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REDH:A database of RNA editome in hematopoietic differentiation and malignancy

Chinese Medical Journal 2024年第3期137卷 283-293页

作者： Jiayue Xu Jiahuan He Jiabin Yang Fengjiao Wang Yue Huo Yuehong Guo Yanmin Si Yufeng Gao Fang Wang Hui Cheng Tao Cheng Jia Yu Xiaoshuang Wang Yanni Ma State Key laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Key laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China department of Biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Institute of blood Transfusion Chinese Academy of Medical SciencesChengduSichuan 610052China

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets.However,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used.We performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and malignancy.REDH is a curated database of associations between RNA editome and hematopoiesis.REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological conditions.Furthermore,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions:REDH is accessible at http://***/.This user-friendly database would aid in understanding the mechanisms of RNA editing in hema

关键词： RNA editing Hematopoietic differentiation Hematopoietic malignancy Database management systems

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Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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Military Medical Research 2024年第1期11卷 80-97页

作者： Qian-Yun Guo Jia-Qi Yang Xun-Xun Feng Yu-Jie Zhou Beijing Key laboratory of Precision Medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

关键词： Heart regeneration Cardiac disease Therapeutics Signaling mechanisms

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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 ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS 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 POTE.According 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 activity of the mitogen activated protein kinase and e

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

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MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

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Oncology Research 2024年第6期32卷 1011-1019页

作者： ELHAM SHAKIBA SETI BOROOMAND SIMA KHERADMAND KIA MEHDI HEDAYATI department of Biochemistry Faculty of Biological SciencesNorth Tehran BranchIslamic Azad UniversityTehran***Iran department of Pathology and laboratory Medicine Vancouver General HospitalVancouverV5Z 1M9Canada department of blood Cell Research Laboratory for Red Blood Cell DiagnosticsSanquinAmsterdam1006 ANThe Netherlands Cellular and Molecular Endocrine Research Center Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehran***Iran

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

关键词： Thyroid cancer MicroRNAs Biomarker Bioinformatics analysis Medullary thyroid carcinoma(MTC) OncomiRs Antioncoges

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Updates of developments in interventional therapy for elderly patients with cardiovascular diseases

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Journal of Geriatric Cardiology 2024年第1期21卷 1-3页

作者： Hua SHEN Xun-Xun FENG Qian-Yun GUO Yu-Jie ZHOU Beijing Key laboratory of Precision Medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijingChina

Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patients.One report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.

关键词： diseases patients prognosis

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Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic lineages.We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells.Mechanistically,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its enhancer.Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation.In conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

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Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

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World Journal of Stem Cells 2024年第2期16卷 163-175页

作者： Yan Ren Yan-Ni Cui Hong-Wei Wang The Second Clinical Medical College Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of Hematology The Second Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of Hematology Key Laboratory of Molecular Diagnosis and Treatment of Blood Diseases in Shanxi ProvinceTaiyuan 030001Shanxi ProvinceChina

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital resource.Nicotinamide(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet known.As a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and differentiation.However,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or cells.We propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of HSCs.AIM To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and differentiation.METHODS CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental requirements.Flow cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured cells.Real-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant enzymes.Dichloro-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array.RESULTS Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly higher than those of the control and 10 mmol/L N

关键词： Hematopoietic stem cells Nicotinamide Concentration Proliferation Differentiation Sirtuin 1

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Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

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Military Medical Research 2024年第2期11卷 157-179页

作者： Yong‑Lin Yu Jun‑Jie Wu Chuan‑Chuan Lin Xian Qin Franklin R.Tay Li Miao Bai‑Long Tao Yang Jiao department of Pathology Affiliated Hospital of Zunyi Medical UniversityZunyi 563003GuizhouChina laboratory Research Center the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of blood Transfusion Laboratory of Radiation Biologythe Second Affiliated HospitalArmy Military Medical UniversityChongqing 400037China department of Reproductive Endocrinology Chongqing Health Center for Women and ChildrenChongqing 401147China The Graduate School Augusta UniversityAugustaGA 30912USA department of Stomatology the Seventh Medical Center of PLA General HospitalBeijing 100700China

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0

关键词： Polydopamine nanoparticles Methicillin-resistant Staphylococcus aureus Nitric oxide Osseointegration Osteo-immunomodulation Photothermal effect Titanium implants

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EBV-associated lymphoproliferative disease post-CAR-T cell therapy

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Frontiers of Medicine 2024年第2期18卷 394-398页

作者： Shiyuan Zhang Xiaoxi Zhou Shangkun Zhang Na Wang Tongcun Zhang Donghua Zhang Qilin Ao Yang Cao Liang Huang department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan430030China Institute of Biology and Medicine College of Life and Health SciencesWuhan University of Science and TechnologyWuhan430081China department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300020China Tianjin Institutes of Health Science Tianjin301600China

Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.

关键词： EBV-associated lymphoproliferative disease chimeric antigen receptor T-cell autologous stem cell transplantation immune checkpoint inhibitor

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Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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中华医学杂志(英文版) 2024年第10期137卷 1207-1217页

作者： Pan Tianzhong Ding Peng Huang Aijie Tang Baolin Song Kaidi Sun Guangyu Wu Yue Yang Shiying Chen Xingchi Wang Dongyao Zhu Xiaoyu department of Hematology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Anhui Provincial Key laboratory of blood Research and Applications Hefei Anhui China blood and Cell Therapy Institute Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China

Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684,P = 0.039 andF = 5.583,P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93;P = 0.031).Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

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