Viruses as a potential environmental trigger of type 1 diabetes mellitus (Review).

The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic ß-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic ß-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.

Biology and Natural History of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus is a clinical condition characterized by insufficient insulin production due to progressive loss of pancreatic islet ß-cells mediated by an autoimmune response. This deregulation of the immune system is caused by the action of genetic, epigenetic, and environmental factors in varying combinations for each individual. Although the inflammation of the islets with immune cell infiltration, known as insulitis, is an important element in pathogenesis, other factors are necessary for disease initiation. Associations with variants of HLA and other genes related to immune system function, mainly haplotypes HLA-DR3-DQ2 and HLA-DR4-DQ8, are more evident. The influence of polymorphisms and epigenetic modifications, as well as the microbiome, is convincing proof of the existence of a complex interaction between genetic, immune, and environmental factors in the etiology and pathogenesis of this metabolic disorder. Loss of selftolerance to autoimmunity is a critical point in the development of the disease, and regulatory T cells play a key role in this process. Thus, any failure of these cells, either due to an insufficient number or altered expression of cytokines and transcription factors, may be the trigger for the onset of the disease. The protective action of regulatory T cells is controlled by gene expression that is modulated by epigenetic modifications, including the dysregulation of noncoding RNAs. This review takes an updated approach to the natural history of type 1 diabetes, focusing on the factors involved in the etiology and pathogenesis.

The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review).

Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.

Th17 response in patients with cervical cancer.

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

Antibacterial, Antiproliferative, and Immunomodulatory Activity of Silver Nanoparticles Synthesized with Fucans from the Alga Dictyota mertensii.

In this study, we aimed to synthesize silver nanoparticles containing fucans from Dictyota mertensii (Martius) Kützing using an environmentally friendly method and to characterize their structure as well as antiproliferative, immunomodulatory, and antibacterial effects. Fucan-coated silver nanoparticles (FN) were characterized by Fourier-transform infrared analysis, dynamic light scattering, zeta potential, atomic force microscopy, energy dispersive X-ray spectroscopy, and inductively coupled plasma emission spectrometry. They were evaluated for their effect on cell viability, minimum inhibitory bactericidal concentration, and release of nitric oxide and cytokines. The FN were successfully synthesized using an environmentally friendly method. They were size-stable for 16 months, of a spherical shape, negative charge (-19.1 mV), and an average size of 103.3 ± 43 nm. They were able to inhibit the proliferation of the melanoma tumor cell line B16F10 (60%). In addition, they had immunomodulatory properties: they caused an up to 7000-fold increase in the release of nitric oxide and cytokines (IL-10; IL-6 and TNF-α) up to 7000 times. In addition, the FN showed inhibitory effect on Gram-positive and -negative bacteria, with MIC values of 50 µg/mL. Overall, the data showed that FN are nanoparticles with the potential to be used as antitumor, immunomodulatory, and antibacterial agents.

Uma proposta de ensino integrado a acao comunitaria: programa de assistencia materno-infantil a adolescente gravida / A proposal of integrated to community action: maternal-child assistance program directed to pregnant teenagers

Desenvolve programa multidisciplinar voltado para a assistencia materno-infantil as adolescentes gravidas e seus conceptos. Participam do trabalho professores e alunos dos cursos de graduacao da area de saude e profissionais dos servicos de saude vinculados ao Sistema Unico de Saude (MMSC)

Tipos de hemoglobinas em escolares da cidade de Natal,RN / Hemoglobin types in students of Natal city,RN

Os autores determinaram a frequencia dos tipos de hemoglobinas em 5l8 escolares pertencentes a escolas de primeiro grau da rede estadual de ensino da cidade de Natal,RN. As amostras de sangue coletadas em EDTA foramsubmetidas a eletroforese de hemoglobina em acetado de celulose usando tampao Tris-glicina pH9,1. A analise das amostras demonstrou que 507 (97,88%) tinham Hb AA e 11 (2,12%) apresentavam hemoglobinas anormais representadas pelos genotipos AS (1,93%) e AC (0,19%).

Estigma beta talassemico em uma amostra da populaçao de Natal, RN / Beta thalassemia trait in a sample from the population of Natal,RN

Foi realizado um estudo com objetivo de determinar a prevalencia de talassemia beta em uma amostra da populaçao da cidade de Natal,RN. Foram analisadas 1.106 amostras de sangue de individuos de ambos os sexos e diferentes faixas etarias. Os sangues foram coletados por punçao venosa,adicionados a EDTA e analisados mediante o teste de fragilidade osmotica em soluçao de NaC1a0,36%.As amostras que apresentaram teste positivo foram submetidas a eletroforese quantitativa para dosagem de HbA2 e a determinaçao bioquimica da hemoglobina fetal por desnaturaçao alcalina. Dentre os individuos estudados, foram identificados 19 com traço talassemico beta representando uma prevalencia em torno de 1,72%.