Luana Santos Louro

Twenty-first century trends indicate that the central characteristic of contemporary education is the shift from an individual focus to a social, political, and ideological focus. Active teaching–learning methodologies, particularly with a problematizing approach, have been used in training and health professionals, as a strategy aimed at integrating knowledge and promoting a critical and reflective attitude towards practice. In view of this, the present study sought to build, standardize, and apply the problem-based learning (PBL) methodology in teaching the Medical Genetics discipline for the Medicine course at the Federal University of Espírito Santo (UFES), seeking to contribute to the consolidation of the study of genetic determinants of diseases and their applications in medical education and practice, in order to provide possible examples of medical conduct, given the different realities experienced by doctors. Through the application of PBL, students received a case study in the area of Genetic Counseling/Oncogenetics to apply their knowledge together with the use of different tools and software, in order to exemplify a model of medical conduct for that particular condition. The results indicate that the proposed class model was efficiently constructed, standardized, and applied to the third semester class of the UFES Medicine course, in which the students positively evaluated the application and use of the methodology in the proposed activity, highlighting its positive effects for medical training. The use of this class model based on the PBL methodology favors the development of the necessary skills, abilities, and attitudes recommended in the guiding documents for medical graduates, within the scope of Medical Genetics, in order to encourage the practice of personalized care in the formative years.

Brazil is the world leader in pesticide consumption, and its indiscriminate use puts farmers’ health at risk. The CYP2C9 gene stands out for encoding the CYP2C9 enzyme, which metabolizes several endogenous substrates and specific xenobiotics, especially pesticides. Our goal is to study the risk of pesticide use, espe-cially the herbicide glyphosate, in the development of diseases and the association with two CYP2C9 poly-morphisms, in farmers living in the southern region of Espírito Santo state, Brazil. The allelic frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was determined in blood samples from individuals exposed or not to pesticides using real-time PCR. 304 blood samples were analyzed, dividing CYP2C9 genotypes into three metabolization classes: normal, intermediate, and slow. Our results show that normal metabolizers are more vulnerable to diseases such as blood pressure changes and cardiovascular and kidney problems, while in-termediate metabolizers show an association with attention deficit disorder and miscarriages, suggesting that farmers in the studied region developed symptoms correlated to the CYP2C9 genotype they have. This work is pioneering in associating specific genetic variations and health risks with pesticide exposure, em-phasizing the importance of personalized medicine and stricter regulation of pesticide use for public health and occupational safety.

One of the main limitations of Regenerative Medicine was growth factor selection for stem cell culture to obtain optimal differentiation, resulting in functional tissue. For neural regeneration tissue engineering techniques, this choice became even harder due to tissue complexity. This work aimed to use a systems biology approach allied to bioinformatics to identify growth factors for nervous cell regeneration in protein-protein interaction (PPI) networks, potentially resulting in more effective therapy design. Articles were curated using the PubMed database, and protein coding genes related to neuroregeneration and nervous tissue engineering were extracted for PPI network construction, in which enrichment analysis of Gene Ontology, clustering, and protein centrality were applied. The work generated a main network with 64 nodes, 440 edges, and 3 clusters: one with 21 nodes and 187 edges, another with 6 nodes and 12 edges, and a third one with 3 nodes and 3 edges. Some of the proteins identified, such as NGF, BDNF, GDNF and NTFs, had known functions in neuroregeneration, validating our method efficiency. Protein-coding genes with ambiguous functions or less described in the literature were also found, such as IL6, IL1B, and CXCL12, suggesting more studies to clarify their roles in neuroregeneration.

A regeneração celular e tecidual, muito abordada em diversas áreas da medicina e da biologia, ainda permanece com lacunas sobre seus processos e funcionamento. Na última década, elucidou-se o papel da epigenética na referida função, dando-se ênfase para RNAs não codificantes, e entre eles, os piRNAs (PIWI-interacting RNAs), antes conhecidos por sua atuação em células germinativas e no controle de elementos transponíveis. Estudos recentes demonstraram funções dos piRNA em células de tecidos somáticos, como o nervoso, e pesquisas com pequenos roedores, especialmente em Mus musculus, apontaram uma importante ligação entre a expressão dessa via e o correto funcionamento do processo de regeneração. Por ser um desafio relevante para a medicina regenerativa entender esses processos, através de estudos robustos aqui descritos e utilizando ferramentas de Bioinformática, construiu-se redes de interação proteína-proteína (PPIN) para identificar proteínas-alvo para tratamentos terapêuticos com base no funcionamento da via do gene PIWI/piRNA em Mus musculus. A partir da análise dessas redes, conseguimos identificar proteínas relevantes, assim como suas interações, para o processo regenerativo em mamíferos e, com esses resultados, futuramente, poder-se-á desenvolver testes in vivo com base nos dados obtidos in silico, economizando, assim, tempo e investimentos financeiros.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) “What is the current knowledge about polyploidy in tumors?”; (ii) “What are the applications of computational studies for the understanding of cancer polyploidy?”; and (iii) “How do PGCCs contribute to tumorigenesis?”

Translational Bioinformatics (TBI) is defined as the union of translational medicine and bioinformatics. It emerges as a major advance in science and technology by covering everything, from the most basic database discoveries, to the development of algorithms for molecular and cellular analysis, as well as their clinical applications. This technology makes it possible to access the knowledge of scientific evidence and apply it to clinical practice. This manuscript aims to highlight the role of TBI in the study of complex diseases, as well as its application to the understanding and treatment of cancer. An integrative literature review was carried out, obtaining articles through several websites, among them: PUBMED, Science Direct, NCBI-PMC, Scientific Electronic Library Online (SciELO), and Google Academic, published in English, Spanish, and Portuguese, indexed in the referred databases and answering the following guiding question: “How does TBI provide a scientific understanding of complex diseases?” An additional effort is aimed at the dissemination, inclusion, and perpetuation of TBI knowledge from the academic environment to society, helping the study, understanding, and elucidating of complex disease mechanics and their treatment.