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Pesquisa : D02.455.426.559.847.117.159 [Categoria DeCS]
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  1 / 6241 MEDLINE  
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[PMID]:29267673
[Au] Autor:Yan Y; Qi S; Gong SQ; Shang G; Zhao Y
[Ad] Endereço:Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Pediatric Dentistry, Shanghai, China.
[Ti] Título:Effect of CRABP2 on the proliferation and odontoblastic differentiation of hDPSCs.
[So] Source:Braz Oral Res;31:e112, 2017 Dec 18.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Cellular retinoic acid-binding protein 2 (CRABP2) has been detected in several organs during embryonic development. Recent studies have demonstrated that CRABP2 plays important roles in the retinoic acid, ß-catenin and Notch signaling pathways, as well as in the interaction between epithelial and mesenchymal cells, which are important for human dental pulp stem cells (hDPSCs) and tooth development. In the present study, the expression of CRABP2 during mouse molar development and the role of CRABP2 in hDPSC odontoblastic differentiation were evaluated. CRABP2 was gradually decreased during the development of the first maxillary molar, which exhibited the same trend as the expression of CRABP2 during the odontoblastic induction of hDPSCs. CRABP2 knockdown inhibited the proliferative ability of hDPSCs, while it enhanced odontoblastic differentiation via promoting mineralization nodule formation and upregulating the activity of alkaline phosphatase and the expression of mineralization-related genes. The present study uncovered a novel function of CRABP2 in hDPSCs. Our data suggest that CRABP2 may act as a regulator during the proliferation and differentiation of hDPSCs.
[Mh] Termos MeSH primário: Diferenciação Celular/fisiologia
Proliferação Celular/fisiologia
Polpa Dentária/citologia
Odontoblastos/fisiologia
Receptores do Ácido Retinoico/fisiologia
Células-Tronco/fisiologia
[Mh] Termos MeSH secundário: Fosfatase Alcalina
Análise de Variância
Animais
Antraquinonas
Western Blotting
Comunicação Celular
Células Cultivadas
Corantes
Regulação para Baixo/fisiologia
Feminino
Seres Humanos
Imuno-Histoquímica
Masculino
Camundongos Endogâmicos C57BL
Receptores do Ácido Retinoico/análise
Valores de Referência
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Coloring Agents); 0 (Receptors, Retinoic Acid); 0 (retinoic acid binding protein II, cellular); 60MEW57T9G (alizarin); EC 3.1.3.1 (Alkaline Phosphatase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


  2 / 6241 MEDLINE  
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Costa, Carlos Alberto de Souza
Texto completo SciELO Brasil
[PMID]:29267665
[Au] Autor:Leite MLAES; Soares DG; Basso FG; Hebling J; Costa CAS
[Ad] Endereço:Universidade Estadual Paulista "Júlio de Mesquita Filho" - Unesp, School of Dentistry, Department of Dental Materials and Prosthodontics, Araraquara, SP, Brazil.
[Ti] Título:Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells.
[So] Source:Braz Oral Res;31:e104, 2017 Dec 18.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to evaluate the bioactivity and cytocompatibility of simvastatin (SV) applied to MDPC-23 odontoblast-like cells. For this purpose, MDPC-23 cells were seeded in 96-well plates and submitted to treatments with 0.01 or 0.1 µM of SV for 24 h, 72 h or continuously throughout the experimental protocol. The negative control group (NC) was maintained in DMEM. Cell viability (MTT), ALP activity (thymolphthalein monophosphate), and mineralized matrix deposition (alizarin red) were analyzed at several time points. The data were submitted to ANOVA and Tukey's test (α = 0.05). Although cell viability was observed in the groups treated with SV, these groups did not differ from the NC up to 7 days. There was a reduction in cell viability for the groups treated with 0.1 µM of SV for 72 h, and submitted to continuous mode after 14 days. A significant increase in ALP activity occurred in the group treated with 0.01 µM of SV for 24 h, compared with the NC; however, only the group treated with 0.1 µM of SV in continuous mode reduced the ALP activity, in comparison with the NC. After 14 days, only continuous treatment with 0.1 µM of SV did not differ from NC, whereas the other experimental groups showed increased mineralized matrix deposition. Thus, it was concluded that low concentrations of simvastatin were bioactive and cytocompatible when applied for short periods to cultured MDPC-23 odontoblast-like cells.
[Mh] Termos MeSH primário: Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
Odontoblastos/efeitos dos fármacos
Sinvastatina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antraquinonas
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Ratos
Valores de Referência
Timolftaleína/análogos & derivados
Timolftaleína/análise
Fatores de Tempo
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 17016-43-2 (thymolphthalein monophosphate); 60MEW57T9G (alizarin); AGG2FN16EV (Simvastatin); YG5I28WSQP (Thymolphthalein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:28946118
[Au] Autor:Rybczynska-Tkaczyk K; Swiecilo A; Szychowski KA; Kornillowicz-Kowalska T
[Ad] Endereço:Department of Environmental Microbiology, Laboratory of Mycology, The University of Life Sciences, Leszczynskiego Street 7, Lublin 20-069, Poland. Electronic address: kamila.rybczynska-tkaczyk@up.lublin.pl.
[Ti] Título:Comparative study of eco- and cytotoxicity during biotransformation of anthraquinone dye Alizarin Blue Black B in optimized cultures of microscopic fungi.
[So] Source:Ecotoxicol Environ Saf;147:776-787, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to select optimal conditions (C and N sources, initial pH and temperature) for biodecolorization of 0.03% anthraquinone dye Alizarin Blue Black B (ABBB) by microscopic fungi: Haematonectria haematococca BwIII43, K37 and Trichoderma harzianum BsIII33. The phenolic compounds, phytotoxicity (Lepidium sativum L.), biotoxicity (Microtox), cytotoxicity and yeast viability assay were performed to determine the extent of ABBB detoxification. Biodecolorization and detoxification of 0.03% ABBB in H. haematococca BwIII43 and T. harzianum BsIII33 cultures was correlated with extracellular oxidoreductases activity. In turn, secondary products, toxic to human fibroblasts and respiring sod1 Saccharomyces cerevisiae cells, were formed in H. haematococca K37 strain cultures, despite efficient decolorization.
[Mh] Termos MeSH primário: Antraquinonas/toxicidade
Corantes/toxicidade
Poluentes Químicos da Água/toxicidade
Purificação da Água/métodos
Leveduras/metabolismo
[Mh] Termos MeSH secundário: Antraquinonas/análise
Biodegradação Ambiental
Biotransformação
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Corantes/análise
Seres Humanos
Lepidium sativum/efeitos dos fármacos
Oxirredução
Testes de Toxicidade/métodos
Poluentes Químicos da Água/análise
Leveduras/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Coloring Agents); 0 (Water Pollutants, Chemical)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:29374471
[Au] Autor:Abu N; Zamberi NR; Yeap SK; Nordin N; Mohamad NE; Romli MF; Rasol NE; Subramani T; Ismail NH; Alitheen NB
[Ad] Endereço:UKM Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Yaacob Latif, Bandar Tun Razak 56000 Cheras, Kuala Lumpur, Malaysia.
[Ti] Título:Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.
[So] Source:BMC Complement Altern Med;18(1):31, 2018 Jan 27.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. METHODS: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. RESULTS: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. CONCLUSION: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.
[Mh] Termos MeSH primário: Aldeídos/farmacologia
Antraquinonas/farmacologia
Antineoplásicos/farmacologia
Neoplasias da Mama/metabolismo
Fatores Imunológicos/farmacologia
Morinda/química
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Aldeídos/química
Aldeídos/toxicidade
Animais
Antraquinonas/química
Antraquinonas/toxicidade
Antineoplásicos/química
Antineoplásicos/toxicidade
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Feminino
Seres Humanos
Fatores Imunológicos/química
Fatores Imunológicos/toxicidade
Células MCF-7
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Extratos Vegetais/química
Extratos Vegetais/toxicidade
Testes de Toxicidade Subcrônica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); 0 (Anthraquinones); 0 (Antineoplastic Agents); 0 (Immunologic Factors); 0 (Plant Extracts); 0 (nordamnacanthal)
[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:180129
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-018-2102-3


  5 / 6241 MEDLINE  
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[PMID]:29331654
[Au] Autor:Xu Y; Mao X; Qin B; Peng Y; Zheng J
[Ad] Endereço:Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
[Ti] Título:In vitro and in vivo metabolic activation of rhein and characterization of glutathione conjugates derived from rhein.
[So] Source:Chem Biol Interact;283:1-9, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Rhein (RH), 4,5-dihydroxyanthrauinone-2-carboxylic acid, is found in rhubarb (Dahuang), a traditional herbal medicine. RH has reportedly demonstrated multiple pharmacologic properties. Previous studies have also shown that RH induced hepatotoxicity, but the mechanisms of the adverse effect remain unknown. The major objective of the present study was to study the metabolic pathways of RH in order to identify potential reactive metabolites. One mono-hydroxylation metabolite (M1) was detected in urine and bile of rats given RH. M1 was also observed in rat and human liver microsomal incubations after exposure to RH. A total of three (GSH) conjugates (M2, M3 and M5) were detected in bile of rats treated with RH. We concluded that M2-M3 were directly derived from parent compound RH through spontaneous reaction with GSH. M5 was derived from M1 by reaction with GSH, which required cytoslic GSTs. M5 was further metabolized to the corresponding NAC conjugate (mercapturic acid) and was excreted in urine. P450 2C9 was mainly involved in the oxidation of RH.
[Mh] Termos MeSH primário: Antraquinonas/metabolismo
Glutationa/química
[Mh] Termos MeSH secundário: Acetilcisteína/química
Animais
Antraquinonas/química
Antraquinonas/farmacologia
Antraquinonas/urina
Bile/química
Bile/efeitos dos fármacos
Bile/metabolismo
Cromatografia Líquida de Alta Pressão
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Seres Humanos
Masculino
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
Ratos
Ratos Sprague-Dawley
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Recombinant Proteins); 9035-51-2 (Cytochrome P-450 Enzyme System); GAN16C9B8O (Glutathione); WYQ7N0BPYC (Acetylcysteine); YM64C2P6UX (rhein)
[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:180115
[St] Status:MEDLINE


  6 / 6241 MEDLINE  
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[PMID]:29180865
[Au] Autor:Zeng D; Zhang X; Wang X; Cao L; Zheng A; Du J; Li Y; Huang Q; Jiang X
[Ad] Endereço:Department of Prosthodontics, School of Medicine, Ninth People's Hospital affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.
[Ti] Título:Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone regeneration.
[So] Source:Int J Nanomedicine;12:8277-8287, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Our previous study revealed that mesoporous Ca-Si-based materials exhibited excellent osteoconduction because dissolved ions could form a layer of hydroxycarbonate apatite on the surface of the materials. However, the biological mechanisms underlying bone regeneration were largely unknown. The main aim of this study was to evaluate the osteogenic ability of large-pore mesoporous Ca-Si-based bioceramics (LPMSCs) by alkaline phosphatase assay, real-time PCR analysis, von Kossa, and alizarin red assay. Compared with large-pore mesoporous silica (LPMS), LPMSCs had a better effect on the osteogenic differentiation of dental pulp cells. LPMSC-2 and LPMSC-3 with higher calcium possessed better osteogenic abilities than LPMSC-1, which may be related to the calcium-sensing receptor pathway. Furthermore, the loading capacity for recombinant human platelet-derived growth factor-BB was satisfactory in LPMSCs. In vivo, the areas of new bone formation in the calvarial defect repair were increased in the LPMSC-2 and LPMSC-3 groups compared with the LPMSC-1 and LPMS groups. We concluded that LPMSC-2 and LPMSC-3 possessed both excellent osteogenic abilities and satisfactory loading capacities, which may be attributed to their moderate Ca/Si molar ratio. Therefore, LPMSCs with moderate Ca/Si molar ratio might be potential alterative grafts for craniomaxillofacial bone regeneration.
[Mh] Termos MeSH primário: Regeneração Óssea/fisiologia
Cálcio/química
Teste de Materiais/métodos
Dióxido de Silício/química
[Mh] Termos MeSH secundário: Fosfatase Alcalina/metabolismo
Animais
Antraquinonas/análise
Antraquinonas/metabolismo
Materiais Biocompatíveis/química
Compostos de Cálcio/química
Diferenciação Celular
Cerâmica/química
Polpa Dentária/citologia
Seres Humanos
Masculino
Naftalenos/farmacologia
Nitratos/química
Osteogênese/efeitos dos fármacos
Fator de Crescimento Derivado de Plaquetas/genética
Fator de Crescimento Derivado de Plaquetas/metabolismo
Porosidade
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
Crânio/lesões
Crânio/fisiologia
Tecidos Suporte
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Biocompatible Materials); 0 (Calcium Compounds); 0 (N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine); 0 (Naphthalenes); 0 (Nitrates); 0 (Platelet-Derived Growth Factor); 3F3AT0Q12H (Alizarin Red S); 7631-86-9 (Silicon Dioxide); EC 3.1.3.1 (Alkaline Phosphatase); NF52F38N1N (calcium nitrate); SY7Q814VUP (Calcium)
[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:171129
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S144528


  7 / 6241 MEDLINE  
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[PMID]:28745519
[Au] Autor:Gonçalves RS; Silva EL; Hioka N; Nakamura CV; Bruschi ML; Caetano W
[Ad] Endereço:a Department of Chemistry , State University of Maringá , Maringá , Brazil.
[Ti] Título:An optimized protocol for anthraquinones isolation from Rhamnus frangula L.
[So] Source:Nat Prod Res;32(3):366-369, 2018 Feb.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Different from works described in the literature, which use expansive analytical methods to separation of anthraquinones derivatives (AQs), this communication reported a simple and inexpensive methodology to get them. In this way, the expensive commercial AQs: Chrysophanol, physcione and emodine were extracted from plant material (Rhamnus frangula L.) and isolated by classical column chromatography technique under optimised binary mobile phase gradients (CHCl : AcOEt(a), a = 1 to 5%) in excellent yields.
[Mh] Termos MeSH primário: Antraquinonas/isolamento & purificação
Frangula/química
Rhamnus/química
[Mh] Termos MeSH secundário: Antraquinonas/análise
Cromatografia/métodos
Emodina/análogos & derivados
Emodina/análise
Emodina/isolamento & purificação
Métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); H6PT94IV61 (physcione); KA46RNI6HN (Emodin); N1ST8V8RR2 (chrysophanic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1356836


  8 / 6241 MEDLINE  
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[PMID]:29273567
[Au] Autor:Huang AM; Lin KW; Lin WH; Wu LH; Chang HC; Ni C; Wang DL; Hsu HY; Su CL; Shih C
[Ad] Endereço:Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
[Ti] Título:1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.
[So] Source:Chem Biol Interact;281:60-68, 2018 Feb 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation.
[Mh] Termos MeSH primário: Antraquinonas/toxicidade
Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Adenina/análogos & derivados
Adenina/farmacologia
Antraquinonas/síntese química
Antraquinonas/química
Caspase 3/metabolismo
Linhagem Celular Tumoral
Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos
Seres Humanos
Macrolídeos/farmacologia
Microscopia Eletrônica de Transmissão
Proteínas Associadas aos Microtúbulos/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (MAP1LC3A protein, human); 0 (Macrolides); 0 (Microtubule-Associated Proteins); 0 (Reactive Oxygen Species); 5142-23-4 (3-methyladenine); 88899-55-2 (bafilomycin A1); EC 3.4.22.- (Caspase 3); JAC85A2161 (Adenine); WYQ7N0BPYC (Acetylcysteine)
[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:171224
[St] Status:MEDLINE


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[PMID]:29216561
[Au] Autor:Tapeinou A; Giannopoulou E; Simal C; Hansen BE; Kalofonos H; Apostolopoulos V; Vlamis-Gardikas A; Tselios T
[Ad] Endereço:Department of Chemistry, University of Patras, GR-26504, Rion, Greece.
[Ti] Título:Design, synthesis and evaluation of an anthraquinone derivative conjugated to myelin basic protein immunodominant (MBP ) epitope: Towards selective immunosuppression.
[So] Source:Eur J Med Chem;143:621-631, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described. The compound consists of the myelin basic protein (MBP) 85-99 immunodominant epitope (MBP ) coupled to an anthraquinone type molecule (AQ) via a disulfide (S-S) and 6 amino hexanoic acid (Ahx) residues (AQ-S-S-(Ahx) MBP ). AQ-S-S-(Ahx) MBP could bind to HLA II DRB1*-1501 antigen with reasonable affinity (IC of 56 nM) The compound was localized to the nucleus of Jurkat cells (an immortalized line of human T lymphocytes) 10 min after its addition to the medium and resulted in lowered Bcl-2 levels (apoptosis). Entrance of the compound was abolished when cells were pre-treated with cisplatin, an inhibitor of thioredoxin reductase. Accordingly, levels of free thiols were elevated in the culture supernatants of Jurkat cells exposed to N-succinimidyl 3-(2-pyridyldithio) propionate coupled to (Ahx) MBP via a disulphide (SPDP-S-S-(Ahx) MBP ) but returned to normal after exposure to cisplatin. These results raise the possibility of AQ-S-S-(Ahx) MBP being used as an eliminator of encephalitogenic T cells via implication of the thioredoxin system for the generation of the toxic, thiol-containing moiety (AQ-SH). Future experiments would ideally determine whether SPDP-S-S-(Ahx) MBP could incorporate into HLA II DRB1*-1501 tetramers and neutralize encephalitogenic T cell lines sensitized to MBP .
[Mh] Termos MeSH primário: Antraquinonas/farmacologia
Desenho de Drogas
Epitopos/farmacologia
Imunossupressão
Proteína Básica da Mielina/farmacologia
Fragmentos de Peptídeos/farmacologia
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antraquinonas/síntese química
Antraquinonas/química
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Relação Dose-Resposta a Droga
Epitopos/química
Células HEK293
Seres Humanos
Células Jurkat
Estrutura Molecular
Proteína Básica da Mielina/química
Fragmentos de Peptídeos/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Epitopes); 0 (Myelin Basic Protein); 0 (Peptide Fragments); 0 (myelin basic protein 85-99)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


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[PMID]:28455615
[Au] Autor:Meng S; Wu H; Wang L; Zhang B; Bai L
[Ad] Endereço:State Key Laboratory of Microbial Metabolism and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
[Ti] Título:Enhancement of antibiotic productions by engineered nitrate utilization in actinomycetes.
[So] Source:Appl Microbiol Biotechnol;101(13):5341-5352, 2017 Jul.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved. Moreover, heterologous expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in an increased actinorhodin production. Further incorporation of a nitrite-specific transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher actinorhodin production. Similarly, the titers of salinomycin, ansamitocin, lincomycin, and geldanamycin were increased with the integration of this cassette to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the nitrate-stimulating effect to many antibiotic producers by utilizing the nirC-ABC2 cassette for enhanced nitrate utilization, which could become a general tool for titer increase of antibiotics in actinomycetes.
[Mh] Termos MeSH primário: Actinobacteria/genética
Antibacterianos/biossíntese
Lincomicina/biossíntese
Nitratos/metabolismo
Streptomyces/genética
[Mh] Termos MeSH secundário: Actinobacteria/metabolismo
Proteínas de Transporte de Ânions/genética
Antraquinonas/metabolismo
Antibacterianos/metabolismo
Proteínas de Bactérias/genética
Regulação Bacteriana da Expressão Gênica
Nitrogênio/metabolismo
Piranos/metabolismo
Streptomyces/metabolismo
Streptomyces coelicolor/genética
Transativadores/genética
Transativadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Anthraquinones); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (GlnR protein, Streptomyces coelicolor); 0 (NirC protein, Bacteria); 0 (Nitrates); 0 (Pyrans); 0 (Trans-Activators); 62UXS86T64 (salinomycin); BOD072YW0F (Lincomycin); G4HH387T6Z (actinorhodin); N762921K75 (Nitrogen)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-017-8292-7



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