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2.
Phys Rev E ; 97(4-1): 042417, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29758668

RESUMO

The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.


Assuntos
Redes Reguladoras de Genes , Modelos Biológicos , Transdução de Sinais , Animais , Humanos , Camundongos
3.
J Infect Dis ; 215(3): 387-395, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28003350

RESUMO

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.


Assuntos
Cardiomiopatia Chagásica/genética , Disfunção Ventricular/genética , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/fisiopatologia , Citotoxicidade Imunológica/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Células Matadoras Naturais/imunologia , Análise em Microsséries , Pessoa de Meia-Idade , Miocárdio/patologia , Reação em Cadeia da Polimerase em Tempo Real , Disfunção Ventricular/sangue , Disfunção Ventricular/parasitologia
4.
Oncotarget ; 8(6): 9597-9607, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28030816

RESUMO

Papillary thyroid carcinoma (PTC) is the most prevalent malignant neoplasia of the thyroid gland. A fraction of PTC cases show loss of differentiation and aggressive behavior, with radioiodine therapy resistance and metastasis. Although microRNAs (miRNAs) emerged as promising molecular markers for PTC, their role in the loss of differentiation observed during PTC progression remains to be fully understood. We performed the large-scale analysis of miRNA expression during PTC progression in BRAFT1799A-transgenic animals (Tg-Braf) and thyroid cancer cell lines and identified the marked downregulation of several miRNAs from the region 14q32. Data from The Cancer Genome Atlas (TCGA) confirmed the global downregulation of miRNAs from the 14q32 region in human PTC. The regulatory network potentially suppressed by these miRNAs suggests that key cancer-related biological processes such as cell proliferation, adhesion, migration and angiogenesis. Among the downregulated miRNAs, we observed that miR-654-3p levels decrease with long-term PTC progression in Tg-Braf mice and inversely correlate with EMT. The in vitro restoration of miR-654-3p decreased cell proliferation and migration and induced reprogramming of metastasis-related genes, suggesting a tumor suppressor role for this miRNA. In conclusion, we show global downregulation of 14q32-encoded miRNAs in an in vivo model of PTC progression. The potential circuitry in which these miRNAs are involved suggests that these miRNAs could play a key role in the pathophysiology of PTC and therefore be relevant for the development of new therapeutic strategies.


Assuntos
Carcinoma Papilar/genética , Cromossomos Humanos Par 14 , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Animais , Carcinoma Papilar/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Camundongos Transgênicos , MicroRNAs/metabolismo , Mutação , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Processamento Pós-Transcricional do RNA , Transdução de Sinais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Fatores de Tempo
5.
Cell Immunol ; 300: 18-25, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26632272

RESUMO

Myeloperoxidase (MPO) is an important enzyme in the front-line protection against microorganisms. In peripheral blood, it is accepted that MPO is only produced by myeloid-lineage cells. Thus, MPO presence is unexpected in lymphocytes. We showed recently that B1-lymphocytes from mice have MPO. Here, we showed that subsets of human peripheral B, CD4(+) and CD8(+) T lymphocytes express MPO. The content of MPO in lymphocytes was very low compared to neutrophils/monocytes with a preferential distribution in the nucleus and perinuclear region. Also, we performed a MPO mRNA expression analysis from human blood cells derived from microarray raw data publicly available, showing that MPO is modulated in infectious disease. MPO was increased in CD4(+) T lymphocytes from HIV chronic infection and in CD8(+) T lymphocytes from HCV-positive patients. Our study points out MPO as a multifunctional protein due to its subcellular localization and expression modulation in lymphocytes indicating alternative unknown functions for MPO in lymphocytes.


Assuntos
Linfócitos B/enzimologia , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD8-Positivos/enzimologia , Peroxidase/biossíntese , Linfócitos B/imunologia , Western Blotting , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Separação Celular , Citometria de Fluxo , Infecções por HIV/enzimologia , Infecções por HIV/imunologia , Hepatite C/enzimologia , Hepatite C/imunologia , Humanos , Imunofenotipagem , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Análise de Sequência com Séries de Oligonucleotídeos , Peroxidase/imunologia , Reação em Cadeia da Polimerase em Tempo Real
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