http://repositorio.ufc.br/handle/riufc/180 2026-05-17T19:14:52Z 2026-05-17T19:14:52Z Duque, Bruna Ribeiro http://repositorio.ufc.br/handle/riufc/86326 2026-05-16T11:22:59Z 2026-01-01T00:00:00Z

Título: Investigação da relação do polimorfismo de nucleotídeo único (rs187238) no gene da interleucina-18 e do tempo de isquemia fria com a função do enxerto em receptores de transplante renal de um Hospital Universitário de Fortaleza Autor(es): Duque, Bruna Ribeiro Abstract: Renal dysfunction is a common complication among recipients of organs from deceased donors and can be caused by ischemia-reperfusion injury, which affects the therapeutic success of the transplant. Cold ischemia time (CIT) refers to the period of organ transport, from its removal from the donor to its implantation in the recipient. Prolonged periods of CIT can influence renal graft survival, causing irreversible renal injury. In the search for early biomarkers of renal function, urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) may be potential predictors of graft dysfunction. IL-18 is a proinflammatory cytokine that may be involved in modulating the immune response related to acute kidney injury. The single nucleotide polymorphism rs187238 (-137G/C), located in the gene for this interleukin, is known to cause an increase in the expression of this cytokine, which may influence the individual's inflammatory profile. The present study sought to investigate the influence of the rs187238 polymorphism and CIT on graft function in kidney transplant recipients. The work is structured in three articles. The first is a narrative review on the influence of CIT on delayed graft renal function. The other articles are cross-sectional studies including renal allograft recipients from a university hospital in Fortaleza between 2023 and 2025. These studies evaluated the influence of CIT, urinary IL-18 levels, and rs187238 polymorphism genotypes on graft renal function one month after transplantation. It was observed that prolonged periods of cold ischemia are related to longer hospital stays and graft renal dysfunction, reflected in higher serum creatinine levels, lower estimated glomerular filtration rate (eGFR), and higher urinary NGAL levels. Urinary IL-18 levels and rs187238 polymorphism genotypes had no influence on clinical parameters of renal function one month post-transplant. It is concluded that urinary IL-18 is not characterized as a biomarker of renal injury in this period, and its rs187238 polymorphism did not impact the markers of renal function of the allograft. In addition, the findings demonstrate that CIT can determine the patient's prognosis and the therapeutic success of the transplant. Tipo: Dissertação

2026-01-01T00:00:00Z Rocha, Yasmim Mendes http://repositorio.ufc.br/handle/riufc/86238 2026-05-12T19:04:13Z 2026-01-01T00:00:00Z

Título: Avaliação da atividade in vitro dos derivados sintéticos de N-ciclohexil 3-(3-metilfenil)1,2,4-oxadiazol-5-amina sobre a cepa y de Trypanosoma cruzi e um estudo de toxicidade in vivo Autor(es): Rocha, Yasmim Mendes Abstract: Chagas disease remains a significant public health problem in Latin America, primarily treated with Nifurtimox and Benznidazole. Despite initial proactive strategies, these medications have limitations, such as low efficacy in the chronic phase and adverse effects. In this context, heterocyclic compounds, such as 1,2,4-oxadiazole derivatives, have been investigated as potential therapeutic alternatives. This study aimed to evaluate the trypanocidal activity and toxicity of molecules 2a, 2f, and 2i against the Trypanosoma cruzi strain using in vitro, in silico, and in vivo assays. The results showed a concentration-dependent effect on epimastigote forms, with IC50 values of 31.4 µM, 44.4 µM, and 7.0 µM for 2a, 2f, and 2i, respectively. In trypomastigotes, LC50 values of 14.2 µM, 2.4 µM, and 2.6 µM were observed for these same molecules, in addition to a significant reduction in the amastigote load in infected cells. The selectivity index was 15, 5.8, 9.8, and 4.7 for molecules 2a, 2f, 2i, and benznidazole, respectively. Flow cytometry analyses indicated compromised cell integrity, induction of oxidative stress, and mitochondrial dysfunction, altering different targets of action of the molecules under study. Using free radical neutralization assays in solution, through antioxidant activity and acetylcholinesterase inhibition, the molecules under study showed a high capacity for scavenging free radicals. These findings suggest that such compounds may interfere with the redox balance of the parasite, contributing to oxidative stress and, consequently, to the observed antiparasitic effects. Subsequently, scanning electron microscopy revealed membrane alterations, cell rounding, or flagellar absence. Among the compositions evaluated, molecule 2a stood out for presenting a better balance between efficacy and selectivity in vitro, in addition to interactions developed with the cruzipain enzyme in in silico analyses. In in vivo assays with zebrafish, molecule 2a showed dose-dependent embryonic toxicity (LC50~15 µM); similar to bzn at higher concentrations, decreasing a specific cytotoxic potential. Taken together, these findings reinforce the potential of 1,2,4-oxadiazole derivatives as promising candidates for the development of new therapeutic strategies against Chagas disease, highlighting molecule 2a as a priority target for future studies. Tipo: Tese

2026-01-01T00:00:00Z Teixeira, Izabell Maria Martins http://repositorio.ufc.br/handle/riufc/86220 2026-05-12T13:07:09Z 2026-01-01T00:00:00Z

Título: Efeito citoprotetor de nanopartículas poliméricas contendo resveratrol em modelo in vitro de doença de Parkinson induzida por rotenona: envolvimento da via Nrf2 Autor(es): Teixeira, Izabell Maria Martins Abstract: Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor impairment, whose prevalence is expected to increase in the coming decades. Considering the limitations of current clinical treatment (levodopa), new therapeutic strategies are needed. Resveratrol (RSV) has antioxidant and anti-inflammatory properties, but its low bioavailability limits its clinical application, making nanoencapsulation a promising alternative. The aim of this study was to evaluate the in vitro protective effect of resveratrol polymeric nanoparticles (NP RSV) and the involvement of the Keap1/Nrf2/ARE pathway in a mimetic model of PD induced by rotenone (ROT). For in vitro assays, PC12 neuronal cells and astrocytes were pretreated with NP RSV, RSV, and dopamine (DA) for 1 hour, followed by exposure to ROT for 24 hours. Cell viability was assessed by the MTT assay. The pattern of cell death, reactive oxygen species production, and mitochondrial transmembrane potential (ΔΨm) were evaluated by flow cytometry assays. Cellular morphological changes were assessed by optical microscopy. In silico tests were performed to investigate the theoretical interaction of RSV with the Kelch and Brick-to-Brick (BTB) domains of the Keap1 protein. Gene expression of Nrf2 and HMOX, elements of the Keap1/Nrf2/ARE pathway, was performed by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The results showed that ROT induced a reduction in cell viability, increased oxidative stress, depolarization of ΔΨm, and cell death by apoptosis; however, pretreatment with NP RSV was able to significantly protect the cells, preserving cell viability, reducing the formation of reactive oxygen species, maintaining mitochondrial function, and decreasing apoptosis. The protective effects of NP RSV were observed at concentrations of 1.56 µM, 0.78 µM, and 0.39 µM in PC12 cells and 6.25 µM, 3.12 µM, and 1.56 µM in astrocytes; while RSV showed a protective effect at concentrations of 12.5 µM, 6.25 µM, and 3.12 µM in both cell lines. DA (400 µM-100 µM) showed limited neuroprotective effects. Morphological analyses corroborated these findings, showing cellular changes and reduced cell density after exposure to ROT and maintenance of these characteristics when pretreated with NP RSV. In silico assays indicated a stable interaction between RSV and Keap1 protein, sustained by hydrogen bonds. Regarding gene expression, ROT promoted increased expression of NRF2 and HMOX-1, while pretreatment with NP RSV modulated this response. Together, the data indicate that NP RSVs exert a neuroprotective effect, acting in an integrated manner on the main mechanisms involved in the pathophysiology of PD, with emphasis on the modulation of the Keap1/Nrf2/ARE pathway. Thus, the present study contributes to the understanding of the molecular mechanisms associated with neuroprotection mediated by nanostructured systems, presenting scientific relevance. Tipo: Dissertação

2026-01-01T00:00:00Z Andrade, Samylia Mota de http://repositorio.ufc.br/handle/riufc/85909 2026-04-17T13:07:03Z 2025-01-01T00:00:00Z

Título: Avaliação do conhecimento sobre metotrexato e da adesão ao tratamento em pacientes ambulatoriais com artrite reumatóide: das análises e correlações a uma estratégia educativa Autor(es): Andrade, Samylia Mota de Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease that can affect extra-articular joints. The prevalence of RA in Brazil ranges from 0.2% to 1% and is three times more prevalent in middle-aged women. The objective of this study was to analyze knowledge about methotrexate (MTX) and medication adherence in RA. This was a cross-sectional and prospective study with collection of sociodemographic and clinical data, adherence to rheumatoid arthritis treatment using the Brazilian version of the Compliance Questionnaire Rheumatology (bCQR) and assessment of knowledge about MTX with the Methotrexate Questionnaire (bMTXQ). The sample consisted of 69 patients, with a mean age of 55.11 years and a predominance of females (95.65%). Most participants had been diagnosed with RA for ten years or more (49.28%) and had a family history of the disease (65.22%). Systemic arterial hypertension (47.83%) and diabetes mellitus (27.54%) were the most prevalent comorbidities. The analysis of adherence revealed that 62.3% of patients presented satisfactory adherence, while 37.7% were classified as having unsatisfactory adherence. The knowledge assessment showed that only 18.84% of participants answered all the essential questions for the safe use of the medication correctly. Critical items presented low accuracy rates, such as interaction with trimethoprim (23.99%), hematologic risk (28.99%) and maximum recommended weekly dose (44.93%). The analysis identified a significant association between essential knowledge about MTX and adherence to treatment (p=0.013). Patients with better knowledge demonstrated greater adherence to therapy. In addition, the presence of caregivers was associated with a higher level of knowledge about MTX (p=0.027), suggesting the positive impact of support on therapeutic management. However, the correlation between knowledge and adherence, although positive, was considered weak (r=0.210; p=0.084), indicating the influence of other factors on adherence. The correlation between knowledge about methotrexate and patient adherence to therapy showed that the level of adherence was more satisfactory when the results of knowledge about methotrexate were also higher, which corroborates data from the literature that knowledge about the treatment, such as its risks and benefits, can increase adherence and obtain better results in therapy. The literature reinforces that educational actions improve adherence and reduce the risk of treatment discontinuation. Thus, this study highlights the need for continuous, personalized and accessible educational interventions to optimize the management of RA and the safety of MTX use. Tipo: Dissertação

2025-01-01T00:00:00Z