https://rd.uffs.edu.br/handle/prefix/5423 2025-12-02T18:58:39Z https://rd.uffs.edu.br/handle/prefix/8951 Title: Análise da expressão gênica e proteica do PD-L1 e do CD73 como biomarcadores de prognóstico em pacientes com glioblastoma Author: Santos, Helamã Moraes dos First advisor: Maciel, Sarah Franco Vieira de Oliveira Abstract: Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous tissue, presenting a critical clinical course and an unfavorable prognosis. Its biological behavior is associated with the induction of an immunosuppressive state through the modulation of components of the tumor microenvironment. Immunosuppression enables these tumors to evade immune surveillance and become resistant to immunotherapies. The Programmed Cell Death pathway, represented by the PD-1 and PD-L1 ligands, as well as the adenosinergic axis, mediated by the activity of the CD73 enzyme, play important roles in the immunomodulatory nature of GBM. In this study, we evaluated the protein production and gene expression of CD73 and PD-L1, as well as their prognostic predictive potential in tumor samples from patients with GBM. This is a non-interventional cross-sectional study. The study group consisted of 42 participants diagnosed with grade II, III, and IV gliomas who were eligible for surgery. They were divided into two groups: Low-Grade Gliomas (LGG) (n=21) and GBM (n=21). The samples were subjected to immunohistochemistry and RT-qPCR analyses, and complementary data were obtained from public databases of international health agencies. Immunohistochemistry analysis identified higher protein production through PD-L1 and CD73 immunoreactivity in the GBM group compared to the LGG group (p=0.014 and p=0.021, respectively). Gene expression analysis showed no statistically significant differences between the groups for either PD-L1 (p=0.616) or CD73 (p=0.070). However, a strong and statistically significant positive correlation was observed between PD-L1 and CD73 in GBM (r=0.714; p=0.003), while in LGG the correlation was not significant (p=0.255). These findings suggest that in GBM, the immunosuppressive pathways mediated by PD-L1 and CD73 may act interdependently, indicating a more immunosuppressive tumor microenvironment. Overall survival analysis showed no statistically significant difference for PD-L1 (p=0.214) or CD73 (p=0.370). However, a significant association was found between higher PD-L1 gene expression and lower progression-free survival rates (p=0.002). Our findings indicate that the protein production and gene expression of these immunosuppressive markers are present in human GBM tumor tissue and may directly impact clinical outcomes in this population. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2025-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/8942 Title: Avaliação da sinalização purinérgica e inflamação crônica em pacientes após ressecção cirúrgica de PitNET Author: Oliveira, Luiz Alberto de First advisor: Bagatini, Margarete Dulce Abstract: Introduction: Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors among endocrine neoplasms, with higher prevalence in women and individuals aged 30 to 40 years. Studies indicate that the purinergic system, together with tissue response to injury and inflammatory processes, are among the signaling pathways involved in the formation of the tumor microenvironment and in PitNET progression. Objective: To evaluate the activity, gene expression, and protein expression of the purinergic enzymes E-NTPDase (CD39) and Ecto-5’-nucleotidase (CD73), as well as serum levels of Interleukin-1β (IL-1β) in patients who underwent transsphenoidal surgery for the resection of PitNETs. Methodology: This is a cross-sectional study conducted in January 2024. Seventeen patients with a previous diagnosis of PitNET, who had undergone surgical resection 12 to 24 months prior to this research, were selected, along with 22 individuals in the control group. The activity and expression of the ectonucleotidases CD39 and CD73 in peripheral blood mononuclear cells (PBMCs) and platelets were assessed, in addition to extracellular ATP levels and serum IL-1β. Biological sample collection was carried out at the Regional Hospital, a reference center in western Santa Catarina, located in Chapecó, Brazil. For statistical analyses, data normality was verified using the Shapiro-Wilk test, followed by Student’s t-test, Mann-Whitney, and one-way ANOVA. A 95% significance level was adopted, and analyses were performed using GraphPad Prism 9.0.1. Results: In this study, the PitNET group (PG) presented a mean age of 57.78 years, with a predominance of females (66.7%) and hypertension as the most prevalent chronic disease (23.53%). Regarding tumor characteristics, macroadenomas (94.11%), PIT-1 cell lineage (35.3%), and gonadotroph tumors (23.52%) were more frequent. At the molecular and functional level, the PitNET group exhibited significantly increased levels of extracellular ATP (p = 0.0004) and serum IL-1β (p = 0.0017), indicating a persistent inflammatory environment. In addition, a reduction in CD39 activity in PBMCs was observed (p = 0.0039), associated with lower ATP hydrolysis capacity, contrasting with increased CD73 activity in platelets (p = 0.0096), which favors AMP hydrolysis and, consequently, the production of immunosuppressive adenosine. Furthermore, significant increases were found in CD39 protein expression (p < 0.0001), CD73 protein expression (p = 0.0013), and CD73 gene expression (p = 0.0349). Conclusion: The results demonstrated that PitNETs, even after surgical resection, promote persistent alterations in the activity and expression of purinergic enzymes, in addition to increasing serum IL-1β levels, contributing to a state of chronic inflammation and immunosuppression. These findings expand the understanding of PitNET pathophysiology and suggest that purinergic pathway components and inflammatory mediators may serve as prognostic biomarkers and potential therapeutic targets. The development of longitudinal studies is warranted to validate these biomarkers and guide novel strategies for the treatment and follow-up of affected patients. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2025-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/8836 Title: Efeitos da acupuntura na qualidade de vida e sintomatologia de mulheres na perimenopausa: um ensaio controlado randomizado Author: Marocco, Keli Cristina First advisor: Silva, Shana Ginar da Abstract: Perimenopause is a transitional phase marked by hormonal changes that provoke symptoms such as hot flashes, insomnia, and anxiety, representing a considerable challenge to women's health. It is estimated that more than 80% of women present symptomatology in this phase, with about one third experiencing severe symptoms. In this scenario, integrative practices such as acupuncture have been investigated for their ability to promote symptomatic relief and wellbeing. This study aimed to evaluate the effects of acupuncture on the quality of life and symptomatology of women in perimenopause. This is a randomized controlled trial, conducted from September 2024 to June 2025 with women aged 40 to 60 years residing in the municipality of Xaxim/SC. The sample was selected by convenience via social networks and invitation letters, with 64 eligible participants after screening of 91 recruited, randomized (1:1) into control (n=31) and intervention (n=33) groups by the principal researcher using a Microsoft Excel spreadsheet, in blocks of 6, ensuring equitable distribution between the intervention (acupuncture) and control (no intervention during the study) groups. The primary outcome, symptom intensity, was assessed by the IMK, and the secondary outcome, quality of life, was measured by the SF-36 instrument. Data were collected at baseline and post-intervention and analyzed in the Stata software. The intervention group received five weekly acupuncture sessions (20 minutes of needling, standardized protocol, by a qualified acupuncturist). The groups were similar in the baseline assessed characteristics, except for physical activity practice (p=0.046). In the intervention group, the IMK reduced significantly (26.9 ± 8.1 to 12.4 ± 6.9; p<0.001), with relief of hot flashes (-3.9; p<0.001), vertigo (-1.6; p<0.001), insomnia (-2.5; p<0.001), nervousness (-1.9; p<0.001), fatigue (-0.9; p<0.001), arthralgia/myalgia (-0.7; p<0.001), headache (-0.7; p=0.002), and tachycardia/palpitations (-0.5; p=0.013). In the SF-36, comparing the groups post-intervention (intervention vs. control), significant differences were observed in seven of the eight domains: physical aspects (88.6 ± 21.7 vs. 55.6 ± 39.2; p<0.001), pain (77.5 ± 19.5 vs. 53.0 ± 14.9; p<0.001), general health (65.6 ± 16.5 vs. 56.2 ± 17.1; p=0.029), vitality (66.4 ± 17.0 vs. 47.3 ± 15.3; p<0.001), social aspects (79.2 ± 21.6 vs. 64.1 ± 16.4; p=0.003), emotional aspects (78.8 ± 34.2 vs. 32.3 ± 33.9; p<0.001), and mental health (71.6 ± 13.9 vs. 54.9 ± 14.8; p<0.001), with no significant difference in functional capacity (83.8 ± 14.8 vs. 79.8 ± 15.5; p=0.301), possibly due to the timing of the effect. Limitations include the short follow-up time and convenience sample, which may affect the generalization of the results. The results suggest that acupuncture was effective in reducing symptoms and improving quality of life, aligning with the guidelines of the National Policy on Integrative and Complementary Practices and the National Policy on Comprehensive Care for Women's Health. This research contributes to addressing gaps in the Brazilian literature, providing primary evidence from a randomized controlled trial with implications for practices in the Unified Health System. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2025-01-01T00:00:00Z https://rd.uffs.edu.br/handle/prefix/8802 Title: Comprimento relativo dos telômeros em puérperas e recém-nascidos e sua relação com estresse e ansiedade gestacional Author: Pradella, Nandara First advisor: Acrani, Gustavo Olszanski Abstract: Introduction: Gestational changes, whether physiological, physical, or social, can increase stress and anxiety, which may affect the relative length of telomeres. Objective: To evaluate the relative length of telomeres in oral mucosa cells of puerperal women and newborns and to relate them to stress and anxiety during the gestational period. Methodology: This cross-sectional study was conducted between June 2024 and June 2025 with puerperal women and newborns at the maternity ward of the Regional Hospital of the West, Chapecó/SC, and in the Molecular Biology Laboratories of the Federal University of Fronteira Sul (UFFS), campuses of Chapecó/SC and Passo Fundo/RS. Data were collected using a questionnaire prepared by the research team, followed by swab collection from the oral mucosa of the mother and child for the extraction of cellular samples. To calculate the relative telomere length, the ratio referring to the single-copy gene (T/S ratio) was used through Real-Time Polymerase Chain Reaction (PCR). Statistical analyses were performed using PSPP software, version 3.0, free distribution. The distribution of the outcome in relation to the independent variables was verified using Fisher’s Exact Test and Pearson’s ChiSquare Test, with an alpha error below 5%. Results: In the sample, composed of 131 puerperal women, the following stood out: age between 21 and 34 years (78.6%), with at least complete high school (61.8%), employed puerperal women (58.0%), and those who had a partner (89.3%). A diagnosis of stress before pregnancy was mentioned by 17.6% of participants and, during pregnancy, by 9.2%, while anxiety was 25.2% and 15.0%, before and after pregnancy, respectively. In the last three months of pregnancy, 26.0% presented high-intensity stress and 29.0% high-intensity anxiety. The median T/S ratio was 0.65 among puerperal women and 2.11 among newborns. Among those diagnosed with anxiety before pregnancy, 73.3% presented a T/S ratio ≤ 0.65. In newborns, telomere length showed a statistically significant difference in relation to maternal anxiety before (p = 0.009) and during pregnancy (p = 0.027). Conclusion: These findings suggest that the presence of maternal anxiety, both prior to and during pregnancy, may be related to greater telomeric shortening at birth. Publisher: Universidade Federal da Fronteira Sul Type: Dissertação 2025-01-01T00:00:00Z