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Carneiro, M
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[PMID]:29363152
[Au] Autor:Rodrigues Oliveira JL; Teixeira MM; Lambertucci JR; Antunes CMF; Carneiro M; Negrão-Corrêa D
[Ad] Endereço:Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
[Ti] Título:Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni-infected individuals.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.
[Mh] Termos MeSH primário: Quimiocina CCL24/sangue
Quimiocina CCL3/sangue
Quimiocina CCL7/sangue
Oxirredutases Intramoleculares/sangue
Cirrose Hepática/imunologia
Fatores Inibidores da Migração de Macrófagos/sangue
Receptores Tipo I de Fatores de Necrose Tumoral/sangue
Schistosoma mansoni/imunologia
Esquistossomose mansoni/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Animais
Seres Humanos
Fígado/irrigação sanguínea
Fígado/parasitologia
Fígado/patologia
Cirrose Hepática/parasitologia
Meia-Idade
Veia Porta/patologia
Esquistossomose mansoni/parasitologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCL24 protein, human); 0 (CCL3 protein, human); 0 (CCL7 protein, human); 0 (Chemokine CCL24); 0 (Chemokine CCL3); 0 (Chemokine CCL7); 0 (Macrophage Migration-Inhibitory Factors); 0 (Receptors, Tumor Necrosis Factor, Type I); 0 (TNFRSF1A protein, human); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.2.1 (MIF protein, human)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12642


  2 / 3606 MEDLINE  
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[PMID]:29289260
[Au] Autor:Bilgir O; Gökçen B; Bilgir F; Guler A; Calan M; Yuksel A; Aslanipour B; Aksit M; Bozkaya G
[Ad] Endereço:Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, Izmir, Turkey. Electronic address: oktaybilgir@gmail.com.
[Ti] Título:Relationship Between Serum Macrophage Migration Inhibitory Factor Level and Insulin Resistance, High-Sensitivity C-Reactive Protein and Visceral Fat Mass in Prediabetes.
[So] Source:Am J Med Sci;355(1):37-43, 2018 Jan.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Growing evidence suggest that macrophage migration inhibitory factor (MIF) plays a vital role in glucose metabolism. We aimed to ascertain whether MIF levels are altered in subjects with prediabetes and also to determine the relationship between MIF and metabolic parameters as well as visceral fat mass. MATERIAL AND METHODS: This cross-sectional study included 40 subjects with prediabetes and 40 age-, body mass index (BMI)- and sex-matched subjects with normal glucose tolerance. Circulating MIF levels were measured using enzyme-linked immunosorbent assay. Metabolic parameters of recruited subjects were evaluated. Visceral fat mass was measured using bioelectrical impedance method. RESULTS: Circulating MIF levels were found to be elevated in subjects with prediabetes compared to controls (26.46 ± 16.98 versus 17.44 ± 11.80 ng/mL, P = 0.007). MIF positively correlated with BMI, visceral fat mass and indirect indices of homeostasis model assessment of insulin resistance. In linear regression model, an independent association was found between MIF levels and metabolic parameters, including BMI, visceral fat mass and homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses revealed that the odds ratio for prediabetes was higher in subjects in the highest quartile of MIF compared to those in the lowest quartile, after adjusting for potential confounders. CONCLUSIONS: Increased MIF levels are associated with the elevation of prediabetic risk.
[Mh] Termos MeSH primário: Índice de Massa Corporal
Proteína C-Reativa/metabolismo
Resistência à Insulina/fisiologia
Gordura Intra-Abdominal/metabolismo
Oxirredutases Intramoleculares/sangue
Fatores Inibidores da Migração de Macrófagos/sangue
Estado Pré-Diabético/sangue
[Mh] Termos MeSH secundário: Adulto
Biomarcadores/sangue
Glicemia/metabolismo
Estudos Transversais
Feminino
Seres Humanos
Gordura Intra-Abdominal/patologia
Masculino
Meia-Idade
Estado Pré-Diabético/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Macrophage Migration-Inhibitory Factors); 9007-41-4 (C-Reactive Protein); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.2.1 (MIF protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


  3 / 3606 MEDLINE  
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[PMID]:28451639
[Au] Autor:Kanda H; Kobayashi K; Yamanaka H; Okubo M; Noguchi K
[Ad] Endereço:Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
[Ti] Título:Microglial TNFα Induces COX2 and PGI2 Synthase Expression in Spinal Endothelial Cells during Neuropathic Pain.
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostaglandins (PGs) are typical lipid mediators that play a role in homeostasis and disease. They are synthesized from arachidonic acid by cyclooxygenase 1 (COX1) and COX2. Although COX2 has been reported to be upregulated in the spinal cord after nerve injury, its expression and functional roles in neuropathic pain remain unclear. In this study, we investigated the expression of Cox2, PGI2 synthase (Pgis), and prostaglandin I2 receptor (IP receptor) mRNA in the rat spinal cord after spared nerve injury (SNI). Levels of Cox2 and Pgis mRNA increased in endothelial cells from 24 to 48 h after nerve injury. IP receptor mRNA was constitutively expressed in dorsal horn neurons. A COX2 inhibitor and IP receptor antagonists attenuated pain behavior in the early phase of neuropathic pain. Furthermore, we examined the relationship between COX2 and tumor necrosis factor-α (TNFα) in the spinal cord of a rat SNI model. Levels of TNFα mRNA transiently increased in the spinal microglia 24 h after SNI. The TNF receptors Tnfr1 and Tnfr2 mRNA were colocalized with COX2. Intrathecal injection of TNFα induced Cox2 and Pgis mRNA expression in endothelial cells. These results revealed that microglia-derived TNFα induced COX2 and PGIS expression in spinal endothelial cells and that endothelial PGI2 played a critical role in neuropathic pain via neuronal IP receptor. These findings further suggest that the glia-endothelial cell interaction of the neurovascular unit via transient TNFα is involved in the generation of neuropathic pain.
[Mh] Termos MeSH primário: Ciclo-Oxigenase 2/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Células Endoteliais/enzimologia
Oxirredutases Intramoleculares/metabolismo
Microglia/metabolismo
Neuralgia/metabolismo
Medula Espinal/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Animais
Inflamação/enzimologia
Masculino
Traumatismos dos Nervos Periféricos/metabolismo
RNA Mensageiro
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Tumor Necrosis Factor-alpha); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (Ptgs2 protein, rat); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.99.4 (prostacyclin synthetase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  4 / 3606 MEDLINE  
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[PMID]:29304107
[Au] Autor:Zdyb A; Salgado MG; Demchenko KN; Brenner WG; Plaszczyca M; Stumpe M; Herrfurth C; Feussner I; Pawlowski K
[Ad] Endereço:Department of Ecology, Environment and Plant Sciences, Stockholm University, Stockholm, Sweden.
[Ti] Título:Allene oxide synthase, allene oxide cyclase and jasmonic acid levels in Lotus japonicus nodules.
[So] Source:PLoS One;13(1):e0190884, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Jasmonic acid (JA), its derivatives and its precursor cis-12-oxo phytodienoic acid (OPDA) form a group of phytohormones, the jasmonates, representing signal molecules involved in plant stress responses, in the defense against pathogens as well as in development. Elevated levels of JA have been shown to play a role in arbuscular mycorrhiza and in the induction of nitrogen-fixing root nodules. In this study, the gene families of two committed enzymes of the JA biosynthetic pathway, allene oxide synthase (AOS) and allene oxide cyclase (AOC), were characterized in the determinate nodule-forming model legume Lotus japonicus JA levels were to be analysed in the course of nodulation. Since in all L. japonicus organs examined, JA levels increased upon mechanical disturbance and wounding, an aeroponic culture system was established to allow for a quick harvest, followed by the analysis of JA levels in whole root and shoot systems. Nodulated plants were compared with non-nodulated plants grown on nitrate or ammonium as N source, respectively, over a five week-period. JA levels turned out to be more or less stable independently of the growth conditions. However, L. japonicus nodules formed on aeroponically grown plants often showed patches of cells with reduced bacteroid density, presumably a stress symptom. Immunolocalization using a heterologous antibody showed that the vascular systems of these nodules also seemed to contain less AOC protein than those of nodules of plants grown in perlite/vermiculite. Hence, aeroponically grown L. japonicus plants are likely to be habituated to stress which could have affected JA levels.
[Mh] Termos MeSH primário: Ciclopentanos/metabolismo
Fabaceae/fisiologia
Oxirredutases Intramoleculares/metabolismo
Loteae/metabolismo
Oxilipinas/metabolismo
Nodulação
[Mh] Termos MeSH secundário: Oxirredutases Intramoleculares/genética
Loteae/enzimologia
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Cyclopentanes); 0 (Oxylipins); 0 (RNA, Messenger); 6RI5N05OWW (jasmonic acid); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.99.6 (hydroperoxide isomerase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190884


  5 / 3606 MEDLINE  
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[PMID]:28463490
[Au] Autor:Tomita T; Kim SY; Teramoto K; Meguro A; Ozaki T; Yoshida A; Motoyoshi Y; Mori N; Ishigami K; Watanabe H; Nishiyama M; Kuzuyama T
[Ti] Título:Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol.
[So] Source:ACS Chem Biol;12(6):1621-1628, 2017 06 16.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride shifts, all occurring at a single active site. Here, we report the first high-resolution X-ray crystal structure of CotB2 with bound substrate analog geranylgeranyl thiodiphosphate (GGSPP). In the GGSPP-bound form, GGSPP folds into a unique S-shaped conformation that probably reflects the substrate-bound state prior to ionization of the substrate GGPP. The folded framework of GGSPP is surrounded by hydrophobic residues and several aromatic and asparagine residues that are well-positioned to stabilize a series of reactive carbocation intermediates through a combination of cation-π and dipole charge interactions. The combined crystal structures and mutagenesis-based biochemical assays provide a structural basis for exquisite control of ring formation and stereochemistry during CotB2 catalysis.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Biocatálise
Diterpenos/química
Oxirredutases Intramoleculares/metabolismo
Fosfatos de Poli-Isoprenil/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Cristalografia por Raios X
Ciclização
Ciclo-Octanos/química
Ciclo-Octanos/metabolismo
Enzimas/química
Enzimas/metabolismo
Mutagênese Sítio-Dirigida
Streptomyces/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cyclooctanes); 0 (Diterpenes); 0 (Enzymes); 0 (Polyisoprenyl Phosphates); EC 5.3.- (Intramolecular Oxidoreductases); N21T0D88LX (geranylgeranyl pyrophosphate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00154


  6 / 3606 MEDLINE  
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[PMID]:29236385
[Au] Autor:Babenko LM; Shcherbatiuk MM; Skaterna TD; Kosakivska IV
[Ti] Título:Lipoxygenases and their metabolites in formation of plant stress tolerance.
[So] Source:Ukr Biochem J;89(1):5-21, 2017 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The review focuses on the analysis of new information concerning molecular enzymology of lipoxygenases ­ proteins involved in lipid peroxidation and found in animals and plants. Modern concept of structural features, catalytic characteristics and functions of lipoxygenase family enzymes as well as products of their catalytic activity in plants have been discussed and summarized. Issues of enzyme localization in plant cells and tissues, evolution and distribution of lipoxygenases, involvement in production of signaling substances involved in formation of adaptation response to abiotic and biotic stress factors and in regulation of lipoxygenase signal system activity are highlighted. Participants of the elements signaling of LOX-pathway reception and transduction into genome are considered. Special attention is given to jasmonates, metabolites of the allene oxide synthase branch of the lipoxygenase cascade, because these metabolites have high biological activity, are ubiquitously present in all plant organisms, and are involved in regulation of vitally important processes. Data concerning lipoxygenase phylogeny, possible occurrence of a common predecessor for modern isoforms of the enzyme in pro- and eukaryote have been examined. Some results of our studies that open up possibilities of using the lipoxygenase catalytic activity characteristics as biological markers in plant stress tolerance researches are given.
[Mh] Termos MeSH primário: Adaptação Fisiológica/genética
Regulação da Expressão Gênica de Plantas
Genoma de Planta
Lipoxigenases/genética
Proteínas de Plantas/genética
Plantas/genética
[Mh] Termos MeSH secundário: Evolução Biológica
Ciclopentanos/metabolismo
Oxirredutases Intramoleculares/genética
Oxirredutases Intramoleculares/metabolismo
Lipoxigenases/metabolismo
Redes e Vias Metabólicas/genética
Oxilipinas/metabolismo
Filogenia
Proteínas de Plantas/metabolismo
Plantas/classificação
Plantas/enzimologia
Transdução de Sinais
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cyclopentanes); 0 (Oxylipins); 0 (Plant Proteins); 6RI5N05OWW (jasmonic acid); EC 1.13.11.- (Lipoxygenases); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.99.6 (hydroperoxide isomerase)
[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:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj89.01.005


  7 / 3606 MEDLINE  
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[PMID]:28574571
[Au] Autor:Fujihara Y; Hikita A; Takato T; Hoshi K
[Ad] Endereço:Department of Oral-Maxillofacial Surgery and Orthodontics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:Roles of macrophage migration inhibitory factor in cartilage tissue engineering.
[So] Source:J Cell Physiol;233(2):1490-1499, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To obtain stable outcomes in regenerative medicine, understanding and controlling immunological responses in transplanted tissues are of great importance. In our previous study, auricular chondrocytes in tissue-engineered cartilage transplanted in mice were shown to express immunological factors, including macrophage migration inhibitory factor (MIF). Since MIF exerts pleiotropic functions, in this study, we examined the roles of MIF in cartilage regenerative medicine. We made tissue-engineered cartilage consisting of auricular chondrocytes of C57BL/6J mouse, atellocollagen gel and a PLLA scaffold, and transplanted the construct subcutaneously in a syngeneic manner. Localization of MIF was prominent in cartilage areas of tissue-engineered cartilage at 2 weeks after transplantation, though it became less apparent by 8 weeks. Co-culture with RAW264 significantly increased the expression of MIF in chondrocytes, suggesting that the transplanted chondrocytes in tissue-engineered cartilage could enhance the expression of MIF by stimulation of surrounding macrophages. When MIF was added in the culture of chondrocytes, the expression of type II collagen was increased, indicating that MIF could promote the maturation of chondrocytes. Meanwhile, toluidine blue staining of constructs containing wild type (Mif+/+) chondrocytes showed increased metachromasia compared to MIF-knockout (Mif-/-) constructs at 2 weeks. However, this tendency was reversed by 8 weeks, suggesting that the initial increase in cartilage maturation in Mif+/+ constructs deteriorated by 8 weeks. Since the Mif+/+ constructs included more iNOS-positive inflammatory macrophages at 2 weeks, MIF might induce an M1 macrophage-polarized environment, which may eventually worsen the maturation of tissue-engineered cartilage in the long term.
[Mh] Termos MeSH primário: Comunicação Celular
Condrócitos/metabolismo
Cartilagem da Orelha/metabolismo
Oxirredutases Intramoleculares/metabolismo
Fatores Inibidores da Migração de Macrófagos/metabolismo
Macrófagos/metabolismo
Engenharia Tecidual/métodos
[Mh] Termos MeSH secundário: Animais
Proliferação Celular
Condrócitos/transplante
Condrogênese
Técnicas de Cocultura
Colágeno/metabolismo
Cartilagem da Orelha/citologia
Cartilagem da Orelha/transplante
Géis
Seres Humanos
Oxirredutases Intramoleculares/deficiência
Oxirredutases Intramoleculares/genética
Fatores Inibidores da Migração de Macrófagos/deficiência
Fatores Inibidores da Migração de Macrófagos/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Óxido Nítrico Sintase Tipo II/metabolismo
Fenótipo
Poliésteres/química
Células RAW 264.7
Transdução de Sinais
Fatores de Tempo
Tecidos Suporte
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gels); 0 (Macrophage Migration-Inhibitory Factors); 0 (Polyesters); 0 (atelocollagen); 459TN2L5F5 (poly(lactide)); 9007-34-5 (Collagen); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.2.1 (MIF protein, human); EC 5.3.2.1 (Mif protein, mouse)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.26036


  8 / 3606 MEDLINE  
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[PMID]:29059176
[Au] Autor:Ahouty B; Koffi M; Ilboudo H; Simo G; Matovu E; Mulindwa J; Hertz-Fowler C; Bucheton B; Sidibé I; Jamonneau V; MacLeod A; Noyes H; N'Guetta SP; TrypanoGEN Research Group as members of The H3Africa Consortium
[Ad] Endereço:Laboratoire de Génétique, Félix Houphouët Boigny University, Abidjan, Côte d'Ivoire.
[Ti] Título:Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d'Ivoire.
[So] Source:PLoS Negl Trop Dis;11(10):e0005992, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d'Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.
[Mh] Termos MeSH primário: Estudos de Associação Genética
Predisposição Genética para Doença
Tripanossomíase Africana/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Apolipoproteína L1
Apolipoproteínas/genética
Estudos de Casos e Controles
Criança
Costa do Marfim/epidemiologia
Feminino
Seres Humanos
Interleucina-4/genética
Interleucina-6/genética
Oxirredutases Intramoleculares/genética
Lipoproteínas HDL/genética
Fatores Inibidores da Migração de Macrófagos/genética
Masculino
Meia-Idade
Fenótipo
Polimorfismo de Nucleotídeo Único
Análise de Componente Principal
Trypanosoma brucei gambiense
Tripanossomíase Africana/epidemiologia
Tripanossomíase Africana/parasitologia
Fator de Necrose Tumoral alfa/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (APOL1 protein, human); 0 (Apolipoprotein L1); 0 (Apolipoproteins); 0 (IL4 protein, human); 0 (IL6 protein, human); 0 (Interleukin-6); 0 (Lipoproteins, HDL); 0 (Macrophage Migration-Inhibitory Factors); 0 (Tumor Necrosis Factor-alpha); 207137-56-2 (Interleukin-4); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.2.1 (MIF protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005992


  9 / 3606 MEDLINE  
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[PMID]:28953966
[Au] Autor:Teder T; Lõhelaid H; Samel N
[Ad] Endereço:Department of Chemistry and Biotechnolgy, Tallinn University of Technology, Tallinn, Estonia.
[Ti] Título:Structural and functional insights into the reaction specificity of catalase-related hydroperoxide lyase: A shift from lyase activity to allene oxide synthase by site-directed mutagenesis.
[So] Source:PLoS One;12(9):e0185291, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Two highly identical fusion proteins, an allene oxide synthase-lipoxygenase (AOS-LOX) and a hydroperoxide lyase-lipoxygenase (HPL-LOX), were identified in the soft coral Capnella imbricata. Both enzymes initially catalyze the formation of 8R-hydroperoxy-eicosatetraenoic acid (8R-HpETE) from arachidonic acid by the C-terminal lipoxygenase (LOX) domain. Despite the fact that the defined catalytically important residues of N-terminal catalase-related allene oxide synthase (cAOS) domain are also conserved in C. imbricata hydroperoxide lyase (cHPL), their reaction specificities differ. In the present study, we tested which of the amino acid substitutions around the active site of cHPL are responsible for a control in the reaction specificity. The possible candidates were determined via comparative sequence and structural analysis of the substrate channel and the heme region of coral cAOSs and C. imbricata cHPL. The amino acid replacements in cHPL-R56G, ME59-60LK, P65A, F150L, YS176-177NL, I357V, and SSSAGE155-160PVKEGD-with the corresponding residues of cAOS were conducted by site-directed mutagenesis. Although all these mutations influenced the catalytic efficiency of cHPL, only F150L and YS176-177NL substitutions caused a shift in the reaction specificity from HPL to AOS. The docking analysis of P. homomalla cAOS with 8R-HpETE substrate revealed that the Leu150 of cAOS interacts with the C5-C6 double bond and the Leu177 with the hydrophobic tail of 8R-HpETE. We propose that the corresponding residues in cHPL, Phe150 and Ser177, are involved in a proper coordination of the epoxy allylic radical intermediate necessary for aldehyde formation in the hydroperoxide lyase reaction.
[Mh] Termos MeSH primário: Aldeído Liases/química
Aldeído Liases/metabolismo
Antozoários/enzimologia
Catalase/metabolismo
Sistema Enzimático do Citocromo P-450/química
Sistema Enzimático do Citocromo P-450/metabolismo
Oxirredutases Intramoleculares/metabolismo
Mutagênese Sítio-Dirigida/métodos
[Mh] Termos MeSH secundário: Aldeído Liases/isolamento & purificação
Sequência de Aminoácidos
Animais
Sistema Enzimático do Citocromo P-450/isolamento & purificação
Eletroforese em Gel de Poliacrilamida
Peróxido de Hidrogênio/metabolismo
Oxirredutases Intramoleculares/química
Cinética
Leucotrienos/química
Leucotrienos/metabolismo
Ligantes
Simulação de Acoplamento Molecular
Proteínas Mutantes/química
Proteínas Mutantes/metabolismo
Multimerização Proteica
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Leukotrienes); 0 (Ligands); 0 (Mutant Proteins); 100896-35-3 (8-hydroperoxyeicosatetraenoic acid); 9035-51-2 (Cytochrome P-450 Enzyme System); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.6 (Catalase); EC 4.1.2.- (Aldehyde-Lyases); EC 4.1.2.- (hydroperoxide lyase); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.99.6 (hydroperoxide isomerase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185291


  10 / 3606 MEDLINE  
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[PMID]:28803983
[Au] Autor:Yamamoto K; Higashiura A; Suzuki M; Aritake K; Urade Y; Nakagawa A
[Ad] Endereço:Faculty of Agriculture, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. Electronic address: yamamok@agr.kyushu-u.ac.jp.
[Ti] Título:Molecular structure of a prostaglandin D synthase requiring glutathione from the brown planthopper, Nilaparvata lugens.
[So] Source:Biochem Biophys Res Commun;492(2):166-171, 2017 Oct 14.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostaglandins are involved in many physiological processes, and prostaglandin synthases facilitate the detoxification of xenobiotics as well as endogenous compounds, such as through glutathione conjugation. Specifically, prostaglandin D synthase (PGDS) catalyzes the isomerization of PGH to PGD . Here we report the identification and structural analysis of PGDS from the brown planthopper rice pest Nilaparvata lugens (nlPGDS), which belongs to the sigma-class glutathione transferases. The structure of nlPGDS in complex with glutathione was determined at a resolution of 2.0 Å by X-ray crystallography. Bound glutathione was localized to the glutathione-binding site (G-site). Enzyme activity measurements following site-directed mutagenesis of nlPGDS indicated that amino acid residues Tyr8, Leu14, Trp39, Lys43, Gln50, Val51, Gln63, and Ser64 in the G-site contribute to its catalytic activity. To our knowledge, this represents the first report of a PGDS in insects. Our findings provide insights into the mechanism of nlPGDS activity and potentially that of other insects and therefore may facilitate the development of more effective and safe insecticides.
[Mh] Termos MeSH primário: Glutationa/metabolismo
Hemípteros/enzimologia
Oxirredutases Intramoleculares/química
Oxirredutases Intramoleculares/metabolismo
Lipocalinas/química
Lipocalinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Domínio Catalítico
Cristalografia por Raios X
Hemípteros/química
Hemípteros/metabolismo
Modelos Moleculares
Oryza/parasitologia
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipocalins); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.99.2 (prostaglandin R2 D-isomerase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE



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