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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 1105-1114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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Biomarkers in aortic dissection:Diagnostic and prognostic value from clinical research

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Chinese Medical Journal 2024年第3期137卷 257-269页

作者： Yufei Zhao Weiguo Fu Lixin Wang Department of vascular surgery Zhongshan HospitalFudan UniversityShanghai 200032China vascular surgery institute Zhongshan HospitalFudan UniversityShanghai 200032China National Clinical Research Center for Interventional Medicine Zhongshan HospitalFudan UniversityShanghai 200032China Department of vascular surgery Xiamen BranchZhongshan HospitalFudan UniversityXiamenFujian 361015China

Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations,while reliable biomarkers to detect or monitor are still under investigation.Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers,including proteins,ribonucleic acids(RNAs),and deoxyribonucleic acids(DNAs),for early detection of pathological changes in susceptible patients,rapid diagnosis at the bedside after onset,and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.

关键词： Aortic dissection Biomarker Protein Cell-free DNA miRNA Inflammation Lipid-metabolism

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Identification of genes responsive to apoptosis in HL-60 cells

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Acta Pharmacologica Sinica 2004年第3期25卷 65-72页

作者： Wei JIN2,Le-feng QU3,Ping MIN2,Shan CHEN2,Hong LI4,He LU2,4,Yong-tai HOU2,5 2Shanghai instituteof Materia Medica,Chinese Academyof Sciences,Shanghai 201203 3Departmentof vascular surgery & institute of vascular surgery of PLA,Changhai Hospital,Shanghai 200433 4 Le p?le franco-chinois du science du vivant et génomique,Ruijin Hospital,Shanghai 200025,China Shanghai institute of Materia Medica Chinese Academy of Sciences 上海 201203 Department of vascular surgery & institute of vascular surgery of PLA Changhai Hospital 上海 200433 institute of Endocrinology and Metabolism Ruijin Hospital School of Medicine Shanghai Jiaotong University 上海 200025

AIM: To identify genes responsive to apoptosis in HL-60 cells treated by homoharringtonine. METHODS: cDNA microarray technology was used to detect gene expression and the result of microarrays for genes (TIEG and VDUP1) was confirmed by Northern analysis. RESULTS: Seventy-five individual mRNAs whose mass changed significantly were identified. Among these genes (25 were up-regulated and 50 were down-regulated), most are known related to oncogenes and tumor suppressor. Some genes were involved in apoptosis signaling pathways. CONCLUSION: TGFβ and TNF apoptosis signaling pathways were initiated during apoptosis in HL-60 cells. TIEG and VDUP1 play important roles in mediating apoptosis.

关键词： HL-60 cells homoharringtonine apoptosis oligonucleotide array sequence analysis gene expression

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Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao Department of vascular surgery.Nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary surgery and Transplantation surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen Research institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

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Gene expression pattern in apoptotic QGY-7703 cells induced by homoharringtonine

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Acta Pharmacologica Sinica 2007年第6期28卷 859-868页

作者： Wei JIN~2,Le-feng QU~3,Qin CHEN~4,Xin-zhong CHANG~2,Jiong WU~2,Zhi-min SHAO~(2,5)~2 Breast Cancer institute,Cancer Hospital,Department of Oncology,Shanghai Medical College,institute of Biomedical Science,FudanUniversity,Shanghai 200032,China ~3 Department of vascular surgery and institute of vascular surgery of PLA,Changhai Hospital,Shanghai 200433,China ~4 Shanghai institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China Department of Oncology Breast Cancer Institute Cancer Hospital Shanghai Medical College Institute of Biomedical Science Fudan University Shanghai China Department of vascular surgery and institute of vascular surgery of PLA Changhai Hospital Shanghai China Shanghai institute of Materia Medica Chinese Academy of Sciences Shanghai China

Aim:To classify the genes responsible for apoptosis in QGY-7703 cells in-duced by homoharringtonine (HHT).Methods:Apoptosis in QGY-7703 cellsinduced by HHT was demonstrated by DNA fragmentation and morphologicalobservation,cDNA microarray technology was used to detect gene transcription,and the result of microarrays for genes was confirmed by RT-PCR.Results:Seventy-eight individual mRNA were identified and their transcription levelschanged significantly.Those genes,of which 68% were upregulated and 32%were downregulated,were partially related to apoptosis.They were mostlyoncogenes,tumor suppressors,enzymes,and kinases.Conclusion:HHT is apotential drug in the treatment of liver cancer.TGF-β,TNF,FAS,p38MAPK,and p53 apoptosis signaling pathways were activated during apoptosis in QGY-7703 cells.Such inducible genes may play important roles in apoptosis anddeserve to be further studied.

关键词： QGY-7703 cells homoharringtonine apoptosis gene expression

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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 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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YKL40 potentially via activating the P38 pathway in decreasing atherosclerotic plaque stability

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中华医学杂志(英文版) 2024年第8期137卷 1003-1005页

作者： Wang Chao Liu Yandong Huan Wei Wu Jianjin Jin Jie Zou Sili Chen Yu Qu Lefeng Department of vascular and Endovascular surgery Changzheng Hospital Affiliated to the Naval Medical University Shanghai 200003 China Clinical Research institute of Integrative Medicine Yueyang Hospital Shanghai University of Traditional Chinese Medicine Shanghai 200437

Atherosclerosis is the main pathological feature of ischemic stroke, which remains a major cause of disability and death worldwide. Vulnerable plaque, was characterized by ulceration, platelet activation, and thrombosis, potentially leading to emboli detachment and stroke. vascular smooth muscle cells (VSMCs), a major cellular component within lesions, can display pleiotropic phenotypes, including osteogenic or inflammatory phenotypes, which may be harmful in maintaining advanced atherosclerotic plaque stability. The modulation of the function of VSMCs, including proliferation, migration, and synthesizing the extracellular matrix (ECM) and matrix metalloproteinase (MMP), is thought to markedly affect plaque formation and vulnerability. Therefore, it is of considerable significance to drive harmful VSMCs toward VSMCs having beneficial properties to strengthen plaque stability and retard plaque development.

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Self-fueling ferroptosis-inducing microreactors based on p H-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy

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National Science Review 2024年第1期11卷 74-85页

作者： Chunjie Wang Lei Zhang Zhijuan Yang Dongxu Zhao Zheng Deng Jialu Xu Yumin Wu Yu Hao Ziliang Dong Liangzhu Feng Zhuang Liu institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Soochow University Center of Interventional Radiology & vascular surgery Department of Radiology Zhongda Hospital Medical School Southeast University Department of Interventional Radiology The First Afflliated Hospital of Soochow University

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma(HCC) via transarterial chemoembolization(TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion(LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase(LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE(LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids(PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

关键词： CaCO3 nanoparticles Pickering emulsion ferroptosis lipid peroxidation transarterial ferro-embolization

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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of Interventional Radiology and vascular surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells.Cancer cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis.Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment.However,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown.Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC progression.KN93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells.Above all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

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Evaluation of embedded modular branched stent graft in treating aortic arch aneurysm using imaging-based computational flow analysis

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Medicine in Novel Technology and Devices 2024年第1期21卷 80-87页

作者： Xuehuan Zhang Jiang Xiong Wei Ma Lijuan Xue Zhengyang Xu Hongpeng Zhang Yongsheng Wang Duanduan Chen Wei Guo School of Medical Technology Beijing Institute of TechnologyBeijingChina Department of vascular and Endovascular surgery The First Medical Center of Chinese PLA General HospitalBeijingChina Department of vascular and Endovascular surgery Hainan HospitalChinese PLA General HospitalHainanChina Department of Radiology The First Medical Center of Chinese PLA General HospitalBeijingChina Hangzhou Endonom Medtech Co. LtdZhejiangChina

Embedded modular branched stent graft(EMBSG)was a new option for aortic arch aneurysm.However,the therapeutic effect of this innovative stenting technique has not been fully assessed.Computational fluid dynamics and three-dimensional structural analyses were performed on three patients(Patient Ⅰ,Patient Ⅱ and Patient Ⅲ)with aortic arch aneurysm,both before and after EMBSG implantation.Patient-specific alterations from preoperative to postoperative were analyzed via morphological and functional metrics.Patient Ⅰ and Patient Ⅱ showed notable curvature changes and area reduction after intervention procedure.Three patients showed an increase in flow velocity after EMBSG implantation,while the pressure drop from ascending aorta to the aortic arch was remarkable in Patient I and Patient Ⅱ with the value of 7.09mmHg,and 10.95mmHg,respectively.Patient I and Patient Ⅱ also showed elevated time-averaged wall shear stress(TAWSS)in the stenting region,while Patient Ⅲ showed a trivial change in TAWSS after intervention procedure.Three patients showed low relative residence time after EMBSG insertion.The short-term results of EMBSG in treating aortic arch aneurysm were promising.Hemodynamic parameters have the potential to assist in the outcome evaluation and might be used to guide the stent graft design and wise selection,thereby improving the long-term therapeutic effect in managing complex vascular disease.

关键词： Aortic archaneurysm Embedded modular branched stent graft Endovascul araorti carch repair Computational fluid dynamics Functional evaluation

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