http://repositorio.ufc.br/handle/riufc/364 Thu, 18 Jun 2026 19:27:27 GMT 2026-06-18T19:27:27Z http://repositorio.ufc.br/handle/riufc/86791 Título: Integração de métodos computacionais clássicos e baseados em inteligência artificial para classificação tumoral e identificação de compostos vegetais com potencial anticâncer Autor(es): Azevedo, Francisca Fernanda Nunes Abstract: Cancer is one of the leading causes of morbidity and mortality worldwide, posing a significant challenge to public health and global economic systems. Despite therapeutic advances, many treatments still have limited efficacy and are associated with considerable adverse effects. This limitation is often related to the molecular complexity of the disease and the activation of oncogenic signaling pathways that sustain tumor progression. Among the main molecular mechanisms involved in tumorigenesis, the hyperactivation of the PI3K/AKT/mTOR signaling pathway stands out, often associated with increased cell proliferation, tumor survival, therapeutic resistance, and immune evasion. The PI3Kα isoform, encoded by the PIK3CA gene, is among the most frequently mutated proteins in various types of cancer, including endometrial cancer. Its activation promotes the modulation of multiple cellular processes through the activation of the mTORC1 and mTORC2 complexes, reinforcing its central role in maintaining the tumor phenotype. Given this context, it is essential to identify new molecules capable of acting as selective or dual inhibitors of PI3Kα and mTOR. To this end, computational methods such as structural bioinformatics, machine learning, and deep learning have established themselves as strategic tools in the drug discovery process. In addition to prospecting for new inhibitors, the development of computational models can also contribute to the identification and characterization of tumor burden in different types of cancer, allowing for better molecular and prognostic stratification. In this context, this thesis is structured around three complementary axes. The first chapter presents a review of the main computational approaches applied to rational drug discovery, discussing theoretical foundations, methodological advances, and limitations, with a focus on structural bioinformatics, machine learning, and deep learning in oncology. In the second chapter, structural bioinformatics analyses were performed to identify, characterize, and evaluate atropoisomeric plant compounds with the potential to inhibit PI3Kα and mTOR proteins, including virtual screening in databases, molecular interaction studies, and molecular dynamics. In the third chapter, a multimodal pipeline was developed for predicting TMB in endometrial cancer (TCGA-UCEC), integrating transcriptomic and digital histopathological data to identify and characterize tumor burden. Endometrial cancer is one of the types of cancer with the highest frequency of PIK3CA mutations and with worrying growth in young women, which reinforces the clinical relevance of the proposed approach. The results obtained are expected to contribute to the rational development of new selective and dual inhibitors of PI3Kα and mTOR, in addition to providing computational support for the molecular characterization of endometrial cancer, broadening the prospects for more personalized and precise therapeutic strategies. Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/86791 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86536 Título: Atividades de Iota-Carragenana hidrolisada: influência da massa molecular Autor(es): Castro, George Meredite Cunha de Abstract: Carbohydrates have many applications in several areas, such as food and medical. Sulfated polysaccharides, due to their chemical structure, can be recognized by enzymes or receptors of animal and plant cells to trigger responses such as anticoagulant activity or plant growth and defense. The objective of this work was to demonstrate that the activity of the sulfated polysaccharide ι-carrageenan in animal or vegetable models is directly related to its molecular mass. For this, the acid hydrolysis of this polysaccharide was carried out at a concentration of 3% (m / v) in a reaction cell under shaking and with controlled temperature. A design was elaborated using the Software Statistica with 11 independent hydrolysis experiments for the study of two factors (HCl concentration - 40 to 90 ° C - and reaction temperature - 1 to 100 mM); two response (molecular mass and viscosity) were analyzed. The 11 hydrolysates and the intact polysaccharide were analyzed by Gel Permeation Chromatography and Rheometer. Tables with result ANOVA tables, mathematical models, response surfaces and contour curves for responses were generated. After analysis, two hydrolysates and the intact polysaccharide were selected for further assays. The selected samples were subjected to characterization tests: Fourier Transform Infrared Spectroscopy and Determination of soluble proteins. They were also analyzed for their activities: Cell cytotoxicity, Antioxidant activity in vitro, Anticoagulant activity in vitro (by the methods of activated partial thromboplastin time - APTT - and prothrombin time - PT), Tail bleeding time, Plant growth and defense. After analyzing the molecular masses and viscosity, samples with 123 and 14.1 KDa and the intact ι- carrageenan (1,700 KDa) were selected for subsequent assays. This selection was made due to test ι- carrageenan activities in different order of molecule sizes. The hydrolysis process did not generate changes in the products. The samples had good purity and were considered non-toxic. The hydrolysis of ι- carrageenan promoted a reduction in the antioxidant capacity of the hydrolyzate (64.05 ± 6.11%) in comparison with a whole ι- carrageenan (78.44 ± 8.95%). For the anticoagulant activity ATPP, the longest time of activity of the hydrolysates was 257.5 ± 8.1 s for the sample with 123 KDa at the concentration of 4.0 mg / mL while the intact ι- carrageenan presenting a time of 126,6 ± 19.6 s. An increase of 7.5 times in the normal clotting time was promoted in relation to intact ι- carrageenan, which promoted an increase of 3.7 s. All sources had no PT anticoagulant activity. The sample with 123 KDa was tested at the time of tail bleeding and showed bleeding tendency at 1.0 and 2.0 mg / kg. In the experiments with Vigna unguiculata plants, the sample with 123 KDa promoted an increase in leaf area (71.12 ± 9.31 cm2) compared to the control (57.22 ± 9.62 cm2). It was observed an increase in the height of plants treated with a sample with 14.1 KDa. The sample with 123 KDa promoted an increase in the fresh weight and moisture of the the plants (22.9 ± 3.73 and 20.7 ± 3.37 g, respectively) and did not change the dry mass in relation to the control. None of the samples was able to activate the defense system of V. unguiculata against the Cowpea severe mosaic virus. Tipo: Tese Fri, 01 Jan 2021 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/86536 2021-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85896 Título: Desenvolvimento, caracterização e avaliação da atividade angiogênica de filmes biopoliméricos de alginato e carboximetilcelulose contendo lectina de Canavalia ensiformis Autor(es): Santos, Maria Helena Cruz dos Abstract: The formation of a functional vascular system is a recognized challenge; therefore, tissue engineering has explored chemical and physical strategies to promote neovascularization. Angiogenesis induced by biomaterials occurs predominantly through the formation of new vessels from pre-existing vascular structures, regulated by the migration, proliferation, and differentiation of endothelial cells. Techniques aimed at inducing revascularization have emerged, including natural polymers, biodegradable products capable of regenerating tissues through the interaction of their biodegradation with immune cells. Plant lectins, in turn, are capable of modulating distinct cellular responses and exhibit angiogenic potential; they are proteins or glycoproteins of non-immunological origin that recognize and reversibly bind to specific carbohydrate molecules. The objective of this work is to incorporate the lectin from Canavalia ensiformis (ConA) into alginate and carboxymethylcellulose films to promote angiogenesis pathways and induce vascularization as a therapeutic and pharmacological approach. The characterization of the films and the physicochemical tests demonstrated the efficient incorporation of the lectin into the film, as observed in the differential scanning calorimetry analysis and the FT-Raman spectra. In addition to the significantly prolonged retention capacity of ConA in the film observed by the hemagglutinating activity analysis, SEM and roughness profile assays demonstrated the adhesion capacity of the films. Angiogenic activity was confirmed by the CAM assay, and immunohistochemical assays showed an increase in the expression of the angiogenic factors TGF-β and VEGF. These results demonstrate that the biopolymers used represent an effective alternative in inducing angiogenesis, paving the way for future research in the development of therapeutic and pharmacological biopolymers. Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85896 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85557 Título: Plasticidade de cajueiros à baixa disponibilidade hídrica no solo: mecanismos fisiológicos, metabólicos e epigenéticos Autor(es): Costa, Igor Rafael Sousa Abstract: The cashew tree (Anacardium occidentale L.) is a highly relevant species for the Brazilian semi-arid region, which it develops under environmental conditions characterized by a combination of abiotic stresses, such as high irradiance, salinity, water deficit, and high temperatures. Adaptation to this environment involves physiological and molecular mechanisms that regulate acclimation to environmental stress. This thesis investigated the processes that support tolerance and the ability to adjust to water deficit in the cashew tree, integrating different biological levels to identify functional patterns associated with adaptation. In the first chapter, physiological, biochemical, metabolic, and molecular responses were evaluated in two contrasting cashew genotypes subjected to successive cycles of water deficit followed by rehydration. The BRS 226 genotype showed greater osmotic stability during stress, more efficient photosynthetic recovery, and greater functional adjustment capacity after repeated drought exposures. The regulation of the redox state and the progressive activation of the antioxidant system indicated physiological adjustment to recurrent stress, accompanied by extensive metabolic reorganization, with modulation of compounds associated with energy metabolism and cellular adaptation. In contrast, the CCP 09 genotype showed more restricted physiological and metabolic responses, with less recovery capacity after successive stress cycles. The differential modulation of the expression of genes associated with the stress response and the activation of markers re ated to DNA methylation during recovery suggest the participation of epigenetic mechanisms in the physiological reorganization induced by drought cycles. Taken together, the results indicate that the differential tolerance between genotypes is associated with the coordination between physiological, metabolic, and molecular adjustments in response to recurrent water stress. The second chapter investigated the epigenetic dynamics associated with a single water deficit event followed by recovery in cashew seedlings, using enzymatic sequencing of DNA methylation. Although the overall methylation profile remained relatively stable across water conditions, extensive local alterations were detected throughout the genome, indicating epigenetic reorganization associated with the plant's physiological state. These modifications were related to distinct regulatory and metabolic processes between stress and recovery phases, suggesting that DNA methylation participates in the functional modulation of the water response. The observed epigenetic variations accompanied changes in photosynthetic performance and the expression of marker genes, highlighting an association between epigenetic modulation and physiological adjustments to water deficit. In an integrated manner, the results demonstrate that the cashew tree's response to water deficit involves coordination between physiological, metabolic, and epigenetic processes that contribute to functional adjustments of metabolism and the photosynthetic apparatus during stress and recovery. These findings broaden the understanding of the regulatory mechanisms associated with the water response in tropical perennial species and provide a basis for the development of genetic improvement strategies and adaptive management under scenarios of greater climate variability. Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85557 2026-01-01T00:00:00Z