http://repositorio.ufc.br/handle/riufc/11048 2026-06-18T23:12:20Z http://repositorio.ufc.br/handle/riufc/86816 Título: Análise da expressão de genes envolvidos na síntese de translesão e na integridade do DNA em pacientes com leucemia mieloide crônica em uso de inibidores de tirosina-quinase Autor(es): Gadelha, Anna Thawanny Gadelha Abstract: Introduction: Chronic Myeloid Leukemia (CML) is a hematologic neoplasm characterized by the presence of the Philadelphia chromosome (Ph), resulting from the t(9;22)(q34;q11) translocation, which generates the BCR-ABL fusion gene. This gene encodes an oncoprotein with constitutive tyrosine kinase activity that drives CML pathogenesis by promoting DNA damage and compromising genomic integrity. Tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and nilotinib, are fundamental in the treatment of CML; however, concerns remain regarding their genotoxic effects and the role of DNA damage repair and damage tolerance mechanisms under therapeutic pressure. Objective: This study aimed to investigate the expression of genes involved in translesion synthesis and maintenance of genomic integrity (REV1, SETD2, APEX1, and POLB) in patients with CML receiving first- or second-generation TKIs, and to explore their implications for genomic stability and treatment response. Methods: A cross-sectional study was conducted involving 71 patients with chronic-phase CML and 25 healthy individuals as the control group. Clinical and laboratory data were collected from medical records. Peripheral blood samples were obtained, and gene expression was quantified by RT-qPCR. Differences in gene expression between groups and prognostic variables were evaluated using Mann-Whitney and Kruskal-Wallis tests with Dunn/Bonferroni post hoc analysis. Multivariate logistic regression (stepwise method) and ROC curve analyses were employed to assess the predictive value of genes for the absence of complete cytogenetic response (CCyR) and molecular response (MR). Additionally, a MANOVA was performed, adjusted for therapeutic response (CCyR, MR) and type of TKI, to identify joint effects on gene expression. Results: In the initial comparison, a significant reduction in POLB and APEX1 expression was observed in CML patients compared to controls (p < 0.0001), indicating impairment of the base excision repair (BER) pathway. Patients with an altered karyotype showed higher expression of APEX1 (p < 0.0001), and those classified as low-risk according to the EUTOS score exhibited higher POLB levels (p = 0.049). Stratification by type of TKI demonstrated that dasatinib or nilotinib use was associated with increased expression of REV1 and SETD2 (p < 0.005) compared to imatinib. MANOVA indicated a statistically significant effect on REV1 (p = 0.001) and SETD2 (p = 0.045) expression, reflecting the influence of treatment type and clinical response. In ROC curve analyses, REV1 showed an AUC of 0.733 for absence of CCyR (95% CI: 0.564–0.909) and 0.721 for absence of MR (95% CI: 0.564–0.877). In multivariate logistic regression, REV1 overexpression increased the odds of absence of CCyR by approximately 16-fold (OR = 15.9; p = 0.039), while high SETD2 expression exerted a protective effect (OR = 0.358; p = 0.022). Additionally, low APEX1 expression was more pronounced in patients refractory to achieving CCyR, underscoring the essential role of BER in maintaining genomic stability. Conclusion: The results indicate that deficiency of POLB and APEX1, combined with activation of REV1 and SETD2, is strongly associated with genomic instability and therapeutic resistance in CML. The use of second-generation TKIs further reinforced the reliance on damage tolerance mechanisms, highlighting the importance of the REV1-mediated TLS pathway. REV1 overexpression emerged as an independent predictor of poor prognosis, whereas SETD2 exerted a protective effect, suggesting their potential as molecular biomarkers for risk stratification and optimization of therapeutic strategies. In this context, an integrated understanding of DNA repair and damage tolerance pathways provides critical insights for preventing clonal evolution and improving the clinical management of CML patients. Tipo: Tese 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86009 Título: Avaliação antimicrobiana e prevenção de lesões de cárie dentária com o uso do dentifrício de própolis vermelha brasileira: estudo laboratorial e ensaio clínico randomizado Autor(es): Chagas, Francineudo Oliveira Abstract: The development of dental formulations with propolis is a growing reality in the pharmaceutical industry, especially for diseases related to biofilm. This study evaluated in vitro and in vivo the use of fluoridated toothpaste containing 1% Brazilian red propolis (BRP) in controlling marginal bleeding and preventing caries lesions in orthodontic patients. In the in vitro phase, the antimicrobial activity of the BRP extract and the toothpaste incorporating the extract was evaluated against Streptococcus mutans ATCC UA159. The clinical phase consisted of a randomized, double-blind, controlled, longitudinal clinical trial involving 60 orthodontic patients aged 12 to 18 years, followed for a period of six months. Participants were divided into two groups: a test group (toothpaste with BRP + 1500 ppm fluoride) and a control group (toothpaste with 1500 ppm fluoride). Clinical assessments were performed at baseline, and at 2, 4, and 6 months, using the ICDAS II criteria for detecting carious lesions and the gingival bleeding index. Statistical analyses were performed using the Kruskal-Wallis and Mann-Whitney tests, and significance adjustment was performed using the Bonferroni method, considering a significance level of 5%. The results demonstrated that both the PVB extract and the toothpaste containing PVB showed significant antimicrobial activity, with a reduction in bacterial viability up to a concentration of 0.3906 µg/mL (p < 0.05). The minimum bactericidal effect (MBC) was observed at a concentration of 1.5625 µg/mL for both groups. No statistically significant differences were observed between the PVB extract and the toothpaste formulated with the extract (p > 0.05), indicating that the incorporation process did not compromise the antimicrobial activity. The commercial toothpaste Parodontax® showed antimicrobial activity in all dilutions tested, with MBC equivalent to that of PVB (1.5625 µg/mL), showing greater overall antimicrobial potency (p < 0.05). These findings confirm the ability of PVB to directly interfere with the viability of cariogenic microorganisms. In the clinical phase, the results demonstrated that the group using the toothpaste containing PVB maintained a higher proportion of healthy surfaces (ICDAS II = 0) throughout the follow-up, while the control group showed significant progression to initial lesions (ICDAS II = 1), with a statistically significant difference between the groups (p ≤ 0.05). Regarding gingival condition, a significant reduction in the gingival bleeding index was observed in the PVB group at 4 and 6 months of follow-up (p ≤ 0.05), contrasting with the progressive increase observed in the control group. The in vitro and clinical results demonstrate that the fluoridated toothpaste containing PVB has antimicrobial activity, associated with significant clinical benefits in the prevention of initial caries and in the control of gingival inflammation in orthodontic patients. The combination of PVB with fluoride proved to be effective, safe, and biocompatible, without compromising traditional anti-caries action, consolidating this toothpaste as a promising preventive strategy for managing dental biofilm in at-risk populations. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/84064 Título: Tratamento com gel fitoterápico à base de Myracrodruon urundeuva na cicatrização de úlceras orais por Cisplastina in vitro Autor(es): Vasconcelos, Raquel Bastos Abstract: The Brazilian pepper tree (Myracrodruon urundeuva Allemão - Mu), Anacardiaceae, is a species from northeastern Brazil widely used in traditional medicine due to its property’s therapeutics recognized, as actions anti-inflammatory, antimicrobial and healing. These properties are mainly attributed to the presence of polyphenolic compounds such as tannins and chalcones dimeric. Despite of your use to be infused in the culture, studies that evaluate the toxicity of plant-derived formulations and their nociceptive and anti-inflammatory capacity, especially in orofacial models in vivo, do not yet present information considered in the literature. In this context, the present work has the general objective of evaluating the dental phytotherapeutic gel the base of Myracrodruon urundeuva German in oral mucositis, which is presented in four chapters: Chapter 1: Traditional uses, phytochemical studies and activities biological of Myracrodruon urundeuva (aroeira-do-sertão): a narrative review. This is an article with your methodology extensive on Mu, where it was realized that this is a remarkable plant of ethnopharmacological, technical-scientific and socioeconomic values; Chapter 2: From traditions to innovations: the pharmacochemical potential of aroeira-do-sertão (Myracrodroun) urundeuva German . It is an article that addresses Mu's technological and sustainable innovations, where the patent search took place between August and September 2024, with no time restrictions on the date of application or publication , thus allowing mapping the panorama of development technological related to this plant; Chapter 3: Preclinical evaluation of activity toxicological and nociceptive of gel of Myracrodruon urundeuva German for dental purposes in zebrafish ( danio rerio ) adult. Initially, preliminary pharmacognostic studies were carried out with the inner bark and gel preparation at 10% and 20%. Animal experiments were then performed using zebrafish to test toxicity and orofacial pain; the results demonstrated a satisfactory safety profile in zebrafish mucosa, causing no toxicity and demonstrating significant signs of nociceptive action, suggesting it could have analgesic properties. thus proving what the gel and effective in controlling nociception ; Chapter 4: Analysis of the efficacy and efficiency of Myracrodruon -based herbal gel urundeuva Allemão in the healing of oral ulcers in experiments with rats Wister , where it was observed that the 10% phytotherapeutic gel is effective in oral treatments, with healing potential, possible analgesic and antiulcer effect , in line with the trials with zebrafish, demonstrating promising results with predictability of its safety in oral mucositis. Tipo: Tese 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/83321 Título: Avaliação do potencial farmacoquímico da Dimorphandra mollis Benth. (fava- d’anta): do extrativismo sustentável ao desenvolvimento de fitoterápico Autor(es): Silva, Willams Alves da Abstract: Introduction: Dimorphandra mollis Benth. is a native Brazilian plant, widely valued due to its high content of rutin, a flavonoid with antioxidant, anti-inflammatory, cardioprotective, and antidiabetic properties. Objective: To develop a herbal medicine from the hydroalcoholic extract of D. mollis pods for the treatment of atopic dermatitis (AD). Materials and methods: The bibliometric analysis included 122 publications collected from the Scopus and Web of Science databases, using the Bibliometrix, VOSviewer, Biblioshiny, Excel, and OriginPro software packages. Patent prospecting was performed in the USPTO, WIPO, EPO, and INPI databases, using terms related to the species and filtering by language and CPC classification. The botanical material was collected in Jardim (CE). The pods were dried, pulverized, and analyzed for particle size, moisture, and total ash. Preliminary phytochemical screening identified secondary metabolites, and extracts were obtained by fractional percolation with hydroalcoholic solvents under different conditions. Rutin and quercetin were quantified by High Performance Liquid Chromatography (HPLC). Analyses were performed using an Ultra Performance Liquid Chromatography (UPLC) system. n silico studies were performed with the isolated molecules to predict biological activity, cytotoxicity, antibacterial potential, pharmacokinetic and toxicological parameters, and skin permeation. In vivo tests were conducted with zebrafish (Danio rerio). The procedures were approved by CEUA-UECE, protocol no. 04009489/2023. Based on the fluid extract of D. mollis, a phytotherapeutic formulation was developed. The parameters evaluated included pH, spreadability, viscosity, density, optical microscopy, and centrifugation. Finally, the quantification of the active ingredients in the formulation was performed by CLAE, using methanol extraction, sonication, and centrifugation, with comparison to analytical standards. Results: Bibliometric analysis identified 122 publications on Dimorphandra between 1969 and 2023, with an annual growth of 2.6%, 3,592 citations, and international collaboration in 10.66% of the studies. The Journal of Ethnopharmacology was the most cited, and the article with the greatest impact had 157 citations. The patentometric analysis revealed 109 records, with 26 eligible patents (classes A23 and A61), mostly in WIPO (45%), highlighting Brazil's low participation in the international scenario. In the pharmacognostic study of D. mollis, the plant powder was classified as coarse (0.774 mm), with moisture content (9,67 ± 0,86) and ash content (1,0447 ± 0,0140%) within standards. Phytochemistry revealed a high concentration of flavonoids in the fruits, in addition to saponins, resins, tannins, triterpenes, alkaloids, and steroids. Extraction with 50% ethanol resulted in a better chromatographic profile and higher flavonoid content, with hot 50% ethanol extraction showing a better chromatographic profile (Rf = 0.37 for rutin and Rf = 0.67 for quercetin) and higher total flavonoid content. In addition, among the compounds detected by UPLC, hispidulin, syringetin, and protocatechuic acid stand out as the first report for the genus Dimorphandra. In silico analyses indicated anti-inflammatory, antioxidant, and vasoprotective potential for rutin and quercetin, with low cytotoxicity. In the in vivo model with zebrafish, the extract was non-toxic (LC50 > 950 mg/mL), increased locomotion, and reduced edema, confirming antinociceptive and anti-inflammatory effects. The emulgel formulation showed stability for 60 days, maintaining pH, viscosity, spreadability, and concentration of markers under refrigeration and room temperature. In the oven, there was thermal degradation of flavonoids, highlighting the importance of temperature control to ensure the effectiveness of the formulation. Conclusion: The results validate the feasibility of using fava-d'anta as an active ingredient of bioactive plant origin in pharmaceutical and cosmetic formulations. Tipo: Tese 2025-01-01T00:00:00Z