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[PMID]:29349655
[Au] Autor:Lo WJ; Lin CL; Chang YC; Bai LY; Lin CY; Liang JA; Li LY; Chao LM; Chiu CF; Chen CM; Yeh SP
[Ad] Endereço:Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
[Ti] Título:Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.
[So] Source:Ann Hematol;97(4):697-707, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.
[Mh] Termos MeSH primário: Apoptose/efeitos da radiação
Células da Medula Óssea/efeitos da radiação
Aberrações Cromossômicas/efeitos da radiação
Células-Tronco Hematopoéticas/efeitos da radiação
Células Mesenquimais Estromais/efeitos da radiação
Lesões por Radiação/patologia
Irradiação Corporal Total/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Células-Tronco Adultas/efeitos da radiação
Células da Medula Óssea/citologia
Células da Medula Óssea/patologia
Diferenciação Celular/efeitos da radiação
Proliferação Celular/efeitos da radiação
Células Cultivadas
China
Transtornos Cromossômicos/etiologia
Transtornos Cromossômicos/patologia
Feminino
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/patologia
Hospitais Universitários
Seres Humanos
Leucemia/patologia
Leucemia/terapia
Masculino
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/patologia
Necrose
Lesões por Radiação/etiologia
Condicionamento Pré-Transplante/efeitos adversos
Células Tumorais Cultivadas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3231-y


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[PMID]:29335408
[Au] Autor:Ju JM; Jung MH; Nam G; Kim W; Oh S; Kim HD; Kim JY; Chang J; Lee SH; Park GS; Min CK; Lee DS; Kim MG; Choi K; Choi EY
[Ad] Endereço:Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.
[Ti] Título:Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen.
[So] Source:Nat Commun;9(1):225, 2018 01 15.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific thymic deletion escapee CD8 T cells exhibit effector differentiation potentials in the periphery and contribute to graft-versus-leukemia effects in the recipients of H60-mismatched BMT, regressing H60 hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Células-Tronco Hematopoéticas/imunologia
Antígenos de Histocompatibilidade Menor/imunologia
Timo/imunologia
[Mh] Termos MeSH secundário: Animais
Células Apresentadoras de Antígenos/imunologia
Células Apresentadoras de Antígenos/metabolismo
Transplante de Medula Óssea/métodos
Linfócitos T CD8-Positivos/metabolismo
Citometria de Fluxo
Células-Tronco Hematopoéticas/metabolismo
Camundongos Knockout
Camundongos Transgênicos
Antígenos de Histocompatibilidade Menor/genética
Antígenos de Histocompatibilidade Menor/metabolismo
Timócitos/imunologia
Timócitos/metabolismo
Timo/metabolismo
Imunologia de Transplantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Minor Histocompatibility Antigens); 0 (minor H antigen H60)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02665-z


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[PMID]:29178837
[Au] Autor:Spinozzi G; Calabria A; Brasca S; Beretta S; Merelli I; Milanesi L; Montini E
[Ad] Endereço:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
[Ti] Título:VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.
[So] Source:BMC Bioinformatics;18(1):520, 2017 Nov 25.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. RESULTS: Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). CONCLUSIONS: We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).
[Mh] Termos MeSH primário: Interface Usuário-Computador
[Mh] Termos MeSH secundário: Algoritmos
Terapia Genética
Vetores Genéticos/genética
Vetores Genéticos/metabolismo
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Lentivirus/genética
Lentivirus/fisiologia
Alinhamento de Sequência
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1937-9


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[PMID]:29311541
[Au] Autor:Stremmel C; Schuchert R; Wagner F; Thaler R; Weinberger T; Pick R; Mass E; Ishikawa-Ankerhold HC; Margraf A; Hutter S; Vagnozzi R; Klapproth S; Frampton J; Yona S; Scheiermann C; Molkentin JD; Jeschke U; Moser M; Sperandio M; Massberg S; Geissmann F; Schulz C
[Ad] Endereço:Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Marchioninistrasse 15, 81377, Munich, Germany.
[Ti] Título:Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.
[So] Source:Nat Commun;9(1):75, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.
[Mh] Termos MeSH primário: Movimento Celular
Células-Tronco Embrionárias/citologia
Macrófagos/citologia
Saco Vitelino/citologia
[Mh] Termos MeSH secundário: Animais
Circulação Sanguínea
Linhagem da Célula
Proliferação Celular
Embrião de Mamíferos/irrigação sanguínea
Embrião de Mamíferos/citologia
Embrião de Mamíferos/embriologia
Células-Tronco Hematopoéticas/citologia
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Microscopia Confocal
Fatores de Tempo
Saco Vitelino/embriologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02492-2


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[PMID]:28456747
[Au] Autor:He Q; Gao S; Lv J; Li W; Liu F
[Ad] Endereço:State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
[Ti] Título:BLOS2 maintains hematopoietic stem cells in the fetal liver via repressing Notch signaling.
[So] Source:Exp Hematol;51:1-6.e2, 2017 07.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) after their emergence in the aorta-gonad-mesonephros (AGM) region. We recently reported that the endolysosomal trafficking factor BLOS2, encoded by the Bloc1s2 gene, regulates HSC/hematopoietic progenitor cell emergence in the AGM region; however, whether it plays a role in the FL remains unknown. Here, we show that BLOS2 plays an essential role in the regulation of HSC proliferation and differentiation in the FL. Bloc1s2 depletion leads to elevated Notch signaling, with an increased frequency but weakened self-renewal ability of FL HSCs. Functional assays show that Bloc1s2 FL HSCs harbor impaired lymphoid and myeloid differentiation abilities. These findings reveal that balanced control of Notch signaling by BLOS2 is required for HSC homeostasis during FL hematopoiesis.
[Mh] Termos MeSH primário: Diferenciação Celular/fisiologia
Proliferação Celular/fisiologia
Feto/embriologia
Células-Tronco Hematopoéticas/metabolismo
Fígado/embriologia
Proteínas/metabolismo
Receptores Notch/metabolismo
[Mh] Termos MeSH secundário: Animais
Feto/citologia
Hematopoese Extramedular/fisiologia
Células-Tronco Hematopoéticas/citologia
Seres Humanos
Fígado/citologia
Camundongos
Camundongos Knockout
Proteínas/genética
Receptores Notch/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (BLOS2 protein, mouse); 0 (Proteins); 0 (Receptors, Notch)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180224
[Lr] Data última revisão:
180224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28452257
[Au] Autor:Boddu PC; Kadia TM
[Ad] Endereço:a Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
[Ti] Título:Updates on the pathophysiology and treatment of aplastic anemia: a comprehensive review.
[So] Source:Expert Rev Hematol;10(5):433-448, 2017 05.
[Is] ISSN:1747-4094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The past decade or longer has witnessed an acceleration in our understanding of previously developed immune system and clonal evolution mechanisms, and the genesis of more novel concepts of telomere attrition. Many of these concepts are steadily finding their way into translation in various aspects of clinical practice, and provide prospects to improve AA management and inform therapeutic strategy development. In this review, we intend to discuss the pathophysiology and treatments with an emphasis on most recent developments to provide an update on our understanding of disease mechanisms. Areas covered: A literature search was undertaken addressing various aspects of pathophysiology with a focus on the role of immune system repertoire, telomeres and mutational events surrounding AA. We also reviewed upon the temporal evolution of treatment strategies in AA to the contemporary management of today and commented briefly upon the more recently investigated novel therapies and their expanding niche especially in the transplant and salvage setting. Expert commentary: Immune-mediated destruction of hematopoietic stem and progenitor cells, leading to a marrow devoid of hematopoietic elements, and peripheral pancytopenia are the hallmarks of AA. Recent studies have shed light on another facet of the disease - as a clonal disorder characterized by karyotypic abnormalities, genomic instability, telomere attrition, and recurrent somatic mutations reminiscent of myeloid malignancies. Further understanding of this underlying pathophysiology can help in improving prognostication and treatment of this disease.
[Mh] Termos MeSH primário: Anemia Aplástica
[Mh] Termos MeSH secundário: Cariótipo Anormal
Anemia Aplástica/genética
Anemia Aplástica/metabolismo
Anemia Aplástica/fisiopatologia
Anemia Aplástica/terapia
Instabilidade Genômica
Células-Tronco Hematopoéticas/metabolismo
Seres Humanos
Telômero/genética
Telômero/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180225
[Lr] Data última revisão:
180225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1080/17474086.2017.1313700


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[PMID]:28450163
[Au] Autor:Ganuza M; Hadland B; Chabot A; Li C; Kang G; Bernstein I; McKinney-Freeman S
[Ad] Endereço:Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.
[Ti] Título:Murine hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo.
[So] Source:Exp Hematol;51:25-35.e6, 2017 07.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Hematopoietic stem and progenitor cells (HSPCs) sustain life-long hematopoiesis and are first detected in the embryo by transplantation at embryonic day 10.5 (E10.5). HSPCs are mesodermal in origin and ultimately emerge from a subset of arterial endothelium (i.e., hemogenic endothelium [HE]), which is highly concentrated in the aorta-gonad-mesonephros region of the midgestation embryo. Here, we used clonal ex vivo assays, in which endothelial cells isolated from the midgestation aorta and vitelline and umbilical arteries are co-cultured on supportive stroma, to show that only about 0.1%, 1.3%, and 0.29% of E9.5, E10.5, and E11.5 endothelium are functional HE, respectively. We further show high phenotypic and functional variability in the hematopoietic potential of individual hemogenic endothelial precursors. Using unique niche stroma capable of providing the signals necessary for definitive hematopoietic stem cell (dHSC) induction, we demonstrate that this variability in HE includes their potential to support phenotypic dHSCs. These data suggest the presence of a continuum of maturing HE with distinct hematopoietic potential or HE representative of a heterogeneous pool of precursors that give rise to HSPCs with disparate hematopoietic potential.
[Mh] Termos MeSH primário: Linhagem da Célula/fisiologia
Embrião de Mamíferos/embriologia
Células Endoteliais/metabolismo
Hematopoese/fisiologia
Células-Tronco Hematopoéticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Embrião de Mamíferos/citologia
Células Endoteliais/citologia
Células-Tronco Hematopoéticas/citologia
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180224
[Lr] Data última revisão:
180224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29205259
[Au] Autor:Mainardi C; Ebinger M; Enkel S; Feuchtinger T; Teltschik HM; Eyrich M; Schumm M; Rabsteyn A; Schlegel P; Seitz C; Schwarze CP; Müller I; Greil J; Bader P; Schlegel PG; Martin D; Holzer U; Döring M; Handgretinger R; Lang P
[Ad] Endereço:Department of Paediatric Oncology, Children's University Hospital, University of Padova, Padova, Italy.
[Ti] Título:CD34 selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation.
[So] Source:Br J Haematol;180(1):90-99, 2018 01.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Poor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34 selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n = 25) or mismatched related (n = 25) donors. Within 8 weeks, a significant increase in median neutrophil counts (0·6 vs. 1·516 × 10 /l, P < 0·05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs. 0, P < 0·0001 and <0·001), were observed, and 78·8% of patients resolved one or two of their cytopenias. 36·5% had a complete haematological response. Median lymphocyte counts for CD3 , CD3 CD4 , CD19 and CD56 increased 8·3-, 14·2-, 22.- and 1·6-fold. The rate of de novo acute graft-versus-host disease (GvHD) grade I-III was only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred. Patients who responded to SCB displayed a trend toward better overall survival (OS) (P = 0·07). Thus, administration of CD34 selected SCBs from alternative donors is safe and effective. Further studies are warranted to clarify the impact on immune reconstitution and survival.
[Mh] Termos MeSH primário: Sobrevivência de Enxerto
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos CD34/metabolismo
Linhagem da Célula
Criança
Pré-Escolar
Estudos de Coortes
Feminino
Doença Enxerto-Hospedeiro/etiologia
Hematopoese
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Transplante de Células-Tronco Hematopoéticas/métodos
Células-Tronco Hematopoéticas/metabolismo
Seres Humanos
Lactente
Masculino
Prognóstico
Retratamento
Estudos Retrospectivos
Quimeras de Transplante
Condicionamento Pré-Transplante
Transplante Homólogo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15012


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[PMID]:28468251
[Au] Autor:Han X; Xue X; Zhao Y; Li Y; Liu W; Zhang J; Fan S
[Ad] Endereço:Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China. hanxiaodan1202@gmail.com.
[Ti] Título:Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 29.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress.
[Mh] Termos MeSH primário: Coriandrum/química
Células-Tronco Hematopoéticas/efeitos dos fármacos
Células-Tronco Hematopoéticas/efeitos da radiação
Lesões por Radiação/tratamento farmacológico
Protetores contra Radiação/uso terapêutico
Rutina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/efeitos da radiação
Células Cultivadas
Dano ao DNA/efeitos dos fármacos
Células-Tronco Hematopoéticas/metabolismo
Células-Tronco Hematopoéticas/patologia
Masculino
Camundongos Endogâmicos C57BL
Estresse Oxidativo/efeitos dos fármacos
Estresse Oxidativo/efeitos da radiação
Lesões por Radiação/genética
Lesões por Radiação/metabolismo
Lesões por Radiação/patologia
Radiação Ionizante
Protetores contra Radiação/química
Espécies Reativas de Oxigênio/metabolismo
Rutina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiation-Protective Agents); 0 (Reactive Oxygen Species); 5G06TVY3R7 (Rutin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


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[PMID]:29309785
[Au] Autor:Pathak V; Colah R; Ghosh K
[Ad] Endereço:Department of Haematogenetics, National Institute of Immunohaematology (ICMR), KEM Hospital, Parel 400012, Mumbai, India.
[Ti] Título:Plasmodium falciparum malaria skews globin gene expression balance in in-vitro haematopoietic stem cell culture system: Its implications in malaria associated anemia.
[So] Source:Exp Parasitol;185:29-38, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the pathophysiology and associated host parasite interactions of the malaria infection is the prerequisite for developing effective prevention and treatment strategies. The exact mechanism underlying malaria associated ineffective and dyserythropoiesis is not yet fully understood. Being an important protein, haemoglobin serves as the main amino acid reservoir available to the intra-erythrocytic plasmodium. It is important to check the expression profiling of globin genes which may help us to understand host parasite interactions and its potential contribution to both infection and disease. Here, an in-vitro culture system was used to study the effect of different doses of Plasmodium falciparum on haematopoietic stem cell expansion, differentiation and expression of globin genes. Upon exposure to the different doses of P. falciparum parasites of strains 3D7, Dd2 and RKL9 (intact and lysed form) at different stages of erythroid development, cells demonstrated suppression in growth and differentiation. At almost all stages of erythroid development upon parasite exposure, the γ globin gene was found to be downregulated and the α/ß as well as α/non- α globin mRNA ratios in late stage erythroid cells were found to be reduced (p < .01) compared to the untreated controls. The imbalance in globin chain expression might be considered as one of the factors involved in malaria associated inappropriate erythropoietic responses.
[Mh] Termos MeSH primário: Anemia/etiologia
Regulação da Expressão Gênica/genética
Globinas/genética
Células-Tronco Hematopoéticas/parasitologia
Malária Falciparum/genética
[Mh] Termos MeSH secundário: Anemia/genética
Anemia/metabolismo
Antígenos CD34/sangue
Biomarcadores/metabolismo
Células Cultivadas
Eritrócitos/parasitologia
Eritrócitos/patologia
Células Eritroides/imunologia
Sangue Fetal/citologia
Globinas/metabolismo
Células-Tronco Hematopoéticas/metabolismo
Hemólise
Interações Hospedeiro-Parasita/genética
Seres Humanos
Malária Falciparum/complicações
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Biomarkers); 9004-22-2 (Globins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE



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