http://repositorio.ufc.br/handle/riufc/399 2026-05-14T12:20:28Z http://repositorio.ufc.br/handle/riufc/86109 Título: Alterações moleculares em gliomas: perfil imuno-histoquímico, biomarcadores tumorais e potenciais alvos terapêuticos Autor(es): Gerson, Gunter Abstract: Gliomas are the most common primary malignant tumours of the central nervous system, presenting several molecular alterations that account for the mechanisms of gliomagenesis. This study is a retrospective cross-sectional analysis of 241 adult patients with cerebral gliomas, presented between 2013 and 2023 at a reference hospital in Brazil. The research aimed to evaluate the biomarkers EGFR, Pan-TRK, IDH1, PD-L1, H3K27M, ATRX, P53, HER2, and Ki-67 in patients with specific gliomas and their correlations with epidemiological, clinical, radiological, histopathological aspects, overall and progression-free survival, as well as the relationship between these gliomagenic pathways, highlighting their therapeutic potential. The selected cases underwent tissue microarray (TMA) and immunohistochemical study. Immunological detection of H3K27M, Pan-TRK, ATRX mutations, IDH1, and the non-mutated p53 pattern confirmed them as good prognostic markers. The H3K27M biomarker exhibited lower tumour grade, predominance of low-grade morphological characteristics, IDH1 mutation, and a non-mutated p53 pattern, in addition to better survival curves. Pan-TRK immunodetection was related to less infiltration of structures, IDH1 mutation, absence of PD-L1 immunodetection, lower Ki-67 index, and a non-mutated p53 pattern, as well as better survival curves and a reduced risk of tumour recurrence. The ATRX mutation is associated with the absence of micro vascularization. IDH1 showed a relationship with the population up to 50 years old, immunodetection of H3K27M, Pan-TRK, and PD-L1, in addition to lower Ki-67 indices, absence of EGFR immunodetection, and better survival curves. The non-mutated p53 pattern exhibits a lower need for adjuvant therapy. The biomarkers EGFR, PD-L1, and the mutated p53 pattern were confirmed as markers of worse prognosis. PD-L1 immunodetection was associated with higher mitotic activity and worse survival curves. EGFR positivity showed higher detection in GBMs and a relationship with wild-type IDH tumours. The mutated p53 pattern was associated with higher detection in patients over 50 years of age. The immunoreaction for the HER2 marker was excluded in only one patient, with no statistically significant results. Molecular characterization in routine tumour management is gaining increasing importance, providing therapeutic guidance and prognosis. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86096 Título: Investigação do papel das nets (armadilhas extracelulares de neutrófilos) na imunopatogênese da chikungunya Autor(es): Leal, Alberto Rubens Siqueira Nogueira Abstract: Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and antimicrobial proteins released by neutrophils as part of the innate immune response. Although NETs have been extensively studied in bacterial infections, their role in viral diseases, such as Chikungunya virus (CHIKV) infection, remains poorly understood. In viral infections, NETs have an ambiguous role, being able to act as a defense mechanism, but can intensify inflammation and cause tissue damage when released excessively. CHIKV infection causes symptoms such as fever, malaise, rash, myalgia, and especially prolonged arthralgia, which can compromise quality of life. Although it is usually self-limiting, it can lead to death in at-risk groups, such as infants, the elderly, and people with comorbidities. The scarcity of studies on the role of NETs in CHIKV infection compromises the understanding of host defense mechanisms and limits the advancement of more effective therapeutic and diagnostic strategies. This study investigated the presence of NET markers during CHIKV infection over time in female patients. The study included 40 women with CHIKV infection, evaluated on days D0, D21, D90, D180 and D360, and the control group consisted of 10 healthy women. Tipo: Dissertação 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86089 Título: Leishmania braziliensis resistente ao antimoniato de meglumina imunomodula a resposta de macrófagos murinos M1 e M2 in vitro Autor(es): Eugenio, Ana Lívia Rodrigues Abstract: Leishmania braziliensis is the main etiological agent of cutaneous leishmaniasis (CL), a disease with a high incidence in Brazil, representing a significant public health challenge. Meglumine antimoniate is the standard drug for treating the disease; however, the emergence of resistant strains has hampered its effectiveness. Macrophages act as host cells for Leishmania and play a fundamental role in the immune response against these parasites. The activation of macrophages to the M1 inflammatory profile is crucial for parasite elimination, but there is still little knowledge about how resistant strains of L. braziliensis modulate the plasticity of these cells. Therefore, the objective was to eva-luate the immunomodulation of murine macrophages in in vitro infection by L. brazi-liensis strains resistant (LbR) and susceptible (LbS) to meglumine antimoniate. To this end, murine J774 macrophages were polarized to M1 (with 1μg/ml of LPS) or M2 (with 1μg/ml of IL-4) and then infected with LbR or LbS strains. After 24 and 48h, the fol-lowing were analyzed: parasite load, cytokine production (TNF-α, IL-12, IL-6, IL-4 and IL-10), nitric oxide (NO), urea and arginase activity. The results demonstrated that M1 macrophages infected with LbR presented a significantly higher parasite load compared to those infected with LbS, in both periods evaluated. Regarding inflammatory media-tors, infection with LbR resulted in lower levels of TNF-α, IL-12, and NO in the group of M1 macrophages infected with the LbR strain, compared to M1 macrophages in-fected with the LbS strain. Conversely, in M2 macrophages, infection with LbR induced a significant production of IL-10, IL-4, and IL-6, while LbS did not provoke a relevant response in the production of these cytokines. Arginase and urea modulate the immune response by influencing macrophage polarization and the efficiency of the immune re-sponse to the parasite. These data suggest that the LbR strain has the ability to decrease the production of inflammatory cytokines and NO in M1 macrophages, as well as in-duce the production of regulatory cytokines in M2. This results in a less inflammatory intracellular environment, favoring the survival of the parasite and, consequently, its persistence, which hinders the treatment and cure of the disease. These findings high-light the need for further studies that can deepen the understanding of the resistance mechanisms of these protozoa to traditional therapies, which may contribute to the de-velopment of new, more effective therapeutic strategies. Tipo: Dissertação 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85991 Título: Efeito antifúngico do anlodipino em cepas de Candida spp. e em biofilmes mistos com Staphylococcus aureus resistente à meticilina (SARM): avaliação in vitro Autor(es): Queiroz, Helaine Almeida Abstract: Antimicrobial resistance (AMR) has become one of the main threats to global public health, driven by the excessive and inappropriate use of antimicrobials , which favors the emergence and spread of multidrug-resistant strains. In this context, invasive fungal infections caused by Candida yeasts have become a growing problem, with candidemia associated with high mor-tality rates (30-40%). Simultaneously, Methicillin-Resistant Staphylococcus aureus (MRSA) remains an important bacterial pathogen, responsible for infections ranging from skin condi-tions to potentially fatal situations. The management of these infections is even more challen-ging due to the ability of these microorganisms to form biofilms, communities adhered to sur-faces, which offer significant protection and confer antimicrobial tolerance up to a thousand times greater than in planktonic cells. Medical devices, widely used in clinical procedures, re-present environments conducive to the formation of these biofilms, especially when there is colonization by Candida spp. and MRSA. The objective of this study was to investigate the antifungal activity of amlodipine against Candida spp. strains in planktonic and biofilm forms, to elucidate its possible mechanism of action, and to evaluate its effect on mixed biofilms of Candida spp. and MRSA, both in 96-well polystyrene plates and in Peripheral Venous Cathe-ters (PVCs). To this, an Antifungal Susceptibility Test was performed to determine the Mi-nimum Inhibitory Concentrations (MICs). The action of amlodipine against Candida spp. and Candida spp. plus MRSA biofilms was determined by the MTT assay, and its possible me-chanism of action was investigated through flow cytometry tests. The results demonstrated that amlodipine exhibited Minimum Inhibitory Concentrations (MICs) ranging from 62.5 to 250μg/mL, as well as significant action on mature and pre-formed and forming biofilms, promoting reductions between 50% and 90%. Additionally, the drug increased phosphatidyl-serine externalization and reduced fungal cell viability, suggesting induction of apoptosis. It was also observed that amlodipine reduced metabolic viability by approximately 90% in “in vitro’ polymicrobial biofilms at a concentration equivalent to 8xMIC (1000-2000 μg/mL), in all combinations tested, as well as exerting a potent action on mixed biofilms in CVPs, with a reduction in the number of colonies between 60% and 90%. Furthermore, the morphology was evaluated by light microscopy, confirmed by Scanning Electron Microscopy (SEM). Ba-sed on these findings, amlodipine emerges as a potential candidate for the treatment of fungal and mixed infections. However, additional in vivo studies are needed to validate and expand these results Tipo: Tese 2026-01-01T00:00:00Z