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[PMID]:28470264
[Au] Autor:Jiang H; Ma R; Zou S; Wang Y; Li Z; Li W
[Ad] Endereço:College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China. jhanbing@163.com and Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, 230031, China and Institute for Cardiovascular and Metabolic Diseas
[Ti] Título:Reconstruction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis.
[So] Source:Mol Biosyst;13(6):1182-1192, 2017 Jun 01.
[Is] ISSN:1742-2051
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population. More and more studies have suggested that long non-coding RNAs (lncRNAs) could play important roles in various biological processes and be associated with the pathogenesis of different kinds of diseases including RA. Although a large number of lncRNAs have been found, our knowledge of their function and physiological/pathological significance is still in its infancy. In order to reveal functional lncRNAs and identify the key lncRNAs in RA, we reconstructed a global triple network based on the competitive endogenous RNA (ceRNA) theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and our previous paper. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using Cytoscape plug-in BinGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively. We found that the lncRNA-miRNA-mRNA network was composed of 7 lncRNA nodes, 90 mRNA nodes, 24 miRNA nodes, and 301 edges. The functional assay showed that 147 GO terms and 23 pathways were enriched. In addition, three lncRNAs (S5645.1, XR_006437.1, J01878) were highly related to RA, and therefore, were selected as key lncRNAs. This study suggests that specific lncRNAs are associated with the development of RA, and three lncRNAs (S5645.1, XR_006437.1, J01878) could be used as potential diagnostic biomarkers and therapeutic targets.
[Mh] Termos MeSH primário: Artrite Reumatoide/metabolismo
MicroRNAs/metabolismo
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Artrite Reumatoide/genética
Perfilação da Expressão Gênica
Regulação Neoplásica da Expressão Gênica/genética
Ontologia Genética
Seres Humanos
Análise de Sequência com Séries de Oligonucleotídeos
RNA Longo não Codificante/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (RNA, Long Noncoding); 0 (RNA, Messenger)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.1039/c7mb00094d


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[PMID]:28456786
[Au] Autor:Moon S; Kim DK; Kim J
[Ad] Endereço:Department of Dental Hygiene, College of Nursing Healthcare, Sorabol College, Gyeongju 38063, Republic of Korea.
[Ti] Título:Apoptosis-related microRNA-145-5p enhances the effects of pheophorbide a-based photodynamic therapy in oral cancer.
[So] Source:Oncotarget;8(21):35184-35192, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs) regulate key biological processes, and their aberrant expression has been related to cancer development. Photodynamic therapy (PDT) has emerged as one of the most promising modalities for cancer treatment. However, the application of PDT has been limited to superficially localized human cancerous and precancerous lesions. To increase the usefulness of both PDT and miRNAs in cancer therapy, this study investigated whether apoptosis-related miRNA expression is influenced by PDT in oral cancer and whether miRNAs can enhance PDT efficacy. To achieve this goal, we performed a miRNA array-based comparison of apoptosis-related miRNA expression patterns following PDT using pheophorbide a (Pa) as a photosensitizer. After Pa-PDT, 13.1% of the miRNAs were down-regulated, and 16.7% of the miRNAs were up-regulated. Representative miRNAs were selected according to expression difference: miR-9-5p, miR-32-5p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-5p, miR-204-5p, miR-212-3p, miR-338-3p, and miR-451a. Among them, only miR-145-5p showed the consistent reduction repeatedly in all cell lines after Pa-PDT. Further, the combined treatment of a miR-145-5p mimic and Pa-PDT increased phototoxicity, reactive oxygen species generation, and apoptotic cell death, suggesting that miRNAs expression could be a useful marker for enhancing the therapeutic effect of Pa-PDT. This study will provide a promising strategy for introducing miRNA as cancer therapy.
[Mh] Termos MeSH primário: Clorofila/análogos & derivados
MicroRNAs/genética
Neoplasias Bucais/genética
Fármacos Fotossensibilizantes/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Clorofila/farmacologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Neoplasias Bucais/tratamento farmacológico
Neoplasias Bucais/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Fotoquimioterapia
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN145 microRNA, human); 0 (MicroRNAs); 0 (Photosensitizing Agents); 0 (Reactive Oxygen Species); 1406-65-1 (Chlorophyll); IA2WNI2HO2 (pheophorbide a)
[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:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17059


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[PMID]:29288362
[Au] Autor:Goonesekere NCW; Andersen W; Smith A; Wang X
[Ad] Endereço:Department of Chemistry and Biochemistry, University of Northern Iowa, 1227 W. 27th Street, Cedar Falls, IA, 50613-0423, USA. nalin.goonesekere@uni.edu.
[Ti] Título:Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.
[So] Source:J Cancer Res Clin Oncol;144(2):309-320, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. METHODS: In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. RESULTS: This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. CONCLUSIONS: While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
Genes Supressores de Tumor
Neoplasias Pancreáticas/genética
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Conjuntos de Dados como Assunto
Regulação para Baixo
Seres Humanos
Terapia de Alvo Molecular
Análise de Sequência com Séries de Oligonucleotídeos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2558-4


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[PMID]:28453760
[Au] Autor:Hibiya S; Tsuchiya K; Hayashi R; Fukushima K; Horita N; Watanabe S; Shirasaki T; Nishimura R; Kimura N; Nishimura T; Gotoh N; Oshima S; Okamoto R; Nakamura T; Watanabe M
[Ad] Endereço:Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
[Ti] Título:Long-term Inflammation Transforms Intestinal Epithelial Cells of Colonic Organoids.
[So] Source:J Crohns Colitis;11(5):621-630, 2017 May 01.
[Is] ISSN:1876-4479
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background and Aims: Patients with ulcerative colitis [UC] are at an increased risk of developing colitis-associated cancer [CAC], suggesting that continuous inflammation in the colon promotes the transformation of colonic epithelial cells. However, the mechanisms underlying cell transformation in UC remain unknown. We therefore aimed to investigate the effect of long-term inflammation on intestinal epithelial cells [IECs] using organoid culture. Methods: IECs were isolated from mouse colon, and were cultured according to a method for a three-dimensional [3D] organoid culture. To mimic chronic inflammation, a mixture of cytokines and bacterial components were added to the medium for over a year. Cell signal intensity was assessed by 3D immunofluorescence. Cell transformation was assessed by microarray with gene set enrichment analysis. Results: Stimulation with cytokines resulted in a significant induction of target genes for the nuclear factor [NF]-κB pathway in colonic organoids. Following 60 weeks of continuous stimulation, cell differentiation was suppressed. Continuous stimulation also resulted in significant amplification of NF-κB signalling. Amplified NF-κB signalling by long-term stimulation remained in colonic organoids even 11 weeks after the removal of all cytokines. Some genes were specifically upregulated only in colonic organoids after the removal all cytokines following long-term stimulation. Conclusions: Colonic organoids stimulated with cytokines for a prolonged period were established as in vitro model to assess long-term epithelial responses to inflammatory cytokines. Chronic inflammation led to sustained NF-κB signalling activation in colonic organoids, resulting in cell transformation that might be related to the carcinogenesis of CAC in UC.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/patologia
Colite/patologia
Mucosa Intestinal/citologia
Organoides/patologia
[Mh] Termos MeSH secundário: Animais
Colo/citologia
Colo/patologia
Citocinas/metabolismo
Feminino
Mucosa Intestinal/patologia
Camundongos
Camundongos Endogâmicos C57BL
NF-kappa B/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (NF-kappa B)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/ecco-jcc/jjw186


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[PMID]:29187149
[Au] Autor:Meng Q; Catchpoole D; Skillicorn D; Kennedy PJ
[Ad] Endereço:School of Software, Faculty of Engineering and Information Technology and the Centre for Artificial Intelligence, University of Technology Sydney (UTS), PO Box 123, 15 Broadway, Ultimo, NSW, 2007, Australia. Qinxue.Meng@uts.edu.au.
[Ti] Título:DBNorm: normalizing high-density oligonucleotide microarray data based on distributions.
[So] Source:BMC Bioinformatics;18(1):527, 2017 Nov 29.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Data from patients with rare diseases is often produced using different platforms and probe sets because patients are widely distributed in space and time. Aggregating such data requires a method of normalization that makes patient records comparable. RESULTS: This paper proposed DBNorm, implemented as an R package, is an algorithm that normalizes arbitrarily distributed data to a common, comparable form. Specifically, DBNorm merges data distributions by fitting functions to each of them, and using the probability of each element drawn from the fitted distribution to merge it into a global distribution. DBNorm contains state-of-the-art fitting functions including Polynomial, Fourier and Gaussian distributions, and also allows users to define their own fitting functions if required. CONCLUSIONS: The performance of DBNorm is compared with z-score, average difference, quantile normalization and ComBat on a set of datasets, including several that are publically available. The performance of these normalization methods are compared using statistics, visualization, and classification when class labels are known based on a number of self-generated and public microarray datasets. The experimental results show that DBNorm achieves better normalization results than conventional methods. Finally, the approach has the potential to be applicable outside bioinformatics analysis.
[Mh] Termos MeSH primário: Análise de Sequência com Séries de Oligonucleotídeos/métodos
Software
[Mh] Termos MeSH secundário: Área Sob a Curva
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Distribuição Normal
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Análise de Componente Principal
Curva ROC
Interface Usuário-Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1912-5


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[PMID]:28468787
[Au] Autor:Chandran S; Watkins J; Abdul-Aziz A; Shafat M; Calvert PA; Bowles KM; Flather MD; Rushworth SA; Ryding AD
[Ad] Endereço:Norfolk and Norwich University Hospital, Norwich, United Kingdom.
[Ti] Título:Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST-Segment Elevation Myocardial Infarction.
[So] Source:J Am Heart Assoc;6(5), 2017 May 03.
[Is] ISSN:2047-9980
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Plaque erosion causes 30% of ST-segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo. METHODS AND RESULTS: Forty ST-segment elevation myocardial infarction patients with <6 hours of chest pain were classified as ruptured fibrous cap (RFC) or intact fibrous cap (IFC) using optical coherence tomography. Plasma samples from the infarct-related artery and a peripheral artery were analyzed for expression of 102 cytokines using arrays; results were confirmed with ELISA. Thrombectomy samples were analyzed for differential mRNA expression using quantitative real-time polymerase chain reaction. Twenty-three lesions were classified as RFC (58%), 15 as IFC (38%), and 2 were undefined (4%). In addition, 12% (12 of 102) of cytokines were differentially expressed in both coronary and peripheral plasma. I-TAC was preferentially expressed in RFC (significance analysis of microarrays adjusted <0.001; ELISA IFC 10.2 versus RFC 10.8 log pg/mL; =0.042). IFC was associated with preferential expression of epidermal growth factor (significance analysis of microarrays adjusted <0.001; ELISA IFC 7.42 versus RFC 6.63 log pg/mL, =0.036) and thrombospondin 1 (significance analysis of microarrays adjusted =0.03; ELISA IFC 10.4 versus RFC 8.65 log ng/mL, =0.0041). Thrombectomy mRNA showed elevated I-TAC in RFC ( =0.0007) epidermal growth factor expression in IFC ( =0.0264) but no differences in expression of thrombospondin 1. CONCLUSIONS: These results demonstrate differential intracoronary cytokine expression in RFC and IFC. Elevated thrombospondin 1 and epidermal growth factor may play an etiological role in erosion.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/complicações
Citocinas/sangue
Mediadores da Inflamação/sangue
Placa Aterosclerótica
Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia
[Mh] Termos MeSH secundário: Idoso
Biomarcadores/sangue
Angiografia Coronária
Doença da Artéria Coronariana/sangue
Doença da Artéria Coronariana/diagnóstico por imagem
Doença da Artéria Coronariana/terapia
Citocinas/genética
Ensaio de Imunoadsorção Enzimática
Fator de Crescimento Epidérmico/sangue
Feminino
Fibrose
Perfilação da Expressão Gênica/métodos
Seres Humanos
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Intervenção Coronária Percutânea
Estudos Prospectivos
Reação em Cadeia da Polimerase em Tempo Real
Fatores de Risco
Ruptura Espontânea
Infarto do Miocárdio com Supradesnível do Segmento ST/sangue
Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
Infarto do Miocárdio com Supradesnível do Segmento ST/terapia
Trombectomia
Trombospondina 1/sangue
Tomografia de Coerência Óptica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Inflammation Mediators); 0 (Thrombospondin 1); 0 (thrombospondin-1, human); 62229-50-9 (Epidermal Growth Factor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


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[PMID]:29348493
[Au] Autor:Song Y; Kim S; Heller MJ; Huang X
[Ad] Endereço:Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. yjunsong@gmail.com.
[Ti] Título:DNA multi-bit non-volatile memory and bit-shifting operations using addressable electrode arrays and electric field-induced hybridization.
[So] Source:Nat Commun;9(1):281, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA has been employed to either store digital information or to perform parallel molecular computing. Relatively unexplored is the ability to combine DNA-based memory and logical operations in a single platform. Here, we show a DNA tri-level cell non-volatile memory system capable of parallel random-access writing of memory and bit shifting operations. A microchip with an array of individually addressable electrodes was employed to enable random access of the memory cells using electric fields. Three segments on a DNA template molecule were used to encode three data bits. Rapid writing of data bits was enabled by electric field-induced hybridization of fluorescently labeled complementary probes and the data bits were read by fluorescence imaging. We demonstrated the rapid parallel writing and reading of 8 (2 ) combinations of 3-bit memory data and bit shifting operations by electric field-induced strand displacement. Our system may find potential applications in DNA-based memory and computations.
[Mh] Termos MeSH primário: Computadores Moleculares
DNA/química
Armazenamento e Recuperação da Informação
[Mh] Termos MeSH secundário: Biomimética
DNA/genética
Desenho de Equipamento
Hibridização Genética
Análise de Sequência com Séries de Oligonucleotídeos
Processamento de Sinais Assistido por Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
9007-49-2 (DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02705-8


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[PMID]:28450077
[Au] Autor:Kasoju N; Wang H; Zhang B; George J; Gao S; Triffitt JT; Cui Z; Ye H
[Ad] Endereço:Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects.
[So] Source:Biotechnol Adv;35(4):407-418, 2017 07.
[Is] ISSN:1873-1899
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The plastic-adherent, fibroblast-like, clonogenic cells found in the human body now defined as multipotent "Mesenchymal Stromal Cells" (MSCs) hold immense potential for cell-based therapies. Recently, research and basic knowledge of these cells has fast-tracked, both from fundamental and translational perspectives. There have been important discoveries with respect to the available variety of tissue sources, the development of protocols for their easy isolation and in vitro expansion and for directed differentiation into various cell types. In addition, there has been discovery of novel abilities such as immune-modulation and further development of the use of biomaterials to aid isolation, expansion and differentiation together with improved delivery to the selected optimal tissue site. However, the molecular fingerprint of MSCs in these contexts remains imprecise and inadequate. Consequently, without this crucial knowledge it is difficult to achieve progress to determine with precision their practical developmental potentials. Detailed investigations on the global gene expression, or transcriptome, of MSCs could offer essential clues in this regard. In this article, we address the challenges associated with MSC transcriptome studies, the paradoxes observed in published experimental results and the need for careful transcriptomic analysis. We describe the exemplary applications with various transcriptome platforms that are used to address the variation in biomarkers and the identification of differentiation processes. The evolution and the potentials for adapting next-generation sequencing (NGS) technology in transcriptome analysis are discussed. Lastly, based on review of the existing understanding and published studies, we propose how NGS may be applied to promote further understanding of the biology of MSCs and their use in allied fields such as regenerative medicine.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica
Células Mesenquimais Estromais
Transcriptoma
[Mh] Termos MeSH secundário: Diferenciação Celular
Perfilação da Expressão Gênica/métodos
Perfilação da Expressão Gênica/tendências
Seres Humanos
Análise de Sequência com Séries de Oligonucleotídeos
Medicina Regenerativa
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29377892
[Au] Autor:Wang LX; Li Y; Chen GZ
[Ad] Endereço:Department of Dermatology, The Affiliated Hospital of Qingdao University, Shandong, China.
[Ti] Título:Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma.
[So] Source:PLoS One;13(1):e0190447, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica/métodos
Redes Reguladoras de Genes/genética
Melanoma/diagnóstico
Metástase Neoplásica/diagnóstico
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/genética
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Melanoma/genética
Melanoma/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Mapas de Interação de Proteínas
RNA Mensageiro/metabolismo
Neoplasias Cutâneas/genética
Software
Fatores de Transcrição/metabolismo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (RNA, Messenger); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190447


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[PMID]:29309433
[Au] Autor:Kobayashi M; Jitoku D; Iwayama Y; Yamamoto N; Toyota T; Suzuki K; Kikuchi M; Hashimoto T; Kanahara N; Kurumaji A; Yoshikawa T; Nishikawa T
[Ad] Endereço:Department of Psychiatry and Behavioral Sciences, Graduate School of Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:Association studies of WD repeat domain 3 and chitobiosyldiphosphodolichol beta-mannosyltransferase genes with schizophrenia in a Japanese population.
[So] Source:PLoS One;13(1):e0190991, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs; W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)-W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.
[Mh] Termos MeSH primário: Manosiltransferases/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Epistasia Genética
Feminino
Seres Humanos
Japão
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Polimorfismo de Nucleotídeo Único
Esquizofrenia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nuclear Proteins); 0 (WDR3 protein, human); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.142 (chitobiosyldiphosphodolichol beta-mannosyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190991



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