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Pesquisa : B01.050.150.900.649.313.992.635.075.250 [Categoria DeCS]
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[PMID]:28467418
[Au] Autor:Khare S; Nick JA; Zhang Y; Galeano K; Butler B; Khoshbouei H; Rayaprolu S; Hathorn T; Ranum LPW; Smithson L; Golde TE; Paucar M; Morse R; Raff M; Simon J; Nordenskjöld M; Wirdefeldt K; Rincon-Limas DE; Lewis J; Kaczmarek LK; Fernandez-Funez P; Nick HS; Waters MF
[Ad] Endereço:Department of Neurology, University of Florida, Gainesville, FL, United States of America.
[Ti] Título:A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
[So] Source:PLoS One;12(5):e0173565, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of KCNC3R423H may be mediated through indirect effects on EGFR signaling in the developing cerebellum. Our results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology.
[Mh] Termos MeSH primário: Receptor do Fator de Crescimento Epidérmico/metabolismo
Canais de Potássio Shaw/genética
Degenerações Espinocerebelares/genética
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Drosophila melanogaster
Feminino
Seres Humanos
Masculino
Linhagem
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KCNC3 protein, human); 0 (Shaw Potassium Channels); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173565


  2 / 110811 MEDLINE  
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[PMID]:29320818
[Au] Autor:Chai JY; Sohn WM; Na BK; Park JB; Jeoung HG; Hoang EH; Htoon TT; Tin HH
[Ad] Endereço:Korea Association of Health Promotion, Seoul 07653, Korea.
[Ti] Título:Zoonotic Trematode Metacercariae in Fish from Yangon, Myanmar and Their Adults Recovered from Experimental Animals.
[So] Source:Korean J Parasitol;55(6):631-641, 2017 Dec.
[Is] ISSN:1738-0006
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:A survey was performed to investigate the infection status of zoonotic trematode (ZT) metacercariae in fish from a local market in Yangon City, Myanmar. A total of 264 fish (12 species) were collected through 4 times from December 2013 to June 2015. All collected fish were transferred to our laboratory on ice and examined by the artificial digestion method. More than 7 species of ZT metacercariae, i.e., Haplorchis taichui, H. pumilio, H. yokogawai, Centrocestus spp., Stellantchasmus falcatus, Pygidiopsis cambodiensis, and Procerovum sp. were detected. Metacercariae of H. taichui were collected in 58 (42.3%) out of 137 fish (5 species), and their average density was 42.9 per fish infected. Metacercariae of H. pumilio were detected in 96 (49.0%) out of 196 fish (9 species), and their average density was 23.6 per fish infected. H. yokogawai metacercariae were found in 40 (50.0%) out of 80 fish (5 species), and Centrocestus spp. metacercariae in 91 (50.8%) out of 179 fish (8 species), and their densities were 306 and 25.8 per fish infected, respectively. Metacercariae of S. falcatus and P. cambodiensis were detected only in mullets, Chelon macrolepis. A total of 280 Procerovum sp. metacercariae were found in 6 out of 12 climbing perch, Anabas testudineus. Morphological characteristics of adult flukes recovered from experimental animals were described. It has been first confirmed that fish from Yangon, Myanmar are commonly infected with various species of ZT metacercariae.
[Mh] Termos MeSH primário: Peixes/parasitologia
Metacercárias/isolamento & purificação
Trematódeos/isolamento & purificação
[Mh] Termos MeSH secundário: Animais
Gatos
Cricetinae
Seres Humanos
Metacercárias/anatomia & histologia
Mianmar/epidemiologia
Trematódeos/anatomia & histologia
Infecções por Trematódeos/epidemiologia
Infecções por Trematódeos/parasitologia
Zoonoses
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:180112
[St] Status:MEDLINE
[do] DOI:10.3347/kjp.2017.55.6.631


  3 / 110811 MEDLINE  
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[PMID]:29031765
[Au] Autor:Boakye YD; Groyer L; Heiss EH
[Ad] Endereço:Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
[Ti] Título:An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages.
[So] Source:Biochim Biophys Acta;1862(1):61-70, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An extract of Phyllanthus muellerianus and its constituent geraniin have been reported to exert anti-inflammatory activity in vivo. However, orally consumed geraniin, an ellagitannin, shows low bioavailability and undergoes metabolization to urolithins by gut microbiota. This study aimed at comparing geraniin and urolithin A with respect to inhibition of M1 (LPS) polarization of murine J774.1 macrophages and shedding more light on possible underlying mechanisms. METHODS: Photometric, fluorimetric as well as luminescence-based assays monitored production of reactive oxygen species (ROS) and nitric oxide (NO), cell viability or reporter gene expression. Western blot analyses and confocal microscopy showed abundance and localization of target proteins, respectively. RESULTS: Urolithin A is a stronger inhibitor of M1 (LPS) macrophage polarization (production of NO, ROS and pro-inflammatory proteins) than geraniin. Urolithin A leads to an elevated autophagic flux in macrophages. Inhibition of autophagy in M1 (LPS) macrophages overcomes the suppressed nuclear translocation of p65 (NF-kB; nuclear factor kB), the reduced expression of pro-inflammatory genes as well as the diminished NO production brought about by urolithin A. The increased autophagic flux is furthermore associated with impaired Akt/mTOR (mammalian target of rapamycin) signaling in urolithin A-treated macrophages. CONCLUSIONS AND GENERAL SIGNIFICANCE: Intestinal metabolization may boost the potential health benefit of widely consumed dietary ellagitannins, as suggested by side by side comparison of geraniin and urolithin A in M1(LPS) macrophages. Increased activity of the autophagic cellular recycling machinery aids the anti-inflammatory bioactivity of urolithin A.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Autofagia/efeitos dos fármacos
Cumarínicos/farmacologia
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Animais
Células CHO
Núcleo Celular/metabolismo
Cricetinae
Cricetulus
Células HEK293
Seres Humanos
Lipopolissacarídeos/toxicidade
Camundongos
Óxido Nítrico/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fator de Transcrição RelA/metabolismo
Proteínas ral de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Coumarins); 0 (Lipopolysaccharides); 0 (RELA protein, human); 0 (Reactive Oxygen Species); 0 (Transcription Factor RelA); 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one); 31C4KY9ESH (Nitric Oxide); EC 3.6.1.- (Rala protein, mouse); EC 3.6.5.2 (ral GTP-Binding Proteins)
[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:171017
[St] Status:MEDLINE


  4 / 110811 MEDLINE  
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[PMID]:29339251
[Au] Autor:Carta A; Sanna G; Briguglio I; Madeddu S; Vitale G; Piras S; Corona P; Peana AT; Laurini E; Fermeglia M; Pricl S; Serra A; Carta E; Loddo R; Giliberti G
[Ad] Endereço:Department of Chemistry and Pharmacy, University of Sassari, Via Muroni 23, 07100 Sassari, Italy. Electronic address: acarta@uniss.it.
[Ti] Título:Quinoxaline derivatives as new inhibitors of coxsackievirus B5.
[So] Source:Eur J Med Chem;145:559-569, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses. Promisingly, three compounds showed a very potent and selective antiviral activity against coxsackievirus B5, with EC in the sub-micromolar range (0.3-0.06 µM). A combination of experimental techniques (i.e. virucidal activity, time of drug addition and adsorption assays) and in silico modeling studies were further performed, aiming to understand the mode of action of the most active, selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6-yl)methylthio]benzoate (6).
[Mh] Termos MeSH primário: Antivirais/farmacologia
Enterovirus Humano B/efeitos dos fármacos
Quinoxalinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antivirais/síntese química
Antivirais/química
Bovinos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Cricetinae
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Testes de Sensibilidade Microbiana
Modelos Moleculares
Estrutura Molecular
Quinoxalinas/síntese química
Quinoxalinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Quinoxalines)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  5 / 110811 MEDLINE  
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[PMID]:29335818
[Au] Autor:Ohrnberger SA; Brinkmann K; Palme R; Valencak TG
[Ad] Endereço:Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria. sarah.ohrnberger@vetmeduni.ac.at.
[Ti] Título:Dorsal shaving affects concentrations of faecal cortisol metabolites in lactating golden hamsters.
[So] Source:Naturwissenschaften;105(1-2):13, 2018 Jan 15.
[Is] ISSN:1432-1904
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Breeding of golden hamsters is classically performed at thermal conditions ranging from 20 to 24 °C. However, growing evidence suggests that lactating females suffer from heat stress. We hypothesised that shaving females dorsally to maximise heat dissipation may reduce stress during reproduction. We thus compared faecal cortisol metabolites (FCM) from shaved golden hamster mothers with those from unshaved controls. We observed significantly lower FCM levels in the shaved mothers (F = 8.69, p = 0.0075) pointing to lower stress due to ameliorated heat dissipation over the body surface. In addition, we observed 0.4 °C lower mean subcutaneous body temperatures in the shaved females, although this effect did not reach significance (F = 1.86, p = 0.18). Our results suggest that golden hamsters having body masses being more than four times that of laboratory mice provide a very interesting model to study aspects of lactation and heat production at the same time.
[Mh] Termos MeSH primário: Regulação da Temperatura Corporal
Cricetinae/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Domésticos
Temperatura Corporal/fisiologia
Fezes/química
Feminino
Remoção de Cabelo/veterinária
Hidrocortisona/metabolismo
Lactação
Reprodução/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1007/s00114-017-1536-7


  6 / 110811 MEDLINE  
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[PMID]:29391062
[Au] Autor:Lee MY; Park YC; Jin M; Kim E; Choi JJ; Jung IC
[Ad] Endereço:Genogen Co., Ltd, Room 402, 125, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28161, Republic of Korea.
[Ti] Título:Genotoxicity evaluation of So-ochim-tang-gamibang (SOCG), a herbal medicine.
[So] Source:BMC Complement Altern Med;18(1):47, 2018 Feb 02.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: So-ochim-tang-gamibang (SOCG) is a traditional Korean medicine frequently used for depression in the clinical field. In this study, we evaluated the potential genotoxicity of SOCG using three standard batteries of tests as part of a safety evaluation. METHODS: SOCG was evaluated for potential genotoxic effects using the standard three tests recommended by the Ministry of Food and Drug Safety (MFDS) of Korea. These tests were the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test using Chinese hamster lung cells, and in vivo micronucleus test using ICR mice. RESULTS: The Ames test with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and the Escherichia coli strain WP2uvrA(pKM101) showed that SOCG did not induce gene mutations at any dose level in all of the strains. SOCG did not induce any chromosomal aberrations in the in vitro chromosomal aberration test (for both the 6 and 24 h test) and the in vivo micronucleus test. CONCLUSIONS: Based on the results of these tests, it was concluded that SOCG does not exhibit any genotoxic risk under the experimental conditions of this study.
[Mh] Termos MeSH primário: Mutagênicos/toxicidade
Extratos Vegetais/toxicidade
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Aberrações Cromossômicas/efeitos dos fármacos
Cricetinae
Cricetulus
Escherichia coli/efeitos dos fármacos
Masculino
Medicina Tradicional Coreana
Camundongos
Camundongos Endogâmicos ICR
Micronúcleos com Defeito Cromossômico/efeitos dos fármacos
Testes para Micronúcleos
Testes de Mutagenicidade
Salmonella typhimurium/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Plant Extracts); 0 (so-ochim-tang-gamibang)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-018-2111-2


  7 / 110811 MEDLINE  
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[PMID]:29324849
[Au] Autor:Lee JW; Heo W; Lee J; Jin N; Yoon SM; Park KY; Kim EY; Kim WT; Kim JY
[Ad] Endereço:Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
[Ti] Título:The B cell death function of obinutuzumab-HDEL produced in plant (Nicotiana benthamiana L.) is equivalent to obinutuzumab produced in CHO cells.
[So] Source:PLoS One;13(1):e0191075, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody. In this study, Obinutuzumab, a third generation anti-CD20 antibody, was produced in N. benthamiana leaves (plant-obinutuzumab) and compared to the original antibody produced in glyco-engineered Chinese hamster ovary (CHO) cells (CHO-obinutuzumab). Two forms (with or without an HDEL tag) were generated and antibody yields were compared. The HDEL-tagged form was more highly expressed than the non-HDEL-tagged form which was cleaved in the N-terminus. To determine the equivalence in functions of the Fab region between the two forms, we compared the CD20 binding affinities and direct binding induced cell death of a CD20-positive B cells. Both forms showed similar CD20 binding affinities and direct cell death of B cell. The results suggested that plant-obinutuzumab was equivalent to CHO-obinutuzumab in CD20 binding, cell aggregation, and direct cell death via binding. Therefore, our findings suggest that Obinutuzumab is a promising biosimilar candidate that can be produced efficiently in plants.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/farmacologia
Antineoplásicos Imunológicos/farmacologia
Linfócitos B/citologia
Morte Celular
Tabaco/genética
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Epitopos/imunologia
Citometria de Fluxo
Folhas de Planta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents, Immunological); 0 (Epitopes); O43472U9X8 (obinutuzumab)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191075


  8 / 110811 MEDLINE  
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[PMID]:29233614
[Au] Autor:Paterna A; Khonkarn R; Mulhovo S; Moreno A; Madeira Girio P; Baubichon-Cortay H; Falson P; Ferreira MU
[Ad] Endereço:Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
[Ti] Título:Monoterpene indole alkaloid azine derivatives as MDR reversal agents.
[So] Source:Bioorg Med Chem;26(2):421-434, 2018 01 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aiming at generating a library of bioactive indole alkaloid derivatives as multidrug resistance (MDR) reversers, two epimeric indole alkaloids (1 and 2) were submitted to chemical transformations, giving rise to twenty-four derivatives (5-28), bearing new aromatic or aliphatic azine moieties. The structure of the compounds was established by 1D and 2D NMR (COSY, HMBC, HMQC and NOESY) experiments. Two different strategies were employed for assessing their anti-MDR potential, namely through the evaluation of their activity as inhibitors of typical MDR ABC transporters overexpressed by cell transfection, such as ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP), or by evaluating their ability as collateral sensitivity (CS) agents in cells overexpressing MRP1. A considerable MDR reversing activity was observed for compounds bearing the aromatic azine moiety. The strongest and most selective P-gp inhibition was found for the epimeric azines 5 and 6, bearing a para-methylbenzylidene moiety. Instead, compounds 17 and 18 that possess a di-substituted benzylidene portion with methoxy and hydroxyl groups, selectively inhibited MRP1 drug-efflux. None of these compounds inhibited BCRP. Compounds 5, 6 and 18 were further investigated in drug combination experiments, which corroborated their anti-MDR potential. Moreover, it was observed that compound 12, with an aromatic azine moiety, and compounds 23-26, sharing a new aliphatic substituent, displayed a CS activity, selectively killing MRP1-overexpressing cells. Among these last compounds, it could be established that addition of 19, 23 and 25 to MRP1-overexpressing cells led to glutathione depletion triggering cell death through apoptosis.
[Mh] Termos MeSH primário: Alcaloides/farmacologia
Resistência a Múltiplos Medicamentos/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Hidrazinas/farmacologia
Indóis/farmacologia
[Mh] Termos MeSH secundário: Alcaloides/síntese química
Alcaloides/química
Animais
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Cricetinae
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Hidrazinas/síntese química
Hidrazinas/química
Indóis/síntese química
Indóis/química
Camundongos
Estrutura Molecular
Células NIH 3T3
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Alkaloids); 0 (Hydrazines); 0 (Indoles)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


  9 / 110811 MEDLINE  
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[PMID]:28464894
[Au] Autor:Zhao MJ; Wang SS; Jiang Y; Wang Y; Shen H; Xu P; Xiang H; Xiao H
[Ad] Endereço:Nanjing Medical University, Affiliated Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.
[Ti] Título:Hypolipidemic effect of XH601 on hamsters of Hyperlipidemia and its potential mechanism.
[So] Source:Lipids Health Dis;16(1):85, 2017 May 02.
[Is] ISSN:1476-511X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The novel compound XH601 is a synthesized derivative of formononetin. The present study was to investigate the hypolipidemia effect and potential mechanism of XH601. METHODS: Male Golden Syrian hamsters were induced by high-fat diet (HFD) for eight weeks and the hyperlipidemic model was established successfully. After XH601 treatment, serum and hepatic biochemistry parameters of hamsters were detected and the effect of XH601 on adipose tissue was also analyzed. Furthermore, 3 T3-L1 cell differentiation by Oil-Red-O staining was observed and the mRNA and protein expression of peroxisome proliferator-activated receptors (PPARs) were measured by qRT-PCR and Western-blot in mature adipocytes. RESULTS: The in vivo results suggest that XH601 significantly decreased the adipose weight and levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (Apo-B), apolipoprotein E (Apo-E), while increased serum high-density lipoprotein (HDL-C). The in vitro results implied that XH601 up-regulated the mRNA and protein expression of both PPARα and PPARß/δ in a dose-dependent manner. CONCLUSIONS: The study suggests that XH601 exhibited strong ability to improve the dyslipidemia in hamsters fed with high-fat diet. The potential mechanism of XH601 was associated with the up-regulation of PPARα and PPARß/δ mRNA and protein expression.
[Mh] Termos MeSH primário: Hiperlipidemias/tratamento farmacológico
Hipolipemiantes/farmacologia
Isoflavonas/farmacologia
PPAR alfa/agonistas
PPAR delta/agonistas
PPAR beta/agonistas
[Mh] Termos MeSH secundário: Células 3T3-L1
Tecido Adiposo/efeitos dos fármacos
Tecido Adiposo/metabolismo
Tecido Adiposo/patologia
Animais
Apolipoproteínas B/sangue
Apolipoproteínas E/sangue
Diferenciação Celular
HDL-Colesterol/sangue
LDL-Colesterol/sangue
Cricetinae
Dieta Hiperlipídica/efeitos adversos
Regulação da Expressão Gênica
Hiperlipidemias/etiologia
Hiperlipidemias/metabolismo
Hiperlipidemias/patologia
Masculino
Mesocricetus
Camundongos
PPAR alfa/genética
PPAR alfa/metabolismo
PPAR delta/genética
PPAR delta/metabolismo
PPAR beta/genética
PPAR beta/metabolismo
RNA Mensageiro/agonistas
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Triglicerídeos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoproteins B); 0 (Apolipoproteins E); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Hypolipidemic Agents); 0 (Isoflavones); 0 (PPAR alpha); 0 (PPAR delta); 0 (PPAR-beta); 0 (RNA, Messenger); 0 (Triglycerides); 295DQC67BJ (formononetin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s12944-017-0472-z


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[PMID]:29357857
[Au] Autor:Lee MY; Seo CS; Ha H; Park E; Kim JY; Shin HK
[Ad] Endereço:K-herb Research Center, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea.
[Ti] Título:The genotoxicity of an aqueous extract of Gyejibokryeong-hwan.
[So] Source:BMC Complement Altern Med;18(1):21, 2018 Jan 22.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Gyejibokryeong-hwan (Guizhi Fuling Wan in China), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. However, the genotoxicity of Gyejibokryeong-hwan has not yet been well established. METHODS: The present study investigated that the genotoxicity of an aqueous extract of Gyejibokryeong-hwan (GJBRHE): an in vitro chromosomal aberration test using Chinese hamster lung cells, an in vitro bacterial reverse mutation assay (Ames test) with Salmonella typhimurium and Escherichia coli strains, and an in vivo micronucleus test using ICR mouse bone marrow. RESULTS: GJBRHE with or without the S9 mix showed no genotoxicity in the Ames test up to 5000 µg/plate or in the in vivo MN test up to 2000 mg/kg body weight. In contrast, the chromosomal aberration test showed that GJBRHE induced an increase in the number of chromosomal aberrations compared with the control after treatment for 6 h with 4200 µg/mL GJBRHE in the presence of the S9 mix and for 22 h with 800 µg/mL GJBRHE in the absence of the S9 mix. CONCLUSIONS: GJBRHE did not cause detectable genotoxic effects in the bacterial mutation test or the in vivo MN test, however genotoxic effect was detected in the in vitro chromosomal aberration assay. Our results suggest that GJBRHE may be associated with a low risk of carcinogenesis. Thus, further detailed experiments would be needed to clarify the compound responsible for inducing this genotoxicity of GJBRHE and to determine its mechanism.
[Mh] Termos MeSH primário: Aberrações Cromossômicas/efeitos dos fármacos
Dano ao DNA/efeitos dos fármacos
Medicamentos de Ervas Chinesas/toxicidade
Mutagênicos/toxicidade
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Medula Óssea/efeitos dos fármacos
Linhagem Celular
Cricetinae
Escherichia coli/efeitos dos fármacos
Camundongos
Testes para Micronúcleos
Testes de Mutagenicidade
Salmonella typhimurium/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 0 (Mutagens); 0 (keishibukuryogan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2054-z



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