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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


  2 / 42407 MEDLINE  
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[PMID]:28462532
[Au] Autor:Daley SR; Teh C; Hu DY; Strasser A; Gray DHD
[Ad] Endereço:Infection and Immunity Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
[Ti] Título:Cell death and thymic tolerance.
[So] Source:Immunol Rev;277(1):9-20, 2017 05.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The differentiation of hematopoietic precursors into the many functionally distinct T-cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T-cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T-cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death. The regulation of thymocyte death is critical for the efficiency of thymic T-cell differentiation and the preservation of immune tolerance. A detailed knowledge of mechanisms that eliminate thymocytes from the T-cell repertoire is essential to understand the "logic" of T-cell selection in the thymus. This review focuses on the central role of the BCL-2 family of proteins in the apoptotic checkpoints that punctuate thymocyte differentiation and the consequences of defects in these processes.
[Mh] Termos MeSH primário: Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Linfócitos T/fisiologia
Timócitos/fisiologia
Timo/imunologia
[Mh] Termos MeSH secundário: Animais
Morte Celular
Diferenciação Celular
Microambiente Celular
Tolerância Central
Hematopoese
Seres Humanos
Receptores de Antígenos de Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins c-bcl-2); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1111/imr.12532


  3 / 42407 MEDLINE  
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[PMID]:28455312
[Au] Autor:Lopes N; Vachon H; Marie J; Irla M
[Ad] Endereço:Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille Cedex 09, France.
[Ti] Título:Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.
[So] Source:EMBO Mol Med;9(6):835-851, 2017 Jun.
[Is] ISSN:1757-4684
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration.
[Mh] Termos MeSH primário: Transplante de Medula Óssea/efeitos adversos
Células Epiteliais/fisiologia
Ligante RANK/administração & dosagem
Radioterapia/efeitos adversos
Regeneração
Timo/fisiologia
[Mh] Termos MeSH secundário: Animais
Linfotoxina-alfa/metabolismo
Camundongos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lymphotoxin-alpha); 0 (RANK Ligand)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.15252/emmm.201607176


  4 / 42407 MEDLINE  
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[PMID]:29326336
[Au] Autor:Leong WZ; Tan SH; Ngoc PCT; Amanda S; Yam AWY; Liau WS; Gong Z; Lawton LN; Tenen DG; Sanda T
[Ad] Endereço:Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore.
[Ti] Título:ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.
[So] Source:Genes Dev;31(23-24):2343-2360, 2017 12 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The oncogenic transcription factor induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified ( ) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. ARID5B positively regulates the expression of TAL1 and its regulatory partners. ARID5B also activates the expression of the oncogene Importantly, ARID5B is required for the survival and growth of T-ALL cells and forced expression of ARID5B in immature thymocytes results in thymus retention, differentiation arrest, radioresistance, and tumor formation in zebrafish. Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and in T-ALL, thereby contributing to T-cell leukemogenesis.
[Mh] Termos MeSH primário: Carcinogênese/genética
Proteínas de Ligação a DNA/metabolismo
Regulação Neoplásica da Expressão Gênica
Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular/genética
Proteínas de Ligação a DNA/genética
Elementos Facilitadores Genéticos/genética
Perfilação da Expressão Gênica
Genes myc/genética
Células HEK293
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Ligação Proteica
Domínios Proteicos/genética
Timócitos/metabolismo
Timo/crescimento & desenvolvimento
Fatores de Transcrição/genética
Ativação Transcricional/genética
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ARID5B protein, human); 0 (DNA-Binding Proteins); 0 (T-Cell Acute Lymphocytic Leukemia Protein 1); 0 (Transcription Factors); 135471-20-4 (TAL1 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1101/gad.302646.117


  5 / 42407 MEDLINE  
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[PMID]:27776542
[Au] Autor:Danan-Gotthold M; Guyon C; Giraud M; Levanon EY; Abramson J
[Ad] Endereço:The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
[Ti] Título:Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells.
[So] Source:Genome Biol;17(1):219, 2016 10 24.
[Is] ISSN:1474-760X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells that have a unique capacity to express, and subsequently present, a large fraction of body antigens. While the scope of promiscuously expressed genes by medullary thymic epithelial cells is well-established, relatively little is known about the expression of variants that are generated by co-transcriptional and post-transcriptional processes. RESULTS: Our study reveals that in comparison to other cell types, medullary thymic epithelial cells display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of promiscuous gene expression in these cells, plays a limited role in the regulation of these transcriptional processes. CONCLUSIONS: Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity.
[Mh] Termos MeSH primário: Células Epiteliais/imunologia
Edição de RNA/genética
Timo/imunologia
[Mh] Termos MeSH secundário: Processamento Alternativo/genética
Processamento Alternativo/imunologia
Animais
Autoantígenos/genética
Autoantígenos/imunologia
Diferenciação Celular/imunologia
Regulação da Expressão Gênica/imunologia
Seres Humanos
Camundongos
Edição de RNA/imunologia
Tolerância a Antígenos Próprios/imunologia
Linfócitos T/imunologia
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autoantigens); 0 (Transcription Factors)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29223568
[Au] Autor:Nishimura-Danjobara Y; Oyama K; Kanemaru K; Takahashi K; Yokoigawa K; Oyama Y
[Ad] Endereço:Department of Food Science, Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8513, Japan.
[Ti] Título:N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, affects cellular content of nonprotein thiol content in rat lymphocytes: Its relation with intracellular Zn .
[So] Source:Chem Biol Interact;280:28-32, 2018 Jan 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cellular actions of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum sensing molecule of bacteria, were studied on rat thymocytes using a flow cytometer with appropriate fluorescent dyes to elucidate the effects of ODHL on host cells. A bell-shaped concentration-response relation was observed in the ODHL-induced changes in cellular glutathione content ([GSH]i). ODHL concentration-dependently increased intracellular Zn levels ([Zn ]i) and cellular O content ([O ]i). The bell-shaped relation induced by ODHL can be explained as follows: a low concentration of ODHL is expected to induce moderate oxidative stress that intracellularly releases Zn by converting thiols to disulfides. A slight elevation of [Zn ]i may increase the [GSH]i. On the other hand, it is likely that a high concentration of ODHL causes severe oxidative stress that further causes both the decrease in [GSH]i and the increase in [Zn ]i. Excessive increase in [Zn ]i may augment oxidative stress that further decreases the [GSH]i. Other notable actions induced by ODHL included the elevation of [Zn ]i by Zn influx and the increase in [GSH]i under Zn -free conditions. Therefore, it is suggested that ODHL elicits diverse actions on host cells.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Homosserina/análogos & derivados
Estresse Oxidativo/efeitos dos fármacos
Compostos de Sulfidrila/metabolismo
Zinco/metabolismo
[Mh] Termos MeSH secundário: 4-Butirolactona/farmacologia
Animais
Apoptose/efeitos dos fármacos
Células Cultivadas
Glutationa/metabolismo
Homosserina/farmacologia
Linfócitos/citologia
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Masculino
Percepção de Quorum/efeitos dos fármacos
Ratos
Ratos Wistar
Timo/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Sulfhydryl Compounds); 6KA95X0IVO (Homoserine); GAN16C9B8O (Glutathione); J41CSQ7QDS (Zinc); OL659KIY4X (4-Butyrolactone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


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[PMID]:28468970
[Au] Autor:Chowdhary VR; Krogman A; Tilahun AY; Alexander MP; David CS; Rajagopalan G
[Ad] Endereço:Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905.
[Ti] Título:Concomitant Disruption of and Genes Facilitates the Development of Double Negative αß TCR Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.
[So] Source:J Immunol;198(11):4413-4424, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mature peripheral double negative T (DNT) cells expressing αß TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated and genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3 αß TCR thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3 αß TCR cells and Foxp3 T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
[Mh] Termos MeSH primário: Antígenos CD4/genética
Antígenos CD4/imunologia
Antígenos CD8/genética
Antígenos CD8/imunologia
Enterotoxinas/imunologia
Superantígenos/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Antígeno HLA-DR3/genética
Antígeno HLA-DR3/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Receptores de Antígenos de Linfócitos T alfa-beta/genética
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
Baço/citologia
Baço/imunologia
Timo/citologia
Timo/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (CD8 Antigens); 0 (Enterotoxins); 0 (HLA-DQ Antigens); 0 (HLA-DQ8 antigen); 0 (HLA-DR3 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Superantigens); 39424-53-8 (enterotoxin B, staphylococcal)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601991


  8 / 42407 MEDLINE  
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[PMID]:28741728
[Au] Autor:Ki S; Thyagarajan HM; Hu Z; Lancaster JN; Ehrlich LIR
[Ad] Endereço:Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
[Ti] Título:EBI2 contributes to the induction of thymic central tolerance in mice by promoting rapid motility of medullary thymocytes.
[So] Source:Eur J Immunol;47(11):1906-1917, 2017 11.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T-cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs. The chemokine receptor EBI2 governs localization of T cells, B cells, and dendritic cells (DCs) during immune responses in secondary lymphoid organs. However, the role of EBI2 in thymocyte development has not been elucidated. Here, we demonstrate that EBI2 is expressed by murine CD4 single positive (CD4SP) thymocytes and thymic DCs. EBI2 deficiency alters the TCR repertoire, but does not grossly impact thymocyte cellularity or subset distribution. EBI2 deficiency also impairs negative selection of OT-II TCR transgenic thymocytes responding to an endogenous self-antigen. Two-photon imaging revealed that EBI2 deficiency results in reduced migration and impaired medullary accumulation of CD4SP thymocytes. These data identify a role for EBI2 in promoting efficient thymic central tolerance.
[Mh] Termos MeSH primário: Diferenciação Celular/imunologia
Tolerância Central/imunologia
Receptores Acoplados a Proteínas-G/imunologia
Timócitos/imunologia
Timo/imunologia
[Mh] Termos MeSH secundário: Animais
Quimiotaxia de Leucócito/imunologia
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gpr183 protein, mouse); 0 (Receptors, G-Protein-Coupled)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180124
[Lr] Data última revisão:
180124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201747020


  9 / 42407 MEDLINE  
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[PMID]:29227084
[Au] Autor:Gudkova OO; Latyshko NV; Shandrenko SG
[Ti] Título:Amine oxidases as important agents of pathological processes of rhabdomyolysis in rats.
[So] Source:Ukr Biochem J;88(1):79-87, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:In this study we have tested an idea on the important role of amine oxidases (semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase) as an additional source of oxidative/carbonyl stress under glycerol-induced rhabdomyolysis, since the enhanced formation of reactive oxygen species and reactive carbonyl species in a variety of tissues is linked to various diseases. In our experiments we used the sensitive fluorescent method devised for estimation of amine oxidases activity in the rat kidney and thymus as targeted organs under rhabdomyolysis. We have found in vivo the multiple rises in activity of semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase (2-4.5 times) in the corresponding cell fractions, whole cells or their lysates at the 3-6th day after glycerol injection. Aberrant antioxidant activities depended on rhabdomyolysis stage and had organ specificity. Additional treatment of animals with metal chelator 'Unithiol' adjusted only the activity of antioxidant enzymes but not amine oxidases in both organs. Furthermore the in vitro experiment showed that Fenton reaction (hydrogen peroxide in the presence of iron) products alone had no effect on semicarbazide-sensitive amine oxidase activity in rat liver cell fraction whereas supplementation with methylglyoxal resulted in its significant 2.5-fold enhancement. Combined action of the both agents had additive effect on semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine and polyamine catabolism by amine oxidases is upregulated by oxidative and carbonyl stress factors directly under rhabdomyolysis progression, and the increase in catabolic products concentration contributes to tissue damage in glycerol-induced acute renal failure and apoptosis stimulation in thymus.
[Mh] Termos MeSH primário: Amina Oxidase (contendo Cobre)/metabolismo
Monoaminoxidase/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Rabdomiólise/enzimologia
[Mh] Termos MeSH secundário: Animais
Quelantes/farmacologia
Glicerol
Hepatócitos/efeitos dos fármacos
Hepatócitos/enzimologia
Hepatócitos/patologia
Peróxido de Hidrogênio/antagonistas & inibidores
Peróxido de Hidrogênio/farmacologia
Rim/efeitos dos fármacos
Rim/enzimologia
Rim/patologia
Fígado/efeitos dos fármacos
Fígado/enzimologia
Fígado/patologia
Masculino
Especificidade de Órgãos
Oxirredução
Carbonilação Proteica
Aldeído Pirúvico/antagonistas & inibidores
Aldeído Pirúvico/farmacologia
Ratos
Ratos Wistar
Rabdomiólise/induzido quimicamente
Rabdomiólise/tratamento farmacológico
Rabdomiólise/patologia
Semicarbazidas/antagonistas & inibidores
Semicarbazidas/farmacologia
Timo/efeitos dos fármacos
Timo/enzimologia
Timo/patologia
Unitiol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chelating Agents); 0 (Reactive Oxygen Species); 0 (Semicarbazides); 37QUC23K2X (carbamylhydrazine); 4076-02-2 (Unithiol); 722KLD7415 (Pyruvaldehyde); BBX060AN9V (Hydrogen Peroxide); EC 1.4.3.21 (Amine Oxidase (Copper-Containing)); EC 1.4.3.4 (Monoamine Oxidase); EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors); EC 1.5.3.- (polyamine oxidase); PDC6A3C0OX (Glycerol)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.079


  10 / 42407 MEDLINE  
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[PMID]:29246138
[Au] Autor:Ayeka PA; Bian Y; Githaiga PM; Zhao Y
[Ad] Endereço:International College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road, 312 Anshan Western Road, Nankai District, Tianjin, 300193, People's Republic of China.
[Ti] Título:The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice.
[So] Source:BMC Complement Altern Med;17(1):536, 2017 Dec 15.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional Chinese medicine (TCM) has attracted great attention for its antitumor and immunomodulatory activities, the mechanism of action of its polysaccharides is still unclear. Here we report the immunomodulatory activity of licorice polysaccharides in vivo. METHODS: The differential anticancer activities of licorice polysaccharides by tumorigenesis and immunomodulation was evaluated in vivo. Six weeks old, 120 CT-26 tumor bearing BALB/c mice, weighing 20 ± 2 g were used. They were randomly divided into six groups, three groups receiving high molecular weight (fraction A), low molecular weight (fraction B) polysaccharides and crude extract (fraction C); positive, negative and normal groups receiving cytoxin, saline and normal diet respectively. Weight of mice and tumors was determined and tumorigenicity assay calculated to determine the anticancer effects. Immunomodulatory potential was determined by immune organ indices, immune cell population and serum cytokine levels using immune organ weight and index, flow cytometry and cytokine/chemokine bead panel kit respectively. RESULTS: Licorice polysaccharides exhibited immunomodulatory activities in CT 26 tumor bearing BALB/c mice. The polysaccharides significantly suppressed tumor growth and increased immune organ index. Furthermore, the immunomodulatory effect was evident with activation of CD4 and CD8 immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels. CONCLUSION: In summary, licorice polysaccharide especially of low molecular weight exhibit anticancer and immunomodulatory activities by suppressing tumor growth and improving general health of mice. They also augment the thymus/spleen index and population of T lymphocytes. Furthermore, the polysaccharides enhance the levels of serum antitumor cytokines, IL 2, IL 6 and IL 7 while decreasing pro-tumor cytokine TNFα.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Glycyrrhiza uralensis
Fatores Imunológicos/farmacologia
Extratos Vegetais/farmacologia
Polissacarídeos/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Linhagem Celular Tumoral
Citocinas/sangue
Fatores Imunológicos/química
Camundongos
Camundongos Endogâmicos BALB C
Neoplasias Experimentais
Extratos Vegetais/química
Polissacarídeos/química
Baço/química
Baço/efeitos dos fármacos
Timo/química
Timo/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytokines); 0 (Immunologic Factors); 0 (Plant Extracts); 0 (Polysaccharides)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2030-7



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