https://rd.uffs.edu.br/handle/prefix/5423 2026-08-29T12:28:44Z https://rd.uffs.edu.br/handle/prefix/9428 Title: O potencial citotóxico, antiproliferativo e anticoagulante de um derivado organometálico do ácido valpróico em uma Linhagem de câncer endometrial Author: Meyer, Aschley First advisor: Leiria, Leonardo Barbosa Abstract: Valproic acid (AVP), widely used in the treatment of epilepsy, psychiatric disorders, and migraine, also exhibits antitumor properties mainly associated with the inhibition of histone deacetylases (HDACs), promoting epigenetic modulation and increased cellular sensitivity to cytotoxic agents. However, its prolonged use is associated with significant adverse effects, such as hepatotoxicity and systemic toxicity, which motivates the search for new, safer, and more effective derivative compounds. In this context, organometallic complexes emerge as a promising alternative, notably the derivative [Zn(Valp)₂Phen], which combines valproate with zinc and 1,10-phenanthroline, enhancing interactions with DNA and cytotoxic effects. In parallel, endometrial cancer is a significant public health problem, with a substantial increase in incidence and a need for new therapeutic approaches, especially given the resistance to conventional treatments. Thus, the present study aimed to evaluate the cytotoxic, antiproliferative, and anticoagulant effects of sodium valproate (NaValp) and its derivative [Zn(Valp)₂Phen] on human endometrial tumor cells (Ishikawa), comparing them with endometrial stromal cells (ESCs), and to investigate possible synergism with cisplatin. The results demonstrated that NaValp showed low cytotoxicity, not reaching the IC50 at the tested concentrations, especially in normal cells. In contrast, the organometallic derivative significantly reduced cell viability, with an approximate IC50 of 586 μM (24 h) and 340 μM (72 h) in Ishikawa cells. Furthermore, clonogenic assays confirmed a significant reduction in proliferative capacity, with a decrease of up to 73% in colony formation at higher concentrations of the derivative. Analysis of cell kinetics revealed an increase in population doubling time, indicating a sustained antiproliferative effect. Regarding the interaction with cisplatin, a relevant synergistic effect was observed, especially in the combination of 10 μM cisplatin with 100 μM [Zn(Valp)₂Phen], potentiating cytotoxicity in tumor cells without a significant increase in toxicity in normal cells, suggesting greater therapeutic safety. In relation to anticoagulant activity, NaValp showed a more pronounced effect with prolonged exposure, while the derivative demonstrated a more acute and concentration-dependent action, with a reduction in this effect over time. It is concluded that the organometallic derivative [Zn(Valp)₂Phen] exhibits superior cytotoxic, antiproliferative, and anticoagulant activity compared to sodium valproate, standing out as a potential candidate for the development of new, more selective and effective antitumor therapies. However, further in vitro and in vivo studies are needed for a better understanding of its mechanisms of action and to enable its safe clinical application. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2027-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/9376 Title: Efeito tipo antidepressivo do óleo de cannabis sativa de espectro completo na modulação do estresse oxidativo e sistema purinérgico em ratos submetidos a estresse no início da vida Author: Silva, Brunna Varela da First advisor: Ignácio, Zuleide Maria Abstract: Major Depressive Disorder (MDD) has a complex and multifactorial etiology, where both traumatic events and chronic stress play significant roles, leading to neural and systemic biological dysfunctions. These factors can affect individuals from early developmental stages through to adulthood. Chronic stress during childhood impairs brain development, and when combined with a lack of social support in adulthood, it can lead to severe depression and resistance to antidepressant treatments. Clinical medications not only require a long time to manifest antidepressant effects but also fail to provide therapeutic benefits for a significant percentage of patients. Consequently, the search for more effective treatments for MDD has included medicinal plants as therapeutic strategies that may influence relevant biological mechanisms in this disorder. The objective of this study was to evaluate depressive-like behavior and mechanisms involved in the endocannabinoid system, purinergic system, and oxidative stress in rats subjected to maternal deprivation (MD) during early life, combined with social isolation (SI) in young adulthood, as well as to assess the effect of treatment with full spectrum C. sativa oil. Male Wistar rats were divided into four groups (N = 10 per group): Control without stress + saline; MD+SI + saline; MD+SI + Escitalopram; MD+SI + full spectrum C. sativa oil. The rats underwent the MD and SI stress model at the beginning of adulthood, except for the control group. Subsequently, they received chronic treatment for 14 days according to their group’s objective. At the end of the treatment, the animals were subjected to behavioral protocols assessing locomotor activity in the open field and mobility in the forced swimming test. After the behavioral tests, the animals were euthanized, and biological samples were collected for analysis of oxidative stress and purinergic system biomarkers. The MD+SI + saline group showed increased immobility time in the forced swimming test compared to the other groups, indicating that the MD+SI protocol induced depressive-like behavior. The stress protocol also induced oxidative stress in the MD + saline group, evidenced by increased MPO activity in plasma compared to the control + saline group. Treatment with full spectrum C. sativa oil reversed depressive-like behavior and reduced MPO activity and TBARS levels in plasma. Furthermore, the oil-treated group exhibited increased hydrolysis of purinergic system biomarkers ATP, ADP, and AMP compared to all other groups. These findings suggest enhanced activity of ectonucleotidases CD39 and CD73, which may have physiological effects on purinergic receptor activation. Therefore, chronic treatment with full spectrum C. sativa oil demonstrated significant modulatory effects on both oxidative stress and the purinergic system, contributing to the understanding of mechanisms involved in the treatment of MDD Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2024-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/9334 Title: Inibição do gene CD73 em linhagem de câncer de bexiga: uma estratégia terapêutica de resposta a quimioterápicos que atuam na biossíntese de purinas Author: Rosa, Vandriel Pedone da First advisor: Maciel, Sarah Franco Vieira de Oliveira Abstract: The ectonucleotidase CD73 has been widely recognized as an important modulator of the tumor microenvironment, mainly due to its role in the conversion of AMP into adenosine, promoting immunosuppression and favoring tumor progression. The present study aimed to correlate CD73 expression as a biomarker of cell viability in response to treatment with cell death– inducing chemotherapeutic agents, such as cisplatin, paclitaxel, and doxorubicin, in the T24 bladder cancer cell line, using a strategy of protein translation modulation through RNA interference, as well as a CD73 knockout T24 cell line. Gene expression analysis did not demonstrate increased CD73 expression in the T24 tumor cell line compared to a set of non- tumoral bladder tissue samples used as control. In contrast, protein expression showed a reduction after RNA interference treatment, confirming modulation at the transcriptional level. In cell viability assays, the isolated or combined application of chemotherapeutic agents in the unmodified T24 cell line did not show a significant effect. After CD73 silencing by RNA interference, a change in the drug response profile was observed. Combinations such as cisplatin + paclitaxel and cisplatin + doxorubicin resulted in a significant reduction in cell viability at all tested concentrations, indicating a potentiated cytotoxic effect under conditions of purinergic pathway modulation. In the CD73 knockout T24 cell line, the isolated application of paclitaxel and cisplatin did not promote a significant reduction in cell viability, while doxorubicin at the lowest concentration maintained a cytotoxic effect. In this cell line, combined treatments generally did not show consistent significant reductions in cell viability, suggesting that the absence of CD73 may alter the response to combination therapies. Overall, the results indicate that CD73 silencing or inhibition plays a relevant role in modulating cellular response in the presence of the chemotherapeutic agents cisplatin, doxorubicin, and paclitaxel, whether used alone or in combination, influencing resistance or sensitivity mechanisms depending on the experimental context and therapeutic strategy adopted. Thus, CD73 stands out as a potential biomarker and promising therapeutic target in bladder cancer Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2026-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/9326 Title: Qualidade de vida relacionada à saúde (QVRS) materna: relação com comprimento relativo dos telômeros da mãe e do neonato Author: Dariff, Marina Suelen Trevisol First advisor: Polettini, Jossimara Abstract: Pregnancy induces physiological and psychosocial changes that can significantly affect both maternal health and newborn (NB) development. Telomeres — DNA-protein structures located at the ends of chromosomes — play a crucial role in genetic stability and protection against cellular aging. Evidence suggests that adverse conditions during pregnancy, such as stress, inflammation, and harmful lifestyle habits, may influence maternal health-related quality of life (HRQoL) and be associated with telomere shortening. The primary objective of this study was to describe sociodemographic, behavioral, health, and clinical characteristics, as well as to analyze the relative telomere length of maternal and newborn cells and its association with the HRQoL of postpartum women. A cross-sectional study was conducted at the maternity unit of Hospital Regional do Oeste (Chapecó, Santa Catarina, Brazil) between June 2024 and November 2025. Data collection included sociodemographic questionnaires, obstetric history, the EQ-5D-5L instrument with the Visual Analogue Scale (EQ-VAS) for self-rated health assessment, and oral mucosa swab sampling for telomere analysis by quantitative polymerase chain reaction (qPCR), expressed as the T/S ratio. Statistical analyses were performed using PSPP software, adopting a 5% significance level. A total of 131 mother-newborn dyads were included. Among the mothers, 78.6% were aged between 20 and 34 years, and 38.2% had low educational attainment. Smoking during pregnancy was reported by 11.5% of participants, alcohol consumption by 7.8%, and 19.1% reported maintaining physical activity during pregnancy. Regarding HRQoL, 74% of women reported high HRQoL perception prior to pregnancy, whereas 26% reported the same scores in the last trimester of pregnancy; 0.8% reported scores worse than death. In the EQ-VAS assessment, 30.5% of women rated their health as excellent before pregnancy, compared with 19.8% during the last trimester of pregnancy. With respect to telomere length, the median maternal T/S ratio was 0.65, while the median newborn T/S ratio was 2.11. No statistically significant associations were observed between maternal and newborn telomere length and HRQoL in the evaluated periods — pre-pregnancy and the last trimester of pregnancy (p > 0.05). These findings indicate a decline in perceived health during the last trimester of pregnancy and suggest that maternal factors may influence newborn telomere biology, although no statistically significant associations were identified in this sample. The results highlight the need for longitudinal follow-up and larger sample sizes to further investigate epigenetic mechanisms related to cellular aging processes during pregnancy. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2025-01-01T00:00:00Z