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Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

World Journal of Stem Cells 2024年第5期16卷 591-603页

作者： Jin-Bo Wang Ming-Wei Du Yan Zheng Internal Medicine of Traditional Chinese Medicine Tongde Hospital of Zhejiang ProvinceHangzhou 310012Zhejiang ProvinceChina Institute of Cardiovascular Disease Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Molecular Medical Mycology Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shanghai 201203China Department of Hepatic The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese MedicineHangzhou 310023Zhejiang ProvinceChina

BACKGROUND aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably *** To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at *** We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 *** invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin ***,orbital blood of mice was collected for blood routine *** cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA ***,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western *** Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of *** Rg1 successfully reversed hematopoietic dysfunction in AA *** comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by ***,it helped alleviate the blockade in the cell *** with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling *** This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

关键词： aplastic anemia Ginsenoside Rg1 Myelosuppression MAPK signaling pathway Bone marrow Hematopoietic stem cells

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Distinct Overexpression of Fas Ligand on T Lymphocytes in aplastic anemia

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Cellular & Molecular Immunology 2004年第2期1卷 142-147页

作者： WenxinLi JinxiangFu FengmingWang GehuaYu YongWang XueguangZhang JiangsuInstituteofNuclearMedicine Wuxi214063China No.2AffiliatedHospitalofSoochowUniversity Suzhou215004China InstituteofBiotechnology SoochowUniversitySuzhou215007China

Increased expression of Fas by hematopoietic progenitors in aplastic anemia(AA)suggests that Fas/Fas ligand (FasL)system plays a key role in the formation of severe *** further confirm the above hypo- thesis,T cells from 8 patients with AA were systematically studied for their FasL's distribution pattern, releasing manner and proapoptotic activity,compared with normal resting T cells and artificially activated T cell *** results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasL and contained high levels of intracellular FasL which could be triggered to release by high-dose phyto- hemagglutinin(PHA)*** supernatants from the PHA-stimulated AA T cells had apparent cytotoxicity against FasL-sensitive Jurkat cells,which could be significantly inhibited by monocional antibody against FasL in a dose-dependent manner,or nearly completely abrogated by *** above phenomena also appeared on artificially activated T cell blasts,but this was not the case on normal resting T *** results indicate that AA T cell is a type of“preactivated”T lymphocyte,characterized by over- expression of FasL,especially intracellular FasL which can be stimulated to release in bioavtive exosomes- bound *** together,our data provide further and direct evidence for the hypothesis that T cells might mediate the destruction of hematopietic progenitor in AA through Fas/FasL *** & Molecular Immunology.2004;1(2):142-147.

关键词： aplastic anemia T cell activation Fas Fas ligand exosome

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Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

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Science China(Life Sciences) 2023年第11期66卷 2553-2570页

作者： Shu-Qian Tang Tong Xing Zhong-Shi Lyu Li-Ping Guo Mi Liang Chen-Yuan Li Yuan-Yuan Zhang Yu Wang Lan-Ping Xu Xiao-Hui Zhang Xiao-Jun Huang Yuan Kong Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationCollaborative Innovation Center of HematologyPeking UniversityBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China

aplastic anemia(AA)is a life-threatening disease characterized by bone marrow(BM)failure and *** an important component of the BM microenvironment,endothelial cells(ECs)play a crucial role in supporting hematopoiesis and regulating ***,whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain *** this study,a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of ***-L-cysteine(NAC,a reactive oxygen species scavenger)or exogenous EC infusion was administered to AA ***,the frequency and functions of BM ECs from AA patients and healthy donors were *** ECs from AA patients were treated with NAC in vitro,and then the functions of BM ECs were *** found that BM ECs were significantly decreased and damaged in AA *** failure and immune imbalance became more severe when the function of BM ECs was antagonized,whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA ***,BM ECs in AA patients were decreased and ***,dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes,which could be repaired by NAC in *** reactive oxygen species pathway was activated,and hematopoiesis-and immune-related signaling pathways were enriched in BM ECs of AA *** conclusion,our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA,suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.

关键词： aplastic anemia endothelial cell N-acetyl-L-cysteine hematopoietic stem cell T cell

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

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Frontiers of Medicine 2022年第3期16卷 459-466页

作者： Daijing Nie Jing Zhang Fang Wang Xvxin Li Lili Liu Wei Zhang Panxiang Cao Xue Chen Yang Zhang Jiaqi Chen Xiaoli Ma Xiaosu Zhou Qisheng Wu Ming Liu Mingyue Liu Wenjun Tian Hongxing Liu Division of Laboratory Medicine Hebei Yanda Lu Daopei HospitalLangfang 065201China Beijing Lu Daopei Institute of Hematology Beijing 100176China Division of Pathology&Laboratory Medicine Beijing Lu Daopei HospitalBeijing 100176China Department of Clinical Laboratory Medicine Shandong Provincial Hospital Affiliated to Shandong UniversityJinan 250021China

Whether Fanconi anemia(FA)heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family *** retrospectively analyzed rare possibly significant variations(PSVs)in the five most obligated FA genes,BRCA2,FANCA,FANCC,FANCD2,and FANCG,in 788 patients with aplastic anemia(AA)and hematologic ***-eight variants were identified in 66 patients(8.38%).FANCA was the most frequently mutated gene(n=29),followed by BRCA2(n=20).Compared with that of the ExAC East Asian dataset,the overall frequency of rare PSVs was higher in our cohort(P=0.016).BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia(P=0.038),and FANCA PSVs were significantly enriched in AA and AML subgroups(P=0.020;P=0.008).FA-PSV-positive MDS/AML patients had a higher tumor mutation burden,higher rate of cytogenetic abnormalities,less epigenetic regulation,and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients(P=0.024,P=0.029,P=0.024,and P=0.013).The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia aplastic anemia hematologic malignancy germline predisposition

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A New Immunosuppressive Therapy for Very Severe aplastic anemia in Children with Autoantibodies

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Current Medical Science 2022年第2期42卷 379-386页

作者： Zhong-jian WANG Hong-bo CHEN Fen ZHOU Hui YU Xiao-yan WU Ya-qing SHEN Yi-ning QIU Run-ming JIN Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the *** addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial *** the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August *** The median follow-up time for these patients was 24.9 *** overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at *** patients achieved complete remission and four patients met the criteria for partial response at the last *** median time to response for responders was 110 *** patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant *** and clonal evolution were not found in any of these *** estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,*** addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most *** The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.

关键词： aplastic anemia cyclosporine A prednisone immunosuppressive therapy children

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What is responsible for acute myocardial infarction in combination with aplastic anemia? A case report and literature review

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World Journal of Clinical Cases 2022年第32期10卷 11955-11966页

作者： Ya-Nan Zhao Wei-Wei Chen Xiao-Yu Yan Kun Liu Guo-Hui Liu Ping Yang Department of Cardiology China-Japan Union Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Cardiology Jilin Provincial Cardiovascular Research InstituteChangchun 130000Jilin ProvinceChina Department of Cardiology Jilin Provincial Engineering Laboratory for Endothelial Function and Genetic Diagnosis of Cardiovascular DiseaseChangchun 130000Jilin ProvinceChina

BACKGROUND aplastic anemia(AA)complicated with myocardial infarction(MI)is rare and associated with poor ***,we present a case of AA with recurrent acute MI(AMI)in a patient treated with cyclosporine A(CsA)and *** this patient,we suspect the long-term use of medication linked to platelets *** SUMMARY In 2017,a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 *** on his symptoms,medical history,blood tests,and findings from coronary angiography(CAG),the patient was diagnosed with acute anterior wall,ST-segment elevated MI,Killip II grade,AA,and *** 2021,the patient was readmitted to the hospital for 2 h due to chest *** the patient’s platelet count was 30×109/L and he had severe thrombocytopenia,we performed CAG following platelet *** coherence tomography revealed lipid plaque and thrombus mass in his right coronary *** antithrombotic approach was adjusted to employ only anticoagulants(factor Xa inhibitors)and adenosine diphosphate inhibitors(clopidogrel)after assessing the risk of bleeding/thrombotic ***-term follow-up revealed that the patient had made a good *** Patients with AA should be closely monitored for the risk of thrombosis and cardiovascularevents, particularly when taking stanozolol or CsA for an extended period of time.

关键词： aplastic anemia Myocardial infarction Cyclosporine A Stanozolol Percutaneous coronary intervention Case report

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Bone Marrow Angiogenesis in Patients Presenting with Differential Chinese Medicine Syndrome:Correlation with the Clinico-pathological Features of aplastic anemia

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Chinese Journal of Integrative Medicine 2013年第12期19卷 905-912页

作者：吴迪炯叶宝东胡致平沈一平沈建平林圣云陈明涛刘永林周郁鸿 Department of Hematology the First Affiliated HospitalZhejiang University of Traditional Chinese Medicine

Objective： To explore differences in bone marrow angiogenesis seen in aplastic anemia （AA） patients presenting with differential Chinese medicine （CM） syndrome, and to correlate these differences with clinical pathology. Methods： Thirty-five patients were enrolled, including 18 with ＂yang deficiency syndrome＂ and 17 with ＂yin deficiency syndrome.＂ Bone marrow biopsies and serum were collected. Microvessel density （MVD） and positive expression of vascular endothelial-derived growth factor （VEGF） were detected by immunohistochemisty. Hypoxia inducible factor -α （HIF-α ）, and VEGF expression were assayed by enzyme-linked immunoabsorbent assay （ELISA）, serum lactate dehydrogenase （LDH） was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin （IL）-2, IL-4, IL-6, IL-10, interferon （IFN）-＇y and tumor necrosis factor （TNF）-α. Results： Counts for leukocytes, absolute neutrophils and platelets in ＂yin deficiency syndrome＂ were lower than those found in ＂yang deficiency syndrome＂（P〈0.05）. MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in hA, especially in ＂yin deficiency syndrome＂（P〈0.01 or P〈0.05）. ＂Yin deficiency syndrome＂ displayed decreased VEGF and LDH expression, and enhanced expression of HIF-α as compared to ＂yang deficiency syndrome＂（P〈0.05）. Levels of IL-4 and IL-6 were higher in AA （P〈0.01）, but IL-10 was decreased （P〈0.05）. High TNF-c~ expression was seen in ＂yang deficiency syndrome＂ and IFN- γ expression was decreased in ＂yin deficiency syndrome＂ as compared with normals （P〈0.01 and P〈0.05, respectively）. Conclusion： AA patients have lower MVD than normals, especially in ＂yin deficiency syndrome.＂ MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN- γ were negatively associated while IL-6 and TNF- α were positively associated with MVD.

关键词： aplastic anemia angiogenesis Chinese medicine syndrome clinico-pathological vascular endothelial- derived growth factor tumor necrosis factor-αL

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Effects of Serum from aplastic anemia patients on the Expression of Cyclin D3 Isoform in Umbilical Cord Blood CD34^+ Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第3期24卷 236-238页

作者：孟凡凯谭细友刘文励孙汉英周剑锋李春蕊刘丹何莉孙岚 Department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Summary: The pathogenesis of aplastic anemia (AA) was explored and the effects of AA serum on the expression of crucial cyclin D isoform (cyclin D3) in umbilical cord blood hematopoietic stem/progenitor cells were observed. The CD34+ cells were isolated from the cord blood with MIDI-MACS Semi-solid methylcellulose culture technique was used to measure the formation of CFU-GM; The expression level of cyclin D3 was assayed by semi-quantitative RT-PCR and Western-blot after the hematopoietic stem/progenitor cells were incubated in AA serum. The results showed that the AA serum could inhibit the formation of CFU-GM and down regulate the expression level of the cyclin D3 at the mRNA and protein level respectively. In conclusion, the AA serum could inhibit the proliferation of hematopoietic stem cells and down regulate level of cyclin D3, which might be one mechanism of hematopoiesis inhibition in AA.

关键词： aplastic anemia hematopoiesis stem/progenitor cells cyclin D3

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Trichosporon asahii ankle cavity effusion infection in a patient with severe aplastic anemia

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Asian Pacific Journal of Tropical Medicine 2020年第6期13卷 278-280页

作者： Peng Zhang Zhenghai Yang Jie Li Xiaoning Li Department of Clinical Laboratory Yijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina

Rationale:Trichosporon,an anamorphic fungus,proliferates under high humidity,causing serious opportunistic infections collectively called *** the Trichosporon species causing trichosporonosis are Trichosporon(T.)asahii,***,*** *** concerns:A 38-year-old Chinese male with severe aplastic anemia was admitted due to multiple joints pain,poor appetite,and right ankle *** year earlier he had undergone allogeneic hematopoietic stem cell ***:*** infection and severe aplastic ***:Combined treatment of amphotericin B liposomes(55 mg/24 h)and voriconazole(200 mg/12 h)for 8 ***:The symptoms of the patient’s ankle were relieved and effusion cultures showed no ***:To the best of our knowledge,*** ankle cavity effusion infections are *** infections may be attributed to risk factors such as improper long-term use of antimicrobials for an underlying disease(e.g.,anemia,hypoalbuminemia).Attention should be paid to prevent and control Trichosporon infections in order to avoid comorbidities.

关键词： Trichosporon asahii Ankle cavity effusion aplastic anemia

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Bowel inflammatory presentations on computed tomography in adult patients with severe aplastic anemia during flared inflammatory episodes

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World Journal of Clinical Cases 2023年第3期11卷 576-597页

作者： Xi-Chen Zhao Cheng-Jiang Xue Hui Song Bin-Han Gao Fu-Shen Han Shu-Xin Xiao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Neurosurgery The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Radiology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Pneumology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

BACKGROUND Patients with severe aplastic anemia(SAA)frequently present with inflammatory episodes,and during flared inflammatory episodes,hematopoietic function is further *** gastrointestinal tract is the most common site for infectious and inflammatory diseases,and its structural and functional features confer on it the most potent capacity to affect hematopoietic and immune *** tomography(CT)is a readily accessible approach to provide highly useful information in detecting morphological changes and guiding further *** To explore CT imaging presentations of gut inflammatory damage in adult SAA patients during inflammatory *** We retrospectively evaluated the abdominal CT imaging presentations of 17hospitalized adult patients with SAA in search of the inflammatory niche when they presented with systemic inflammatory stress and exacerbated hematopoietic *** this descriptive manuscript,the characteristic images that suggested the presence of gastrointestinal inflammatory damage and related imaging presentations of individual patients were enumerated,analyzed and *** All eligible patients with SAA had CT imaging abnormalities that suggested the presence of an impaired intestinal barrier and increased epithelial *** inflammatory damages were concurrently present in the small intestine,the ileocecal region and the large *** readily identified imaging signs,such as bowel wall thickening with mural stratification(“water holo sign”,“fat holo sign”,intramural gas and subserosal pneumatosis)and mesenteric fat proliferation(fat stranding and“creeping fat sign”),fibrotic bowel wall thickening,“balloon sign”,rugged colonic configuration,heterogeneity in the bowel wall texture,and adhered and clustered small bowel loop(including various patterns of“abdominal cocoon”),occurred at a high incidence,which suggested that the damaged gastrointestinal tract is a common inflammatory niche res

关键词： aplastic anemia Computed tomography Bowel inflammatory damage Fat holo sign Balloon sign Abdominal cocoon

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