Base de dados : MEDLINE
Pesquisa : D02.172.300 [Categoria DeCS]
Referências encontradas : 1015 [refinar]
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[PMID]:28625734
[Au] Autor:Gao J; Chen M; Ren XC; Zhou XB; Shang Q; Lu WQ; Luo P; Jiang ZH
[Ad] Endereço:State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau; Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau; Livzon Pharmaceutical Group Inc., Zhuhai, China; National Eng
[Ti] Título:Synthesis and cardiomyocyte protection activity of crocetin diamide derivatives.
[So] Source:Fitoterapia;121:106-111, 2017 Sep.
[Is] ISSN:1873-6971
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A series of novel diamide derivatives (2-8) of crocetin (1) were synthesized and evaluated for their cardioprotective activity in vitro. Using well-established model of hypoxia-induced injury in H9c2 cells, we investigated the effects of 9 compounds and positive drug nicorandil on cellular cytotoxicity by MTT assay, mitochondrial viable staining, LDH activity and mitochondrial membrane potential (MMP). Among the new derivatives, compounds 3 and 4 with good liposolubility showed significantly potent activity than crocetin (1) against hypoxia-induced cytotoxicity. Further mechanisms studies indicated that the cardioprotective effect of compounds 3 and 4 was due to these abilities by decreasing LDH release, preserving mitochondrial viabilities and reducing oxidative stress-induced depolarization of MMP. Our results demonstrated that compounds 3 and 4 as a new class of crocetin diamide derivatives could be developed as potential agents in our further drug development studies for ischemic heart disease.
[Mh] Termos MeSH primário: Carotenoides/farmacologia
Diamida/farmacologia
Miócitos Cardíacos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Carotenoides/síntese química
Hipóxia Celular
Linhagem Celular
Diamida/síntese química
L-Lactato Desidrogenase/metabolismo
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Estrutura Molecular
Estresse Oxidativo/efeitos dos fármacos
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
10465-78-8 (Diamide); 20TC155L9C (crocetin); 36-88-4 (Carotenoids); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE


  2 / 1015 MEDLINE  
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[PMID]:28366823
[Au] Autor:Yamauchi K; Ebihara Y; Kawakami Y
[Ad] Endereço:Department of Laboratory Medicine, Faculty of Medicine, University of Tsukuba, Japan; Department of Medical Sciences, Faculty of Medicine, University of Tsukuba, Japan. Electronic address: yamauchi@md.tsukuba.ac.jp.
[Ti] Título:Redox status of serum apolipoprotein E and its impact on HDL cholesterol levels.
[So] Source:Clin Biochem;50(13-14):777-783, 2017 Sep.
[Is] ISSN:1873-2933
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Apolipoprotein E (apoE) is closely involved in the pathogenesis of apoE-related diseases, such as Alzheimer's disease and cardiovascular disease. The redox modulation of cysteine-thiols in a protein is involved in various pathophysiological regulations; however, that of apoE has not been studied in detail. Herein, we devised an analytical method to determine the redox status of serum apoE and assessed its relation to serum cholesterol levels and apoE phenotype. METHODS: The present method was based on a band shift assay, using a photocleavable maleimide-conjugated polyethylene glycol. RESULTS: The basic characteristics of the present method were found to be satisfactory to determine the redox status of serum apoE quantitatively. Serum apoE was separated into its reduced-form (r-), non-reduced-form (nr-), apoE-AII complex, and homodimer using this method. R-apoE could be detected as a 40-kDa band, whereas nr-apoE remained as monomeric apoE. R-apoE displayed a preference for VLDL; however, the levels showed the correlation with HDL-cholesterol levels (p<0.005). Redox status of serum apoE was significantly different among apoE phenotypes. The quantitative ratios of nr-apoE to total apoE in serum from subjects with apoE4/E3 were higher than in serum from subjects with apoE3/E3 (p<0.0001) and apoE3/E2 (p<0.001). CONCLUSION: The redox status of serum apoE might be related to the synthesis of HDL. The information concerning the redox status of serum apoE provided by the present method may be a potent indicator to evaluate various apoE-related diseases.
[Mh] Termos MeSH primário: Apolipoproteínas E/sangue
HDL-Colesterol/sangue
[Mh] Termos MeSH secundário: Apolipoproteína A-II/sangue
Apolipoproteína A-II/química
Apolipoproteína A-II/isolamento & purificação
Apolipoproteína E2/sangue
Apolipoproteína E2/química
Apolipoproteína E2/isolamento & purificação
Apolipoproteína E3/sangue
Apolipoproteína E3/química
Apolipoproteína E3/isolamento & purificação
Apolipoproteína E4/sangue
Apolipoproteína E4/química
Apolipoproteína E4/isolamento & purificação
Apolipoproteínas E/química
Apolipoproteínas E/isolamento & purificação
HDL-Colesterol/química
Cisteína/química
Diamida/química
Dimerização
Ditiotreitol/química
Ensaio de Desvio de Mobilidade Eletroforética
Células HEK293
Seres Humanos
Indicadores e Reagentes/química
Peso Molecular
Oxirredução
Processos Fotoquímicos
Polietilenoglicóis/química
Solubilidade
Reagentes de Sulfidrila/química
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoprotein A-II); 0 (Apolipoprotein E2); 0 (Apolipoprotein E3); 0 (Apolipoprotein E4); 0 (Apolipoproteins E); 0 (Cholesterol, HDL); 0 (Indicators and Reagents); 0 (Sulfhydryl Reagents); 0 (apo E-apo A-II complex); 10465-78-8 (Diamide); 30IQX730WE (Polyethylene Glycols); K848JZ4886 (Cysteine); T8ID5YZU6Y (Dithiothreitol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE


  3 / 1015 MEDLINE  
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[PMID]:28242353
[Au] Autor:Wezena CA; Krafczyk J; Staudacher V; Deponte M
[Ad] Endereço:Department of Parasitology, Ruprecht-Karls University, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
[Ti] Título:Growth inhibitory effects of standard pro- and antioxidants on the human malaria parasite Plasmodium falciparum.
[So] Source:Exp Parasitol;180:64-70, 2017 Sep.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The redox metabolism of the malaria parasite Plasmodium falciparum and its human host has been suggested to play a central role for parasite survival and clearance. A common approach to test hypotheses in redox research is to challenge or rescue cells with pro- and antioxidants. However, quantitative data on the susceptibility of infected erythrocytes towards standard redox agents is surprisingly scarce. Here we determined the IC values of P. falciparum strains 3D7 and Dd2 for a set of redox agents using a SYBR green-based growth assay. Parasite killing in this assay required extremely high concentrations of hydrogen peroxide with a millimolar IC value, whereas IC values for tert-butyl hydroperoxide and diamide were between 67 and 121 µM. Thus, in contrast to tert-butyl hydroperoxide and the disulfide-inducing agent diamide, the host-parasite unit appears to be very robust against challenges with hydrogen peroxide with implications for host defense mechanisms. N-acetylcysteine, ascorbate, and dithiothreitol also had antiproliferative instead of growth-promoting effects with IC values around 12, 3 and 0.4 mM, respectively. So-called antioxidants can therefore also inhibit parasite growth with implications for clinical trials and studies on 'oxidative stress'. Furthermore, the addition of reductants to parasite cultures resulted in the gelation of albumin, the formation of methemoglobin and hemolysis. These effects can alter the fluorescence in SYBR green assays and have to be taken into account for the determination of IC values. In summary, standard oxidants and reductants both inhibit the growth of P. falciparum with IC values differing by three orders of magnitude.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Oxidantes/farmacologia
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Ácido Ascórbico/farmacologia
Diamida/farmacologia
Ditiotreitol/farmacologia
Relação Dose-Resposta a Droga
Eritrócitos/parasitologia
Corantes Fluorescentes
Interações Hospedeiro-Parasita/efeitos dos fármacos
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Concentração Inibidora 50
Malária Falciparum/parasitologia
Compostos Orgânicos
Oxirredução
Estresse Oxidativo
Parasitemia/parasitologia
Plasmodium falciparum/crescimento & desenvolvimento
Fatores de Tempo
terc-Butil Hidroperóxido/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Fluorescent Dyes); 0 (Organic Chemicals); 0 (Oxidants); 10465-78-8 (Diamide); 163795-75-3 (SYBR Green I); 955VYL842B (tert-Butylhydroperoxide); BBX060AN9V (Hydrogen Peroxide); PQ6CK8PD0R (Ascorbic Acid); T8ID5YZU6Y (Dithiothreitol); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE


  4 / 1015 MEDLINE  
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[PMID]:28167699
[Au] Autor:Gergondey R; Garcia C; Marchand CH; Lemaire SD; Camadro JM; Auchère F
[Ad] Endereço:Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France.
[Ti] Título:Modulation of the specific glutathionylation of mitochondrial proteins in the yeast under basal and stress conditions.
[So] Source:Biochem J;474(7):1175-1193, 2017 Mar 15.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The potential biological consequences of oxidative stress and changes in glutathione levels include the oxidation of susceptible protein thiols and reversible covalent binding of glutathione to the -SH groups of proteins by S-glutathionylation. Mitochondria are central to the response to oxidative stress and redox signaling. It is therefore crucial to explore the adaptive response to changes in thiol-dependent redox status in these organelles. We optimized the purification protocol of glutathionylated proteins in the yeast and present a detailed proteomic analysis of the targets of protein glutathionylation in cells undergoing constitutive metabolism and after exposure to various stress conditions. This work establishes the physiological importance of the glutathionylation process in under basal conditions and provides evidence for an atypical and unexpected cellular distribution of the process between the cytosol and mitochondria. In addition, our data indicate that each oxidative condition (diamide, GSSG, H O , or the presence of iron) elicits an adaptive metabolic response affecting specific mitochondrial metabolic pathways, mainly involved in the energetic maintenance of the cells. The correlation of protein modifications with intracellular glutathione levels suggests that protein deglutathionylation may play a role in protecting mitochondria from oxidative stress. This work provides further insights into the diversity of proteins undergoing glutathionylation and the role of this post-translational modification as a regulatory process in the adaptive response of the cell.
[Mh] Termos MeSH primário: Glutationa/metabolismo
Proteínas Mitocondriais/metabolismo
Estresse Oxidativo
Processamento de Proteína Pós-Traducional
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Citosol/efeitos dos fármacos
Citosol/metabolismo
Diamida/farmacologia
Ontologia Genética
Dissulfeto de Glutationa/farmacologia
Peróxido de Hidrogênio/farmacologia
Ferro/metabolismo
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Proteínas Mitocondriais/genética
Anotação de Sequência Molecular
Oxirredução
Proteômica
Saccharomyces cerevisiae/efeitos dos fármacos
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (Saccharomyces cerevisiae Proteins); 10465-78-8 (Diamide); BBX060AN9V (Hydrogen Peroxide); E1UOL152H7 (Iron); GAN16C9B8O (Glutathione); ULW86O013H (Glutathione Disulfide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170615
[Lr] Data última revisão:
170615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160927


  5 / 1015 MEDLINE  
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[PMID]:27870931
[Au] Autor:Cui F; Chai T; Qian L; Wang C
[Ad] Endereço:College of Sciences, China Agricultural University, Beijing, People's Republic of China.
[Ti] Título:Effects of three diamides (chlorantraniliprole, cyantraniliprole and flubendiamide) on life history, embryonic development and oxidative stress biomarkers of Daphnia magna.
[So] Source:Chemosphere;169:107-116, 2017 Feb.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The diamides have become one of the most promising new classes of insecticides. In this study, we evaluated the toxicity of three diamides (chlorantraniliprole, cyantraniliprole and flubendiamide) to Daphnia magna. The acute toxicity test showed that the 48-h EC of chlorantraniliprole, cyantraniliprole and flubendiamide were 8.5, 23.9 and 63.5 µg/L, respectively. Biochemical measurements revealed a significant increase in reactive oxygen species (ROS) in D. magna after acute exposure to the three diamides. A significant decrease in activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was observed, which was consistent with the down-regulated transcription of antioxidant genes sod and gpx. Catalase (CAT) activity exhibited a significant increase while the related gene cat showed no obvious change in daphnids acutely exposed to the three diamides. The chronic test revealed that the three diamides could cause lethal and sub-lethal effects on daphnids within constricted range of concentrations at µg/L level. The 21-d EC of chlorantraniliprole, cyantraniliprole and flubendiamide for mobility were 5.0, 13.6 and 36.8 µg/L, respectively. The chronic LOEC of chlorantraniliprole, cyantraniliprole and flubendiamide based on survival, growth and reproduction of D. magna were 4.05, 10.24 and 19.36 µg/L, respectively. Moreover, these three diamides can induce severe developmental abnormalities in D. magna embryos including underdeveloped second antennae, curved tail spine and abnormal body region after acute exposure and the 48-h EC were 6.2, 14.1 and 30.8 µg/L for chlorantraniliprole, cyantraniliprole and flubendiamide respectively. Our findings indicate that even low levels of diamides can pose ecological risks to aquatic ecosystems.
[Mh] Termos MeSH primário: Benzamidas/toxicidade
Daphnia/fisiologia
Inseticidas/toxicidade
Pirazóis/toxicidade
Sulfonas/toxicidade
ortoaminobenzoatos/toxicidade
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Catalase/metabolismo
Daphnia/efeitos dos fármacos
Diamida
Desenvolvimento Embrionário/efeitos dos fármacos
Estágios do Ciclo de Vida
Estresse Oxidativo/fisiologia
Espécies Reativas de Oxigênio
Reprodução/efeitos dos fármacos
Testes de Toxicidade Aguda
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (Biomarkers); 0 (Insecticides); 0 (Pyrazoles); 0 (Reactive Oxygen Species); 0 (Sulfones); 0 (ortho-Aminobenzoates); 10465-78-8 (Diamide); 622AK9DH9G (chlorantranilipole); EC 1.11.1.6 (Catalase); GEV84ZI4K6 (flubendiamide); LO6K6H48FD (cyantraniliprole)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161122
[St] Status:MEDLINE


  6 / 1015 MEDLINE  
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[PMID]:27664222
[Au] Autor:He Y; Chen Y; Song W; Zhu L; Dong Z; Ow DW
[Ad] Endereço:Plant Gene Engineering Center, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China.
[Ti] Título:A Pap1-Oxs1 signaling pathway for disulfide stress in Schizosaccharomyces pombe.
[So] Source:Nucleic Acids Res;45(1):106-114, 2017 Jan 09.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We describe a Pap1-Oxs1 pathway for diamide-induced disulfide stress in Schizosaccharomyces pombe, where the nucleocytoplasmic HMG protein Oxs1 acts cooperatively with Pap1 to regulate transcription. Oxs1 and Pap1 form a complex when cells are exposed to diamide or Cd that causes disulfide stress. When examined for promoters up-regulated by diamide, effective Pap1 binding to these targets requires Oxs1, and vice versa. With some genes, each protein alone enhances transcription, but the presence of both exerts an additive positive effect. In other genes, although transcription is induced by diamide, Oxs1 or Pap1 plays a negative role with full de-repression requiring loss of both proteins. In a third class of genes, Oxs1 positively regulates expression, but in its absence, Pap1 plays a negative role. The Oxs1-Pap1 regulatory interaction appears evolutionarily conserved, as heterologous (human, mouse and Arabidopsis) Oxs1 and Pap1-homologues can bind interchangeably with each other in vitro, and at least in the fission yeast, heterologous Oxs1 and Pap1-homologues can substitute for S. pombe Oxs1 and Pap1 to enhance stress tolerance.
[Mh] Termos MeSH primário: Fatores de Transcrição de Zíper de Leucina Básica/genética
Dissulfetos/metabolismo
Regulação Fúngica da Expressão Gênica
Proteínas HMGB/genética
Proteínas de Schizosaccharomyces pombe/genética
Schizosaccharomyces/genética
[Mh] Termos MeSH secundário: Animais
Arabidopsis/genética
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
Cádmio/farmacologia
Diamida/farmacologia
Teste de Complementação Genética
Proteínas HMGB/metabolismo
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Camundongos
Estresse Oxidativo
Proteínas Associadas a Pancreatite
Regiões Promotoras Genéticas
Ligação Proteica
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Schizosaccharomyces/efeitos dos fármacos
Schizosaccharomyces/metabolismo
Proteínas de Schizosaccharomyces pombe/metabolismo
Transdução de Sinais
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Basic-Leucine Zipper Transcription Factors); 0 (Disulfides); 0 (HMGB Proteins); 0 (Pancreatitis-Associated Proteins); 0 (Pap1 protein, S pombe); 0 (Protein Isoforms); 0 (REG3A protein, human); 0 (Schizosaccharomyces pombe Proteins); 00BH33GNGH (Cadmium); 10465-78-8 (Diamide); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw818


  7 / 1015 MEDLINE  
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[PMID]:27427282
[Au] Autor:Liu Q; Zhu R; Gao S; Ma SH; Tang HJ; Yang JJ; Diao YM; Wang HL; Zhu HJ
[Ad] Endereço:Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, China.
[Ti] Título:Structure-based bioisosterism design, synthesis, insecticidal activity and structure-activity relationship (SAR) of anthranilic diamide analogues containing 1,2,4-oxadiazole rings.
[So] Source:Pest Manag Sci;73(5):917-924, 2017 May.
[Is] ISSN:1526-4998
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Anthranilic diamide derivatives are among the most important classes of synthetic insecticides. Moreover, the 1,2,4-oxadiazole heterocycle, a bioisostere of amide, has been extensively used in pesticides. In order to discover novel molecules with high insecticidal activities, a series of anthranilic diamide analogues containing 1,2,4-oxadiazole rings were designed and synthesised. RESULTS: A series of novel anthranilic diamide derivatives containing 1,2,4-oxadiazole were obtained, and confirmed by H and C nuclear magnetic resonance and high-resolution mass spectrometry. The structure of 3-bromo-N-(4-chloro-2-methyl-6-{3-[(methylsulphonyl)methyl]-1,2,4-oxadiazol-5-yl}phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide was further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed 100% mortality against Plutella xylostella at 100 mg L , and compound 3IIl showed 90% larvicidal activities at a concentration of 0.5 mg L . The LC value of 3IIl was 0.20 mg L , which indicated that it may be used as a potential leading compound for further structural optimisation. Furthermore, brief comparative molecular field analysis (CoMFA) models were established to study the structure-activity relationships (SARs) of the title compounds. CONCLUSION: Compound 3IIl may be used as a potential leading compound for further structural optimisation, and SARs and CoMFA models could provide reliable clues for further structural optimisation. © 2016 Society of Chemical Industry.
[Mh] Termos MeSH primário: Diamida/química
Diamida/síntese química
Desenho de Drogas
Inseticidas/química
Inseticidas/síntese química
Isoxazóis/química
Oxidiazóis/química
[Mh] Termos MeSH secundário: Animais
Técnicas de Química Sintética
Modelos Moleculares
Conformação Molecular
Mariposas
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insecticides); 0 (Isoxazoles); 0 (Oxadiazoles); 10465-78-8 (Diamide); 271-58-9 (anthranil)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160719
[St] Status:MEDLINE
[do] DOI:10.1002/ps.4363


  8 / 1015 MEDLINE  
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[PMID]:27729257
[Au] Autor:Veatch AV; Niu T; Caskey J; McGillivray A; Gautam US; Subramanian R; Kousoulas KG; Mehra S; Kaushal D
[Ad] Endereço:Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Covington LA, USA; Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
[Ti] Título:Sequencing-relative to hybridization-based transcriptomics approaches better define Mycobacterium tuberculosis stress-response regulons.
[So] Source:Tuberculosis (Edinb);101S:S9-S17, 2016 Dec.
[Is] ISSN:1873-281X
[Cp] País de publicação:Scotland
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis (Mtb) infections cause tuberculosis (TB), an infectious disease which causes ∼1.5 million deaths annually. The ability of this pathogen to evade, escape and encounter immune surveillance is fueled by its adaptability. Thus, Mtb induces a transition in its transcriptome in response to environmental changes. Global transcriptome profiling has been key to our understanding of how Mtb responds to the different stress conditions it faces during its life cycle. While this was initially achieved using microarray technology, RNAseq is now widely employed. It is important to understand the correlation between the large amount of microarray based transcriptome data, which continues to shape our understanding of Mtb stress networks, and newer data being generated using RNAseq. We assessed how well the two platforms correlate using three well-defined stress conditions: diamide, hypoxia, and re-aeration. The data used here was generated by different individuals over time using distinct samples, providing a stringent test of platform correlation. While correlation between microarrays and sequencing was high upon diamide treatment, which causes a rapid reprogramming of the transcriptome, RNAseq allowed a better definition of the hypoxic response, characterized by subtle changes in the magnitude of gene-expression. RNAseq also allows for the best cross-platform reproducibility.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica/métodos
Regulação Bacteriana da Expressão Gênica
Mycobacterium tuberculosis/genética
Análise de Sequência com Séries de Oligonucleotídeos
RNA Bacteriano/genética
Regulon
Análise de Sequência de RNA
Estresse Fisiológico
Transcriptoma
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Diamida/farmacologia
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/metabolismo
Mycobacterium tuberculosis/patogenicidade
Variações Dependentes do Observador
Oxirredução
Estresse Oxidativo
Oxigênio/metabolismo
Proteínas Quinases/genética
Reprodutibilidade dos Testes
Fator sigma/genética
Fatores de Tempo
Transcriptoma/efeitos dos fármacos
Tuberculose/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (RNA, Bacterial); 0 (SigH protein, bacteria); 0 (Sigma Factor); 10465-78-8 (Diamide); EC 2.7.- (Protein Kinases); EC 2.7.3.- (DosR protein, Mycobacterium tuberculosis); S88TT14065 (Oxygen)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE


  9 / 1015 MEDLINE  
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[PMID]:27448915
[Au] Autor:Mao SW; Chen H; Yu LF; Lv F; Xing YJ; Liu T; Xie J; Tang J; Yi Z; Yang F
[Ad] Endereço:Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China.
[Ti] Título:Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents.
[So] Source:Eur J Med Chem;122:574-583, 2016 Oct 21.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50 > 80 µM), especially the piperazine conjugated compound 27 with IC50 values of 1.07, 4.58 and 3.86 µM against PC3M, HT29 and ES-2 cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SI(PC3M) = 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Ácidos e Sais Biliares/química
Ácidos e Sais Biliares/farmacologia
Movimento Celular/efeitos dos fármacos
Diamida/química
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Bile Acids and Salts); 10465-78-8 (Diamide)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160725
[St] Status:MEDLINE


  10 / 1015 MEDLINE  
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[PMID]:27240271
[Au] Autor:Saudi M; Zmurko J; Kaptein S; Rozenski J; Gadakh B; Chaltin P; Marchand A; Neyts J; Van Aerschot A
[Ad] Endereço:KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.
[Ti] Título:Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus.
[So] Source:Eur J Med Chem;121:158-168, 2016 Oct 04.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:High-throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 µM), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 µM) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 µM and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 µM, with compound 6n being the most potent for this series with an EC50 0.4 µM and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity.
[Mh] Termos MeSH primário: Vírus da Dengue/efeitos dos fármacos
Diamida/farmacologia
Compostos Heterocíclicos/farmacologia
Vírus da Febre Amarela/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antivirais/química
Antivirais/farmacologia
Cercopithecus aethiops
Diamida/química
Descoberta de Drogas/métodos
Compostos Heterocíclicos/química
Relação Estrutura-Atividade
Células Vero
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Heterocyclic Compounds); 10465-78-8 (Diamide)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160531
[St] Status:MEDLINE



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