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Pesquisa : D04.210.500.247.222.222.347 [Categoria DeCS]
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[PMID]:27974267
[Au] Autor:Procházková T; Sychrová E; Javurková B; Vecerková J; Kohoutek J; Lepsová-Skácelová O; Bláha L; Hilscherová K
[Ad] Endereço:RECETOX - Research Centre for Toxic Compounds in the Environment, Masaryk University, Faculty of Science, Brno, Czech Republic.
[Ti] Título:Phytoestrogens and sterols in waters with cyanobacterial blooms - Analytical methods and estrogenic potencies.
[So] Source:Chemosphere;170:104-112, 2017 Mar.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Compounds with estrogenic potencies and their adverse effects in surface waters have received much attention. Both anthropogenic and natural compounds contribute to overall estrogenic activity in freshwaters. Recently, estrogenic potencies were also found to be associated with cyanobacteria and their blooms in surface waters. The present study developed and compared the solid phase extraction and LC-MS/MS analytical approaches for determination of phytoestrogens (8 flavonoids - biochanin A, coumestrol, daidzein, equol, formononetin, genistein, naringenin, apigenin - and 5 sterols - ergosterol, ß-sitosterol, stigmasterol, campesterol, brassicasterol) and cholesterol in water. The method was used for analyses of samples collected in stagnant water bodies dominated by different cyanobacterial species. Concentrations of individual flavonoids ranged from below the limit of detection to 3.58 ng/L. Sterols were present in higher amounts up to 2.25 µg/L. Biological potencies of these phytoestrogens in vitro were characterized using the hERα-HeLa-9903 cell line. The relative estrogenic potencies (compared to model estrogen - 17ß-estradiol) of flavonoids ranged from 2.25E-05 to 1.26E-03 with coumestrol being the most potent. None of the sterols elicited estrogenic response in the used bioassay. Estrogenic activity was detected in collected field water samples (maximum effect corresponding to 2.07 ng/L of 17ß-estradiol equivalents, transcriptional assay). At maximum phytoestrogens accounted for only 1.56 pg/L of 17ß-estradiol equivalents, contributing maximally 8.5% of the total estrogenicity of the water samples. Other compounds therefore, most likely of anthropogenic origin such as steroid estrogens, are probably the major drivers of total estrogenic effects in these surface waters.
[Mh] Termos MeSH primário: Cianobactérias/efeitos dos fármacos
Estradiol/análise
Fitoestrógenos/análise
Esteróis/análise
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Colestadienóis
Colesterol/análogos & derivados
Cianobactérias/metabolismo
Estrogênios/análise
Estrona/análise
Água Doce
Genisteína/análise
Células HeLa
Seres Humanos
Isoflavonas/análise
Fitosteróis
Receptores Estrogênicos/metabolismo
Sitosteroides/análise
Espectrometria de Massas em Tandem
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Estrogens); 0 (Isoflavones); 0 (Phytoestrogens); 0 (Phytosterols); 0 (Receptors, Estrogen); 0 (Sitosterols); 0 (Sterols); 0 (Water Pollutants, Chemical); 059QF0KO0R (Water); 295DQC67BJ (formononetin); 2B0KG2XFOF (brassicasterol); 2DI9HA706A (Estrone); 4TI98Z838E (Estradiol); 5L5O665639 (campesterol); 5LI01C78DD (gamma-sitosterol); 6287WC5J2L (daidzein); 97C5T2UQ7J (Cholesterol); DH2M523P0H (Genistein); U13J6U390T (biochanin A)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


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[PMID]:26976653
[Au] Autor:Griffiths WJ; Abdel-Khalik J; Crick PJ; Ogundare M; Shackleton CH; Tuschl K; Kwok MK; Bigger BW; Morris AA; Honda A; Xu L; Porter NA; Björkhem I; Clayton PT; Wang Y
[Ad] Endereço:College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
[Ti] Título:Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients.
[So] Source:J Steroid Biochem Mol Biol;169:77-87, 2017 May.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ -sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3ß,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5ng/mL).
[Mh] Termos MeSH primário: Oxisteróis/sangue
Síndrome de Smith-Lemli-Opitz/sangue
Esteróis/sangue
[Mh] Termos MeSH secundário: Colestadienóis/sangue
Desidrocolesteróis/sangue
Radicais Livres/química
Seres Humanos
Mutação
Oxirredutases atuantes sobre Doadores de Grupo CH-CH
Plasma/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Dehydrocholesterols); 0 (Free Radicals); 0 (Oxysterols); 0 (Sterols); 70741-38-7 (cholesta-5,8-dien-3 beta-ol); BK1IU07GKF (7-dehydrocholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE


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[PMID]:28071031
[Au] Autor:Cegielska-Taras T; Nogala-Kalucka M; Szala L; Siger A
[Ad] Endereço:Plant Breeding and Acclimatization Institute &#; Research Division Poznan, Department of Genetics and Breeding of Oilseed Crops, Poland.
[Ti] Título:Study of variation of tocochromanol and phytosterol contents in black and yellow seeds of Brassica napus L. doubled haploid populations.
[So] Source:Acta Sci Pol Technol Aliment;15(3):321-332, 2016 Jul-Sep.
[Is] ISSN:1898-9594
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In the study, an analysis of tocopherols, plastochomanol-8 and phytosterols was conducted using DH lines obtained from F1 hybrids of reciprocal crosses between yellow- and black-seeded lines. METHODS: The biological material for the study consisted of two DH populations of winter oilseed rape obtained from F1 hybrids of reciprocal crosses between two DH lines: yellow- and black-seeded. Seed color was determined using a ColorFlex spectrophotometer. Fat content was determined via pulsed NMR. The levels of tocopherols, and plastochromanol-8 are analyzed using HPLC. Phytosterol contents and composition were determined by the GC method. RESULTS: The fat content of the black-seeded parental line was 49% and this was higher than that of the yellow-seeded parental line (44%). The fat content of DH line populations ranged from 44 to 51%. Total tocopherol content ranged from 460 to 602 mg/kg and the α-T/γ-T ratio was from 0.66 to 1.09. In parental lines H2-26 and Z-114 the total tocopherol content was 534 and 525 mg/kg, but the α-T/γ-T ratios were 0.81 and 1.21, respectively. The yellow-seeded parental line (Z-114) was characterized by a higher PC-8 content (81 mg/kg) than the H2-26 black-seeded parental line (58 mg/kg). The largest part of the total phytosterol content in seeds of both populations was ß-sitosterol from 976 to 2148 mg/kg, followed by campasterol, from 636 to 1364 mg/kg, and brassicasterol from 375 to 678 mg/kg. The total tocopherol content ranged from 462 to 595 mg/kg (population HxZ) and from 460 to 602 mg/kg (population ZxH). Significantly positive correlations were observed between the seed color with α-T (r = 0.38, p < 0.01), γ-T (r = -0,34, p < 0.01) and PC-8 content (r = 0.29, p < 0.01). Correlations between the seed color with total tocopherol and total phytosterol content were not noted. CONCLUSIONS: Considering the range of genetic variation among doubled haploids of two populations, selected DH lines may be good parents for further breeding programs focused on increasing the amount and improving the quality of oilseed rapeseed oil. However, further studies will also be made to determine the influence of the environment on bioactive compounds in rapeseed oil. Cross direction of parental DH lines: yellow- and black-seeded has some influence, albeit not statistically significant, on the diversity of doubled haploid in their populations with regard to average fat, tocochromanol and phytosterol content.
[Mh] Termos MeSH primário: Brassica napus/química
Cromanos/análise
Fitosteróis/análise
Sementes/química
Tocoferóis/análise
Vitamina E/análogos & derivados
[Mh] Termos MeSH secundário: Colestadienóis/análise
Ácidos Graxos/análise
Haploidia
Sitosteroides/análise
Vitamina E/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Chromans); 0 (Fatty Acids); 0 (Phytosterols); 0 (Sitosterols); 1406-18-4 (Vitamin E); 2B0KG2XFOF (brassicasterol); 4382-43-8 (plastochromanol 8); 5LI01C78DD (gamma-sitosterol); R0ZB2556P8 (Tocopherols)
[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:170111
[St] Status:MEDLINE
[do] DOI:10.17306/J.AFS.2016.3.31


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[PMID]:28036382
[Au] Autor:Jancic S; Frisvad JC; Kocev D; Gostincar C; Dzeroski S; Gunde-Cimerman N
[Ad] Endereço:Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, Ljubljana, Slovenia.
[Ti] Título:Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions.
[So] Source:PLoS One;11(12):e0169116, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A and UCA 1064-B). In particular an increase in NaCl concentration from 5% to 15% in the growth media increased the production of the toxic metabolites wallimidione, walleminol and walleminone.
[Mh] Termos MeSH primário: Basidiomycota/genética
Basidiomycota/metabolismo
Ambientes Extremos
Micotoxinas/metabolismo
Metabolismo Secundário/genética
Cloreto de Sódio/metabolismo
[Mh] Termos MeSH secundário: Azasteroides/metabolismo
Basidiomycota/classificação
Colestadienóis/metabolismo
Cromatografia Líquida de Alta Pressão
Contaminação de Alimentos
Microbiologia de Alimentos
Glucose/metabolismo
Cloreto de Magnésio/metabolismo
Metabolismo Secundário/fisiologia
Sesquiterpenos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azasteroids); 0 (Cholestadienols); 0 (Mycotoxins); 0 (Sesquiterpenes); 0 (walleminone); 02F3473H9O (Magnesium Chloride); 126039-09-6 (walleminol A); 144773-49-9 (UCA 1064-B); 451W47IQ8X (Sodium Chloride); 50686-98-1 (A25822B); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169116


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[PMID]:27534104
[Au] Autor:Bailen M; Khamlichi MD; Benharref A; Martinez-Diaz RA; Gonzalez-Coloma A
[Ti] Título:New Bioactive Semisynthetic Derivatives of 31-Norlanostenol and Obtusifoliol from Euphorbia officinarum.
[So] Source:Nat Prod Commun;11(6):733-8, 2016 Jun.
[Is] ISSN:1934-578X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fifteen semisynthetic terpenoid derivatives from the major latex components of Euphorbia officinarum have been evaluated against the insect pest Spodoptera littoralis, two species of protozoan parasites, Trypanosoma cruzi and Leishmania infantum, and also against insect Sf9 and mammalian CHO cells to test their selective cytotoxicity. Our results showed that 40% of the test substances were postingestive toxicants to S. littoralis. All the tested derivatives had cytotoxic effects on insect-derived Sf9 cells, whereas mammalian CHO cells were affected by a lower number of compounds (47%). Furthermore, 87% of the test compounds had antiparasitic effects on both L. infantum and T. cruzi, with some of them being selective parasite toxicants.
[Mh] Termos MeSH primário: Antiparasitários/síntese química
Colestadienóis/síntese química
Euphorbia/química
Lanosterol/análogos & derivados
Extratos Vegetais/síntese química
[Mh] Termos MeSH secundário: Animais
Antiparasitários/química
Antiparasitários/farmacologia
Células CHO
Colestadienóis/química
Colestadienóis/farmacologia
Cricetinae
Cricetulus
Lanosterol/síntese química
Lanosterol/química
Lanosterol/farmacologia
Leishmania infantum/efeitos dos fármacos
Estrutura Molecular
Extratos Vegetais/química
Extratos Vegetais/farmacologia
Trypanosoma cruzi/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiparasitic Agents); 0 (Cholestadienols); 0 (Plant Extracts); 1J05Z83K3M (Lanosterol); 3RH57E39ER (obtusifoliol); 79-62-9 (lanostenol)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160818
[Lr] Data última revisão:
160818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE


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[PMID]:27474490
[Au] Autor:Aghaei M; Yazdiniapour Z; Ghanadian M; Zolfaghari B; Lanzotti V; Mirsafaee V
[Ad] Endereço:Department of Biochemistry, Isfahan University of Medical Sciences, Isfahan, Iran.
[Ti] Título:Obtusifoliol related steroids from Euphorbia sogdiana with cell growth inhibitory activity and apoptotic effects on breast cancer cells (MCF-7 and MDA-MB231).
[So] Source:Steroids;115:90-97, 2016 Nov.
[Is] ISSN:1878-5867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:From the aerial parts of Euphorbia sogdiana Popov, obtusifoliol (1) and two related steroids (2-3) have been isolated and characterized along with a known cycloartane derivative (4). The chemical structure of the obtusifoliol-related compounds, obtained by 1D and 2D NMR, and MS measurements, have been determined as: 3ß,7α-dihydroxy-4α,14α-dimethyl-5α-ergosta-8,24(28)-diene-11-one (2) and 3ß-hydroxy-4α,14α-dimethyl-5α-ergosta-8,24(28)-diene-1-one (3). Compound 2 has been previously isolated from Euphorbia chamaesyce while compound 3 was never reported before. The isolated compounds 1-4 were subjected to cytotoxic tests on the breast cancer cells, MCF-7 and MDA-MB231. Further pharmacological tests on the more active compounds 2 and 3 indicated their action to be related to cell growth inhibitory activity and apoptotic effects on the tested cells.
[Mh] Termos MeSH primário: Colestadienóis/química
Euphorbia/química
Esteroides/química
Esteroides/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Neoplasias da Mama/metabolismo
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Células MCF-7
Espectroscopia de Ressonância Magnética
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Steroids); 3RH57E39ER (obtusifoliol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160731
[St] Status:MEDLINE


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[PMID]:27313059
[Au] Autor:Hargrove TY; Friggeri L; Wawrzak Z; Sivakumaran S; Yazlovitskaya EM; Hiebert SW; Guengerich FP; Waterman MR; Lepesheva GI
[Ad] Endereço:Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
[Ti] Título:Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design.
[So] Source:J Lipid Res;57(8):1552-63, 2016 Aug.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rapidly multiplying cancer cells synthesize greater amounts of cholesterol to build their membranes. Cholesterol-lowering drugs (statins) are currently in clinical trials for anticancer chemotherapy. However, given at higher doses, statins cause serious side effects by inhibiting the formation of other biologically important molecules derived from mevalonate. Sterol 14α-demethylase (CYP51), which acts 10 steps downstream, is potentially a more specific drug target because this portion of the pathway is fully committed to cholesterol production. However, screening a variety of commercial and experimental inhibitors of microbial CYP51 orthologs revealed that most of them (including all clinical antifungals) weakly inhibit human CYP51 activity, even if they display high apparent spectral binding affinity. Only one relatively potent compound, (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV), was identified. VFV has been further tested in cellular experiments and found to decrease proliferation of different cancer cell types. The crystal structures of human CYP51-VFV complexes (2.0 and 2.5 Å) both display a 2:1 inhibitor/enzyme stoichiometry, provide molecular insights regarding a broader substrate profile, faster catalysis, and weaker susceptibility of human CYP51 to inhibition, and outline directions for the development of more potent inhibitors.
[Mh] Termos MeSH primário: Inibidores de 14-alfa Desmetilase/química
Antineoplásicos/química
Esterol 14-Desmetilase/química
[Mh] Termos MeSH secundário: Antifúngicos
Antiprotozoários/química
Domínio Catalítico
Linhagem Celular Tumoral
Colestadienóis/química
Cristalografia por Raios X
Desenho de Drogas
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Ligações de Hidrogênio
Lanosterol/química
Modelos Moleculares
Ligação Proteica
Conformação Proteica em alfa-Hélice
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (14-alpha Demethylase Inhibitors); 0 (Antifungal Agents); 0 (Antineoplastic Agents); 0 (Antiprotozoal Agents); 0 (Cholestadienols); 1J05Z83K3M (Lanosterol); 3RH57E39ER (obtusifoliol); EC 1.14.13.70 (CYP51A1 protein, human); EC 1.14.13.70 (Sterol 14-Demethylase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160618
[St] Status:MEDLINE
[do] DOI:10.1194/jlr.M069229


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[PMID]:26806045
[Au] Autor:Ras RT; Koppenol WP; Garczarek U; Otten-Hofman A; Fuchs D; Wagner F; Trautwein EA
[Ad] Endereço:Unilever Research and Development Vlaardingen, Vlaardingen, the Netherlands. Electronic address: Rouyanne.Ras@unilever.com.
[Ti] Título:Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism.
[So] Source:Nutr Metab Cardiovasc Dis;26(4):302-9, 2016 Apr.
[Is] ISSN:1590-3729
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored. METHODS AND RESULTS: The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 µmol/L and by 28% (95%CI: 19; 39) starting at 11.4 µmol/L, respectively, and remained stable during the following 8 weeks. Placebo-corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)). CONCLUSIONS: Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov (NCT01803178).
[Mh] Termos MeSH primário: Metabolismo dos Lipídeos/efeitos dos fármacos
Fitosteróis/administração & dosagem
Fitosteróis/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Colestadienóis/sangue
Colesterol/análogos & derivados
Colesterol/sangue
LDL-Colesterol/sangue
Método Duplo-Cego
Feminino
Seres Humanos
Hipercolesterolemia/sangue
Hipercolesterolemia/tratamento farmacológico
Absorção Intestinal/efeitos dos fármacos
Masculino
Meia-Idade
Estudos Prospectivos
Sitosteroides/sangue
Estigmasterol/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Cholesterol, LDL); 0 (Phytosterols); 0 (Sitosterols); 2B0KG2XFOF (brassicasterol); 5L5O665639 (campesterol); 5LI01C78DD (gamma-sitosterol); 80-99-9 (lathosterol); 97C5T2UQ7J (Cholesterol); 99WUK5D0Y8 (Stigmasterol)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160126
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:26752299
[Au] Autor:Somintara S; Leardkamolkarn V; Suttiarporn P; Mahatheeranont S
[Ad] Endereço:Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
[Ti] Título:Anti-Tumor and Immune Enhancing Activities of Rice Bran Gramisterol on Acute Myelogenous Leukemia.
[So] Source:PLoS One;11(1):e0146869, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute myelogenous leukemia (AML) is a cancer of the blood that most commonly affects human adults. The specific cause of AML is unclear, but it induces abnormality of white blood cells that grow rapidly and accumulate in bone marrow interfering with the production and functions of the normal blood cells. AML patients face poor prognosis and low quality of life during chemotherapy or transplantation of hematopoietic stem cells due to the progressive impairment of their immune system. The goal of this study is to find natural products that have the potential to delay growth or eliminate the abnormal leukemic cells but cause less harmful effect to the body's immune system. METHODS AND FINDINGS: The unsaponified fraction of Riceberry rice bran (RBDS) and the main pure compound, gramisterol, were studied for cytotoxicity and biological activities in WEHI-3 cells and in the leukemic mouse model induced by transplantation of WEHI-3 cells intraperitoneally. In the in vitro assay, RBDS and gramisterol exerted sub-G1 phase cell cycle arrest with a potent induction of apoptosis. Both of them effectively decreased cell cycle controlling proteins (cyclin D1 and cyclin E), suppressed cellular DNA synthesis and mitotic division, and reduced anti-apoptosis Bcl-2 protein, but increased apoptotic proteins (p53 and Bax) and activated caspase-3 enzyme in the intrinsic cell death stimulation pathway. In leukemic mice, daily feeding of RBDS significantly increased the amount of immune function-related cells including CD3+, CD19+, and CD11b+, and elevated the serum levels of IFN-γ, TNF-α, IL-2, and IL-12ß cytokines, but suppressed IL-10 level. At the tumor sites, CD11b+ cells were polarized and became active phagocytotic cells. Treatment of mice normal immune cells with gramisterol alone or a combination of gramisterol with cytokines released from RBDS-treated leukemic mice splenocytes culture synergistically increased pSTAT1 transcriptional factor that up-regulated the genes controlling cell survival and function. Phosphorylation of STAT1 was absent in WEHI-3. Instead, similar treatments significantly decreased pSTAT3 signaling that regulates transcription of genes controlling tumor growth and proliferation. CONCLUSIONS: Rice bran gramisterol possesses a promising anti-cancer effect against a tumor of white blood cells and induces the production of anti-cancer immune-related cytokines. Gramisterol induces cell cycle arrest and apoptosis via suppression of pSTAT3 signaling control of tumor cells' growth and progression. Gramisterol increased IFN-γ production and prevented the dysfunctional immune system of leukemic mice by enhancing pSTAT1 transcription signal controlling proliferation and functions of hematopoietic cells in the spleen. Together with IFN-γ, gramisterol efficiently facilitates leukemic mice immune system modulation leading to improvement of the AML condition. Administration of RBDS containing gramisterol potentiates immune recovery of leukemic mice and extends their survival. This finding encourages the medicinal application of rice bran gramisterol as a palliative treatment or an alternative agent for future drug development against AML.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Colestadienóis/uso terapêutico
Regulação Leucêmica da Expressão Gênica
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/imunologia
Oryza/química
Esteróis/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antígenos CD19/metabolismo
Antineoplásicos/química
Apoptose
Antígeno CD11b/metabolismo
Complexo CD3/metabolismo
Caspase 3/metabolismo
Proliferação Celular
Colestadienóis/química
Ciclina D1/metabolismo
Ciclina E/metabolismo
Modelos Animais de Doenças
Ensaios de Seleção de Medicamentos Antitumorais
Fase G1/efeitos dos fármacos
Sistema Imunitário
Camundongos
Camundongos Endogâmicos BALB C
Extratos Vegetais/química
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Transdução de Sinais
Esteróis/química
Proteína Supressora de Tumor p53/metabolismo
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (24-methylenelophenol); 0 (Antigens, CD19); 0 (Antineoplastic Agents); 0 (Bax protein, mouse); 0 (CD11b Antigen); 0 (CD3 Complex); 0 (Cholestadienols); 0 (Cyclin E); 0 (Plant Extracts); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Sterols); 0 (Tumor Suppressor Protein p53); 0 (bcl-2-Associated X Protein); 114100-40-2 (Bcl2 protein, mouse); 136601-57-5 (Cyclin D1); EC 3.4.22.- (Casp3 protein, mouse); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0146869


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[PMID]:26576007
[Au] Autor:Sachs JP; Kawka OE
[Ad] Endereço:School of Oceanography, University of Washington, Seattle, Washington, 98195, United States of America.
[Ti] Título:The Influence of Growth Rate on 2H/1H Fractionation in Continuous Cultures of the Coccolithophorid Emiliania huxleyi and the Diatom Thalassiosira pseudonana.
[So] Source:PLoS One;10(11):e0141643, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The hydrogen isotope (2H/1H) ratio of lipids from phytoplankton is a powerful new tool for reconstructing hydroclimate variations in the geologic past from marine and lacustrine sediments. Water 2H/1H changes are reflected in lipid 2H/1H changes with R2 > 0.99, and salinity variations have been shown to cause about a 1‰ change in lipid δ2H values per unit (ppt) change in salinity. Less understood are the effects of growth rate, nutrient limitation and light on 2H/1H fractionation in phytoplankton. Here we present the first published study of growth rate effects on 2H/1H fractionation in the lipids of coccolithophorids grown in continuous cultures. Emiliania huxleyi was cultivated in steady state at four growth rates and the δ2H value of individual alkenones (C37:2, C37:3, C38:2, C38:3), fatty acids (C14:0, C16:0, C18:0), and 24-methyl cholest-5,22-dien-3ß-ol (brassicasterol) were measured. 2H/1H fractionation increased in all lipids as growth rate increased by 24‰ to 79‰ (div d-1)-1. We attribute this response to a proportional increase in the fraction of NADPH from Photosystem I (PS1) of photosynthesis relative to NADPH from the cytosolic oxidative pentose phosphate (OPP) pathway in the synthesis of lipids as growth rate increases. A 3-endmember model is presented in which lipid hydrogen comes from NADPH produced in PS1, NADPH produced by OPP, and intracellular water. With published values or best estimates of the fractionation factors for these sources (αPS1 = 0.4, αOPP = 0.75, and αH2O = 0) and half of the hydrogen in a lipid derived from water the model indicates αlipid = 0.79. This value is within the range measured for alkenones (αalkenone = 0.77 to 0.81) and fatty acids (αFA = 0.75 to 0.82) in the chemostat cultures, but is greater than the range for brassicasterol (αbrassicasterol = 0.68 to 0.72). The latter is attributed to a greater proportion of hydrogen from NADPH relative to water in isoprenoid lipids. The model successfully explains the increase in 2H/1H fractionation in the sterol 24-methyl-cholesta-5,24(28)-dien-3ß-ol from marine centric diatom T. pseudonana chemostat cultures as growth rate increases. Insensitivity of αFA in those same cultures may be attributable to a larger fraction of hydrogen in fatty acids sourced from intracellular water at the expense of NADPH as growth rate increases. The high sensitivity of α to growth rate in E. huxleyi lipids and a T. pseudonana sterol implies that any change in growth rate larger than ~0.15 div d-1 can cause a change in δ2Hlipid that is larger than the analytical error of the measurement (~5‰), and needs to be considered when interpreting δ2Hlipid variations in sediments.
[Mh] Termos MeSH primário: Diatomáceas/crescimento & desenvolvimento
Haptófitas/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Colestadienóis/metabolismo
Deutério/metabolismo
Diatomáceas/metabolismo
Haptófitas/metabolismo
Metabolismo dos Lipídeos
Fitosteróis/metabolismo
Salinidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Phytosterols); 2B0KG2XFOF (brassicasterol); AR09D82C7G (Deuterium)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0141643



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