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[PMID]:28650658
[Au] Autor:Mao R; Shao J; Zhu K; Zhang Y; Ding H; Zhang C; Shi Z; Jiang H; Sun D; Duan W; Luo C
[Ad] Endereço:Marine College, Shandong University , Weihai 264209, P.R. China.
[Ti] Título:Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization.
[So] Source:J Med Chem;60(14):6289-6304, 2017 Jul 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC = 0.33 µM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a K of 0.987 µM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
[Mh] Termos MeSH primário: Acetanilidas/química
Antineoplásicos/química
Benzimidazóis/química
Proteína-Arginina N-Metiltransferases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Acetanilidas/síntese química
Acetanilidas/farmacologia
Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Benzimidazóis/síntese química
Benzimidazóis/farmacologia
Linhagem Celular
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Bases de Dados de Compostos Químicos
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Cinética
Leucemia
Linfoma
Metilação
Modelos Moleculares
Simulação de Acoplamento Molecular
Ligação Proteica
Proteína-Arginina N-Metiltransferases/química
Proteína-Arginina N-Metiltransferases/metabolismo
Relação Estrutura-Atividade
Proteínas Centrais de snRNP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetanilides); 0 (Antineoplastic Agents); 0 (Benzimidazoles); 0 (SNRPD3 protein, human); 0 (methyl 2-(2-((5-methoxy-1H-benzo(d)imidazol-2-yl)thio)acetamido)benzoate); 0 (snRNP Core Proteins); EC 2.1.1.319 (PRMT5 protein, human); EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
[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:170627
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00587


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[PMID]:28281463
[Au] Autor:Flechsig A; Rose T; Barkhudarova F; Strauss R; Klotsche J; Dähnrich C; Schlumberger W; Enghard P; Burmester GR; Hiepe F; Biesen R
[Ad] Endereço:Department of Rheumatology and Clinical Immunology, Charité University Hospital Berlin, Germany.
[Ti] Título:What is the clinical significance of anti-Sm antibodies in systemic lupus erythematosus? A comparison with anti-dsDNA antibodies and C3.
[So] Source:Clin Exp Rheumatol;35(4):598-606, 2017 Jul-Aug.
[Is] ISSN:0392-856X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To investigate the clinical value of anti-Sm antibodies in diagnosis and monitoring of systemic lupus erythematosus (SLE) and their ability to predict lupus flares compared with that of anti-dsDNA antibody and complement (C3) assays. METHODS: Autoantibodies against Smith antigen (Sm) and double-stranded DNA (dsDNA) in sera from SLE (n=232), myositis (n=26), systemic sclerosis (n=81), Sjögren's syndrome (n=88), and rheumatoid arthritis patients (n=165) and healthy donors (n=400) were determined by using enzyme-linked immunosorbent assays (both from Euroimmun). New thresholds for both autoantibodies were calculated by receiver operating characteristics (ROC) curve analysis. Cross-sectional, longitudinal and predictive analyses of anti-Sm and disease activity were also performed. RESULTS: Sensitivities of 25.9% for anti-Sm (cut-off: 3.6 relative units/ml) and 30.2% for anti-dsDNA (cut-off 157.4 international units/ml) were obtained at a specificity of 99%. 14.8% of anti-dsDNA-negative patients were positive for anti-Sm, and more than half (51.4%) of anti-dsDNA-positive patients were also positive for anti-Sm. Anti-Sm antibodies were associated with age (p=0.0174), the number of ACR criteria (p=0.0242), the ACR criteria renal (p=0.0350) and neurologic disorder (p=0.0239), the BILAG category constitutional symptoms (p=0.0227), fatigue (p=0.0311) and cross-sectional disease activity (r=0.2519, p=0.0224). Although no correlations with lupus activity were observed in the longitudinal and predictive analysis, a remarkable association was found between anti-Sm and proteinuria. CONCLUSIONS: Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients. However, our data suggest that anti-Sm monitoring is only helpful in SLE patients with active lupus nephritis.
[Mh] Termos MeSH primário: Anticorpos Antinucleares/imunologia
Complemento C3/imunologia
DNA/imunologia
Lúpus Eritematoso Sistêmico/imunologia
Proteínas Centrais de snRNP/imunologia
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Estudos Transversais
Seres Humanos
Estudos Longitudinais
Lúpus Eritematoso Sistêmico/diagnóstico
Razão de Chances
Curva ROC
Doenças Reumáticas/diagnóstico
Doenças Reumáticas/imunologia
Sensibilidade e Especificidade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Antinuclear); 0 (Complement C3); 0 (snRNP Core Proteins); 9007-49-2 (DNA)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE


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[PMID]:28259006
[Au] Autor:Xu GF; Liao Y; Li JY; Liu YF; Huang Y; Wu YQ; Liu J; Lv PP; Zhang RJ; Zhang D
[Ad] Endereço:Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
[Ti] Título:Ovarian stimulation perturbs methylation status of placental imprinting genes and reduces blood pressure in the second generation offspring.
[So] Source:Eur J Obstet Gynecol Reprod Biol;211:140-145, 2017 Apr.
[Is] ISSN:1872-7654
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE(S): Assisted reproductive technology (ART) is associated with DNA methylation dysfunction of offspring. However, it is unclear whether ovarian stimulation (OS) is responsible for DNA methylation dysfunction of offspring STUDY DESIGN: We built the first-generation (F1) and second-generation (F2) offspring mice model of ovarian stimulation. Bodyweight of F1 and F2 were measured. Expression levels of several imprinted genes (Impact, H19, Igf2, Plagl1, Mest, and Snrpn) in F1 placenta were tested. Methylation status of Plagl1 and H19 promoters was examined with bisulfite sequencing. Glucose tolerance, blood pressure, and heart rate were evaluated in F2 mice. RESULTS: The OS F1 showed elevated bodyweights in the 2nd, 3rd and 4th weeks, but the difference disappeared in the 5th week. Plagl1 was down-regulated in OS F1. Promoters of Plagl1 and H19 were also hypermethylated in OS F1. F2 of OS mice had the similar bodyweight and glucose tolerance compared with the control F2. However, F2 of OS ♂F1+OS♀ F1 showed the decreased systolic pressure, diastolic pressure, and heart rate. CONCLUSIONS: Ovarian stimulation perturbs expression levels and methylation status of imprinted genes in offspring. The effect of ovarian stimulation may be passed to F2.
[Mh] Termos MeSH primário: Pressão Sanguínea/fisiologia
Peso Corporal/genética
Metilação de DNA
Impressão Genômica
Indução da Ovulação
[Mh] Termos MeSH secundário: Animais
Proteínas de Ciclo Celular/genética
Feminino
Genes Supressores de Tumor
Fator de Crescimento Insulin-Like II/genética
Camundongos
Gravidez
Regiões Promotoras Genéticas
Proteínas/genética
RNA Longo não Codificante/genética
Fatores de Transcrição/genética
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (H19 long non-coding RNA); 0 (IGF2 protein, mouse); 0 (Impact protein, mouse); 0 (Plagl1 protein, mouse); 0 (Proteins); 0 (RNA, Long Noncoding); 0 (Transcription Factors); 0 (mesoderm specific transcript protein); 0 (snRNP Core Proteins); 67763-97-7 (Insulin-Like Growth Factor II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE


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[PMID]:28211971
[Au] Autor:Le Fevre A; Beygo J; Silveira C; Kamien B; Clayton-Smith J; Colley A; Buiting K; Dudding-Byth T
[Ad] Endereço:Hunter Genetics, Newcastle, Australia.
[Ti] Título:Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature.
[So] Source:Am J Med Genet A;173(3):753-757, 2017 Mar.
[Is] ISSN:1552-4833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angelman syndrome (AS) is characterized by severe intellectual disability, limited, or absent speech and a generally happy demeanor. The four known etiological mechanisms; deletions, uniparental disomy, imprinting defects, and UBE3A mutation all affect expression of the UBE3A gene at 15q11-q13. An atypical phenotype is seen in individuals who are mosaic for a chromosome 15q11-q13 imprinting defect on the maternal allele. These patients present with a milder phenotype, often with hyperphagia and obesity or non-specific intellectual disability. Unlike typical AS syndrome, they can have a vocabulary up to 100 words and speak in sentences. Ataxia and seizures may not be present, and the majority of individuals do not have microcephaly. Here we review the current literature and present three individuals with atypical AS caused by a mosaic imprinting defect to demonstrate why DNA methylation analysis at the SNRPN locus needs to be considered in a broader clinical context. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Síndrome de Angelman/diagnóstico
Síndrome de Angelman/genética
Impressão Genômica
Mosaicismo
Fenótipo
[Mh] Termos MeSH secundário: Adolescente
Criança
Mapeamento Cromossômico
Metilação de DNA
Facies
Feminino
Estudos de Associação Genética
Heterogeneidade Genética
Seres Humanos
Incidência
Masculino
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (snRNP Core Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE
[do] DOI:10.1002/ajmg.a.38072


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[PMID]:28024084
[Au] Autor:Kim Y; Lee HM; Xiong Y; Sciaky N; Hulbert SW; Cao X; Everitt JI; Jin J; Roth BL; Jiang YH
[Ad] Endereço:Department of Pediatrics, School of Medicine, Duke University, Durham, North Carolina, USA.
[Ti] Título:Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome.
[So] Source:Nat Med;23(2):213-222, 2017 Feb.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prader-Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11-q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642-two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)-activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m /p ). Both UNC0642 and UNC0638 caused a selective reduction of the dimethylation of histone H3 lysine 9 (H3K9me2) at PWS-IC, without changing DNA methylation, when analyzed by bisulfite genomic sequencing. This indicates that histone modification is essential for the imprinting of candidate genes underlying PWS. UNC0642 displayed therapeutic effects in the PWS mouse model by improving the survival and the growth of m /p newborn pups. This study provides the first proof of principle for an epigenetics-based therapy for PWS.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/farmacologia
Expressão Gênica/efeitos dos fármacos
Código das Histonas/efeitos dos fármacos
Histona-Lisina N-Metiltransferase/antagonistas & inibidores
Síndrome de Prader-Willi/genética
Quinazolinas/farmacologia
RNA Nucleolar Pequeno/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Western Blotting
Linhagem Celular
Modelos Animais de Doenças
Epigênese Genética
Feminino
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Expressão Gênica/genética
Impressão Genômica
Código das Histonas/genética
Seres Humanos
Imuno-Histoquímica
Masculino
Metilação/efeitos dos fármacos
Camundongos
Síndrome de Prader-Willi/metabolismo
RNA Nucleolar Pequeno/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Taxa de Sobrevida
Ubiquitina-Proteína Ligases/genética
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Quinazolines); 0 (RNA, Small Nucleolar); 0 (SNORD116 RNA, human); 0 (SNORD116 RNA, mouse); 0 (UNC 0638); 0 (UNC0642); 0 (snRNP Core Proteins); EC 2.1.1.43 (G9a protein, mouse); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase); EC 2.3.2.26 (Ube3a protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161227
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4257


  6 / 1052 MEDLINE  
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[PMID]:27071665
[Au] Autor:Zhang Q; Zhang F; Gao HH; Zhang JM
[Ad] Endereço:Radiology Department, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
[Ti] Título:Effects of varicocele on DNA methylation pattern of H19 and Snrpn gene in spermatozoa and behavioural characteristics of adult rat offspring.
[So] Source:Andrologia;49(1), 2017 Feb.
[Is] ISSN:1439-0272
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to explore the effects of varicocele on DNA methylation pattern of H19 and Snrpn gene in spermatozoa and behavioural characteristics of adult rat offspring. Wistar rats with experimentally induced varicocele were used. The status of promoter methylation of H19 and Snrpn gene in spermatozoa of rats with varicocele or without varicocele was investigated. In addition, the Morris water maze test, elevated plus maze test and forced swimming test were employed to evaluate the learning and memory capability, and emotional behaviour of adult rat offspring. There were no significant differences in DNA methylation levels of H19 and Snrpn gene in spermatozoa among the control group, sham operation group and varicocele-induced group. Furthermore, no significant differences were found in Morris water maze test and elevated plus maze test among the offspring in the three groups. However, in forced swimming test, the immobility time of offspring (both male and female) in the varicocele-induced group was significantly longer than that in the control group and the sham operation group. Varicocele does not alter the methylation profiles of H19 and Snrpn gene, but exerts depressant-like effect on the adult rat offspring.
[Mh] Termos MeSH primário: RNA Longo não Codificante/genética
Espermatozoides/metabolismo
Varicocele/genética
Proteínas Centrais de snRNP/genética
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/fisiologia
Metilação de DNA
Masculino
Aprendizagem em Labirinto/fisiologia
Atividade Motora/genética
Regiões Promotoras Genéticas
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (H19 long non-coding RNA); 0 (RNA, Long Noncoding); 0 (snRNP Core Proteins)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170209
[Lr] Data última revisão:
170209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160414
[St] Status:MEDLINE
[do] DOI:10.1111/and.12591


  7 / 1052 MEDLINE  
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[PMID]:27956081
[Au] Autor:Wang C; Qi B; Tan L; Cheng J
[Ad] Endereço:The First Hospital of Jilin University, China.
[Ti] Título:Gene markers of fracture healing in early stage and the regulatory mechanism during the process using microarray analysis.
[So] Source:Acta Orthop Traumatol Turc;50(6):681-685, 2016 Dec.
[Is] ISSN:1017-995X
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to explore crucial markers and uncover the regulatory mechanisms of fracture healing in the early stage. METHODS: Gene expression profile of GSE45156 was downloaded, in which 3 fractured samples and 3 unfractured samples were used in our present study. Based on the threshold value, differentially expressed genes (DEGs) were selected between two kinds of samples using limma package in R. Enrichment analysis of these DEGs was performed by DAVID software. Furthermore, protein-protein interaction (PPI) network was established integrating information in STRING database, and visualized by Cytoscape software. RESULTS: We identified a set of 960 DEGs including 509 up-regulated and 451 downregulated genes. Biological processes involving RNA splicing and cell cycle were significantly enriched for the up-regulated genes such as Snrpd2, Eftud2, Plk1 and Bub1b, whereas skeletal system development and bone development processes were predominant for down-regulated genes like Ubc. In the constructed PPI network, all the five genes were the predominant nodes, of which Snrpd2 was linked to Eftud2, while Bub1b was to interact with Plk1. CONCLUSION: Five candidate genes crucial for indicating the process of fracture in early stage were identified. Eftud2, Snrpd2, Bub1b and Plk1 might function through the involvement of cell-cycle-related BP, while Ubc might influence the protein degradation during bone development. However, more experimental validations are needed to confirm these results.
[Mh] Termos MeSH primário: Consolidação da Fratura/genética
Marcadores Genéticos
Mapas de Interação de Proteínas/genética
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/genética
Regulação para Baixo
Seres Humanos
Análise em Microsséries
Fatores de Alongamento de Peptídeos/genética
Proteínas Serina-Treonina Quinases/genética
Proteínas Proto-Oncogênicas/genética
Ribonucleoproteína Nuclear Pequena U5/genética
Regulação para Cima
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BUB1B protein, human); 0 (Cell Cycle Proteins); 0 (EFTUD2 protein, human); 0 (Genetic Markers); 0 (Peptide Elongation Factors); 0 (Proto-Oncogene Proteins); 0 (Ribonucleoprotein, U5 Small Nuclear); 0 (SNRPD2 protein, human); 0 (snRNP Core Proteins); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170209
[Lr] Data última revisão:
170209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE


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[PMID]:27931182
[Au] Autor:Desmet KL; Van Hoeck V; Gagné D; Fournier E; Thakur A; O'Doherty AM; Walsh CP; Sirard MA; Bols PE; Leroy JL
[Ad] Endereço:Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium. karolien.desmet@uantwerpen.be.
[Ti] Título:Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.
[So] Source:BMC Genomics;17(1):1004, 2016 12 08.
[Is] ISSN:1471-2164
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. RESULTS: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. CONCLUSIONS: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.
[Mh] Termos MeSH primário: Blastocisto/metabolismo
Embrião de Mamíferos/metabolismo
Epigênese Genética/efeitos dos fármacos
Ácidos Graxos não Esterificados/toxicidade
Oócitos/metabolismo
Transcriptoma/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Bovinos
DNA/química
DNA/isolamento & purificação
DNA/metabolismo
Metilação de DNA/efeitos dos fármacos
Embrião de Mamíferos/efeitos dos fármacos
Feminino
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Histonas/genética
Análise de Sequência com Séries de Oligonucleotídeos
Oócitos/efeitos dos fármacos
Análise de Sequência de DNA
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Acids, Nonesterified); 0 (Histones); 0 (snRNP Core Proteins); 9007-49-2 (DNA)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE


  9 / 1052 MEDLINE  
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[PMID]:27900999
[Au] Autor:Yang HO; Zhang XQ; Fu QH
[Ad] Endereço:Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
[Ti] Título:Evaluating Anti-SmD1-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases.
[So] Source:Chin Med J (Engl);129(23):2840-2844, 2016 12 05.
[Is] ISSN:0366-6999
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: SmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE. METHODS: Samples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant. RESULTS: Thirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria. CONCLUSIONS: Measurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.
[Mh] Termos MeSH primário: Doenças do Sistema Imune/imunologia
Lúpus Eritematoso Sistêmico/imunologia
Peptídeos/imunologia
Proteínas Centrais de snRNP/imunologia
[Mh] Termos MeSH secundário: Autoanticorpos/imunologia
Autoantígenos/imunologia
Criança
Feminino
Seres Humanos
Immunoblotting
Masculino
Peptídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Autoantigens); 0 (Peptides); 0 (SNRPD1 protein, human); 0 (snRNP Core Proteins)
[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:161201
[St] Status:MEDLINE
[do] DOI:10.4103/0366-6999.194653


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[PMID]:27659713
[Au] Autor:Hassan M; Butler MG
[Ad] Endereço:Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS, USA; Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS, USA.
[Ti] Título:Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects.
[So] Source:Eur J Med Genet;59(11):584-589, 2016 Nov.
[Is] ISSN:1878-0849
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100-200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype.
[Mh] Termos MeSH primário: Deleção Cromossômica
Síndrome de Prader-Willi/genética
RNA Nucleolar Pequeno/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Cromossomos Humanos Par 15/genética
Metilação de DNA/genética
Feminino
Impressão Genômica/genética
Seres Humanos
Hibridização in Situ Fluorescente
Masculino
Fenótipo
Síndrome de Prader-Willi/fisiopatologia
Proteínas Centrais de snRNP/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Nucleolar); 0 (SNORD116 RNA, human); 0 (SNRPN protein, human); 0 (snRNP Core Proteins)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170207
[Lr] Data última revisão:
170207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160924
[St] Status:MEDLINE



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