Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery

Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.info:eu-repo/semantics/publishedVersio

Cytokeratin 7/19 expression inN-diethylnitrosamine-induced mouse hepatocellular lesions: implications for histogenesis International

Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression ofcytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is proposed to reflect a possible progenitor cell origin or tumour dedifferentiation towardsa primitive phenotype. This work addresses that problem by studying CKs 7 and 19expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice weredivided into six DEN-exposed and six matched control groups. Samples were takenfrom each group at consecutive time points. Hyperplastic foci (13 lesions) occurredat 29-40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19 lesions) andwith one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4 lesions) wereobserved 40 weeks after the first DEN administration (group 12). CKs 7 and 19showed identical expression patterns and located to large, mature hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA were consistentlynegative for both markers, while dysplastic areas and HCCs were positive. Theseresults support the hypothesis that CKs 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin

In vivo and in vitro effects of RAD001 on bladder cancer

Objective: To evaluate the influence of Everolimus (RAD001) on chemically induced urothelial lesions in mice and its influence on in vitro human bladder cancer cell lines. Methods: ICR male mice were given N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for a period of 12 weeks. Subsequently, RAD001 was administered via oral gavage, for 6 weeks. At the end of the experiment, all the animals were sacrificed and tumor development was determined by means of histopathologic evaluation; mammalian target of rapamycin (mTOR) expressivity was evaluated by immunohistochemistry. Three human bladder cancer cell lines (T24, HT1376, and 5637) were treated using a range of RAD001 concentrations. MTT assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to assess cell proliferation, apoptosis index, and cell cycle analysis, respectively. Immunoblotting analysis of 3 cell line extracts using mTOR and Akt antibodies was performed in order to study the expression of Akt and mTOR proteins and their phosphorylated forms. Results: The incidence of urothelial lesions in animals treated with RAD001 was similar to those animals not treated. RAD001 did not block T24 and HT1376 cell proliferation or induce apoptosis. A reduction in cell proliferation rate and therefore G0/G1 phase arrest, as well as a statistically significant induction of apoptosis (P 0.001), was only observed in the 5637 cell line. Conclusion: RAD001 seems not to have a significant effect on chemically induced murine bladder tumors. The effect of RAD001 on tumor proliferation and apoptosis was achieved only in superficial derived bladder cancer cell line, no effect was observed in invasive cell lines

ENSINO INDIVIDUALIZADO: ADAPTAR O ENSINO DE ACORDO COM AS NECESSIDADES INDIVIDUAIS DE CADA ALUNO, OFERECENDO INSTRUÇÕES CLARAS, ORGANIZAÇÃO E ESTRUTURAÇÃO DAS TAREFAS, E FEEDBACK ESPECÍFICO E IMEDIATO.

Individualized teaching refers to the educational practice of personalizing the teaching process according to the individual needs and characteristics of each student. This includes providing clear and precise instructions, establishing an organizational structure for tasks, as well as offering specific and immediate feedback to promote development and learning. This approach aims to cater to the different skills, interests and learning styles of each student, providing an adaptable and flexible learning environment. By recognizing individual differences, educators can adjust content and teaching strategies to maximize each student's engagement and academic success. Specific and immediate feedback plays a crucial role in the individualized learning process, allowing students to understand their strengths and areas for improvement, as well as encouraging them to progress in their skills and knowledge. This contributes to building a solid foundation for students’ continued growth and development.O ensino individualizado refere-se à prática educacional de personalizar o processo de ensino de acordo com as necessidades e características individuais de cada aluno. Isso inclui fornecer instruções claras e precisas, estabelecer uma estrutura organizacional para as tarefas, bem como oferecer feedback específico e imediato para promover o desenvolvimento e o aprendizado. Essa abordagem visa atender às diferentes habilidades, interesses e estilos de aprendizagem de cada aluno, proporcionando um ambiente de aprendizagem adaptável e flexível. Ao reconhecer as diferenças individuais, os educadores podem ajustar o conteúdo e as estratégias de ensino para maximizar o engajamento e o sucesso acadêmico de cada aluno. O feedback específico e imediato desempenha um papel crucial no processo de aprendizagem individualizada, permitindo que os alunos compreendam seus pontos fortes e áreas de melhoria, além de incentivá-los a progredir em suas habilidades e conhecimentos. Isso contribui para a construção de uma base sólida para o crescimento e o desenvolvimento contínuo dos alunos

Alimentação popular em São Paulo (1920 a 1950): políticas públicas, discursos técnicos e práticas profissionais

This article discusses how the concept of lower-class eating habits came about and developed in the intellectual circles of São Paulo during the first half of the 20th century. It starts by reconstructing the elements of the debate around the income and ignorance of the underprivileged as the main reasons behind their bad eating habits. Then, it looks at the focal points for interventions and public policies proposed by the government to deal with the problem thus identified, namely: training methods to produce sanitation counselors capable of offering dietary guidance as well; popular educational campaigns and new learning sites in addition to schools (e.g. healthcare centers and households); lunch and other means of offering food at schools; and diagnostic studies about food intake and eating habits among laborers. Because they were translated into technical and scientific language, the proposals and policies implemented in São Paulo left traces in a variety of supporting documents and media (photographs, primers, posters, inquiry notebooks, and academic literature).O artigo discute a construção da idéia de alimentação popular nos meios intelectuais em São Paulo, na primeira metade do século XX. Para isso, reconstitui, como motivos da má alimentação, elementos do debate em torno da renda e da ignorância dos mais pobres. Identificado o problema, as propostas de intervenção e as políticas públicas concentraram-se em alguns setores, abordados neste trabalho: métodos para a formação de educadores sanitários aptos a atuar também na educação alimentar; campanhas de instrução popular e criação de novos lugares de aprendizado (além das escolas, os centros de saúde e os lares); merenda escolar e outras alternativas de alimentação nas escolas; e diagnósticos referentes ao conteúdo e à forma da alimentação dos operários. Traduzidas em discurso técnico-científicos, as propostas e políticas implementadas na cidade deixaram indícios em documentação de suporte e tipologia variados (fotografias, cartilhas, cartazes, cadernetas de inquéritos e textos acadêmicos).Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice

Estudos Artísticos

O número 18 da revista Gama apresenta 16 artigos respondendo ao desafio a editorial lançado por esta revista. Trata-se de apresentar a obra de artistas contemporâneos ou mais antigos numa perspetiva de um resgate patrimonial, uma revisitação valorizadora do seu testemunho artístico.info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio