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CPAL, as a New Mediator of Cardiomyocyte Metabolic Alterations and Pyroptosis, Regulates Myocardial Infarction Injury in Mice

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Engineering 2023年第1期20卷 49-62页

作者： Jiamin Li Hongru Xue Ning Xu Liling Gong Ming Li Sijia Li Di Huang Qingwei Zhang Pengyu Li Qingsui Li Hang Yu Yining Liu Yadong Xue Haixin Chen Jiali Liu Wanyu Zhang Mingbin Liu Siyu Chang Xianzhi Lang Xingmiao Zhao Weijie Du Benzhi Cai Ning Wang Baofeng Yang State-Province Key Laboratories of biomedicine-Pharmaceutics of China&Key Laboratory of Cardiovascular Medicine Research(Ministry of Education of the People’s Republic of China) Department of PharmacologyCollege of PharmacyHarbin Medical UniversityHarbin 150081China institute of Clinical Pharmacy The University Key Laboratory of Drug ResearchHeilongjiang Higher Education InstitutionsDepartment of Pharmacythe Second Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Research Unit of Noninfectious Chronic Diseases in Frigid Zones(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China Northern translational Medicine Research and Cooperation Center Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China

Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.

关键词： Myocar dial infarction Pyroptosis CPAL NFkB Inflammation

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Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease:a phaseⅠ/Ⅱclinical trial

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General Psychiatry 2023年第5期36卷 350-360页

作者： Xinyi Xie Qingxiang Song Chengxiang Dai Shishuang Cui Ran Tang Suke Li Jing Chang Ping Li Jintao Wang Jianping Li Chao Gao Hongzhuan Chen Shengdi Chen Rujing Ren Xiaoling Gao Gang Wang Department of Neurology and institute of Neurology Shanghai Jiao Tong University Medical School Affiliated Ruijin HospitalShanghaiChina Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghaiChina Department of Regenerative Medicine Business Cellular Biomedicine GroupShanghaiChina Daxing Research institute University of Science and TechnologyBeijingChina Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghaiChina

Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until *** preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure *** The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate *** The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and *** No adverse events were *** the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive ***,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week *** were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some *** Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.

关键词： clinical Alzheimer dosage

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High special surface area and“warm light”responsive ZnO:Synthesis mechanism,application and optimization

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Bioactive Materials 2022年第1期7卷 181-191页

作者： Xinxin Miao Fen Yu Kuan Liu Zhongsheng Lv Jianjian Deng Tianlong Wu Xinyan Cheng Wei Zhang Xigao Cheng Xiaolei Wang Department of Orthopaedic Surgery The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi330006PR China College of Chemistry NanChang UniversityNanChangJiangxi330031PR China institute of translational Medicine Nanchang UniversityNanchangJiangxi330031PR China Jiangxi Key Laboratory of Nanobiomaterials Institute of Advanced MaterialsEast China Jiaotong UniversityNanchangJiangxi330013PR China

In this study,a new series of zinc oxide(ZnO)with high specific surface area and narrow energy band gap are prepared using a facile microwave-induced *** corresponding formation mechanism is also discussed for the first *** to the introduction of C,these ZnO can be excited by long wave temperature light without harmful short wave radiation,and play an efficient photocatalytic *** valuable property fundamentally improves the biological safety of its photocatalytic ***,taking teeth whitening as an example,the photocatalytic performance of ZnO is ***“pure”yellow light-emitting diode(PYLED)with high biological safety is used as the excitation *** is found that this method could effectively remove pigment on the tooth surface through physical *** addition,these ZnO could generate active oxygen to degrade the pigment on the tooth surface under the irradiation of yellow *** further optimization of these“warm light”responsive ZnO is also discussed in this systematical study,which could open up new opportunities in biomedical field.

关键词： ZnO Photocatalysis Yellow light Teeth whitening

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Longitudinal proteomic investigation of cOVID-19 vaccination

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Protein & Cell 2023年第9期14卷 668-682页

作者： Yingrui Wang Qianru Zhu Rui Sun Xiao Yi Lingling Huang Yifan Hu Weigang Ge Huanhuan Gao Xinfu Ye Yu Song Li Shao Yantao Li Jie Li Tiannan Guo Junping Shi Marker Lab Westlake Laboratory of Life Sciences and BiomedicineKey Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake University18 Shilongshan RoadHangzhou 310024China institute of Basic Medical Sciences Westlake Institute for Advanced Study18 Shilongshan RoadHangzhou 310024China Research Centerfor Industries of theFuture WestlakeUniversity600D unyu RoadHangzhou 310030China Center for Infectious Disease Research Westlake University18 Shilongshan RoadHangzhou 310024China Westlake Omics(Hangzhou)Biotechnology Co. Ltd.Hangzhou 310024China Department of translational Medicine Platform The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015China The Fourth School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Medical college of Hangzhou Normal university Hangzhou 311121China Department of Infectious Diseases Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China institute of Viruses and Infectious Diseases Nanjing UniversityNanjing 210093China Department of Infectious and Hepatology Diseases The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015China

Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to *** this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day *** TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)*** proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune *** study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.

关键词： COVID-19 vaccination proteomics neutralizing antibodies(NAbs) machine learning

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LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3602-3617页

作者： Jian Sun Tongzhu Jin Zhihui Niu Jiayu Guo Yingying Guo Ruoxuan Yang Qianqian Wang Huiying Gao Yuhan Zhang Tianyu Li Wenxin He Zhixin Li Wenchao Ma Wei Su Liangliang Li Xingxing Fan Hongli Shan Haihai Liang Department of Pharmacology(State-Province Key Laboratories of biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Northern translational Medicine Research and Cooperation Center Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China Department of Thoracic Surgery Shanghai Pulmonary HospitalTongji UniversityShanghai 200433China State Key Laboratory of Quality Research in Chinese Medicine/Macao institute for Applied Research in Medicine and Health Macao University of Science and TechnologyMacao(SAR)China Research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China Zhuhai People's hospital Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and TreatmentZhuhai Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai 519000China

Idiopathic pulmonary fibrosis(IPF)is a progressive disease with unknown etiology and limited therapeutic *** of fibroblasts is a prominent feature of pulmonary *** we report that lncRNA DACH1(dachshund homolog 1)is downregulated in the lungs of IPF patients and in an experimental mouse model of lung ***1 knockout mice develop spontaneous pulmonary fibrosis,whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation,collagen deposition and differentiation of mouse lung ***,forced expression of LncDACH1 not only prevented bleomycin(BLM)-induced lung fibrosis,but also reversed established lung fibrosis in a BLM ***,LncDACH1 binding to the serine/arginine-rich splicing factor 1(SRSF1)protein decreases its activity and inhibits the accumulation of *** expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung ***,loss of LncDACH1 promoted proliferation,differentiation,and extracellular matrix(ECM)deposition in mouse lung fibroblasts,whereas such effects were abolished by silencing of *** addition,a conserved fragment of LncDACH1 alleviated hyperproliferation,ECM deposition and differentiation of MRC-5 cells driven by TGF-β***,LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation,suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

关键词： Idiopathic pulmonary fibrosis LncRNA DACH1 SRSF1 CTNNB1 Fibroblast Myofibroblast Extracellular matrix Proliferation

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^(23)Na relaxometry: An overview of theory and applications

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Magnetic Resonance Letters 2023年第2期3卷 150-174,I0004页

作者： Yifan Song Yu Yin Qinlong Chen Alessandro Marchetti Xueqian Kong Key Laboratory of Excited-State Materials of Zhejiang Province Department of ChemistryZhejiang UniversityHangzhouZhejiang310027China Department of Physical Medicine and Rehabilitation Sir Run Run Shaw HospitalZhejiang UniversityHangzhouZhejiang310016China institute of translational Medicine Shanghai Jiao Tong UniversityShanghai200240China

^(23)Na is a nuclear magnetic resonance(NMR)-active isotope with a nuclear spin quantum number of 3/2.^(23)Na relaxation phenomenon is at the core of ^(23)Na NMR measurement and *** to the dominance of quadrupolar interaction,the relaxation behavior of ^(23)Na is physically and mathematically more complex than that of a typical spin-1/2 *** this review,we overview the semi-classical Redfield theory for deriving the formulations of ^(23)Na *** show that the relaxation behaviors of ^(23)Na can be quantitatively described by constructing the spectral density functions based on the second-order perturbation *** addition,we summarize the applications of ^(23)Na relaxometry in different research fields,including biomedicine,sodium ion batteries,and quantum information *** sodium is an essential element in our body,food and industrial materials,the research on sodium by ^(23)Na NMR emerges as important future *** theoretical and practical understandings on ^(23)Na relaxation are the step stones for mastering advanced ^(23)Na NMR techniques.

关键词： ^(23)Na relaxation Quadrupolar interactions Redfield theory Biological systems Sodium ion batteries Quantum information processing

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Nuclear genome-derived circular RNA circPUMl localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2022年第3期7卷 816-828页

作者： Wei Gong Jiancheng Xu Yan Wang Qingjie Min Xu Chen Weimin Zhang Jie Chen Qimin Zhan Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina institute of Systems biomedicine School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Peking university International Cancer institute 100191 BeijingChina Shenzhen Bay Laboratory Shenzhen 518132China Research Unit of Molecular Cancer Research Chinese Academy of Medical Sciences100021 BeijingChina

Circular RNAs(circRNAs)were shown to play an important role in the occurrence and progression of ***,the functions of nuclear genome-derived circRNAs localized in mitochondria of tumor cells remain largely ***,we report that circPUMl,a circular RNA derived from back-splicing of pre-mRNAs of nuclear genome PUM1,localizes in mitochondria.

关键词： esophageal circular squamous

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Coagulation factor Ⅶ gene polymorphisms are not associated with the occurrence or the survival of hepatocellular carcinoma:a report of 37 cases

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Cancer Biology & Medicine 2018年第3期15卷 275-281页

作者： Chih-Che Lin Chun-Hsien Wu Li-Yu Chen Ming-Chao Tsai Ahmed M.Elsarawy Kuang-Tzu Huang Liver Transplantation Center Department of Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine institute for translational Research in biomedicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Division of Hepato-Gastroenterology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine

Objective: Coagulation factor VII(FVII) triggers the extrinsic pathway of blood coagulation. In our previous study, we showed that FVII plays an important role in tumorigenesis of hepatocellular carcinoma(HCC). However, the role of FVII polymorphism in HCC is still unknown. The present study aimed to investigate the relationship between HCC carcinogenesis and single nucleotide polymorphism of ***: Thirty-seven HCC patients and 30 healthy donors were recruited in this study. Four common FVII gene polymorphisms– a decanucleotide insertion at position –323(–323 ins10-bp), a G to T substitution at position –401(–401 G/T), a G to A substitution at position –402(–402 G/A), and a T to C substitution at position –122(–122 T/C) – were analyzed by sequencing or commercialized assays using genomic DNA isolated from blood samples. Clinicopathological parameters between control and HCC subjects were compared according to the specific ***: The most common nucleotide variation was –402 G/A. However, no statistically significant difference was observed between healthy controls and HCC subjects for all four polymorphisms in terms of genotype distribution and allele frequencies,indicating that these polymorphisms may not affect HCC tumorigenesis. Furthermore, no association was found between–402 G/A polymorphisms and tumor stage, recurrence, and overall ***: Our results indicate that FVII polymorphisms may not be a key factor that clinically impact tumorigenesis and outcomes of HCC, although further investigations should be conducted to confirm our findings.

关键词： Factor Ⅶ gene polymorphism liver hepatocellular cancer survival

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表征不同DNA高阶结构的单分子方法

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工程(英文) 2023年第5期24卷 276-291,I0008页

作者： Yonglin Liu Tianyuan Bian Yan Liu Zhimin Li Yufeng Pei Jie Song School of Molecular Medicine Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China The Cancer hospital of the university of Chinese Academy of Sciences Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Academy of Medical Engineering and translational Medicine(AMT) Tianjin UniversityTianjin 300072China institute of Nano biomedicine and Engineering Department of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China

DNA不仅是生命遗传信息的载体,而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物和化学功能有关。因此,了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而,批量分析忽略了溶液中DNA结构的异质性... 详细信息

DNA不仅是生命遗传信息的载体,而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物和化学功能有关。因此,了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而,批量分析忽略了溶液中DNA结构的异质性。单分子方法是观察单个分子行为和探测自由能态高度非均质性的有力工具。在本文中,介绍了单分子方法,包括单分子检测和操作方法,并讨论了这些方法如何有助于测量单链/双链DNA(ss/dsDNA)、DNA高阶结构和DNA纳米结构的分子性质。本文为DNA纳米技术与单分子方法的结合提供了一个新的视角,以了解DNA和其他生物物质和软物质的生物物理特性。

关键词： DNA结构单分子生物物质分子性质软物质遗传信息操作方法批量分析

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Human adipose, placenta, and umbilical cord-derived mesenchymal stem cells ameliorate imiquimod-induced psoriatic mice via reducing T cells infiltration

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BIOCELL 2021年第3期45卷 537-546页

作者： JIGANG LEI ZHENYAO XU SUKE LI MENG LI ZHIKAI WANG PING LI JING WANG YINGLU CHEN X IAOLE SONG CHENGJIE REN MEIPING SHEN CHENGXIANG DAI Cellular biomedicine Group Shanghai200233China translational Medicine Center Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200025China Shanghai institute of Immunology Shanghai Jiaotong University School of MedicineShanghai200025China

Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte ***,Th17 cells and IL-17 play critical roles in the pathogenesis of *** monoclonal antibodies against cytokines have been shown to have effectively immunosuppressive effects on human ***,there are still some patients that have no response to these *** patients have even serious side-effects which may affect their *** stem cells have the ability of immunosuppressive and anti-inflammatory effects,which may be an alternative therapy with more safety and efficacy for human ***,the underlying mechanisms by which the MSCs prevent or ameliorate psoriasis are still poorly ***,we first isolated and characterized human adipose,placenta,and umbilical cord-derived mesenchymal stem cells(haMSCs,hpMSCs,and huMSCs).After that,the animal model of imiquimod(IMQ)-induced psoriasis in C57BL/6 mice was *** investigated the impact of haMSCs,hpMSCs,and huMSCs on this model by H&E staining,immunohistochemistry staining,and quantitative real-time *** analysis showed that mice subcutaneously injected with these MSCs had a significantly decreased epidermal thickness,which was caused by obviously reduced hyper-proliferation of ***,our findings revealed that the infiltration of T cells to psoriatic lesions in IMQ-induced psoriasis mice was markedly downregulated by intradermal administration of haMSCs,hpMSCs,and huMSCs,***,the production of IL-17 from Th17 cells was reduced,which inhibits the proliferation of keratinocytes in lesioned skin of IMQ-induced psoriasis *** data suggest that haMSCs,hpMSCs,and huMSCs can inhibit the effects of proinflammatory Th17 cells on the development of psoriasis,which may be potential therapeutic candidates for skin inflammatory disease or other autoimmune

关键词： Mesenchymal stem cells Psoriasis T cells Skin inflammation Cell therapy

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