Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis. This work aimed to characterize the epithelial–mesenchymal transition and doxorubicin (dox) response in a mammary tumor spheroid (MTS) model. We evaluated the doxorubicin treatment effect on MCF-7 spheroid diameter, cell viability, death, migration and proteins involved in the epithelial–mesenchymal transition (EMT) process. Spheroids were also produced from tumors formed from 4T1 and 67NR cell lines. MTSs mimicked avascular tumor characteristics, exhibited adherens junction proteins and independently produced their own extracellular matrix. Our spheroid model supports the 3D culturing of cells isolated from mice mammary tumors. Through the migration assay, we verified a reduction in E-cadherin expression and an increase in vimentin expression as the cells became more distant from spheroids. Dox promoted cytotoxicity in MTSs and inhibited cell migration and the EMT process. These results suggest, for the first time, that this model reproduces aspects of the EMT process and describes the potential of dox in inhibiting the metastatic process, which can be further explored.

Central nervous system alterations was described in Chagas disease in both human and experimental models, leading to meningoencephalitis, stroke and cognitive impairment. Recently, our group demonstrated that acute infection by Trypanossoma cruzi leads to cerebral microvasculophaty in mice with endothelial dysfunction, capillary rarefaction, increased rolling and leukocyte adhesion. Only benznidazole and nifurtimox are available for clinical treatment, they have an efficiency of 80% in the acute phase and less than 20% in chronic phase. However, the effect of these drugs on brain microcirculation has not yet been evaluated. We hypothesized that early treatment with benznidazole could protect brain microcirculation during acute experimental Chagas disease. Swiss Webster mice were inoculated with 10⁴ trypomastigotes forms of T. cruzi, and after 24 h they were treated with 50 or 100 mg/kg/day of benznidazole for 14 consecutive days. In untreated infected mice, we observed cerebral microvascular rarefaction, increase in leukocyte rolling and adhesion, reduced cerebral blood flow, and increased CD3+ and F4-80+ cells in brain tissue. Early treatment with benznidazole at 100 mg/kg/day and 50 mg/kg/day prevented the occurrence of the alterations mentioned. Here, we show that BZ is able to protect the microcirculation and reduced brain inflammation in acute experimental Chagas disease.

Em 2020 o mundo foi atingido pela pandemia da COVID-19, causada pelo vírus SARS-CoV-2, que desencadeou a impossibilidade de realizar atividades presenciais pelo isolamento e o distanciamento social. A Internet se tornou uma grande fonte de informações sobre a COVID-19. Versões distorcidas dos fatos começaram a ser disseminadas pelas pessoas por este meio, as quais se aproveitaram da desinformação, do medo, e da insegurança da população para criar narrativas de comunicação científica errôneas. No auge da pandemia, devido às condições sociais, o Instagram, que é uma poderosa ferramenta de comunicação no contexto das redes sociais, e possui um alto alcance, foi altamente utilizado para disseminar informações sobre a pandemia. Visando contribuir para disseminação de informação acessível e segura sobre COVID-19 e assuntos relacionados a saúde, nosso grupo criou um perfil no Instagram denominado @grupo.cienciagram em julho de 2021. O @grupo.cienciagram foi criado por estudantes do Instituto Oswaldo Cruz, sendo composto por: uma doutora, uma aluna de doutorado, um aluno de mestrado e três alunas de iniciação científica. Nele são disponibilizadas informações nos formatos: (1) “postagem rápida”, (2) “postagem carrossel”, (3) vídeos em reels e (4) vídeos de IGTV, abordando temas como: segurança e eficácia das vacinas; a diferença entre seus mecanismos (diferentes tipos); o significado dos testes de IgG e IgM; o que são variantes de um vírus, entre outros. Em seis meses de atividade, foram feitas 68 postagens e durante esse período o perfil acumulou mais de sete mil seguidores, com reels que chegaram a atingir mais de 2 milhões de visualizações. As análises das métricas de acesso e visualizações foram feitas a partir dos dados do Instagram Insights. Nossos dados demonstram que o Instagram é uma rede social com grande potencial para disseminação de informações de qualidade sobre saúde e para a divulgação científica com grande visibilidade. PALAVRAS-CHAVE: COVID-19; coronavírus; divulgação científica; Instagram.

A three-dimensional (3D) cell culture can more precisely mimic tissues architecture and functionality, being a promising alternative model to study disease pathophysiology and drug screening. Chagas disease (CD) is a neglected parasitosis that affects 7 million people worldwide. Trypanosoma cruzi’s (T. cruzi) mechanisms of invasion/persistence continue to be elucidated. Benznidazole (BZ) and Nifurtimox (NF) are trypanocidal drugs with few effects on the clinical manifestations of the chronic disease. Chronic Chagas cardiomyopathy (CCC) is the main manifestation of CD due to its frequency and severity. The development of fibrosis and hypertrophy in cardiac tissue can lead to heart failure and sudden death. Thus, there is an urgent need for novel therapeutic options. Our group has more than fifteen years of expertise using 3D primary cardiac cell cultures, being the first to reproduce fibrosis and hypertrophy induced by T. cruzi infection in vitro. These primary cardiac spheroids exhibit morphological and functional characteristics that are similar to heart tissue, making them an interesting model for studying CD cardiac fibrosis. Here, we aim to demonstrate that our primary cardiac spheroids are great preclinical models which can be used to develop new insights into CD cardiac fibrosis, presenting advances already achieved in the field, including disease modeling and drug screening.

Central nervous system alterations was described in Chagas disease in both human and experimental models, leading to meningoencephalitis, stroke and cognitive impairment. Recently, our group demonstrated that acute infection by Trypanossoma cruzi leads to cerebral microvasculophaty in mice with endothelial dysfunction, capillary rarefaction, increased rolling and leukocyte adhesion. Only benznidazole and nifurtimox are available for clinical treatment, they have an efficiency of 80% in the acute phase and less than 20% in chronic phase. However, the effect of these drugs on brain microcirculation has not yet been evaluated. We hypothesized that early treatment with benznidazole could protect brain microcirculation during acute experimental Chagas disease. Swiss Webster mice were inoculated with 10⁴ trypomastigotes forms of T. cruzi, and after 24 h they were treated with 50 or 100 mg/kg/day of benznidazole for 14 consecutive days. In untreated infected mice, we observed cerebral microvascular rarefaction, increase in leukocyte rolling and adhesion, reduced cerebral blood flow, and increased CD3 + and F4-80 + cells in brain tissue. Early treatment with benznidazole at 100mg/kg/day and 50mg/kg/day prevented the occurrence of the alterations mentioned. Here, we show that BZ is able to protect the microcirculation and reduced brain inflammation in acute experimental Chagas disease.

Anais do Congresso de Fisiologia e Patologia (978-65-272-1162-4) - Efeito Do Tratamento Com Selênio Em Monoterapia Ou Combinado Ao Benznidazol Sobre A Microvasculopatia Observada Em Modelo De Infecção Aguda Por T. Cruzi