RESUMO
The relevance of the study is expressed by the improvement and development of tools for managing social processes and public procedures. There are a large number of concepts and theories that explain certain aspects of public opinion: exposure to influence, an impact on people's actions, and its contradictory nature. The main forming factors of individual behavior are the stereotypes and values that are developed within society. In moments of social instability, the problem of governance and expression of public opinion progresses. The purpose of the study is to consider public opinion similarly and to search for patterns of its functioning. At present, there is a lack of an expressly unified model that allows characterizing all the laws of existence and its phenomena. Public opinion is understudied, despite the large volumes of theoretical research. This is explained by the predominance of psychological and sociological scientific concepts in the analysis of public opinion. This study is based on specific methods of conducting various sociological monitoring and developments in the field of methodology. Modern humanitarian knowledge misses certain problems related to the role of public opinion in the context of social processes. The practical significance of this study lies in the investigation and distribution of approaches to the study of public opinion as a means of managing social processes.
Assuntos
Opinião Pública , HumanosRESUMO
DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p < 2.1 × 10(-4)) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p < 1.9 × 10(-7)). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Receptores de Grelina/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ilhas de CpG , Metilação de DNA , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Análise em Microsséries , Valor Preditivo dos Testes , Curva ROC , Receptores de Grelina/metabolismo , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1α-dependent manner. XOD produces uric acid and reactive oxygen species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1ß into active IL-1ß. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1ß release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice.