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Prostate cancer ranks second in incidence worldwide. To date, there are no available therapies to effectively treat advanced and metastatic prostate cancer. Sulforaphane and vitamin D alone are promising anticancer agents in vitro and in vivo, but their low bioavailability has limited their effects in clinical trials. The present study examined whether sulforaphane combined with vitamin D at clinically relevant concentrations improved the cytotoxicity of the compounds alone towards DU145 and PC-3 human prostate tumor cells. To assess the anticancer activity of this combination, we analyzed cell viability (MTT assay), oxidative stress (CM-H2DCFDA), autophagy (fluorescence), DNA damage (comet assay), and protein expression (Western blot). The sulforaphane–vitamin D combination (i) decreased cell viability, induced oxidative stress, DNA damage, and autophagy, upregulated BAX, CASP8, CASP3, JNK, and NRF2 expression, and downregulated BCL2 expression in DU145 cells; and (ii) decreased cell viability, increased autophagy and oxidative stress, upregulated BAX and NRF2 expression, and downregulated JNK, CASP8, and BCL2 expression in PC-3 cells. Therefore, sulforaphane and vitamin D in combination have a potential application in prostate cancer therapy, and act to modulate the JNK/MAPK signaling pathway.

Introdução: A malária é considerada um dos maiores problemas de saúde pública no mundo como um todo, sendo isto levado em consideração pela Organização Mundial da Saúde e que em 2017 estimou um número de 219 milhões de casos para esta doença, com um aumento de 2 milhões ao ano anterior, mas apenas as três primeiras são encontradas na região brasileira. Seus aspectos clínicos incluem febre elevada, calafrios, cefaleia, os seus padrões na clínica vão de acordo com o seu agente etiológico e se não for tratado de forma cabível o seu quadro pode chegar causar um coma e até mesmo óbito. Tem-se 54 espécies do gênero Anopheles no Brasil, sendo muito distribuídos por todo o país e dentre dos que se destacam mais é o Anopheles darlingi, muito presente na região amazônica, sendo considerado o seu principal vetor. Com uma vasta distribuição geográfica e boa adaptabilidade. O seu ciclo de sazonalidade está muito ligado ao período das chuvas já que a criação dos seus criadouros depende desses fatores, além de estar ausente ou com muita pouca presença, em regiões onde se tem períodos longos de seca. Objetivo: Avaliar o perfil epidemiológico e espacial da malária na região norte na última década. Métodos: Revisão narrativa com estudo epidemiológico, e abordagem literária retirada dos bancos de dados do Google acadêmico e Scielo, sendo encontrados nos idiomas português e inglês. Resultados: A distribuição da malária pelas capitais os dados estavam tendo uma variação muito pequena, Porto Velho teve o maior número de casos na faixa etária de 20-39 e 40-59, Rio Branco e Palmas tiveram os menores números em todas as faixas etárias. Discussão: A malária ainda é um problema de saúde pública em todo o mundo, no Brasil, a doença ainda apresenta elevado risco de transmissão na região da Amazônia Legal, sendo a causa de consideráveis perdas sociais e econômicas das populações sob risco, principalmente daquelas que vivem em condições precárias de habitação e saneamento. Conclusão: A malária continua sendo um dos principais problemas de saúde pública no mundo, fatores sociais, econômicos e até mesmo políticos são agravantes para a propagação desta doença, no entanto, existem atitudes que podem influenciar positivamente para sua não reprodução, desde o individual até o coletivo, tais como a extrema importância um alerta sobre a doença, podendo haver o investimento em propagandas e meios que viabilizem a informação e que seja de fácil entendimento a todos.

Sea urchins live in a challenging environment that requires rapid and efficient responses against pathogens and invaders. This response may be also important in reproductive processes once males and females release their gametes into water. In addition, the gonads are organs with dual function: reproductive organ and nutrient reserve, therefore it needs efficient protective mechanisms to preserve the nutrients as well as the reproductive cells. The aim of this study was to evaluate the presence and characterize antimicrobial molecules in the male and female gonads of the sea urchin Lytechinus variegatus. Through HPLC purification, antimicrobial activity test and mass spectrometry several antimicrobial molecules were found in the gonads of both gender. Computational in silico analyses showed that they are fragments of a glycoprotein called toposome, also known as major yolk protein (MYP) which is one of the major proteins found in the gonads. Although different functions have been reported for this protein, this is the first description of a direct antimicrobial activity in Lytechinus variegatus. The results indicate that when undergoing proteolysis the toposome generates different fragments with antimicrobial activity which may indicate the importance of a rapid defense response strategy against invading microorganisms in the gonads used by both males and females sea urchins.

n Brazil the textbook was regulated with the legislation created in 1938 by the decree of law 1006. The textbooks were increasingly used and to ensure distribution in public schools the federal government created the National Textbook Program (PNLD) through Decree No. 91.542 / 85. This research aimed to analyze the process of choosing and using the science textbook by elementary school teachers in the municipality of Caridade do Piauí. Twenty science teachers from the largest public elementary schools in the municipality were interviewed. Through this research it was observed that teachers do not strictly follow the PNLD guidelines for choosing books, most also revealed that they did not use or had access to the Textbook Guide to select books. Most teachers reveal that they choose teaching material based on criteria they set themselves. Although they do not follow PNLD's instructions for choosing, current science books worked in schools have been well evaluated by teachers on various criteria such as theoretical content, visual aids, proposed activities and additional resources. Regarding the interference of the internet in the use of textbooks, most teachers state that books remain the main material used in the classroom. From all these aspects we can conclude that most teachers do not follow the guidelines of PNLD and Textbook Guide to make textbook choices. KEYWORDS: Guidelines, PNLD, Schools. RESUMO: No Brasil o livro didático foi regulamentado com a legislação criada em 1938 pelo decreto de lei 1006. Os livros didáticos passaram a ser utilizados cada vez mais e para garantir a distribuição em escolas públicas o governo federal criou o Programa Nacional do Livro Didático (PNLD) através do decreto de n° 91.542/85. Com esta pesquisa objetivou-se analisar o processo de escolha e utilização do livro didático de ciências por professores do ensino fundamental do município de Caridade do Piauí. Foram entrevistados 20 professores de ciências das maiores escolas públicas de ensino fundamental do município. Através desta pesquisa observou-se que os professores não seguem à risca as orientações do PNLD para a escolha dos livros, a maioria ainda revelou que não utilizaram ou não tiveram acesso ao Guia do Livro Didático para selecionar os livros. A maior parte dos professores revela que escolhem o material didático baseados em critérios estabelecidos por eles mesmos. Apesar de não seguirem as instruções do PNLD para a escolha, os atuais livros de ciências trabalhados nas escolas foram bem avaliados pelos professores em vários critérios como o conteúdo teórico, recursos visuais, atividades propostas e os recursos adicionais. Sobre a interferência da internet na utilização do livro didático, a maior parte dos professores afirma que os livros continuam sendo o principal material utilizado em sala de aula. Por todos esses aspectos podemos concluir que a maioria dos professores não seguem as orientações do PNLD e Guia do Livro Didático para realizarem as escolhas dos livros didáticos PALAVRAS-CHAVE: Orientações, PNLD, Escolas.

A diet deficient in donors of methyl group, such as methionine, affects DNA methylation and hepatic lipid metabolism. Methionine also affects other epigenetic mechanisms, such as microRNAs. We investigated the effects of methionine-supplemented or methionine-deficient diets on the expression of chromatin-modifying genes, global DNA methylation, the expression and methylation of genes related to lipid metabolism, and the expression of microRNAs in mouse liver. Female Swiss albino mice were fed a control diet (0.3% methionine), a methionine-supplemented diet (2% methionine), and a methionine-deficient diet (0% methionine) for 10 weeks. The genes most affected by the methionine-supplemented diet were associated with histone and DNA methyltransferases activity, while the methionine-deficient diet mostly altered the expression of histone methyltransferases genes. Both diets altered the global DNA methylation and the expression and gene-specific methylation of the lipid metabolism gene Apoa5. Both diets altered the expression of several liver homeostasis-related microRNAs, including miR-190b-5p, miR-130b-3p, miR-376c-3p, miR-411-5p, miR-29c-3p, miR-295-3p, and miR-467d-5p, with the methionine-deficient diet causing a more substantial effect. The effects of improper amounts of methionine in the diet on liver pathologies may involve a cooperative action of chromatin-modifying genes, which results in an aberrant pattern of global and gene-specific methylation, and microRNAs responsible for liver homeostasis.

Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

Snake envenomation is responsible for more than 130,000 deaths worldwide. In Brazil, the Crotalus rattlesnake is responsible for the second largest number of accidental snake bites in the country. Although there are many descriptions of the clinical and biochemical effects of Crotalus envenoming, there are few works describing the molecular events in the central nervous system of an organism due to envenomation. In this study, we analyzed the proteomic effect of Crotalus durissus terrificus snake venom on mice cerebellums. To monitor the envenomation over time, changes in the protein abundance were evaluated at 1 h, 6 h, 12 h and 24 h after venom injection by mass spectrometry. The analysis of the variation of over 4600 identified proteins over time showed a reduction in components of inhibitory synapse signaling, oxidative stress, and maintenance of neuronal cells, which paralleled increasing tissue damage and apoptosis factors. These analyses revealed the potential protein targets of the C. d. terrificus venom on the murine cerebellum, showing new aspects of the snake envenomation effect. These data may contribute to new therapeutic approaches (i.e., approaches directed at protein targets affected by the envenomation) on the treatment of envenomation by the neurotoxic C. d. terrificus snake venom. Significance Snakebites are a neglected global health problem that affects mostly rural and tropical areas of developing countries. It is estimated that over 5.4 million people are bitten by snakes each year, from which 2.7 million people are bitten by venomous snakes, resulting in disabilities such as amputations and in some cases leading to death. The C. d. terrificus snake is the most lethal snake in Brazil. Studying the molecular changes upon envenomation in a specific tissue may lead to a better understanding of the envenomation process by C. d. terrificus snakebites.