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Pesquisa : D12.644.276.374.200.120.500 [Categoria DeCS]
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Id: biblio-889318
Autor: Jiang, Xue; Feng, Lichun; Dai, Baoqiang; Li, Liping; Lu, Weiwei.
Título: Identification of key genes involved in nasopharyngeal carcinoma / Identificação dos principais genes envolvidos no carcinoma nasofaríngeo
Fonte: Braz. j. otorhinolaryngol. (Impr.);83(6):670-676, Nov.-Dec. 2017. tab, graf.
Idioma: en.
Resumo: Abstract Introduction: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. Objective: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. Methods: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package. Using the BiNGO plugin in Cytoscape and pathway enrichment analysis in the PGS package, functional and pathway enrichment analyses were performed separately to predict potential functions of the differentially expressed genes. Furthermore, Transcription factor-differentially expressed gene pairs were searched, and then the transcription factor-differentially expressed gene regulatory network was visualized using Cytoscape software. Results: A total of 487 genes were screened as differentially expressed genes between the nasopharyngeal carcinoma samples and the normal nasopharyngeal tissue samples. Enrichment analysis indicated that PTGS2 was involved in the regulation of biological process and small cell lung cancer. ZIC2 and OVOL1 may function in nasopharyngeal carcinoma through targeting significantly up-regulated genes (such as PTGS2, FN1, CXCL9 and CXCL10) in the Transcription factor-differentially expressed gene regulatory network (e.g., ZIC2→PTGS2 and OVOL1→CXCL10). Conclusion: PTGS2, FN1, CXCL9, CXCL10, ZIC2 and OVOL1 might play roles in nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é o câncer mais comum originário da nasofaringe. Objetivo: Estudar os mecanismos do câncer de nasofaringe; dados do microarray GSE12452 foram analisados. Método: GSE12452 foi obtido da base de dados Gene Expression Omnibus e inclui 31 amostras de carcinoma nasofaríngeo e 10 amostras de tecido nasofaríngeo normal. Os genes diferencialmente expressos foram analisados por ANOVA no kit PGS. Usando o plugin BiNGO no Cytoscape e análise de enriquecimento da via no kit PGS, análises de enriquecimento funcional e da via foram realizadas separadamente para prever as potenciais funções dos genes diferencialmente expressos. Além disso, os pares Fator de Transcrição - genes diferencialmente expressos foram pesquisados e em seguida a sua rede reguladora foi visualizada usando o programa Cytoscape. Resultados: Um total de 487 genes foram analisados como genes diferencialmente expressos entre as amostras de carcinoma nasofaríngeo e amostras de tecido nasofaríngeo normal. A análise de enriquecimento indicou que PTGS2 estava envolvido na regulação do processo biológico e câncer pulmonar de pequenas células. ZIC2 e OVOL1 podem funcionar no carcinoma nasofaríngeo almejando-se de maneira significativa os genes suprarregulados (como o PTGS2, FN1, CXCL9 e CXCL10) na rede reguladora de fator de transcrição - genes diferencialmente expressos (p.ex., ZIC2→PTGS2 e OVOL1→CXCL10). Conclusão: PTGS2, FN1, CXCL9, CXCL10, ZIC2 e OVOL1 podem desempenhar alguns papéis no carcinoma de nasofaringe.
Descritores: Carcinoma/genética
Expressão Gênica
Neoplasias Nasofaríngeas/genética
-Fatores de Transcrição/genética
Proteínas Nucleares/genética
Carcinoma/patologia
Análise por Conglomerados
Regulação para Baixo
Regulação para Cima
Neoplasias Nasofaríngeas/patologia
Análise de Variância
Perfilação da Expressão Gênica
Bases de Dados Genéticas
Análise em Microsséries
Redes Reguladoras de Genes
Quimiocina CXCL9/genética
Quimiocina CXCL10/genética
Carcinoma Nasofaríngeo
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-839183
Autor: Galvão-Lima, Leonardo J; Espíndola, Milena S; Soares, Luana S; Zambuzi, Fabiana A; Cacemiro, Maira; Fontanari, Caroline; Bollela, Valdes R; Frantz, Fabiani G.
Título: Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection
Fonte: Braz. j. infect. dis;21(1):42-50, Jan.-Feb. 2017. tab, graf.
Idioma: en.
Projeto: FAPESP.
Resumo: Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.
Descritores: Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Terapia Antirretroviral de Alta Atividade
Macrófagos/efeitos dos fármacos
-Linfócitos T CD4-Positivos/efeitos dos fármacos
Estudos de Casos e Controles
Infecções por HIV/sangue
Doença Aguda
Doença Crônica
Interleucinas/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
Resultado do Tratamento
Relação CD4-CD8
Estatísticas não Paramétricas
Linfócitos T CD8-Positivos/efeitos dos fármacos
Quimiocina CCL5/metabolismo
Receptores de Lipopolissacarídeos/efeitos dos fármacos
Carga Viral/efeitos dos fármacos
Quimiocina CXCL10/metabolismo
Limites: Humanos
Adulto
Tipo de Publ: Estudo de Avaliação
Responsável: BR1.1 - BIREME


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Id: biblio-894932
Autor: Naveca, Felipe Gomes; Pontes, Gemilson Soares; Chang, Aileen Yu-hen; Silva, George Allan Villarouco da; Nascimento, Valdinete Alves do; Monteiro, Dana Cristina da Silva; Silva, Marineide Souza da; Abdalla, Lígia Fernandes; Santos, João Hugo Abdalla; Almeida, Tatiana Amaral Pires de; Mejía, Matilde del Carmen Contreras; Mesquita, Tirza Gabrielle Ramos de; Encarnação, Helia Valeria de Souza; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues; Campi-Azevedo, Ana Carolina; Coelho-dos-Reis, Jordana Graziela; Antonelli, Lis Ribeiro do Vale; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Ramasawmy, Rajendranath.
Título: Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage
Fonte: Mem. Inst. Oswaldo Cruz;113(6):e170542, 2018. tab, graf.
Idioma: en.
Projeto: CNPq; . CAPES; . FINEP.
Resumo: BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.
Descritores: Quimiocina CXCL10/sangue
Infecção por Zika virus/complicações
-Expressão Gênica
Quimiocinas/imunologia
Infecção por Zika virus/imunologia
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-894865
Autor: Figueiredo, Webertty Mayk Eufrásio; Viana, Sayonara de Melo; Alves, Dorotheia Teixeira; Guerra, Priscila Valera; Coêlho, Zirlane Castelo Branco; Barbosa, Helene Santos; Teixeira, Maria Jania.
Título: Protection mediated by chemokine CXCL10 in BALB/c mice infected by Leishmania infantum
Fonte: Mem. Inst. Oswaldo Cruz;112(8):561-568, Aug. 2017. graf.
Idioma: en.
Projeto: CAPES.
Resumo: BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL.
Descritores: Tamanho do Órgão/fisiologia
Interleucina-4/biossíntese
Interleucina-10/biossíntese
Leishmania infantum
Quimiocina CXCL10/uso terapêutico
Leishmaniose Visceral/imunologia
Leishmaniose Visceral/parasitologia
Leishmaniose Visceral/tratamento farmacológico
Fígado/patologia
Macrófagos/efeitos dos fármacos
-Citocinas/imunologia
Interferon gama/análise
Camundongos Endogâmicos BALB C
Limites: Animais
Masculino
Camundongos
Responsável: BR1.1 - BIREME



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