Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to facilitate its replication and progression to disease. MicroRNAs (miRNAs) are key regulators of gene expression and could be involved during the infection. To address the genetic influence of miRNAs in leprosy, we enrolled 1,098 individuals and conducted a case-control analysis in order to study four miRNAs genes containing single nucleotide polymorphism (miRSNP). We tested miRSNP-125a (rs12975333 G>T), miRSNP-223 (rs34952329 *>T), miRSNP-196a-2 (rs11614913 C>T) and miRSNP-146a (rs2910164 G>C). Amongst them, miRSNP-146a was the unique gene associated with risk to leprosy per se (GC OR = 1.44, p = 0.04; CC OR = 2.18, p = 0.0091). We replicated this finding showing that the C-allele was over-transmitted (p = 0.003) using a transmission-disequilibrium test. A functional analysis revealed that live M. leprae (MOI 100∶1) was able to induce miR-146a expression in THP-1 (p<0.05). Furthermore, pure neural leprosy biopsies expressed augmented levels of that miRNA as compared to biopsy samples from neuropathies not related with leprosy (p = 0.001). Interestingly, carriers of the risk variant (C-allele) produce higher levels of mature miR-146a in nerves (p = 0.04). From skin biopsies, although we observed augmented levels of miR-146a, we were not able to correlate it with a particular clinical form or neither host genotype. MiR-146a is known to modulate TNF levels, thus we assessed TNF expression (nerve biopsies) and released by peripheral blood mononuclear cells infected with BCG Moreau. In both cases lower TNF levels correlates with subjects carrying the risk C-allele, (p = 0.0453 and p = 0.0352; respectively), which is consistent with an immunomodulatory role of this miRNA in leprosy. In spite of the successful drug therapy, leprosy is still affecting people worldwide. It is well known that host genetic background influences leprosy development and that genetic variants have been associated with the disease. Therefore we conducted a study to evaluate the role of microRNAs (miRNAs) polymorphisms in leprosy. We observed that a polymorphism in miR-146a is associated with the risk to develop leprosy in Brazilians. Based on the analysis of clinical specimens, we found that the genetic variant was correlated with elevated levels of miR-146a and it is also a negative regulator of tumor necrosis factor (TNF), an important inflammatory mediator in the leprosy context. These findings provide tenable evidences that miR-146a is important in the control of gene expression during M. leprae infection and also may contribute with leprosy development by controlling TNF levels.

The disturbed vaginal microbiome defined as bacterial vaginosis (BV) and the parasitic infection by Trichomonas vaginalis (TV), the most common non-viral sexually transmitted pathogen, have well-established adverse effects on reproductive outcomes and susceptibility to infection and cancer. Molecular mechanisms underlying these associations and the failure of antibiotic therapy to mitigate adverse consequences are not fully elucidated. In an in vitro human vaginal colonization model, we tested the hypothesis that responses to TV and/or BV-bacteria will disrupt the micro(mi)RNA cargo of extracellular vesicles (EV) with the potential to modify pathways associated with reproductive function, cancer, and infection. miRNAs were quantified by HTG EdgeSeq. MiRNA differential expression (DE) was established in response to TV, the BV signature pathobiont Prevotella bivia and a homeostatic Lactobacillus crispatus with adjusted p < 0.05 using R. Validated gene targets, pathways, protein-protein interaction networks, and hub genes were identified by miRWalk, STRING, Cytoscape, and CytoHubba. In contrast to L. crispatus, TV and the BV pathobiont dysregulated a massive number of EV-miRNAs, over 50% shared by both pathogens. Corresponding target pathways, protein interaction clusters and top hub genes were related to cancer, infectious disease, circadian rhythm, steroid hormone signaling, pregnancy, and reproductive tissue terms. These data support the emerging concept that bacteria and parasitic eukaryotes disturbing the human vaginal microbiome may impact reproductive health through EV-miRNA dysregulation.

Os benefícios alcançados por meio de metodologias de ensino-aprendizagem centradas no educando parecem ser consenso entre os estudiosos da Educação Básica. Assim, observa-se uma crescente preocupação no desenvolvimento de estratégias pedagógicas que viabilizem a implementação de metodologias ativas. Em consonância com essa tendência, desenvolvemos uma atividade de Aprendizagem Baseada em Problemas do tipo Estudo de Caso, no âmbito da Genética, com a finalidade de proporcionar o aprendizado de conteúdos conceituais e atitudinais relacionados ao tema Grupos Sanguíneos. A atividade contou com quatro casos diferentes que tiveram início durante uma aula prática simulada de tipagem sanguínea – sistemas ABO e Rh. A adequação da atividade foi avaliada de modo quali-quantitativo e indicou que os estudantes conseguiram aplicar conhecimentos prévios e desenvolver novos saberes pautados em discussões acerca dos temas geradores, à medida que se envolviam na resolução dos casos. Além disso, a sequência didática adotada permitiu introduzir o conteúdo de Epistasia a partir de um dos casos. Grupos Sanguíneos foi um tema estrategicamente escolhido por estar intimamente relacionado ao cotidiano dos estudantes, com potencial para fomentar discussões contextualizadas com tecnologias, sociedade e ética.