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[PMID]:27777318
[Au] Autor:Rudling M
[Ad] Endereço:Metabolism Unit and KI/AZ Integrated Cardio Metabolic Center, Department of Medicine, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institute at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden mats.rudling@ki.se.
[Ti] Título:Understanding mouse bile acid formation: Is it time to unwind why mice and rats make unique bile acids?
[So] Source:J Lipid Res;57(12):2097-2098, 2016 12.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Ácidos Cólicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Sistema Enzimático do Citocromo P-450/deficiência
Sistema Enzimático do Citocromo P-450/genética
Técnicas de Inativação de Genes
Seres Humanos
Camundongos
Ratos
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Cholic Acids); 39016-49-4 (muricholic acid); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.- (cytochrome P-450 2C70, mouse)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180119
[Lr] Data última revisão:
180119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:28850891
[Au] Autor:Satomi Y; Hirayama M; Kobayashi H
[Ad] Endereço:Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan. Electronic address: yoshinori.satomi@takeda.com.
[Ti] Título:One-step lipid extraction for plasma lipidomics analysis by liquid chromatography mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1063:93-100, 2017 Sep 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In the past decade, various lipidomics methodologies have been developed using mass spectrometry based analytical technologies, enabling wide coverage lipid detection in a quantitative manner. Hence, lipidomics has become a widely-accepted approach for biomarker discovery and mechanism elucidation in both medical and biology research fields; however, there are still technical challenges. In this study, focusing on the sample preparation procedure, a single step deproteinization by a water-soluble organic solvent, such as methanol (MeOH), ethanol (EtOH), isopropanol (IPA) or acetonitrile (ACN), was evaluated and proved to be satisfactory for lipidomics analysis. Moreover, during this investigation ACN deproteinization was revealed to not be an effective method for lipid extraction because lipid decomposition was observed during the protein precipitation process through lipase activation, potentially due to the insufficient protein denaturation. Therefore, excluding ACN, protein precipitation by alcohol was evaluated as the lipid extraction reagent. Moreover, adding the MTBE-MeOH (mMM) method, one of the major liquid-liquid extraction methods for shotgun lipidomics, these four approaches were compared. Lipids were extracted from mouse plasma by these four methods and used for exhaustive lipid profiling by liquid chromatography mass spectrometry (LC/MS) analysis. Comparison of these four methods revealed that alcohol based protein precipitation was a useful sample preparation procedure for LC/MS based lipidomics analysis. Whereas MeOH extraction was appropriate for hydrophilic lipid species, IPA was effective for hydrophobic lipids such as triacylglycerols (TG). In practice, EtOH extraction is thought to be the best approach to cover wide range of lipid species using a simple preparation procedure.
[Mh] Termos MeSH primário: Fracionamento Químico/métodos
Cromatografia Líquida/métodos
Lipídeos/sangue
Espectrometria de Massas/métodos
[Mh] Termos MeSH secundário: Acetonitrilos
Animais
Precipitação Química
Ácidos Cólicos
Gangliosídeos
Lipídeos/química
Lipídeos/isolamento & purificação
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetonitriles); 0 (Cholic Acids); 0 (Gangliosides); 0 (Lipids); Z072SB282N (acetonitrile)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE


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[PMID]:28834453
[Au] Autor:Shore ND; Boorjian SA; Canter DJ; Ogan K; Karsh LI; Downs TM; Gomella LG; Kamat AM; Lotan Y; Svatek RS; Bivalacqua TJ; Grubb RL; Krupski TL; Lerner SP; Woods ME; Inman BA; Milowsky MI; Boyd A; Treasure FP; Gregory G; Sawutz DG; Yla-Herttuala S; Parker NR; Dinney CPN
[Ad] Endereço:Neal D. Shore, Carolina Urologic Research Center, Myrtle Beach, SC; Stephen A. Boorjian, Mayo Clinic, Rochester, MN; Daniel J. Canter, Ochsner Health System, New Orleans, LA; Kenneth Ogan, Emory University, Atlanta, GA; Lawrence I. Karsh, The Urology Center of Colorado, Denver, CO; Tracy M. Downs, U
[Ti] Título:Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.
[So] Source:J Clin Oncol;35(30):3410-3416, 2017 Oct 20.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10 viral particles (vp)/mL or 3 × 10 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10 vp/mL, n = 21; 3 × 10 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.
[Mh] Termos MeSH primário: Terapia Genética/métodos
Interferon-alfa/metabolismo
Neoplasias da Bexiga Urinária/terapia
[Mh] Termos MeSH secundário: Adenoviridae/genética
Administração Intravesical
Idoso
Idoso de 80 Anos ou mais
Vacina BCG/administração & dosagem
Ácidos Cólicos/química
Dissacarídeos/química
Resistência a Medicamentos Antineoplásicos
Fadiga/etiologia
Feminino
Terapia Genética/efeitos adversos
Vetores Genéticos/administração & dosagem
Vetores Genéticos/genética
Seres Humanos
Interferon-alfa/química
Interferon-alfa/genética
Masculino
Meia-Idade
Gradação de Tumores
Invasividade Neoplásica
Recidiva Local de Neoplasia
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Resultado do Tratamento
Neoplasias da Bexiga Urinária/genética
Neoplasias da Bexiga Urinária/patologia
Transtornos Urinários/etiologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (BCG Vaccine); 0 (Cholic Acids); 0 (Disaccharides); 0 (Interferon-alpha); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Syn3 compound); 43K1W2T1M6 (interferon alfa-2b)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2017.72.3064


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[PMID]:28807679
[Au] Autor:Kurogi K; Yoshihama M; Horton A; Schiefer IT; Krasowski MD; Hagey LR; Williams FE; Sakakibara Y; Kenmochi N; Suiko M; Liu MC
[Ad] Endereço:Department of Pharmacology, College of Pharmacy, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki 889-2192, Japan.
[Ti] Título:Identification and characterization of 5α-cyprinol-sulfating cytosolic sulfotransferases (Sults) in the zebrafish (Danio rerio).
[So] Source:J Steroid Biochem Mol Biol;174:120-127, 2017 Nov.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:5α-Cyprinol 27-sulfate is the major biliary bile salt present in cypriniform fish including the zebrafish (Danio rerio). The current study was designed to identify the zebrafish cytosolic sulfotransferase (Sult) enzyme(s) capable of sulfating 5α-cyprinol and to characterize the zebrafish 5α-cyprinol-sulfating Sults in comparison with human SULT2A1. Enzymatic assays using zebrafish homogenates showed 5α-cyprinol-sulfating activity. A systematic analysis, using a panel of recombinant zebrafish Sults, revealed two Sult2 subfamily members, Sult2st2 and Sult2st3, as major 5α-cyprinol-sulfating Sults. Both enzymes showed higher activities using 5α-cyprinol as the substrate, compared to their activity with DHEA, a representative substrate for mammalian SULT2 family members, particularly SULT2A1. pH-Dependence and kinetics experiments indicated that the catalytic properties of zebrafish Sult2 family members in mediating the sulfation of 5α-cyprinol were different from those of either zebrafish Sult3st4 or human SULT2A1. Collectively, these results imply that both Sult2st2 and Sult2st3 have evolved to sulfate specifically C -bile alcohol, 5α-cyprinol, in Cypriniform fish, whereas the enzymatic characteristics of zebrafish Sult3 members, particularly Sult3st4, correlated with those of human SULT2A1.
[Mh] Termos MeSH primário: Arilsulfotransferase/metabolismo
Proteínas de Peixe-Zebra/metabolismo
[Mh] Termos MeSH secundário: Animais
Colestanóis/metabolismo
Ácidos Cólicos/metabolismo
Desidroepiandrosterona/metabolismo
Embrião não Mamífero
Seres Humanos
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestanols); 0 (Cholic Acids); 0 (Zebrafish Proteins); 3692-27-1 (anhydrocyprinol); 459AG36T1B (Dehydroepiandrosterone); EC 2.8.2.1 (Arylsulfotransferase)
[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:170816
[St] Status:MEDLINE


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[PMID]:28700926
[Au] Autor:Tian H; Sakmar TP; Huber T
[Ad] Endereço:Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, New York.
[Ti] Título:The Energetics of Chromophore Binding in the Visual Photoreceptor Rhodopsin.
[So] Source:Biophys J;113(1):60-72, 2017 Jul 11.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The visual photoreceptor rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that stabilizes its inverse agonist ligand, 11-cis-retinal (11CR), by a covalent, protonated Schiff base linkage. In the visual dark adaptation, the fundamental molecular event after photobleaching of rhodopsin is the recombination reaction between its apoprotein opsin and 11CR. Here we present a detailed analysis of the kinetics and thermodynamics of this reaction, also known as the "regeneration reaction". We compared the regeneration of purified rhodopsin reconstituted into phospholipid/detergent bicelles with rhodopsin reconstituted into detergent micelles. We found that the lipid bilayer of bicelles stabilized the chromophore-free opsin over the long timescale required for the regeneration experiments, and also facilitated the ligand reuptake binding reaction. We utilized genetic code expansion and site-specific bioorthogonal labeling of rhodopsin with Alexa488 to enable, to our knowledge, a novel fluorescence resonance energy transfer-based measurement of the binding kinetics between opsin and 11CR. Based on these results, we report a complete energy diagram for the regeneration reaction of rhodopsin. We show that the dissociation reaction of rhodopsin to 11CR and opsin has a 25-pM equilibrium dissociation constant, which corresponds to only 0.3 kcal/mol stabilization compared to the noncovalent, tightly bound antagonist-GPCR complex of iodopindolol and ß-adrenergic receptor. However, 11CR dissociates four orders-of-magnitude slower than iodopindolol, which corresponds to a 6-kcal/mol higher dissociation free energy barrier. We further used isothermal titration calorimetry to show that ligand binding in rhodopsin is enthalpy driven with -22 kcal/mol, which is 12 kcal/mol more stable than the antagonist-GPCR complex. Our data provide insights into the ligand-receptor binding reaction for rhodopsin in particular, and for GPCRs more broadly.
[Mh] Termos MeSH primário: Retinaldeído/metabolismo
Rodopsina/metabolismo
[Mh] Termos MeSH secundário: Animais
Calorimetria
Bovinos
Ácidos Cólicos/química
Difusão Dinâmica da Luz
Transferência Ressonante de Energia de Fluorescência
Hidrodinâmica
Cinética
Bicamadas Lipídicas/química
Micelas
Fosfatidilcolinas/química
Fotodegradação
Ligação Proteica
Estabilidade Proteica
Receptores Adrenérgicos beta/química
Receptores Adrenérgicos beta/metabolismo
Retinaldeído/química
Rodopsina/agonistas
Rodopsina/química
Termodinâmica
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholic Acids); 0 (Lipid Bilayers); 0 (Micelles); 0 (Phosphatidylcholines); 0 (Receptors, Adrenergic, beta); 059QF0KO0R (Water); 9009-81-8 (Rhodopsin); QBP25342AG (3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate); RR725D715M (Retinaldehyde); TE895536Y5 (1-palmitoyl-2-oleoylphosphatidylcholine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE


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[PMID]:28538412
[Au] Autor:Yu XH; Sun J; Wang Y; Zhou YB
[Ad] Endereço:Second Department of Cardiovascular, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
[Ti] Título:Biomarkers of unstable angina pectoris and yangxin decoction intervention: An exploratory metabonomics study of blood plasma.
[So] Source:Medicine (Baltimore);96(21):e6998, 2017 May.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This study aimed to explore the related metabolic biomarkers and to observe the effects of Yangxin Decoction (YXD) on plasma metabolism of patients with unstable angina (UA). METHODS: In total, 10 patients with UA (intervention group) and 10 healthy participants (control group) were recruited for this study from January 2009 to December 2010. Plasma samples from both groups were analyzed using liquid chromatography mass spectrometry (LC-MS). Principle component analysis (PCA) and partial least squares (PLS) were used to explore the correlations between metabolic markers in patients with UA. RESULTS: The LC-MS results indicated that the serum levels of 5 potential metabolic markers, namely, ceramide, glycocholic acid, allocholic acid, lithocholic acid, and leukotriene (LT) B4, were significantly higher in the intervention group than those in the control group. CONCLUSION: The results of this study demonstrated potential metabolic markers that can be used to distinguish and diagnose patients with UA.
[Mh] Termos MeSH primário: Angina Instável/sangue
Angina Instável/tratamento farmacológico
Medicamentos de Ervas Chinesas/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Biomarcadores/sangue
Análise Química do Sangue
Ceramidas/sangue
Ácidos Cólicos/sangue
Cromatografia Líquida
Feminino
Ácido Glicocólico/sangue
Seres Humanos
Leucotrieno B4/sangue
Ácido Litocólico/sangue
Masculino
Espectrometria de Massas
Metabolômica
Meia-Idade
Análise de Componente Principal
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Ceramides); 0 (Cholic Acids); 0 (Drugs, Chinese Herbal); 0 (yangxin decoction); 1HGW4DR56D (Leukotriene B4); 2464-18-8 (allocholic acid); 5QU0I8393U (Lithocholic Acid); G59NX3I3RT (Glycocholic Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006998


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[PMID]:28502376
[Au] Autor:Ferrières J
[Ad] Endereço:CHU Rangueil, TSA 50032, fédération de cardiologie, 31059 Toulouse cedex 9, France. Electronic address: jean.ferrieres@univ-tlse3.fr.
[Ti] Título:[2016 European Society of Cardiology guidelines for the management of dyslipidemias].
[Ti] Título:Les recommandations de 2016 de la Société européenne de cardiologie sur la prise en charge des dyslipidémies..
[So] Source:Presse Med;46(7-8 Pt 1):688-696, 2017 Jul - Aug.
[Is] ISSN:2213-0276
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:Cardiovascular risk evaluation is a fundamental approach in cardiovascular prevention. Cardiovascular risk categories are associated with lipid-lowering drug intensity. LDL cholesterol is the main target of treatment. Statins are the first line lipid-lowering drugs. Lipid-lowering combination therapy is to be used in order to obtain the LDL cholesterol targets. Screening of familial hypercholesterolemia might be included in all prevention population strategy.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/prevenção & controle
Dislipidemias/terapia
[Mh] Termos MeSH secundário: Anticolesterolemiantes/uso terapêutico
LDL-Colesterol/sangue
Ácidos Cólicos/sangue
Dieta Mediterrânea
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Testes de Função Hepática
Mialgia/induzido quimicamente
Guias de Prática Clínica como Assunto
Medição de Risco
Erros Inatos do Metabolismo de Esteroides/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Cholesterol, LDL); 0 (Cholic Acids); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


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[PMID]:28423182
[Au] Autor:Hwang E; Cheong HK; Kim SY; Kwon O; Blain KY; Choe S; Yeo KJ; Jung YW; Jeon YH; Cheong C
[Ad] Endereço:Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Chungbuk, Korea.
[Ti] Título:Crystal structure of the EnvZ periplasmic domain with CHAPS.
[So] Source:FEBS Lett;591(10):1419-1428, 2017 May.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bacteria sense and respond to osmolarity through the EnvZ-OmpR two-component system. The structure of the periplasmic sensor domain of EnvZ (EnvZ-PD) is not available yet. Here, we present the crystal structure of EnvZ-PD in the presence of CHAPS detergent. The structure of EnvZ-PD shows similar folding topology to the PDC domains of PhoQ, DcuS, and CitA, but distinct orientations of helices and ß-hairpin structures. The CD and NMR spectra of EnvZ-PD in the presence of cholate, a major component of bile salts, are similar to those with CHAPS. Chemical cross-linking shows that the dimerization of EnvZ-PD is significantly inhibited by the CHAPS and cholate. Together with ß-galactosidase assay, these results suggest that bile salts may affect the EnvZ structure and function in Escherichia coli.
[Mh] Termos MeSH primário: Proteínas da Membrana Bacteriana Externa/química
Colatos/farmacologia
Ácidos Cólicos/farmacologia
Detergentes/farmacologia
Proteínas de Escherichia coli/química
Escherichia coli/metabolismo
Complexos Multienzimáticos/química
[Mh] Termos MeSH secundário: Proteínas da Membrana Bacteriana Externa/efeitos dos fármacos
Dicroísmo Circular
Cristalografia por Raios X
Proteínas de Escherichia coli/efeitos dos fármacos
Modelos Moleculares
Complexos Multienzimáticos/efeitos dos fármacos
Domínios Proteicos/efeitos dos fármacos
Dobramento de Proteína/efeitos dos fármacos
Estrutura Secundária de Proteína/efeitos dos fármacos
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Bacterial Outer Membrane Proteins); 0 (Cholates); 0 (Cholic Acids); 0 (Detergents); 0 (Escherichia coli Proteins); 0 (Multienzyme Complexes); EC 2.7.3.- (envZ protein, E coli); QBP25342AG (3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12658


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[PMID]:28411018
[Au] Autor:Griffiths WJ; Hearn T; Crick PJ; Abdel-Khalik J; Dickson A; Yutuc E; Wang Y
[Ad] Endereço:Swansea University Medical School, ILS1 Building, Singleton Park, Swansea, SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
[Ti] Título:Charge-tagging liquid chromatography-mass spectrometry methodology targeting oxysterol diastereoisomers.
[So] Source:Chem Phys Lipids;207(Pt B):69-80, 2017 Oct.
[Is] ISSN:1873-2941
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The introduction of a hydroxy group to the cholesterol skeleton introduces not only the possibility for positional isomers but also diastereoisomers, where two or more isomers have different configurations at one or more of the stereocentres but are not mirror images. The differentiation of diastereoisomers is important as differing isomers can have differing biochemical properties and are formed via different biochemical pathways. Separation of diasterioisomers is not always easy by chromatographic methods Here we demonstrate, by application of charge-tagging and derivatisation with the Girard P reagent, the separation and detection of biologically relevant diastereoisomers using liquid chromatography - mass spectrometry with multistage fragmentation.
[Mh] Termos MeSH primário: Oxisteróis/análise
Oxisteróis/química
[Mh] Termos MeSH secundário: Colestenos/análise
Colestenos/química
Ácidos Cólicos/análise
Ácidos Cólicos/química
Cromatografia Líquida
Seres Humanos
Espectrometria de Massas
Conformação Molecular
Oxirredutases/química
Oxirredutases/metabolismo
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestenes); 0 (Cholic Acids); 0 (Oxysterols); 0 (cholestenoic acid); EC 1.- (Oxidoreductases); EC 1.17.99.3 (ACOX2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE


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[PMID]:28315136
[Au] Autor:Fujita K; Iguchi Y; Une M; Watanabe S
[Ad] Endereço:Division of Nutritional Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
[Ti] Título:Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in ß-Muricholic Acid, a Farnesoid X Receptor Antagonist.
[So] Source:Lipids;52(4):335-344, 2017 Apr.
[Is] ISSN:1558-9307
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and ß-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of ß-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.
[Mh] Termos MeSH primário: Lipogênese/efeitos dos fármacos
Fígado/metabolismo
Receptores Citoplasmáticos e Nucleares/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
Ácido Ursodesoxicólico/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Ácido Quenodesoxicólico/metabolismo
Ácidos Cólicos
Ácido Desoxicólico/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Masculino
Camundongos
Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores
Ácido Ursodesoxicólico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholic Acids); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 0 (farnesoid X-activated receptor); 005990WHZZ (Deoxycholic Acid); 0GEI24LG0J (Chenodeoxycholic Acid); 39016-49-4 (muricholic acid); 724L30Y2QR (Ursodeoxycholic Acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171105
[Lr] Data última revisão:
171105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170319
[St] Status:MEDLINE
[do] DOI:10.1007/s11745-017-4242-5



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