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Role of Exosomal Modulation of Macrophages in Liver Fibrosis

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 201-209页

作者： Bin Fan He Xie Qi Tan Qingyuan Li Tao Gong Baoren He Yujia Li Limin Chen institute of blood transfusion(IBT) Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)ChengduSichuanChina The Hospital of Xidian Group Xi’anShaanxiChina Department of Clinical Medicine North Sichuan Medical CollegeNanchongSichuanChina The joint laboratory of transfusion-transmitted diseases(TTDs)between institute of blood transfusion(IBT) Chinese Academy of Medical Sciences(CAMS)and Nanning Blood CenterNanningGuangxiChina

Exosomes are 60–120 nm diameter double-membrane lipid organelles discharged by *** studies have shown that exosomes exert multiple functions in both physical and diseased processes,such as intercellular information exchange,immune response,and disease *** chronic injury to the liver often leads to inflammation and liver fibrosis(LF),a disorder that,if unchecked,may progress to cirrhosis,liver failure,portal hypertension,and even hepatocellular *** an essential component of host innate immunity against pathogen invasion,macrophages play an important role in modulating inflammation homeostasis by finely tuning the polarization process of macrophages into either M1 or M2 subtypes in response to different *** a critical contributor to the inflammation process,macrophages also play a complex and instrumental function in the progression of *** review focuses on recent advancements in the role of macrophage-associated exosomes implicated in LF,including macrophage-released exosomes and macrophage-targeted *** addition,the progress made in exosomebased antifibrotic therapy by in vivo and in vitro studies is also highlighted.

关键词： Exosome Macrophage Liver fibrosis Hepatocyte Mesenchymal stem cell Hepatic stellate cell

Oncolytic Virus Senecavirus A Inhibits Hepatocellular Carcinoma Proliferation and Growth by Inducing Cell Cycle Arrest and Apoptosis

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 713-725页

作者： Tao Gong Xiao Liu Qingyuan Li Donald RBranch Melika Loriamini Wenxian Wen Yaoqiang Shi Qi Tan Bin Fan Zhonghui Zhou Yujia Li Chunhui Yang Shilin Li Xiaoqiong Duan Limin Chen Department of Clinical Medicine North Sichuan Medical CollegeNanchongSichuanChina institute of blood transfusion Chinese Academy of Medical Sciences and Peking Union Medical CollegeChengduSichuanChina College of Animal Science and Technology Southwest UniversityChongqingChina Departments of Medicine and laboratory Medicine and Pathobiology Centre for InnovationCanadian Blood ServicesHamiltonOntarioCanada The Hospital of Xidian Group Xi’anShaanxiChina The joint-laboratory on transfusion-transmitted diseases(TTDs)between institute of blood transfusion and Nanning blood Center Nanning Blood CenterNanningGuangxiChina

Background and Aims:Hepatocellular carcinoma(HCC)isa highly aggressive tumor with limited treatment options andhigh *** A(SVA)has shown potential inselectively targeting tumors while sparing healthy *** study aimed to investigate the effects of SVA on HCCcells in vitro and in vivo and to elucidate its mechanisms ***:The cell counting kit-8 assay and colonyformation assay were conducted to examine cell *** cytometry and nuclear staining were employed toanalyze cell cycle distribution and apoptosis *** tumor xenograft HCC mouse model was createdin vivo using HepG2 cells,and Ki67 expression in thetumor tissues was *** terminal deoxynucleotidyltransferase dUTP nick end labeling assay and hematoxylinand eosin staining were employed to evaluate HCC apoptosisand the toxicity of SVA on mouse ***:In vitro,SVA effectively suppressed the growth of tumor cells by inducingapoptosis and cell cycle ***,it did nothave a notable effect on normal hepatocytes(MIHA cells).In an in vivo setting,SVA effectively suppressed the growthof HCC in a mouse *** treatment resulted in a significantdecrease in Ki67 expression and an increase in apoptosisof tumor *** notable histopathological alterationswere observed in the organs of mice during SVA ***:SVA inhibits the growth of HCC cells byinducing cell cycle arrest and *** does not causeany noticeable toxicity to vital organs.

关键词： Oncolytic virus Senecavirus A Apoptosis Cell cycle arrest Hepatocellular carcinoma HepG2

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State Key laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

BTG2 interference ameliorates high glucose-caused oxidative stress, cell apoptosis, and lipid deposition in HK-2 cells

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BIOCELL 2024年第9期48卷 1379-1388页

作者： WENJUAN ZHU ZHENGZHENG JU FAN CUI Department of blood transfusion The First People’s Hospital of WuhuWuhu241000China Department of Clinical laboratory The First People’s Hospital of WuhuWuhu241000China

Objective:Diabetic nephropathy(DN)is a deleterious microangiopathy of diabetes,constituting a critical determinant of fatality in diabetic *** work is purposed to disclose the effects and modulatory mechanism of BTG anti-proliferation factor 2(BTG2)during the pathological process of ***:BTG2 expression in kidney tissues of diabetic mice and high glucose(HG)-exposed human proximal tubular cell line HK-2 was assessed with Western blot and *** diabetic mice model was constructed by streptozotocin injection and confirmed by the blood glucose level beyond 16.7 mmol/*** and eosin(H&E)staining and measurement of kidney function hallmarks were conducted to assess kidney *** counting kit(CCK)-8 method and TUNEL assay appraised cell activity and *** red O staining assayed lipid *** commercial kits were used to estimate oxidative stress-related ***-immunoprecipitation(Co-IP)assay testified the binding relationship of BTG2 with protein arginine methyltransferase 1(PRMT1).Results:BTG2 expression was significantly raised in renal tissues of diabetic mice and HK-2 cells exposed to ***2 deficiency improved viability and extenuated the apoptosis,lipid deposition as well as oxidative stress in HK-2 cells following HG *** addition,PRMT1 was also overexpressed in HK-2 cells exposed to ***2 interacted with PRMT1 and positively modulated PRMT1 *** effects of BTG2 interference on viability,apoptosis,lipid deposition,and oxidative stress in HG-challenged HK-2 cells were partially abrogated by PRMT1 ***:Altogether,BTG2 might aggravate HK-2 cell injury in response to HG by binding with PRMT1,providing a novel target for the therapeutic strategy of DN.

关键词： BTG2 Diabetic nephropathy Lipid deposition Oxidative stress PRMT1

Towards a blood ecosystem approach to dissect systemic diseases

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Science China(Life Sciences) 2024年第7期67卷 1528-1531页

作者： Hong Wang Tao Cheng State Key laboratory of Experimental Hematology Haihe Laboratory of Cell EcosystemNational Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin institutes of Health Science Tianjin 301600China

Systemic diseases,in contrast to localized ailments,exert widespread effects and can impact the entire *** of systemic diseases encompass autoimmune disorders,infectious diseases,metabolic disorders,and chronic conditions like *** diseases often entail intricate interactions among diverse organs,tissues,and physiological systems,influenced by a myriad of factors.

关键词： diseases organs autoimmune

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan Pei-Pei Xue Teng Yu Xiao-Yan He Li-Xin Xiang Yan-Ni Xiao Xiao-Liang Li Qian Ran Zhong-Jun Li Li Chen laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ***,the positive regulators of ANKRD26 are still *** To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 *** Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family *** to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activi

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin institutes of Health Science Tianjin 301600China National Clinical Research Center for Hematologic diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering Research Centre of Cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients

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Journal of Geriatric Cardiology 2024年第2期21卷 211-218页

作者： Luo-Xi XIAO Zi-Yu WANG Jiang-Tao LI Hai-Mei WANG Yi-Ming HAO Pan ZHOU Yu-Lin HUANG Qiu-Ju DENG Yong-Chen HAO Na YANG Li-Zhen HAN Zhao YANG Ping-Ping JIA Yue QI Jing LIU Center for Clinical and Epidemiologic Research Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing Municipal Key Laboratory of Clinical EpidemiologyBeijingChina

BACKGROUND Hypertension usually clusters with multiple ***,the association between cardiometabolic multimorbidity(CMM)and mortality in hypertensive patients is *** study aimed to investigate the association between CMM and all-cause and cardiovascular disease(CVD)mortality in Chinese patients with *** The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors(CONSIDER),which comprised 5006 participants aged 19–91 *** was defined as the presence of one or more of the following morbidities:diabetes mellitus,dyslipidemia,chronic kidney disease,coronary heart disease,and *** proportional hazard models were used to calculate the hazard ratios(HR)with 95%CI to determine the association between the number of CMMs and both all-cause and CVD *** Among 5006 participants[mean age:58.6±10.4 years,50%women(2509 participants)],76.4%of participants had at least one *** mortality rate was 4.57,4.76,8.48,and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one,two,and three or more morbidities,*** the fully adjusted model,hypertensive participants with two cardiometabolic diseases(HR=1.52,95%CI:1.09–2.13)and those with three or more cardiometabolic diseases(HR=2.44,95%CI:1.71–3.48)had a significantly elevated risk of all-cause *** findings were similar for CVD mortality but with a greater increase in risk *** In this study,three-fourths of hypertensive patients had *** with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients,suggesting more intensive treatment and control in this high-risk patient group.

关键词： hypertensive patients morbidity

Retrospective Study Immune function status of postoperative patients with colon cancer for predicting liver metastasis

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 463-470页

作者： Le Xiong Fang-Chen Liu Department of Clinical laboratory Xiangyang No.1 People’s HospitalHubei University of MedicineXiangyang 441000Hubei ProvinceChina Department of blood transfusion Xiangyang No.1 People’s HospitalHubei University of MedicineXiangyang 441000Hubei ProvinceChina

BACKGROUND Colon cancer(CC)has a high incidence *** resection is the main treatment method for CC;however,liver metastasis(LM)often occurs *** liver contains both innate and adaptive immune cells that monitor and remove abnormal cells and *** LM,tumor cells secrete cytokines and exosomes to adjust the immune microenvironment of the liver,thus forming an inhibitory immune microenvironment for colonization by circulating tumor *** indicates that the immune state of patients with CC plays a crucial role in the occurrence and progression of *** To observe and analyze the relationship between immune status and expression of tumor factors in patients with LM of CC,and to provide a scientific interven-tion method for promoting the patient *** A retrospective analysis was *** baseline data of 100 patients with CC and 100 patients with CC who suffered from postoperative LM and were admitted to our hospital from May 2021 to May 2023 were included in the non-occurrence and occurrence groups,*** immune status of the pa-tients and the expression of tumor factor-related indicators in the two groups were compared,and the predictive value of the indicators for postoperative LM in patients with CC was *** Compared with the non-occurrence group,the expression of serum carcinoem-bryonic antigen(CEA),CA19-9,CA242,CA72-4 and CA50 in patients in the occurrence group were significantly higher,while the expression of CD3+,CD4+,CD8+,natural killer(NK)and CD4+/CD25 in patients in the occurrence group were significantly lower(Pbetween groups(P>0.05).Multivariate logistic regression model analysis revealed that the expressions of CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 were associated with the LM in patients with *** expressions of serum CEA,CA19-9,CA242,CA72-4 and CA50,and low expressions of CD3+,CD4+,CD8+,

关键词： Colon cancer Liver metastases Immune status Tumor factors Predicted value