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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

Graph based recurrent network for context specific synthetic lethality prediction

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Science China Life Sciences 2024年

作者： Yuyang Jiang Jing Wang Yixin Zhang ZhiWei Cao Qinglong Zhang Jinsong Su Song He Xiaochen Bo Academy of Medical Engineering and Translational medicine Tianjin University Department of Bioinformatics Institute of Health Service and Transfusion MedicineBeijing School of medicine Tsinghua University School of Informatics Xiamen University

The concept of synthetic lethality (SL) has been successfully used for targeted therapies. To further explore SL for cancer therapy, identifying more SL interactions with therapeutic potential are essential. Recently, graph neural network-based deep learning methods have been proposed for SL prediction, which reduce the SL search space of wet-lab based methods. However, these methods ignore that most SL interactions depend strongly on genetic context, which limits the application of the predicted results. In this study, we proposed a graph recurrent network-based model for specific context-dependent SL prediction (SLGRN). In particular, we introduced a Graph Recurrent Network-based encoder to acquire a context-specific, low-dimensional feature representation for each node, facilitating the prediction of novel SL. SLGRN leveraged gate recurrent unit (GRU) and it incorporated a context-dependent-level state to effectively integrate information from all nodes. As a result, SLGRN outperforms the state-of-the-arts models for SL prediction. We subsequently validate novel SL interactions under different contexts based on combination therapy or patient survival analysis. Through in vitro experiments and retrospective clinical analysis, we emphasize the potential clinical significance of this context-specific SL prediction model.

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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

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

Treatment refractory mast cell leukemia with dominant gastrointestinal manifestation and concomitant skin symptoms:A case report

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World Journal of Clinical Cases 2024年第20期12卷 4317-4324页

作者： Maciej Tomasz Wysocki Maciej Gonciarz Bartosz Puła Department of Gastroenterology and Internal medicine Military Institute of Medicine-National Research InstituteWarsaw 04-141Poland Department of Hematology Institute of Hematology and Transfusion MedicineWarsaw 02-776Poland

BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor ***,tyrosine kinase inhibitors,and allogeneic hematopoietic cell transplantation are the only treatment options,but they cannot provide the desired outcomes in most cases of ***,other types of SM can be successfully *** disease has no specific manifestation,but gastroenterological symptoms are present in most *** SUMMARY The authors,hereby,report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of *** patient presented to the gastroenterology clinic with multiple,various,and unspecific gastroenterological *** of skin lesions significantly contributed to a relatively prompt *** serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast *** disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of *** Despite its“hematological nature”,MCL,in most cases presents dominantly with unspecific gastroenterological ***,a high disease awareness among physicians other than hematologists is necessary to improve treatment *** tryptase level,due to its non-invasive nature and easy access,may serve as an initial step to estimate the probability of mastocytosis.

关键词： Mastocytosis Systemic mastocytosis Mast cell leukemia Tryptase Case report

Prosaposin hyperglycosylation: a novel tumor immune escape mechanism and implications for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3150-3152页

作者： Matthias Peipp Diana Dudziak Christian Kellner Division of Antibody-Based Immunotherapy Department of Medicine IChristian-Albrechts University and University Hospital Schleswig-HolsteinKielGermany institute of Immunology Jena University HospitalFriedrich-Schiller-UniversityJenaGermany Comprehensive Cancer Center Central Germany Jena/Leipzig JenaGermany Division of transfusion medicine Cell Therapeutics and HaemostaseologyLMU University HospitalLMU MunichMunichGermany

In a recent article published in Science,Sharma et *** the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.

关键词： impaired immunity al.

Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

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Research 2024年第3期2023卷 35-50页

作者： June Li Danielle Karakas Feng Xue Yingyu Chen Guangheng Zhu Yeni H.Yucel Sonya A.MacParland Haibo Zhang John W.Semple John Freedman Qizhen Shi Heyu Ni Department of Laboratory medicine and Pathobiology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research Centre for Biomedical Science of St.Michael's Hospital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada Departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research institute Versiti WisconsinMilwaukeeWIUSA Departments of Ophthalmology and Vision Sciences medicine University of TorontoTorontoONCanada Faculty of Engineering and Architectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada Department of Immunology University of TorontoTorontoONCanada Critical Care medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada Department of Physiology University of TorontoTorontoONCanada Department of Pharmacology University of TorontoTorontoONCanada. Division of Hematology and transfusion medicine Lund UniversityLundSweden clinical Immunology and transfusion medicine Ofice of Medical ServicesRegion SkaneLundSweden Department of medicine University of TorontoTorontoONCanada Children's Research institute Children's WisconsinWauwatosaWIUSA Midwest Athletes Against Childhood Cancer Fund Research Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion homeostasis

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