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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi LUAN Yang YANG Ying LUAN Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN Clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China School of Laboratory Medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Center for Translational Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China henan Engineering Research Center for Application&Translation of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality ***,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for ***-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and ***,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to *** review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in ***,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating ***,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of medical sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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An antioxidant system through conjugating superoxide dismutase onto metal-organic framework for cardiac repair

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Bioactive Materials 2022年第4期7卷 56-67页

作者： Jiacheng Guo Zhenzhen Yang Yongzheng Lu Chunyan Du Chang Cao Bo Wang Xiaoting Yue Zenglei Zhang Yanyan Xu Zhen Qin Tingting Huang Wei Wang Wei Jiang Jinying Zhang Junnan Tang Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Key Laboratory of Cardiac Injury and Repair of henan Province ZhengzhouHenan450018China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Laboratory Animal Center School of Medical SciencesZhengzhou UniversityZhengzhouHenan450052China Department of Polymer science College of ChemistryJilin UniversityChangchunJilin130012China henan medical Association ZhengzhouHenan450052China Academy of medical science Zhengzhou UniversityZhengzhouHenan450052China

Acute myocardial infarction(AMI)remains a dominant origin of morbidity,mortality and disability *** in reactive oxygen species(ROS)are key contributor to excessive cardiac injury after *** we developed an immobilized enzyme with Superoxide Dismutase(SOD)activity cross-link with Zr-based metal-organic framework(ZrMOF)(SOD-ZrMOF)for mitigate ROS-caused *** vitro and in vivo evidence indicates that SOD-ZrMOF exhibits excellent *** efficiently scavenging ROS and suppressing oxidative stress,SOD-ZrMOF can protect the function of mitochondria,reduce cell death and alleviate *** excitingly,long-term study using an animal model of AMI demonstrated that SOD-ZrMOF can reduce the infarct area,protect cardiac function,promote angiogenesis and inhibit pathological myocardial ***,SOD-ZrMOF holds great potential as an efficacious and safe nanomaterial treatment for AMI.

关键词： Acute myocardial infarction Immobilized enzyme Reactive oxygen species Nanomedicine

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An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier

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Bioactive Materials 2024年第7期37卷 517-532页

作者： Zhen Li Junyue Xing Xiaohan Ma Wanjun Zhang Chuan Wang Yingying Wang Xinkun Qi Yanhui Liu Dongdong Jian Xiaolei Cheng Yanjie Zhu Chao Shi Yongjun Guo Huan Zhao Wei Jiang Hao Tang National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular DiseasesHenan Cardiovascular Disease CenterFuwai Central-China Cardiovascular HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou450046China henan Key Laboratory of Chronic Disease Management Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan451464China Zhengzhou Key Laboratory of Cardiovascular Aging Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan451464China Department of Hematology Henan Provincial People’s HospitalZhengzhouHenan450003China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Anesthesiology Affiliated Drum Tower Hospital of Medical School of Nanjing UniversityNanjingJiangsu210008China Department of Pathology Central Hospital of Kaifeng CityKaifengHenan475000China henan Key Laboratory of Molecular Pathology Department of Molecular PathologyThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenan450008China

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing ***,there are no effective treatments *** analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy *** developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100(obtained from intestinal bacteria Akkermansia muciniphila),fluorinated polyetherimide,and hyaluronic *** protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_*** in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota,increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family,and further enhancing the levels of butyrate and pentanoic acids,ultimately regulating the homeostasis repair of lymphocytes in the spleen and ***,we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced *** interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

关键词： Doxorubicin cardiotoxicity Intestinal barrier Protein delivery Oral nanodrugs Homeostasis of lymphocytes

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An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes

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Neural Regeneration Research 2023年第11期18卷 2357-2364页

作者： Sai Wang Haiman Hou Yao Tang Shuang Zhang Gege Wang Ziyan Guo Lina Zhu Jun Wu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor *** with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and *** CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this *** damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral *** CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve ***,because of the low incidence of this disease,few repo rts and no reviews have been published about it so *** article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the ***,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.

关键词： autoimmunity CRMP5 CV2 CV2/CRMP5 antibody paraneoplastic neurological syndromes paraneoplastic syndromes tumor

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PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： Wen Xiao Fazhan Wang Yangzhuo Gu Xi He Na Fan Qian Zheng Shugang Qin Zhongshan He Yuquan Wei Xiangrong Song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor *** targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery *** the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains ***,we designed and constructed DC-targeted mRNA delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by ***,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse ***,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA *** findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mRNA vaccines DC-targeted delivery PEGylated liposomes Cellular uptake

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Alterations of mtDNA copy number and 4977 bp deletion induced by ionizing radiation in human peripheral blood

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Nuclear science and Techniques 2013年第6期24卷 67-73页

作者： LIU Yulong WANG Ping HAN Lin ZHAO Fengling GUO Fei WANG Xiai LYU Yumin The Second Affiliated Hospital of Soochow University henan Institute of Occupational Medicine College of Public Health Zhengzhou University

Alterations of mitochondria DNA(mtDNA)4977 bp common deletion(CD)and mtDNA copy number induced by ionizing radiation were observed in human different cell lines and total body irradiation ***,only few experiments have evaluated the levels of the CD and mtDNA copy number in human peripheral blood exposed to ionizing radiation till *** aim of this study is to analyze the mtDNA alterations in irradiated human peripheral blood from healthy donors as well as to explore their feasibility as biomarkers for constructing new *** blood samples were collected from six healthy donors,and exposed to 60Co gamma ray with the doses of 0 Gy,1 Gy,2 Gy,3 Gy,4 Gy and 5 *** of the CD and mtDNA copy number in irradiated samples after 2h or 24h incubation were detected using TaqMan real-time PCR,and the CD ratio was *** results showed that the mean of the CD ratio and the CD copy number exhibited a dose-dependent increase 2 h in the dose range from 0–5 Gy,and of the mtDNA copy number significantly increased 24 h in irradiated groups compared with 0 Gy group after *** indicates that the parameters in human peripheral blood may be considered as molecular biomarkers to applying construction of new biodosimeter.

关键词：线粒体DNA 电离辐射诱导人外周血拷贝数分子生物标志物 bp mtDNA 全身照射

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Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial

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Cancer Biology & Medicine 2022年第7期19卷 1089-1099页

作者： Jingjing Wu Fenghua Gao Wenhua Wang Xudong Zhang Meng Dong Lei Zhang Xin Li Ling Li Zhenchang Sun Xinhua Wang Xiaorui Fu Linan Zhu Mengjie Ding Songtao Niu Zhaoming Li Yu Chang Feifei Nan Jiaqian Yan Hui Yu Xiaolong Wu Zhiyuan Zhou Jieming Zhang Mingzhi Zhang Cancer Research Institute Department of OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina

Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was *** with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were *** R-FPD regimen consisted of rituximab(375 mg/m2 *** D0),fotemustine(100 mg/m2 *** D1),pemetrexed(600 mg/m2 *** D1),and dexamethasone(40 mg *** D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of ***:A total of 30 patients were *** 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

关键词： Rituximab primary central nervous system lymphoma pemetrexed fotemustine WBRT

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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

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Current medical science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO Department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney ***,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal ***,the regulatory impact of TRPC6 on renal fibrosis remains *** In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham *** and serum were collected on days 7,14,21,and 28 after *** vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 *** anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western *** Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ***6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in ***,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 *** These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β*** TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

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Engineered exosomes from different sources for cancertargeted therapy

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1644-1663页

作者： Menghui Zhang Shengyun Hu Lin Liu Pengyuan Dang Yang Liu Zhenqiang Sun Bingbing Qiao Chengzeng Wang Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450001China Department of Colorectal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450001China henan Institute of Interconnected Intelligent Health Management The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450001China Department of Ultrasound The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450001China Department of Radiotherapy Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenan 450001China

Exosome is a subgroup of extracellular vesicles,which has been serving as an efficient therapeutic tool for various *** exosomes are the sort of exosomes modified with surface decoration and internal therapeutic *** appropriate modification,engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse ***,there still exist many challenges for the clinical translation of engineered *** instance,what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly ***,how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved *** this review,we summarized the characteristics of engineered exosomes,especially the spatial and temporal ***,we concluded the recent advances in engineered exosomes in the cancer fields,including the sources,isolation technologies,modification strategies,and labeling and imaging methods of engineered ***,the applications of engineered exosomes in different antitumor therapies were summarized,such as photodynamic therapy,gene therapy,and ***,the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development,which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.

关键词： summarized Engine instance

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