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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

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 518-528页

作者： Nan Sun Bi-Bo Tan Yong Li department of blood transfusion The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hubei ProvinceChina Third department of General Surgery the Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths *** assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this ***2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric *** To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM *** A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was *** patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic *** performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision *** The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation *** under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination *** plots confirmed the high concordance between the predictions and actual survival *** We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients *** model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical *** validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

关键词： Gastric cancer LATS2 Column line graph Prognosis Advanced gastric cancer survival Molecular biomarkers Predictive analytics in oncology Survival analysis

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

Depletion of anti-CD47mAb in plasma by genetically modified cells for pre-transfusion testing

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Genes & Diseases 2024年第5期11卷 102-104页

作者： Fei Wang Wenting Wang Xiaoshuang Wu Zhixin Liu Yafen Wang Rong Zhang Shunli Gu Qunxing An Yaozhen Chen Xingbin Hu department of transfusion medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China Xi’an Medical University Xi’anShaanxi 710021China

Allogeneic red blood cell(RBC)transfusion is commonly performed in medical practice because of its efficacy and low-risk ***,pre-transfusion tests are susceptible to monoclonal antibody(mAb)interference.1 Currently,mAb therapies are being developed to treat many diseases,such as ***,certain mAbs,such as anti-CD38mAb and anti-CD47mAb,can bind to RBC membranes;this binding interferes with pre-transfusion tests.2 CD47 has gained considerable attention in recent years because of its potential as a therapeutic target for hematologic malignancies and solid tumors.3 The binding of anti-CD47mAb to RBCs may lead to false-positive results in pan-agglutination tests and cause delays and risks in establishing compatible RBCs for transfusion.

关键词： CD47 transfusion diseases

Targeted NGS analysis reveals a complex genetic background of idiopathic erythrocytosis in a large Venetian family

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Genes & Diseases 2024年第2期11卷 561-563页

作者： Bertozzi Irene Benetti Andrea Regazzo Daniela Polese Francesca Biagetti Giacomo Ceolotto Giulio Randi Maria Luigia First Medical Clinic University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy transfusion medicine department Ospedale dell'Angelo - Venezia MestreVia Paccagnella 1Venice 30174Italy Emergency medicine University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy

Absolute erythrocytosis,due to an increased production of red blood cells,becomes manifest with hemoglobin(Hb)levels above 165 or 160 g/L or with a hematocrit(HCT)above 51%and 48%in males and females,respectively.1 A minority of patients have polycythemia vera(PV);acquired secondary erythrocytosis frequently occurs due to appropriate or inappropriate erythropoietin(EPO)excess,while congenital secondary erythrocytosis may derive from genetic defects causing tissue *** erythrocytosis occurs in patients with genetic mutations of the oxygen-sensing pathway(VHL,PHD2,_HIF-1-alpha)or the erythropoietin receptor(EPOR)genes.2 Recently,HFE gene variants have been described in sporadic erythrocytoses.3 In a high proportion(about 70%)of patients with erythrocytosis,a specific etiology remains elusive despite extensive testing,and the diagnosis of idiopathic erythrocytosis(IE)is ruled out.

关键词： diagnosis patients congenital

Core–Shell Microfiber Encapsulation Enables Glycerol‑Free Cryopreservation of RBCs with High Hematocrit

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Nano-Micro Letters 2024年第1期16卷 35-54页

作者： Xianhui Qin Zhongrong Chen Lingxiao Shen Huilan Liu Xilin Ouyang Gang Zhao department of Electronic Engineering and Information Science University of Science and Technology of ChinaHefei 230027People’s Republic of China School of Biomedical Engineering Anhui Medical UniversityHefei 230022People’s Republic of China department of blood transfusion The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001People’s Republic of China The Fourth Medical Center Chinese PLA General HospitalBeijing 100089People’s Republic of China

Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in *** concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully ***,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical *** this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during *** from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional *** may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.

关键词： Cryopreservation Human red blood cells Core-shell microfibers Trehalose Hematocrit

A novel mutation of glycogen synthase kinase-3β leads to a reduced level of GSK3βprotein in a patient with dilated cardiomyopathy

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Genes & Diseases 2024年第1期11卷 84-86页

作者： Ke Gong Zhiping Tan Haidan Liu Xiaobo Liao Xinmin Zhou Bangliang Yin Shi Zeng Yao Yao Yifeng Yang Li Xie department of Cardiovascular Surgery The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan410011China department of Ultrasound The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China department of blood transfusion The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China

Dilated cardiomyopathy(DCM)is a frequently inherited heart condition.A familial transmission rate of 20%-35%has been documented,and most of these cases are autosomal *** condition has a high rate of morbidity and mort... 详细信息

关键词： GSK3β cardiomyopathy mortality

Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China department of Laboratory medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China department of blood transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis *** Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain ***,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse ***,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone ***,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic *** analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic *** together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

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

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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 *** 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 ***,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still ***: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 *** performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic ***:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and *** is a curated database of associations between RNA editome and *** 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 ***,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy ***:REDH is accessible at http://***/.This user-friendly database

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