Bing-Han Jin Rahim Ullah Xue-Lian Zhou Ke Huang Guan-Ping Dong Zhe-ming Li Ying Shen Jie Shao yan Ni Jun-Fen Fu Qiang Shu Wei Wu department of Endocrinology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child Health3333 Binsheng RoadHangzhou310051China department of Data and Information Children’s HospitalZhejiang University School of MedicineHangzhouChina department of Child Health Care Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina department of Thoracic&cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children’s Regional Medical Center3333 Binsheng RoadHangzhou310051China

Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic ***,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations with a large nu... 详细信息

Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic ***,the current reference ranges(department of Pediatric *** applied the least mean square algorithm to establish age-and sex-related reference percentiles of serum levels of *** validation,we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the *** receiver operating characteristic curves,we determined age-and sex-specific upper limit percentiles of liver enzymes for fatty liver *** This study revealed a significant correlation between serum transaminase levels and age and sex(P<0.01).These transaminase levels exhibited age-and sex-specific *** individuals in the non-alcoholic fatty liver disease(NAFLD)cohort,elevated ALT levels displayed a positive association with clinical markers of disease severity,including homeostatic model assessment of insulin resistance,waist-hip ratio,and serum uric acid levels(P<0.01).According to the receiver operating characteristic curves,ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and *** This study provides age-and sex-specific reference ranges for ALT,aspartate aminotransferase,andγ-glutamyltransferase in Chinese children and adolescents,making it the largest population study to ***,the study establishes a precise upper limit for ALT levels,facilitating their use in NAFLD screening.

关键词： Alanine aminotransferase Childhood Fatty liver diseases

The dependence of Na+/Ca2+ exchanger and calpain inhibitors' protective effects against Ca2+ paradox in rat heart on the duration of Ca2+ depletion

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The dependence of Na+/Ca2+ exchanger and calpain inhibitors'...

Antimicrobial peptides: mechanism of action, activity and clinical potential

第九届全国钙信号和细胞功能研讨会

作者： Zhang jian-Ying~1,Tong wei~2,Bi Sheng-hui~3,Wu-Feng~4,Xu ming~1,Zhen-Xiao Jin~3, Jing-Jun Zhou~1 1 department of 1 physiology,2 department of Out-patient clinic,3 cardiovascular surgery, 4 Cardiology,Xijing Hospital,the Fourth Military medical university,Xi’an,china,710032

The Ca paradox represents a good model to study Ca overload injury in myocardial ischemia/*** and others previously have demonstrated that suppressing the activity of Na/Ca exchanger(NCX),or calpain,a Ca-dependent protease,protects heart against Ca paradox-induced ***,as Ca paradox-induced damage was reported to be dependent on the duration of calcium depletion,it is necessary to evaluate their protective *** study was to

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Military medical Research 2022年第2期9卷 231-258页

作者： Qi-Yu Zhang zhi-Bin yan Yue-ming Meng Xiang-Yu Hong Gang Shao Jun-Jie Ma Xu-rui Cheng Jun liu jian Kang Cai-Yun Fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityNo.928Street 2Xiasha Higher Education ZoneHangzhou 310018China department of Oncology The 903rd Hospital of PLAHangzhou 310013China department of Pharmaceutical Chemistry and the cardiovascular Research Institute University of California San Francisco555 Mission Bay Blvd.SouthSan FranciscoCA 94158USA Oncogenic Signaling and Growth Control Program Peter MacCallum Cancer Centre305 Grattan StreetMelbourneVIC 3000Australia Sir Peter MacCallum department of Oncology University of MelbourneParkvilleVIC 3010Australia

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant *** an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low *** peptides possess distinctive structures and functions by employing sophisticated mechanisms of *** comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical *** finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

关键词： Antimicrobial peptides Antimicrobial resistance Mechanism of action Biological activity Clinical application

Ethylene promotes seed iron storage during Arabidopsis seed maturation via ERF95 transcription factor

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Journal of Integrative Plant Biology 2020年第8期62卷 1193-1212页

作者： Ying Sun Jia Qi Li Jing Ying yan Jun Jie Yuan Gui Xin Li Yun rong Wu Ji ming Xu rong Feng Huang Nicholas P.Harberd Zhong Jie Ding Shao jian Zheng State Key Laboratory of Plant physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China Agricultural Experimental Station Zhejiang UniversityHangzhou 310058China College of Agronomy and Biotechnology Zhejiang UniversityHangzhou 310058China Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China department of Plant Science University of OxfordOxford OX13RBUnited Kingdom

Because Iron(Fe)is an essential element,Fe storage in plant seeds is necessary for seedling establishment following ***,the mechanisms controlling seed Fe storage during seed development remain largely *** we reveal that an ERF95 transcription factor regulates Arabidopsis seed Fe *** show that expression of ERF95 increases during seed maturation,and that lack of ERF95 reduces seed Fe accumulation,consequently increasing sensitivity to Fe deficiency during seedling ***,overexpression of ERF95 has the opposite *** show that lack of ERF95 decreases abundance of FER1 messenger RNA in developing seed,which encodes Fe-sequestering ***,a fer1-1 loss-of-function mutation confers reduced seed Fe accumulation,and suppresses ERF95-promoted seed Fe *** addition,ERF95 binds to specific FER1 promoter GCC-boxes and transactivates FER1 *** show that ERF95 expression in maturing seed is dependent on EIN3,the master transcriptional regulator of ethylene *** lack of EIN3 reduces seed Fe content,overexpression of ERF95 rescues Fe accumulation in the seed of ein3 loss-of-function ***,we show that ethylene production increases during seed *** conclude that ethylene promotes seed Fe accumulation during seed maturation via an EIN3-ERF95-FER1-dependent signaling pathway.

关键词： expression. ERF Arabidopsis

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in china(RWE-PCSK study)

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Journal of Geriatric Cardiology 2021年第4期18卷 261-270页

作者： Yu-Qi liu Dan-Dan LI Meng CHAI Hong-Liang CONG Xiao-Qiang CONG Jun DAI rong-Pin DU ming gao Jin-Cheng GUO yan-Qing GUO Xiao-jian HONG rong-Chong HUANG Feng-Shun JIA Jia-Yu LI Qing LI Jia-Mei liu Xin-Ping liu Yu-Guo liu Hong-Gang NIE Bing SHAO Xiao-Yu SHEN Hai-Qing SONG Yi-Jun SONG Li-Jun WANG Shuo WANG Dong-Mei WU Jing XIA zhi-Yong yanG Hong-Ying YU hui ZHANG Tie-Mei ZHANG Ji-Yi zhao Liang-Chen zhao ming-Qi ZHENG Yun-Dai CHEN department of Cardiology Chinese PLA General HospitalBeijingChina department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of Heart Lung and Blood Vessel DiseaseBeijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic DiseaseClinical Center for Coronary Heart DiseaseCapital Medical UniversityBeijingChina department of Cardiology Tianjin Chest HospitalTianjinChina department of Cardiology the First Hospital of Jilin UniversityChangchunChina department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Cardiology Hebei People’s HospitalShijiazhuangChina department of Cardiology Kailuan General HospitalHebei Union UniversityTangshanChina department of Cardiology Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of Cardiology Shanxi Cardiovascular HospitalTaiyuanChina department of Cardiology the Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina department of Cardiology Beijing Friendship HospitalCapital Medical UniversityBeijingChina department of Cardiology Tangshan Worker’s HospitalTangshanChina department of Cardiology China-Japan Friendship Hospital Affiliated Jilin UniversityChangchunChina department of Cardiology Handan Central HospitalHebeiChina Heart Center Beijing Key Laboratory of HypertensionBeijing Chao-Yang HospitalCapital Medical UniversityBeijingChina department of Cardiology the First Affiliated Hospital of Dalian Medical UniversityLiaoningChina department of Cardiology the Second Affiliated Hospital of Harbin Medical UniversityHarbinChina department of Cardiology the Second Affiliated Hospital of Shenyang Medical CollegeShenyangChina department of Cardiology the Second Hospital of Shanxi Medical UniversityTaiyuanChina department of Neurology Xuanwu Hospital Capital Medical UniversityBeijingChina department of Neurology Tianjin Medical University Gen

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in china has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for *** In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real

关键词： LDL RWE-PCSK study Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high r