https://repositorio.ufba.br/handle/ri/9317 2026-05-02T12:39:21Z https://repositorio.ufba.br/handle/ri/43916 Título: Efeitos de dois protocolos de exercício nas alterações hepáticas induzidas pelo diabetes mellitus tipo 1 Autor(es): BRITO, Taílla de Andrade Santos Primeiro Orientador: Soares, Telma de Jesus Abstract: Type 1 Diabetes Mellitus (DM1) is characterized by an absolute deficiency in insulin production, resulting in the development of chronic hyperglycemia, and is associated with various pathological conditions, including liver disease. New therapeutic strategies are needed to improve and/or prevent the progression of diabetic liver disease. This study investigated the effects of moderate-intensity physical exercise before and after the induction of diabetes mellitus on type 1 diabetes mellitus-induced liver changes in Wistar rats. To this end, 30 rats weighing between 290 and 310 g were divided into 5 groups: CS (Sedentary Control, n=6), CT (Trained Control, n=6), DS (Sedentary Diabetic, n=6), DT (Trained Diabetic, n=6), and DPT (Previously Trained Diabetic, n=6). Only the DPT group underwent 4 weeks of training before the induction of diabetes with streptozotocin (STZ/40mg/Kg). After confirmation of diabetes, the DPT, DS, and CT groups underwent 8 weeks of treadmill exercise, 5 times a week. The animals were euthanized, blood samples were collected for liver function assessment, and the liver was removed for histological, redox balance, and ELISA studies. Our results demonstrate a slight increase in serum AST and ALP levels in the DS group. However, only the DPT group showed reduced serum AST levels compared to the DS and DT groups (p<0.05) and ALP levels, although this difference was not statistically significant. Serum ALT, GGT, and bilirubin levels were elevated in the DS group compared to the controls (p<0.001 and p<0.05, respectively). Both exercise protocols prevented this increase in ALT, as the training reduced ALT levels compared to the DS group (p<0.001) and showed no significant change among the controls. GGT and bilirubin levels did not differ between the DS and DT groups. Only the DPT group prevented the changes in GGT and bilirubin, as preventive training reduced these levels compared to the DS group (p<0.05) and showed no significant change compared to the controls. Lipid peroxidation was increased in rats in the DS group compared to the CS and CT groups (p<0.05 and p<0.01, respectively). Both physical exercise protocols were able to prevent these alterations in lipid peroxidation induced by diabetes, since a reduction in lipid peroxidation was observed in the DT and DPT groups compared to the DS group, p<0.01, and they did not show statistical differences compared to the control groups. On the other hand, catalase enzyme activity was elevated in the liver tissue of DS rats when compared to that of the CS (p<0.001) and CT (p<0.05) groups. In contrast, training of rats in the DT and DPT groups promoted a reduction in catalase activity. Liver TNF-α levels were elevated in the DS and DT groups compared to controls (p<0.05). However, we observed a reduction in TNF-α levels only in the DPT group. Necrosis, edema, and increased hyperemic sinusoids in the liver tissue of the DS group were reduced by both exercise protocols, p<0.001. Steatosis was reduced in the trained diabetic groups, p<0.05, and we observed no difference in ballooning degeneration. In conclusion, moderate-intensity aerobic exercise improved liver enzyme levels, TNF-alpha, redox balance, and histological aspects in the liver tissue of rats with type 1 diabetes, with some additional beneficial effects induced by preventive training. Editora / Evento / Instituição: UNIVERSIDADE FEDERAL DA BAHIA Tipo: Dissertação 0010-10-31T00:00:00Z https://repositorio.ufba.br/handle/ri/43363 Título: Efeitos associativos e Isolados do treinamento físico aeróbio moderado e da curcumina no hipocampo de ratas ovariectomizadas com Diabetes Mellitus Tipo 1 Autor(es): Oliveira, Beatriz Anjos de Primeiro Orientador: Soares, Telma de Jesus Abstract: Type 1 diabetes mellitus (T1DM) and postmenopausal estrogen depletion represent risk factors for neurobiological imbalances, promoting a neurodegenerative environment in the hippocampus characterized by oxidative stress, neuroinflammation, and programmed cell death. Although strategies such as physical training and supplementation with the polyphenol curcumin have independently demonstrated neuroprotective potential, the synergistic effects of these interventions in the coexistence of both conditions remain unexplored. Therefore, the present study aimed to investigate the effects of moderate-intensity aerobic physical training and curcumin administration, both individually and in combination, on histopathological, oxidative, inflammatory, and apoptotic parameters in the hippocampus of ovariectomized (OVX) rats with T1DM. Twenty-four rats underwent ovariectomy, and T1DM was induced by streptozotocin (STZ, 40 mg/kg) administration. Subsequently, the animals were divided into four groups: Sedentary Diabetic OVX (SDO), Sedentary Diabetic OVX treated with Curcumin (SDO+CUR), Trained Diabetic OVX (TDO), and Trained Diabetic OVX treated with Curcumin (TDO+CUR) (n=6 per group). The intervention protocol lasted eight weeks, five days per week, during which trained groups underwent treadmill running sessions, while supplemented groups received curcumin via gavage (100 mg/kg body weight), five days per week. At the end of the experimental period, hippocampal tissue was dissected for the evaluation of neuronal morphology and integrity, quantification of oxidative damage biomarkers, such as lipid peroxidation products and nitrites, and measurement of endogenous antioxidant enzyme activity. Additionally, key markers of inflammatory pathways, MAP kinase signaling, and apoptotic profiles were analyzed using immunohistochemistry, immunofluorescence, gene expression, and ELISA techniques. The results demonstrated that the combination of physical training and curcumin reduced pyknosis, oxidative damage markers, Bax/Bcl-2 ratio, and caspase-3 expression. Moreover, the combined therapy enhanced the activity of the antioxidant enzymes SOD and GPx, as well as BDNF gene expression. The isolated interventions also modulated specific parameters: physical training improved neuronal morphology and SIRT1 expression, while curcumin increased cell density and reduced NF-κB, TNF-α, and GFAP expression in hippocampal tissue. In conclusion, these findings indicate that the association between aerobic physical training and curcumin promotes a synergistic neuroprotective response, evidenced by the attenuation of multiple markers of cellular damage in the hippocampus. This finding suggests that the combination of these therapeutic strategies may be more effective than isolated interventions in mitigating neurodegenerative processes in an experimental model of T1DM and postmenopause. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação 2025-08-25T00:00:00Z https://repositorio.ufba.br/handle/ri/43141 Título: Análise do perfil epidemiológico e molecular do SARS-CoV-2 em dois municípios do estado da Bahia entre 2020 e 2022. Autor(es): Dantas, Anna Carolina Saúde Primeiro Orientador: Marques, Lucas Miranda Abstract: Introduction: Coronavirus Disease 2019 (COVID-19) is a clinically diverse disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whose spread in Brazil was heterogeneous and reflected deep social and regional inequalities. The emergence of viral variants carrying mutations in the genome, particularly in the Spike protein, has influenced transmissibility, clinical severity, and public health impact. Spatial dispersion analysis of the virus requires consideration of both biological and social factors, such as population density and structural inequalities, and is essential for effective genomic surveillance. In this context, investigating circulating viral lineages and individual responses to infection may contribute to control strategies and support the understanding of disease severity and immune responses in confirmed SARS-CoV-2 cases. Objective: To conduct a molecular epidemiological and spatial dispersion analysis of SARS-CoV-2 and evaluate its association with the immune response profile in patients from the municipalities of Vitória da Conquista and Salvador, Brazil. Methodology: Clinical and epidemiological data from patients in Vitória da Conquista (2020–2021) were obtained from the municipal SoulMV health system, while data from patients in Salvador (2022) were collected through a socio-behavioral questionnaire. Descriptive statistical analyses were conducted using Stata version 15.1. Genomic sequencing of samples from both cities was performed using Oxford Nanopore MinION technology and analyzed through bioinformatics for variant typing. In Vitória da Conquista, the expression of innate immunity inflammatory markers was evaluated using qPCR array. In Salvador, genomic dispersion analyses and 3D Spike protein mutation mapping were performed to compare vaccinated and unvaccinated individuals in terms of mutation distribution and potential structural implications. Results: In Vitória da Conquista (n=783), risk factors associated with COVID-19 mortality included being male (p = 0.037), having cardiovascular disease (p < 0.001), diabetes (p = 0.002), chronic obstructive pulmonary disease (COPD) (p = 0.001), and Ct (cycle threshold) values below 22 (p < 0.001). Stratification by disease severity (asymptomatic, mild, and moderate/severe) revealed increased activation of inflammatory pathways in severe cases, including cytokine storm induction and downregulation of anti-inflammatory responses. Genomic analysis indicated the circulation of multiple lineages, including Alpha and Gamma, suggesting successive viral introduction events. In Salvador (n=174), most participants were female (68.9%), aged up to 39 years (50.6%), without comorbidities (66.5%), and users of public transportation (66.5%). Most exhibited mild symptoms (41.5%) and had received a second booster vaccine dose (40.6%). The most prevalent Omicron subvariants were BA.5 (32.57%), BA.4 (21.71%), B (18.86%), and BQ.1 (26.2%). Viral dispersion was predominantly localized, with only a few rapid-spreading events. Mutation analysis revealed distinct profiles between vaccinated and unvaccinated individuals, particularly in the Spike protein, suggesting differential selective pressures. Conclusion: Variation in the clinical profiles of patients affected by COVID-19, influenced by both individual and contextual factors over the course of the pandemic, underscores the importance of identifying and understanding the introduction of new viral lineages. The findings of this study—by revealing circulating strains and the actual local epidemiological scenario—demonstrate that the integration of epidemiological and genomic surveillance is essential for informing more effective public health strategies and guiding targeted governmental actions to control transmission. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Tese 2025-08-22T00:00:00Z https://repositorio.ufba.br/handle/ri/42965 Título: IIluminando novas fronteiras: explorando o potencial fotossensibilizador de espécies de Passiflora no controle de infecções por Staphylococcus aureus resistente à meticilina em camundongos senescentes Autor(es): Gonçalves, Caroline Vieira Primeiro Orientador: Silva, Robson Amaro Augusto da Abstract: INTRODUCTION: Antimicrobial Photodynamic Therapy (aPDT) has emerged as a potential alternative for the treatment of multidrug-resistant bacterial skin infections, such as those caused by methicillin-resistant Staphylococcus aureus (MRSA), which pose a high risk in elderly individuals. This approach is based on the use of a chemical agent known as a photosensitizer (PS), considered one of the main components of aPDT. OBJECTIVE: This study aimed to evaluate the photosensitizing activity of Passiflora genus extracts, both incorporated and not incorporated into an emulsion, for controlling MRSA infection in vitro and in vivo using a senescence model. METHODOLOGY: The research methodology comprised in vitro and in vivo stages, in addition to the formulation and characterization of a topical emulsion. Initially, in the in vitro assays, the light absorption spectrum of Passiflora extracts and the effective dose for their photoactivation were determined. Additionally, the cytotoxicity of these extracts on eukaryotic cells was evaluated, and the intracellular localization of the butanolic fraction (BF) of P. cincinnata in MRSA was investigated. Subsequently, in the in vivo study, senescent animals intradermically infected in the ear with MRSA were randomly distributed into three experimental groups: Control (receiving only the vehicle); Treated with nonphotoactivated P. cincinnata butanolic fraction (BF); and Treated with photoactivated P. cincinnata BF (APDT). Throughout the in vivo study, cytokine levels in retromaxillary lymph nodes, animal body weight, bacterial load at the infection site, and the degree of ear tissue inflammation were measured. Finally, for the developed topical formulation, a preliminary stability test was conducted, followed by its physicochemical characterization. RESULTS: Passiflora extracts were considered non-cytotoxic to HUVEC (Human Umbilical Vein Endothelial Cells) cell cultures. P. edulis and P. alata extracts showed photosensitizing capacity at a concentration of 1000 µg/mL. The butanolic fraction of P. cincinnata exhibited significant photosensitizing activity at a concentration of 100 µg/mL. Meanwhile, the crude extract (CE) demonstrated this activity at concentrations lower than BF, at 5-50 µg/mL. Isoorientin, the major compound present in P. cincinnata BF, did not show as significant a reduction as P. cincinnata CE and BF. Animals treated with P. cincinnata BF showed better control of bacterial load, less leukocyte infiltration, and less weight loss throughout the MRSA infection process. Furthermore, the APDT group showed a more distinct pattern of cytokine correlations and influence, with a greater number of cytokines exhibiting negative correlations, for example, both among pro-inflammatory cytokines and with the anti-inflammatory cytokine IL-10. Dendrogram analysis and Principal Component Analysis showed that leukocyte levels in the ear are important for the course of infection among the groups, with differences regarding treated or untreated animals. Zeta potential analysis of MRSA revealed that the butanolic fraction of P. cincinnata does not significantly alter the bacterial membrane potential. In the developed formulation, an oil-in-water emulsion compatible system, statistically significant variations did not show changes that would compromise the formulation. The fluidity index values indicated pseudoplastic fluid behavior. Additionally, the emulsion showed thixotropic behavior, a typical characteristic of non-Newtonian fluids. CONCLUSION: The results are promising, given the limited understanding of APDT in senescent animals, and highlight P. cincinnata as a potential photosensitizer against MRSA. This research lays the foundation for developing targeted APDT strategies using Passiflora species and emphasizes the need to explore new photosensitizers derived from underexplored plants. Furthermore, the standardization of a topical formulation, demonstrating stability at room temperature and suitable rheological properties, paves the way for the development of a new therapeutic approach for MRSA skin infections, especially in elderly individuals. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Tese 2025-07-15T00:00:00Z