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Pesquisa : D02.241.081.901.177 [Categoria DeCS]
Referências encontradas : 148 [refinar]
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[PMID]:28122302
[Au] Autor:Yan J; Wang Y; Jia Y; Liu S; Tian C; Pan W; Liu X; Wang H
[Ad] Endereço:Department of Renal Transplantation, The Second Hospital of Shandong University, Ji'nan 250033, Shandong, PR China.
[Ti] Título:Co-delivery of docetaxel and curcumin prodrug via dual-targeted nanoparticles with synergistic antitumor activity against prostate cancer.
[So] Source:Biomed Pharmacother;88:374-383, 2017 Apr.
[Is] ISSN:1950-6007
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Combination therapy is increasingly used as a primary cancer treatment regimen. In this report, we designed EGFR peptide decorated nanoparticles (NPs) to co-deliver docetaxel (DTX) and pH sensitive curcumin (CUR) prodrug for the treatment of prostate cancer. RESULTS: EGFR peptide (GE11) targeted, pH sensitive, DTX and CUR prodrug NPs (GE11-DTX-CUR NPs) had an average diameter of 167nm and a zeta potential of -37.5mV. The particle size of the NPs was adequately maintained in serum and a sustained drug release pattern was observed. Improved inhibition of cancer cell and tumor tissue growth was shown in the GE11-DTX-CUR NPs group compared to the other groups. CONCLUSION: It can be summarized that DTX and CUR prodrug could be delivered into tumor cells simultaneously by the GE 11 targeting and the EPR effect of NPs. The resulting GE11-DTX-CUR NPs is a promising system for the synergistic antitumor treatment of prostate cancer.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Curcumina/uso terapêutico
Sistemas de Liberação de Medicamentos
Nanopartículas/química
Pró-Fármacos/farmacologia
Neoplasias da Próstata/tratamento farmacológico
Taxoides/uso terapêutico
[Mh] Termos MeSH secundário: Ácido Aconítico/análogos & derivados
Ácido Aconítico/química
Animais
Antineoplásicos/farmacologia
Morte Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Cumarínicos/química
Curcumina/química
Curcumina/farmacologia
Liberação Controlada de Fármacos
Estabilidade de Medicamentos
Sinergismo Farmacológico
Endocitose/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Ácido Láctico/química
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Tamanho da Partícula
Peptídeos/química
Polietilenoglicóis/química
Ácido Poliglicólico/química
Neoplasias da Próstata/patologia
Espectroscopia de Prótons por Ressonância Magnética
Taxoides/química
Taxoides/farmacologia
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coumarins); 0 (GE11 peptide); 0 (Peptides); 0 (Prodrugs); 0 (Taxoids); 0 (Thiazoles); 0 (coumarin 6); 0 (polylactic acid-polyglycolic acid copolymer); 15H5577CQD (docetaxel); 26009-03-0 (Polyglycolic Acid); 30IQX730WE (Polyethylene Glycols); 33X04XA5AT (Lactic Acid); 499-12-7 (Aconitic Acid); 6318-55-4 (aconitic anhydride); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE


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[PMID]:28087696
[Au] Autor:Du C; Cao S; Shi X; Nie X; Zheng J; Deng Y; Ruan L; Peng D; Sun M
[Ad] Endereço:From the State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
[Ti] Título:Genetic and Biochemical Characterization of a Gene Operon for -Aconitic Acid, a Novel Nematicide from .
[So] Source:J Biol Chem;292(8):3517-3530, 2017 Feb 24.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:-Aconitic acid (TAA) is an isomer of -aconitic acid (CAA), an intermediate of the tricarboxylic acid cycle that is synthesized by aconitase. Although TAA production has been detected in bacteria and plants for many years and is known to be a potent inhibitor of aconitase, its biosynthetic origins and the physiological relevance of its activity have remained unclear. We have serendipitously uncovered key information relevant to both of these questions. Specifically, in a search for novel nematicidal factors from , a significant nematode pathogen harboring many protein virulence factors, we discovered a high yielding component that showed activity against the plant-parasitic nematode and surprisingly identified it as TAA. Comparison with CAA, which displayed a much weaker nematicidal effect, suggested that TAA is specifically synthesized by as a virulence factor. Analysis of mutants deficient in plasmids that were anticipated to encode virulence factors allowed us to isolate a TAA biosynthesis-related ( ) operon consisting of two genes, and We expressed the corresponding proteins, TbrA and TbrB, and characterized them as an aconitate isomerase and TAA transporter, respectively. Bioinformatics analysis of the TAA biosynthetic gene cluster revealed the association of the TAA genes with transposable elements relevant for horizontal gene transfer as well as a distribution across bacteria and other strains, suggesting a general role for TAA in the interactions of group bacteria with nematode hosts in the soil environment. This study reveals new bioactivity for TAA and the TAA biosynthetic pathway, improving our understanding of virulence factors employed by pathogenesis and providing potential implications for nematode management applications.
[Mh] Termos MeSH primário: Ácido Aconítico/metabolismo
Antinematódeos/metabolismo
Bacillus thuringiensis/enzimologia
Bacillus thuringiensis/genética
Proteínas de Transporte/genética
Isomerases/genética
Óperon
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Bacillus thuringiensis/química
Bacillus thuringiensis/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Proteínas de Transporte/química
Proteínas de Transporte/metabolismo
Elementos de DNA Transponíveis
Genes Bacterianos
Isomerases/química
Isomerases/metabolismo
Família Multigênica
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antinematodal Agents); 0 (Bacterial Proteins); 0 (Carrier Proteins); 0 (DNA Transposable Elements); 499-12-7 (Aconitic Acid); EC 5.- (Isomerases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.762666


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[PMID]:27507497
[Au] Autor:Piang-Siong W; de Caro P; Marvilliers A; Chasseray X; Payet B; Shum Cheong Sing A; Illien B
[Ad] Endereço:Université de la Réunion, Faculté des Sciences et Technologies, LCSNSA (Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments), 15 avenue René Cassin, CS 92003 - RE-97744 Saint Denis Cedex 9, La Réunion, France.
[Ti] Título:Contribution of trans-aconitic acid to DPPH scavenging ability in different media.
[So] Source:Food Chem;214:447-452, 2017 Jan 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The antioxidant properties of trans-aconitic acid (TAA) alone or in the presence of usual antioxidants were assessed by DPPH assay. The IC50 value equal to 70mM was very high compared to usual antioxidants (vitamin C and trolox). A joint experimental/theoretical study suggested that hydrogen atom abstraction in TAA by DPPH was located on -CH2- methylene bridge because the corresponding radical was more stabilized than COO(·) and CC(·) radicals. In combination with antioxidants (vitamin C, gallic acid, caffeic acid, trolox), synergy or additivity effects were noticed. The magnitude of the synergistic effect varied between 1.06 and 1.24 depending on the type and concentration of antioxidant for a concentration of TAA equal to 22.3mM. Especially, the addition of TAA at a concentration below 32mM to a solution containing 20µM of vitamin C had a synergy effect. Beyond this concentration, TAA showed an additive effect.
[Mh] Termos MeSH primário: Ácido Aconítico/química
Ácido Ascórbico/química
Compostos de Bifenilo/química
Depuradores de Radicais Livres/química
Picratos/química
[Mh] Termos MeSH secundário: Ácido Aconítico/análise
Antioxidantes/química
Ácido Ascórbico/análise
Ácido Gálico/química
Extratos Vegetais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biphenyl Compounds); 0 (Free Radical Scavengers); 0 (Picrates); 0 (Plant Extracts); 499-12-7 (Aconitic Acid); 632XD903SP (Gallic Acid); DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160811
[St] Status:MEDLINE


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[PMID]:27481344
[Au] Autor:Tahvilian R; Tajani B; Sadrjavadi K; Fattahi A
[Ad] Endereço:Department of pharmaceutics, School of pharmacy, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.
[Ti] Título:Preparation and characterization of pH-sensitive camptothecin-cis-aconityl grafted chitosan oligosaccharide nanomicelles.
[So] Source:Int J Biol Macromol;92:795-802, 2016 Nov.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Camptothecin (CPT) was introduced to water-soluble chitosan oligosaccharide (CHO) using cis-aconityl (CA), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. CPTCACHO. The triple conjugates were synthesized in three ratios (5%, 7.5%, and 10%) and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ( HNMR). Thermo gravimetric analysis and critical micelle concentration (CMC) assessments were performed. Prepared nano-micelles were analyzed for particle size, polydispersity index (PDI), drug release and in vitro cytotoxicity. CPTCACHO 7.5% micelles as optimum micelles had a mean diameter of 50nm (observed by transmission electron microscopy), a zeta potential of +45.9mV, and a CMC of about 9.97×10 g/L. The release results showed that CPTCACHO 7.5% has the burst release at acidic pH, and cytotoxicity study indicated that IC of CPTCACHO 7.5% for MCF-7 cell line was 0.8µg/mL. These properties altogether make CPTCACHO micelles, as a pH sensitive cargo with inherent cytotoxicity, a potential candidate for hydrophobic anticancer drugs.
[Mh] Termos MeSH primário: Ácido Aconítico/química
Antineoplásicos Fitogênicos/farmacologia
Camptotecina/farmacologia
Quitosana/química
Portadores de Fármacos
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/química
Camptotecina/química
Sobrevivência Celular/efeitos dos fármacos
Composição de Medicamentos/métodos
Liberação Controlada de Fármacos
Seres Humanos
Concentração de Íons de Hidrogênio
Interações Hidrofóbicas e Hidrofílicas
Concentração Inibidora 50
Cinética
Células MCF-7
Micelas
Tamanho da Partícula
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Drug Carriers); 0 (Micelles); 499-12-7 (Aconitic Acid); 9012-76-4 (Chitosan); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160803
[St] Status:MEDLINE


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[PMID]:26876996
[Au] Autor:Gilfillan WN; Doherty WO
[Ad] Endereço:Centre for Tropical Crops and Biocommodities, Gardens Point Campus, Queensland University of Technology, H-Block Building, Brisbane 2000, QLD, Australia. Electronic address: williamgilfillan@yahoo.com.au.
[Ti] Título:Starch composites with aconitic acid.
[So] Source:Carbohydr Polym;141:60-7, 2016 May 05.
[Is] ISSN:1879-1344
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The aim of this project is to examine the effectiveness of using aconitic acid (AcA), a tricarboxylic acid which contains a carbon/carbon double bond (CC), to enhance the properties of starch-based films. Starch/glycerol cast films were prepared with 0, 2, 5, 10 and 15wt% AcA (starch wt% basis) and the properties analysed. It was shown that AcA acted as both a cross-linking agent and also a strong plasticising agent. The 5wt% AcA derived starch films were the most effectively cross-linked having the lowest solubility (28wt%) and decreased swelling coefficient (35vol.%) by approximately 3 times and 2.4 times respectively compared to the control film submerged in water (23°C). There was also a significant increase in the film elongation at break by approximately 35 times (compared to the control) with the addition of 15wt% AcA, emphasising the plasticising effect of AcA. However, generally there was a reduced tensile strength, softening of the film, and reduced thermal stability with increased amounts of AcA.
[Mh] Termos MeSH primário: Ácido Aconítico/análogos & derivados
Plásticos Biodegradáveis/síntese química
Amido/análogos & derivados
[Mh] Termos MeSH secundário: Solubilidade
Resistência à Tração
Molhabilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biodegradable Plastics); 499-12-7 (Aconitic Acid); 9005-25-8 (Starch)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE


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[PMID]:26875555
[Au] Autor:Steiger MG; Punt PJ; Ram AFJ; Mattanovich D; Sauer M
[Ad] Endereço:Austrian Centre of Industrial Biotechnology (ACIB GmbH), Muthgasse 18, Vienna, Austria; Department of Biotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Institute of Biology, University Leiden, Sylviusweg 72, Leiden, The Netherlands. Electr
[Ti] Título:Characterizing MttA as a mitochondrial cis-aconitic acid transporter by metabolic engineering.
[So] Source:Metab Eng;35:95-104, 2016 May.
[Is] ISSN:1096-7184
[Cp] País de publicação:Belgium
[La] Idioma:eng
[Ab] Resumo:The mitochondrial carrier protein MttA is involved in the biosynthesis of itaconic acid in Aspergillus terreus. In this paper, the transport specificity of MttA is analyzed making use of different metabolically engineered Aspergillus niger strains. Furthermore, the mitochondrial localization of this protein is confirmed using fluorescence microscopy. It was found that MttA preferentially transports cis-aconitic acid over citric acid and does not transport itaconic acid. The expression of MttA in selected A. niger strains results in secretion of aconitic acid. MttA can be used in further strain engineering strategies to transport cis-aconitic acid to the cytosol to produce itaconic acid or related metabolites. The microbial production of aconitic acid (9g/L) is achieved in strains expressing this transport protein. Thus, metabolic engineering can be used for both the in vivo characterization of transport protein function like MttA and to make use of this protein by creating aconitic acid producing strains.
[Mh] Termos MeSH primário: Ácido Aconítico/metabolismo
Aspergillus
Proteínas Fúngicas
Proteínas de Membrana Transportadoras
Engenharia Metabólica
Proteínas Mitocondriais
[Mh] Termos MeSH secundário: Aspergillus/genética
Aspergillus/metabolismo
Transporte Biológico Ativo/genética
Proteínas Fúngicas/biossíntese
Proteínas Fúngicas/genética
Proteínas de Membrana Transportadoras/biossíntese
Proteínas de Membrana Transportadoras/genética
Proteínas Mitocondriais/biossíntese
Proteínas Mitocondriais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Membrane Transport Proteins); 0 (Mitochondrial Proteins); 499-12-7 (Aconitic Acid)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE


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[PMID]:26858255
[Au] Autor:Noy T; Vergnolle O; Hartman TE; Rhee KY; Jacobs WR; Berney M; Blanchard JS
[Ad] Endereço:From the Departments of Biochemistry and.
[Ti] Título:Central Role of Pyruvate Kinase in Carbon Co-catabolism of Mycobacterium tuberculosis.
[So] Source:J Biol Chem;291(13):7060-9, 2016 Mar 25.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis (Mtb) displays a high degree of metabolic plasticity to adapt to challenging host environments. Genetic evidence suggests thatMtbrelies mainly on fatty acid catabolism in the host. However,Mtbalso maintains a functional glycolytic pathway and its role in the cellular metabolism ofMtbhas yet to be understood. Pyruvate kinase catalyzes the last and rate-limiting step in glycolysis and theMtbgenome harbors one putative pyruvate kinase (pykA, Rv1617). Here we show thatpykAencodes an active pyruvate kinase that is allosterically activated by glucose 6-phosphate (Glc-6-P) and adenosine monophosphate (AMP). Deletion ofpykApreventsMtbgrowth in the presence of fermentable carbon sources and has a cidal effect in the presence of glucose that correlates with elevated levels of the toxic catabolite methylglyoxal. Growth attenuation was also observed in media containing a combination of short chain fatty acids and glucose and surprisingly, in media containing odd and even chain fatty acids alone. Untargeted high sensitivity metabolomics revealed that inactivation of pyruvate kinase leads to accumulation of phosphoenolpyruvate (P-enolpyruvate), citrate, and aconitate, which was consistent with allosteric inhibition of isocitrate dehydrogenase by P-enolpyruvate. This metabolic block could be relieved by addition of the α-ketoglutarate precursor glutamate. Taken together, our study identifies an essential role of pyruvate kinase in preventing metabolic block during carbon co-catabolism inMtb.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Carbono/metabolismo
Glicólise/genética
Mycobacterium tuberculosis/metabolismo
Piruvato Quinase/metabolismo
[Mh] Termos MeSH secundário: Ácido Aconítico/metabolismo
Monofosfato de Adenosina/metabolismo
Monofosfato de Adenosina/farmacologia
Regulação Alostérica
Animais
Proteínas de Bactérias/genética
Ácido Cítrico/metabolismo
Meios de Cultura/química
Ativação Enzimática
Ácidos Graxos Voláteis/farmacologia
Feminino
Deleção de Genes
Expressão Gênica
Glucose/metabolismo
Glucose-6-Fosfato/metabolismo
Glucose-6-Fosfato/farmacologia
Ácido Glutâmico/metabolismo
Ácido Glutâmico/farmacologia
Glicólise/efeitos dos fármacos
Isocitrato Desidrogenase/antagonistas & inibidores
Isocitrato Desidrogenase/genética
Isocitrato Desidrogenase/metabolismo
Ácidos Cetoglutáricos/metabolismo
Camundongos
Camundongos SCID
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/genética
Fosfoenolpiruvato/metabolismo
Aldeído Pirúvico/metabolismo
Piruvato Quinase/genética
Análise de Sobrevida
Tuberculose/microbiologia
Tuberculose/mortalidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Culture Media); 0 (Fatty Acids, Volatile); 0 (Ketoglutaric Acids); 2968PHW8QP (Citric Acid); 3KX376GY7L (Glutamic Acid); 415SHH325A (Adenosine Monophosphate); 499-12-7 (Aconitic Acid); 56-73-5 (Glucose-6-Phosphate); 722KLD7415 (Pyruvaldehyde); 73-89-2 (Phosphoenolpyruvate); 7440-44-0 (Carbon); 8ID597Z82X (alpha-ketoglutaric acid); EC 1.1.1.41 (Isocitrate Dehydrogenase); EC 2.7.1.40 (Pyruvate Kinase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160210
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.707430


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[PMID]:26755275
[Au] Autor:Yuan C; Clish CB; Wu C; Mayers JR; Kraft P; Townsend MK; Zhang M; Tworoger SS; Bao Y; Qian ZR; Rubinson DA; Ng K; Giovannucci EL; Ogino S; Stampfer MJ; Gaziano JM; Ma J; Sesso HD; Anderson GL; Cochrane BB; Manson JE; Torrence ME; Kimmelman AC; Amundadottir LT; Vander Heiden MG; Fuchs CS; Wolpin BM
[Ad] Endereço:Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (CY, ZRQ, DAR, KN, SO, MGVH, CSF, BMW); Broad Institute of MIT and Harvard University, Cambridge, MA (CBC, MGVH); Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Acad
[Ti] Título:Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.
[So] Source:J Natl Cancer Inst;108(6):djv409, 2016 Jun.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. RESULTS: Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. CONCLUSIONS: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Proteína 1 Reguladora do Ferro/sangue
Proteína 1 Reguladora do Ferro/genética
Neoplasias Pancreáticas/sangue
Neoplasias Pancreáticas/mortalidade
Polimorfismo de Nucleotídeo Único
Ácidos Tricarboxílicos/sangue
[Mh] Termos MeSH secundário: Ácido Aconítico/sangue
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seguimentos
Genótipo
Seres Humanos
Isocitratos/sangue
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Enfermeiras e Enfermeiros
Razão de Chances
Neoplasias Pancreáticas/diagnóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Estados Unidos/epidemiologia
Saúde da Mulher
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Isocitrates); 0 (Tricarboxylic Acids); 320-77-4 (isocitric acid); 499-12-7 (Aconitic Acid); EC 4.2.1.3 (Iron Regulatory Protein 1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160113
[St] Status:MEDLINE


  9 / 148 MEDLINE  
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[PMID]:26639528
[Au] Autor:Geiser E; Przybilla SK; Friedrich A; Buckel W; Wierckx N; Blank LM; Bölker M
[Ad] Endereço:iAMB - Institute of Applied Microbiology, ABBt - Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, D-52074, Aachen, Germany.
[Ti] Título:Ustilago maydis produces itaconic acid via the unusual intermediate trans-aconitate.
[So] Source:Microb Biotechnol;9(1):116-26, 2016 Jan.
[Is] ISSN:1751-7915
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Itaconic acid is an important biomass-derived chemical building block but has also recently been identified as a metabolite produced in mammals, which has antimicrobial activity. The biosynthetic pathway of itaconic acid has been elucidated in the ascomycetous fungus Aspergillus terreus and in human macrophages. In both organisms itaconic acid is generated by decarboxylation of the tricarboxylic acid (TCA) cycle intermediate cis-aconitate. Here, we show that the basidiomycetous fungus Ustilago maydis uses an alternative pathway and produces itaconic acid via trans-aconitate, the thermodynamically favoured isomer of cis-aconitate. We have identified a gene cluster that contains all genes involved in itaconic acid formation. Trans-aconitate is generated from cis-aconitate by a cytosolic aconitate-Δ-isomerase (Adi1) that belongs to the PrpF family of proteins involved in bacterial propionate degradation. Decarboxylation of trans-aconitate is catalyzed by a novel enzyme, trans-aconitate decarboxylase (Tad1). Tad1 displays significant sequence similarity with bacterial 3-carboxy-cis,cis-muconate lactonizing enzymes (CMLE). This suggests that U. maydis has evolved an alternative biosynthetic pathway for itaconate production using the toxic intermediate trans-aconitate. Overexpression of a pathway-specific transcription factor (Ria1) or a mitochondrial tricarboxylic acid transporter (Mtt1) resulted in a twofold increase in itaconate yield. Therefore, our findings offer new strategies for biotechnological production of this valuable biomass-derived chemical.
[Mh] Termos MeSH primário: Ácido Aconítico/metabolismo
Succinatos/metabolismo
Ustilago/metabolismo
[Mh] Termos MeSH secundário: Ácido Aconítico/química
Vias Biossintéticas
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Isomerismo
Ustilago/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Succinates); 499-12-7 (Aconitic Acid); Q4516562YH (itaconic acid)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151208
[St] Status:MEDLINE
[do] DOI:10.1111/1751-7915.12329


  10 / 148 MEDLINE  
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[PMID]:26483558
[Au] Autor:Domingo-Sananes MR; Szöor B; Ferguson MA; Urbaniak MD; Matthews KR
[Ad] Endereço:Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK.
[Ti] Título:Molecular control of irreversible bistability during trypanosome developmental commitment.
[So] Source:J Cell Biol;211(2):455-68, 2015 Oct 26.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The life cycle of Trypanosoma brucei involves developmental transitions that allow survival, proliferation, and transmission of these parasites. One of these, the differentiation of growth-arrested stumpy forms in the mammalian blood into insect-stage procyclic forms, can be induced synchronously in vitro with cis-aconitate. Here, we show that this transition is an irreversible bistable switch, and we map the point of commitment to differentiation after exposure to cis-aconitate. This irreversibility implies that positive feedback mechanisms operate to allow commitment (i.e., the establishment of "memory" of exposure to the differentiation signal). Using the reversible translational inhibitor cycloheximide, we show that this signal memory requires new protein synthesis. We further performed stable isotope labeling by amino acids in cell culture to analyze synchronized parasite populations, establishing the protein and phosphorylation profile of parasites pre- and postcommitment, thereby defining the "commitment proteome." Functional interrogation of this data set identified Nek-related kinase as the first-discovered protein kinase controlling the initiation of differentiation to procyclic forms.
[Mh] Termos MeSH primário: Ácido Aconítico/farmacologia
Diferenciação Celular/fisiologia
Proteínas de Protozoários/metabolismo
Trypanosoma brucei brucei/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/metabolismo
Diferenciação Celular/efeitos dos fármacos
Cicloeximida/farmacologia
Regulação da Expressão Gênica no Desenvolvimento
Marcação por Isótopo
Estágios do Ciclo de Vida
Quinase 1 Relacionada a NIMA
Fosforilação
Biossíntese de Proteínas/fisiologia
Proteínas Serina-Treonina Quinases/metabolismo
Proteoma/metabolismo
Transdução de Sinais/efeitos dos fármacos
Coloração e Rotulagem
Trypanosoma brucei brucei/citologia
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Proteome); 0 (Protozoan Proteins); 499-12-7 (Aconitic Acid); 98600C0908 (Cycloheximide); EC 2.7.11.1 (NIMA-Related Kinase 1); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151021
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201506114



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