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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

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

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish national blood transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients

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Stroke & Vascular Neurology 2024年第3期9卷 212-220,I0110-I0129页

作者： Qingyuan Liu Shuaiwei Guo Nuochuan Wang Kaiwen Wang Shaohua Mo Xiong Li Yanan Zhang Hongwei He Shuo Wang Jun Wu Department of Neurosurgery and China national Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalBeijingChina Department of blood transfusion Beijing Tiantan HospitalBeijingChina Department of Neurosurgery Beijing Chao-Yang Hospital Capital Medical UniversityBeijingChina Beijing Neurosurgical institution Capital Medical UniversityBeijingChina

Background Aspirin is widely used for preventing ischaemic *** 20%–40%of patients have aspirin resistance(ASR),which prevents them from benefiting from aspirin *** study aimed to develop and validate a model based on single-nucleotide polymorphism(SNP)to distinguish ASR *** We included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre,prospective cohort study as the derivation ***(inhibition of arachidonic acid channel<50%)was used to identify *** was performed to identify the ASR-related *** on the result of the logistic analysis,the aspirin resistance in the Chinese population score(ASR-CN score)was established,and its accuracy was evaluated using the area under the curve(AUC).Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation *** embolism,30-day ischaemic events,including ischaemic stroke,new or more frequent transient ischaemic attack,stent thrombosis and cerebrovascular death,were *** The derivation cohort included 212 patients(155 male patients and the median age as 59).87(41.0%)individuals were identified with *** multivariate logistic analysis demonstrated six SNPs of GP1BA,TBXA2R,PTGS2 and NOS3 as risk factors related to *** ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients(AUC as 0.77).Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism(including 130 ASR patients),the ASR-CN score continued to distinguish ASR patients with good accuracy(AUC as 0.80).Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism(OR,1.28;95%CI,1.10 to 1.50;p=0.002).Conclusion GP1BA,TBXA2R,PTGS2 and NOS3 were SNPs related to *** ASR-CN score is an effective tool to discriminate ASR patients,which

关键词： patients aspirin resistance

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

Extracorporeal membrane oxygenation versus cardiopulmonary bypass during transcatheter aortic valve implantation: a meta-analysis of survival benefits

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World Journal of Emergency Medicine 2024年第4期15卷 306-310页

作者： Huiruo Liu Liangshan Wang Xing Hao Zhongtao Du Chenglong Li Hong Wang Xiaotong Hou centre for Cardiac Intensive Care Beijing Institute of HeartLung and Blood Vessel DiseasesBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Since its approval by the Food and Drug Administration in 2011,transcatheter aortic valve implantation(TAVI)has rapidly evolved to become the preferred ultimate intervention for high-and intermediate-risk patients with severe symptomatic aortic stenosis.[1]This is due to its non-open-heart,minimally invasive and off-pump advantages.[1]Nevertheless,as a result of the frequent frailty and comorbidity profiles of patients undergoing TAVI,such as advanced cardiac dysfunction and extensive coronary artery disease,or technically difficult anatomy for the procedure itself,[2-4]it is common for these patients to experience critical circulatory collapse *** factors are linked to elevated mortality rates,necessitating suitable mechanical circulatory support(MCS)to reverse the disastrous situations.[5]

关键词： anatomy bypass elevated

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

Exploring the potential of micro-nano composite structures for COVID-19 vaccines and beyond

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Biomaterials Translational 2024年第1期5卷 86-88页

作者： Danli Cui Yiting Lei Institution of blood transfusion Chongqing Blood CenterChongqingChina Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityOrthopedic Laboratory of Chongqing Medical UniversityChongqingChina

The coronavirus disease 2019(COVID-19)pandemic has emphasised the crucial role of vaccination in mitigating the spread of the disease.1 While several severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines have been authorised,most of them are administered through intramuscular injections.2 Although these vaccines effectively elicit systemic immune responses,they do not provide immediate protection at the respiratory tract,which is the primary site of viral infection.3,4 To overcome this limitation,researchers are actively investigating the potential of intranasal or nebulised vaccine candidates.

关键词： vaccines respiratory acute

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1593-1601页

作者： Bo Li Yujie Chen Yan Zhou Xuanran Feng Guojun Gu Shuang Han Nianhao Cheng Yawen Sun Yiming Zhang Jiahui Cheng Qi Zhang Wei Zhang Jianhui Liu Department of Radiology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Morphology and Spatial Multi-Omics Technology Platform Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghaiChina Department of Anesthesiology Tongji HospitalSchool of MedicineTongji UniversityShanghaiChina Department of blood transfusion Huashan HospitalFudan UniversityShanghaiChina

Mitochondrial dysfunction is a hallmark of Alzheimer’s *** previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 *** Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a ***,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial ***,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse *** findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-β***,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial *** addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

关键词： Alzheimer’s disease mitochondrial biogenesis neural stem cell-derived exosome SIRT1-PGC1α regional brain distribution whole brain clearing and imaging