Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription–PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Tendo como princípios orientadores a integralidade e a humanização do cuidado, a Faculdade de Medicina de Botucatu (FMB) - Unesp busca reorientar a formação dos profissionais de saúde com o desenvolvimento de pesquisas e educação permanente na Estratégia de Saúde da Família. Este artigo analisa o primeiro ano do PET-Saúde desenvolvido na FMB e Secretaria Municipal de Saúde de Botucatu (SP). Foram selecionados como temas de investigação: saúde bucal de gestante, criança e idoso; imunização do adolescente; saúde do adulto e do idoso; e saúde e meio ambiente. Realizaram-se oficinas com a metodologia da problematização, produzindo-se modelos de intervenção nos quais alunos, docentes e profissionais de saúde dos serviços locais de saúde são protagonistas. O programa é um desdobramento da disciplina Interação Universidade, Serviço e Comunidade, ministrada de modo integrado aos cursos de Medicina e Enfermagem. Há resistências no interior da universidade, reconhecendo-se a desvalorização da prática clínica extra-hospitalar e na Atenção Básica. Nesse processo, o PET-Saúde vem fortalecer a prática acadêmica que interliga a universidade, em suas atividades de ensino, pesquisa, serviço e extensão, com demandas da sociedade, de forma partilhada.

Chronic myeloid leukemia (CML) results from a translocation between chromosomes 9 and 22, which generates the Philadelphia chromosome. This forms BCR/ABL1, an active tyrosine kinase protein that promotes cell growth and replication. Despite great progress in CML treatment in the form of tyrosine kinase inhibitors, allogeneic-hematopoietic stem cell transplantation (allo-HSCT) is currently used as an important treatment alternative for patients resistant to these inhibitors. Studies have shown that unregulated expression of microRNAs, which act as oncogenes or tumor suppressors, is associated with human cancers. This contributes to tumor formation and development by stimulating proliferation, angiogenesis, and invasion. Research has demonstrated the potential of microRNAs as biomarkers for cancer diagnosis, prognosis, and therapeutic targets. In the present study, we compared the circulating microRNA expression profiles of 14 newly diagnosed patients with chronic phase-CML and 14 Philadelphia chromosome-negative patients after allo-HSCT. For each patient, we tested 758 microRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis. The global expression profile of microRNAs revealed 16 upregulated and 30 downregulated microRNAs. Target genes were analyzed, and key pathways were extracted and compared. Bioinformatics tools were used to analyze data. Among the downregulated miRNA target genes, some genes related to cell proliferation pathways were identified. These results reveal the comprehensive microRNA profile of CML patients and the main pathways related to the target genes of these miRNAs in cytogenetic remission after allo-HSCT. These results provide new resources for exploring stem cell transplantation-based CML treatment strategies.

This observational, multicenter study aimed to report the clinical evolution of COVID-19 in patients with chronic myeloid leukemia in Latin America. A total of 92 patients presented with COVID-19 between March and December 2020, 26% of whom were severe or critical. The median age at COVID-19 diagnosis was 48 years (22–79 years), 32% were 60 years or older, and 61% were male. Thirty-nine patients presented with at least one comorbidity (42.3%). Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. There was one case of reinfection. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; p = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (100, 89, 50, and 33%, respectively; p < 0.001).

Chronic myeloid leukemia (CML), a hematopoietic neoplasm arising from the fusion of BCR (breakpoint cluster region) gene on chromosome 22 to the ABL (Abelson leukemia virus) gene on chromosome 9 (BCR-ABL1 oncogene), originates from a small population of leukemic stem cells with extensive capacity for self-renewal and an inflammatory microenvironment. Currently, CML treatment is based on tyrosine kinase inhibitors (TKIs). However, allogeneic hematopoietic stem cell transplantation (HSCT-allo) is currently the only effective treatment of CML. The difficulty of finding a compatible donor and high rates of morbidity and mortality limit transplantation treatment. Despite the safety and efficacy of TKIs, patients can develop resistance. Thus, microRNAs (miRNAs) play a prominent role as biomarkers and post-transcriptional regulators of gene expression. The aim of this study was to analyze the miRNA profile in CML patients who achieved cytogenetic remission after treatment with both HSCT-allo and TKI. Expression analyses of the 758 miRNAs were performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatics tools were used for data analysis. We detected miRNA profiles using their possible target genes and target pathways. MiR-125a-3p stood out among the downregulated miRNAs, showing an interaction network with 52 target genes. MiR-320b was the only upregulated miRNA, with an interaction network of 26 genes. The results are expected to aid future studies of miRNAs, residual leukemic cells, and prognosis in CML.