https://repositorio.ufu.br/handle/123456789/5487 2026-08-26T21:35:00Z 2026-08-26T21:35:00Z https://repositorio.ufu.br/handle/123456789/49796 2026-08-25T06:22:47Z 2026-11-03T00:00:00Z

Title: Impacto dos subtipos moleculares e variáveis clínico-patológicas nos desfechos do câncer de mama: um estudo entre grandes bases de dados Abstract: Breast cancer represents a major global health challenge, and the use of publicly available databases can contribute to a more comprehensive understanding of disease patterns. Given the potential of these data sources to support complementary analyses, this study aimed to explore different publicly available databases to investigate demographic, tumor, and therapeutic characteristics of breast cancer. An observational, retrospective study was conducted using hospital-based, population-based, and molecular records from four databases: the São Paulo Hospital-Based Cancer Registry (HBCR), the National HBCR, the Surveillance, Epidemiology, and End Results (SEER) Program, and the genomic and clinical data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Together, these four databases comprised 1,128,269 breast cancer records. Diagnoses were made between 2000 and 2015, except for the METABRIC database. Fine-Gray competing risks modeling was employed to evaluate tumor recurrence over a 120-month follow-up period, stratified into two time intervals (0–60 and 61–120 months). Cox proportional hazards models were applied to estimate 5-year overall and cause-specific survival. Road travel distances to cancer treatment facilities in Brazil were estimated using the geobr and osrm statistical packages. All analyses were performed in the RStudio computing environment, version 2026.01.1+403. Independent predictors of the average risk of tumor recurrence included tumor size, the number of positive lymph nodes, histological grade 3, and intrinsic molecular subtypes defined by the PAM50 gene expression signature. Temporal dynamics analysis demonstrated that the risk of tumor recurrence was not constant over time. Regarding 5-year survival, age and tumor stage were independent predictors of the average risk of overall and cause-specific mortality. Year of diagnosis was inversely associated with the risk of cause-specific mortality, serving as a temporal marker of changes occurring throughout the study period. An average reduction of 2.81% in the Sâo Paulo HBCR and 2.96% in the population-based registry was observed in the risk of cause-specific mortality for each more recent year of diagnosis. In the National HBCR, 52.09% of the sample received treatment outside their municipality of residence. Median road travel distances by treatment modality ranged from 76.6 km for hormone therapy to 114.0 km for immunotherapy. Geographic mapping revealed inequalities in the distribution of oncology services, demonstrating that treatment centers were highly concentrated in the Southeast, South, and Northeast regions of Brazil. The study concludes that different databases provide complementary information that expands the analytical capabilities for investigating breast cancer outcomes, enabling analyses that would not be possible using a single data source. These findings highlight the value of combining information from multiple data sources to support researchers and healthcare decision-makers in monitoring disease patterns and planning oncology care strategies.

2026-11-03T00:00:00Z https://repositorio.ufu.br/handle/123456789/49440 2026-08-12T06:28:48Z 2026-07-31T00:00:00Z

Title: Desenvolvimento de estratégias antivirais frente a vírus emergentes Abstract: Emerging viruses pose growing threats to public health, particularly in Brazil, where environmental and sociodemographic factors favour epidemic outbreaks. This work aimed to identify and characterise antiviral compounds against the emerging viruses Orthobunyavirus oropoucheense (OROV) and Betacoronavirus pandemicum (SARS-CoV-2) through medium-throughput screening of the Pandemic Response Box (PRB) and Global Health Priority Box (GHPB) libraries from the Medicines for Malaria Venture (MMV). OROV is the causative agent of Oropouche fever, which caused over 13,000 cases in Brazil in 2024, with unprecedented geographical expansion, vertical transmission, neurological complications and confirmed fatalities, with no approved antiviral treatment available. SARS-CoV-2, responsible for the COVID-19 pandemic with over 779 million cases recorded through 2026, remains a therapeutic challenge, particularly against the Delta and Omicron variants of concern. The experimental approach employed fluorescent reporter viruses, BUNV-eGFP (Bunyamwera virus with an enhanced green fluorescent protein reporter) as a prototypic model for OROV, and SARS-CoV-2-mCherry (SARS-CoV-2 with a monomeric red fluorescent protein reporter) for direct screening, in A549 and A549-AT cells, with automated readout using the IncuCyte S3 system. Of the 640 compounds tested, active hits were identified and validated for both viral targets. Against OROV, nine compounds from the PRB inhibited BUNV replication by more than 90%. Following validation against wild-type OROV (epidemic strain AM0088), three hits were confirmed: Trimetrexate, MMV1634385, and GSK-983, being GSK the compound with greatest inhibition (EC50 = 0.5 μM against OROV; DHODH inhibitor; SI > 20), reported here for the first time as an anti-orthobunyavirus compound and identified as the most promising candidate. Against SARS-CoV-2, two hits were mechanistically characterised. Revaprazan (EC50 = 1.3 μM; SI > 7.7), a clinically approved potassium-competitive acid blocker (P-CAB), inhibited viral entry while retaining activity against Delta and Omicron BA.2, representing the first report of antiviral activity for a P-CAB-class compound. Milbemectin (EC50 = 1.6 μM; SI > 6), a milbemycin-class macrolide antiparasitic structurally related to ivermectin, acted predominantly at post-entry stages, interfering with virion assembly and egress. Together, these findings establish GSK-983, Revaprazan and Milbemectin as priority candidates for preclinical investigation, expand the antiviral spectrum of compounds with established safety profiles, and validate the fluorescent reporter-based screening platform as a robust strategy for antiviral discovery against emerging viral threats.

2026-07-31T00:00:00Z https://repositorio.ufu.br/handle/123456789/49312 2026-08-07T06:23:34Z 2026-04-23T00:00:00Z

Title: Caracterização molecular de Escherichia coli multirresistente na interface humano- animal-ambiental: uma abordagem One Health Abstract: In the context of the One Health approach, microorganisms such as Escherichia coli have received increasing attention due to their widespread presence at the human-animal-environment interface and their ability to disseminate antimicrobial resistance genes, highlighting their role as resistance vectors. The aim of this study was to investigate the clonal dissemination of resistant E. coli isolated from the human-animal-environment interface, characterizing their resistance and virulence genes, as well as sequence types (STs), in order to evaluate their role in the circulation of these strains from the perspective of the One Health approach. This study adopted two complementary approaches. In the first, the clonal dissemination of E. coli was evaluated by PFGE using 21 isolates from humans, animals, and environments (sewage). The strains showed high resistance to β-lactams (penicillins and 2nd to 4th generation cephalosporins, monobactams), followed by quinolones, while resistance to aminoglycosides, carbapenems, and tetracyclines/glycylcyclines was low or absent. PFGE analysis identified multiple pulsotypes (A–H) among the isolates, with pulsotype B observed in humans and swine carcasses, pulsotype H in humans and in a canine sample, and pulsotype D in humans, animals, and sewage. In the second approach, 17 genomes were sequenced and analyzed for resistome, viruloma, sequence types (STs), and phylogeny. Thirty-six antimicrobial resistance genes were identified, with mutations associated with quinolone resistance standing out in 53% of the samples. Sixty-four virulence genes were identified, with the most prevalent being csgA, fdeC, fimH, gad, hlyE, nlpl, terC, yehA, yehB, yehC, yehD, and yghJ. Virulence determinants associated with adhesion, iron acquisition, and immune evasion, including lpfA, sitA, iss, traT, and ompT, were detected in human, animal, food, and environmental sources. Among the sequence types (STs) analyzed, ST131 and ST224 stood out, with the former found in four human isolates and the latter present in humans, animals, and the environment, sharing adhesion genes. ST10, identified in an environmental sample, showed low pathogenicity and an absence of resistance genes. Gene co-occurrence analysis revealed that virulence factors predominated in the genetic associations, but that resistance and virulence genes also coexist in several isolates, evidencing the circulation of potentially pathogenic and multidrug-resistant clones at the human-animal-environment interface. The findings reinforce the importance of integrated surveillance and the One Health approach in controlling the spread of multidrug-resistant and potentially pathogenic E. coli. In general, we characterized the genomic profile of E. coli strains from multiple sources and demonstrated their ability to harbor various determinants of resistance and virulence. These results emphasize that antimicrobial resistance is a dynamic, complex, and interconnected phenomenon across different environments. The circulation of the same clones among humans, animals, food, and the environment highlights the interconnectedness within the One Health context. Therefore, this study is important for formulating new surveillance strategies to prevent the spread of high-risk strains across different ecological niches.

2026-04-23T00:00:00Z https://repositorio.ufu.br/handle/123456789/49293 2026-08-05T06:21:32Z 2026-07-24T00:00:00Z

Title: A Quercetina reduz a infecção por Toxoplasma gondii nos modelos placentários in vitro e ex vivo Abstract: Toxoplasmosis is a disease caused by the obligate intracellular protozoan Toxoplasma gondii, which is capable of infecting all nucleated cells of birds and mammals and is therefore considered one of the most successful parasites in terms of infection. One of the routes of toxoplasmosis transmission is congenital transmission, which most often occurs when the mother acquires the infection for the first time during pregnancy. The ability of the parasite to cross the placental barrier and infect the embryo can lead to fetal malformations, spontaneous abortion, and prematurity, among other manifestations. Currently, the traditional treatment recommended by the Brazilian Ministry of Health consists of spiramycin until the 16th week of pregnancy, followed by the combination of pyrimethamine, sulfadiazine, and folinic acid after the 16th week. However, these treatments have limitations, including teratogenic potential and the possibility of parasite resistance development. Quercetin, for instance, is a natural compound belonging to the flavonol class and is found in fruits and vegetables. It has attracted considerable interest due to its diverse pharmacological properties, particularly its antioxidant activity. In this context, we investigated the use of quercetin as a potential treatment for congenital toxoplasmosis using in vitro, ex vivo, and in silico approaches. We demonstrated that quercetin was able to inhibit intracellular parasite proliferation while preserving cell viability in both in vitro and ex vivo models. In the in vitro model, quercetin impaired parasite adhesion and invasion of host cells, reduced lipid droplet production in T. gondii-infected cells, and preserved antioxidant capacity. In addition, quercetin modulated cytokine production, contributing to the regulation of the immune response and preventing its exacerbation through the modulation of IL-4 and IL-8 expression. Finally, in silico analysis demonstrated affinity for the parasite target TgHGPRT and revealed drug-like characteristics based on the pharmacological properties evaluated. Therefore, quercetin exhibited a potential role in controlling T. gondii parasitism while maintaining a cytoprotective profile, which is essential at the maternal–fetal interface.

2026-07-24T00:00:00Z