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

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 angiogenesis.Autophagy plays a critical role in angiogenesis,and HDL regulates autophagy.However,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting autophagy.Endothelial cells(ECs)were treated with n HDL and d HDL with or without an autophagy inhibitor.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 formation.We found that autophagy-related protein 5(ATG5)was a direct target of miR-181a-5p.ATG5 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 HDL.ATG5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 mice.ATG5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)mice.Taken together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted angiogenesis.In 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^(·-)generation.Our findings reveal a novel mechanism by which HDL affects angiogenesis b

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

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo Laboratory of vascular biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity vascular endothelial growth factor C Immune modulation

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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 alleviated.However,long-term health effects and prevention strategy remain unresolved.Thus,it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection.Emerging research indicates a link between COVID-19 and bile acids,traditionally known for facilitating dietary fat absorption.The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor,a bile acid nuclear receptor.The 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 cells.Here,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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Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives

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World Journal of Stem Cells 2024年第1期16卷 33-53页

作者： Hong-Shuo Shi Xin Yuan Fang-Fang Wu Xiao-Yu Li Wei-Jing Fan Xiao Yang Xiao-Ming Hu Guo-Bin Liu Department of Peripheral vascular Surgery Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 250021China

BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of depicting the current global research landscape,identifying the most influential research hotspots,and providing insights for future research directions.METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF.Bibliometric analysis was carried out using CiteSpace,VOSviewer,and R(4.3.1)to identify the most notable studies.RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment.A total of 542 articles published from 2000 to 2023 were identified.The United States had published the most papers on this subject.In this field,Iran’s Shahid Beheshti University Medical Sciences demonstrated the highest productivity.Furthermore,Dr.Bayat from the same university has been an outstanding researcher in this field.Stem Cell Research&Therapy is the journal with the highest number of publications in this field.The main keywords were“diabetic foot ulcers,”“wound healing,”and“angiogenesis.”CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years.Current research findings suggested that the hotspots in this field include stem cell dressings,exosomes,wound healing,and adipose-derived stem cells.Future research should also focus on the clinical translation of stem cell therapies for DF.

关键词： Stem cells Diabetic foot Bibliometric CiteSpace VOSviewer R-bibliometrix

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Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

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Food Science and Human Wellness 2024年第4期13卷 2327-2345页

作者： Chenghao Fu Zhehao Liang Zemiao Niu Ning Chen Yuemin Li Zhenhua Liang Yanwei Huo Hao Xi Rong Wang Yonghuan Yan Xiaoruo Gan Mengtian Wang Yun Huang Yan Zhang Mingming Gao Pin Lü Postdoctoral Station for Basic Medicine Cardiovascular Medical Science CenterDepartment of Cell BiologyKey Laboratory of Neural and Vascular Biology of Ministry of EducationHebei Medical UniversityShijiazhuang 050017China Hebei Key Laboratory of Forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety Key Laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050091China Laboratory of Lipid Metabolism Department of Biochemistry and Molecular BiologyKey Laboratory of Medical Biotechnology of Hebei ProvinceShijiazhuang 050017China

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

关键词： Intermittent fasting Ly6G^(low)myeloid-derived suppressor cell apoptosis Extramedullary hematopoiesis Colony stimulating factor Glucose metabolism restriction

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Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm

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中华医学杂志(英文版) 2024年第9期137卷 2023 Aug 28页

作者： Xie Xinsheng Yuan Ye Huang Yulong Hong Xiang Hong Shichai Chen Gang Chen Yihui Lin Yue Lu Weifeng Fu Weiguo Wang Lixin Department of vascular Surgery Zhongshan Hospital (Xiamen) Fudan University Xiamen Fujian China Department of vascular Surgery Zhongshan Hospital Fudan University Shanghai China vascular Surgery Institute of Fudan University Fudan University Shanghai China

Background: Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods: Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results: A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain (COL1A1) and synaptotagmin like 2 (SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression ofCOL1A1 andSYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally,COL1A1 andSYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed thatCOL1A1 in TAA was mainly derived from fibroblasts andSYTL2 mainly from cluster of differentiation (CD)8+ T cells. In addition, single-cell analysis indicated that fibroblasts and CD8+ T cells in TAA were significantly higher than those in normal arterial wall tissue.Conclusions: COL1A1 andSYTL2 may serve as diagnostic marker genes for TAA. The upregulation ofSYTL2 andCOL1A1 may be involved in the inflammatory infiltrati

关键词： Bioinformatics Thoracic aortic aneurysm Immune response Single cell analysis COL1A1 SYTL2 Machine learning

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A Novel Poly(3-hexylthiophene) Engineered Interface for Electrochemical Monitoring of Ascorbic Acid During the Occurrence of Glutamate-Induced Brain Cytotoxic Edemas

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Research 2024年第1期2023卷 301-313页

作者： Zexuan Meng Yuchan Zhang Lu Yang Shuang Zhao Qiang Zhou Jiajia Chen Jiuxi Sui Jian Wang Lizhong Guo Luyue Chang Jialing He Guixue Wang Guangchao Zang Institute of Life Science and Laboratory of Tissue and Cell BiologyLab Teaching and Management CenterChongqing Medical UniversityChongqing 400016China Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China Jinfeng Laboratory Chongqing 401329China Department of Pathophysiology Chongqing Medical UniversityChongqingChina

Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.

关键词： release microelectrode Engine

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Long-term grape powder feed attenuates experimental ischemic stroke by altering gut microbiota and metabolome

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Food Science and Human Wellness 2024年

作者： Haojie Jin Decao Yang Jia Guo Baohui Xu Yu Fu Lixiang Xue Yan Wang The Key Laboratory for Silviculture and Conservation of Ministry of Education The College of forestry Beijing Forestry University Institute of Medical Innovation and Research Peking University Third Hospital Department of Neurology Peking University Third Hospital Centre of hypertension Care Shanxi Medical University First Hospital Medical Research Centre Peking University Third Hospital Department of Surgery Division of vascular Surgery Stanford University School of Medicine Stanford

Increasing evidence indicates that a healthy diet plays a protective role against ischemic stroke injury. As an antioxidant food， grape powder has been shown to have a neuroprotective function after ischemic injury. In the current research， we aimed to determine whether regular grape powder (GP) feeding before brain damage plays a protective role against ischemic damage and its potential mechanism. Mice had grape powder in drinking water for 4 weeks. Then， fecal samples were collected for 16S RNA analysis and metabolite profiling. Ischemic stroke was triggered using GP prefeed mice by MCAo (middle cerebral artery occlusion) to compare the stroke-induced infarction size to the drinking water (DW) group. The data showed that 4 weeks of GP pretreatment significantly decreased the ischemic infarct size. Meanwhile， GP treatment altered the gut microbiota by enriching the population of Lachnospiraceae and enhancing a gut metabolite called fiestin， which belongs to the flavonoid group. Mechanistically， we demonstrated that fiestin could inhibit LPS-induced proinflammatory macrophage polarization in vitro. We also showed that regular grape power feed could decrease stroke-induced neuroinflammation in vivo. In conclusion， our study demonstrated that 4 weeks of GP feeding attenuates experimental ischemic stroke via the gut-brain-immune axis.

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Current status and impact of the Young Scientist Foundation of the National Natural Science Foundation on Chinese young scholars in cardiovascular research

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Science China Life Sciences 2024年

作者： Fei Gao Zhenzhen Chen Wendong Li Hujun Jiang Rui Wang Department of Cardiology Beijing Anzhen HospitalCapital Medical University hypertension Center Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular Diseases Department of vascular Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School Department of Health Sciences National Natural Science Foundation of China

Cardiovascular disease (CVD) remains the leading cause of disease burden globally,and continued efforts are required in identifying new targets for CVD prevention and treatment (Vaduganathan et al.,2022).Breakthroughs in basic research are urgently needed to fully understand the CVD mechanism and improve clinical treatment modality.

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Research progress on venous thrombosis development in patients with malignant tumors

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World Journal of Clinical Cases 2024年第11期12卷 1900-1908页

作者： Teng-Fei Wang Qian Chen Jie Deng Shi-Liang Li Yuan Xu Si-Xing Ma Department of vascular Surgery The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina Department of Organ Transplantation The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

The coexistence of venous thromboembolism(VTE)within patients with cancer,known as cancer-associated thrombosis(CAT),stands as a prominent cause of mortality in this population.Over recent years,the incidence of VTE has demonstrated a steady increase across diverse tumor types,influenced by several factors such as patient management,tumor-specific risks,and treatment-related aspects.Furthermore,mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes.We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT.This review elucidates the risks,mechanisms,reliable markers,and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

关键词： Malignant tumor Venous thromboembolism Cancer-associated thrombosis Research progress

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