DSpace Coleção:

O receptor P2X7 microglial orquestra neuroinflamação, disfunção autofágica e sinucleinopatia em ratos parkinsonianos

Wed, 01 Jan 2025 00:00:00 GMT

Título: O receptor P2X7 microglial orquestra neuroinflamação, disfunção autofágica e sinucleinopatia em ratos parkinsonianos Autor(es): Nascimento, Tyciane de Souza Abstract: Parkinson’s disease (PD) is a multisystem neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the presence of protein inclusions known as Lewy bodies, which are primarily composed of aggregated α-synuclein. Under physiological conditions, these proteins are targeted for autophagic degradation. Hyperactivity of purinergic P2X7 receptors has been extensively implicated in the pathophysiology of PD, with growing evidence supporting their role in autophagic dysfunction and protein aggregation. Thus, the present study aimed to investigate the neuroprotective effect of the P2X7 receptor antagonist Brilliant Blue G (BBG), administered during a prodromal phase of PD, focusing on its impact on α-synuclein accumulation and dysfunction of autophagic pathways in an experimental model of rotenone-induced parkinsonism. For this purpose, male Wistar rats were divided into four groups: control, control treated, parkinsonian (rotenone 2.75 mg/kg for 21 days, intraperitoneally), and parkinsonian treated with BBG (50 mg/kg for 15 days, intraperitoneally). Animals were subjected to behavioral tests and, at the end of the protocol, euthanized for brain collection for immunohistochemical and molecular analyses. P2X7 receptor blockade significantly protected the animals against deficits in volatile odor detection, locomotor activity (open field test), motor coordination (rotarod test), depressive-like behavior (sucrose preference test), and working memory (Y-maze test) induced by rotenone exposure. BBG prevented the loss of dopaminergic neurons in the substantia nigra and striatum, reduced neuroinflammation, and decreased the accumulation of total and phosphorylated α- synuclein. Additionally, BBG modulated autophagic and mitophagic pathways, as evidenced by reduced expression of proteins such as LC3 and PINK1. The effect of BBG occurred by decreasing the number of microglial P2X7 receptors. The results indicate that rotenone-induced microglial purinergic hyperactivity acts as a multifaceted pathogenic integration center, amplifying neuroinflammation, disrupting autophagic processes, and promoting the accumulation of pathogenic α-synuclein, thereby creating a vicious cycle that culminates in dopaminergic neuronal death. Thus, P2X7 receptor blockade emerges as a promising therapeutic approach for targeting multiple pathological pathways in PD. Tipo: Tese

Envolvimento de biomarcadores endoteliais na chikungunya crônica

Thu, 01 Jan 2026 00:00:00 GMT

Título: Envolvimento de biomarcadores endoteliais na chikungunya crônica Autor(es): Furtado, Frederico Luis Braz Abstract: Introduction: Chikungunya is an arboviral disease responsible for triggering an intense inflammatory response, associated with long-lasting clinical manifestations in chronic cases. In the last decade, it has affected millions of people in the Americas, Africa, Asia, and Europe, becoming a major public health problem due to its significant impact on quality of life. In this context, the study of endothelial biomarkers can contribute to clarifying the prognosis of the disease and its clinical repercussions. Objective: To investigate biomarkers of endothelial injury in chronic chikungunya. Materials and methods: Cross-sectional study with 34 chronic cases, selected from the cohort of the Oliveira Pombo Basic Health Unit, linked to the “Study of the natural history and therapeutic response of Chikungunya focusing on acute and chronic musculoskeletal manifestations in Fortaleza-CE”. Venous blood samples were collected for the measurement of endothelial biomarkers (ANG-2, VCAM-1, and SYN- 1), in addition to clinical data, such as comorbidities and symptoms, extracted from the cohort questionnaires. Results: The mean age of chronic cases was 45.11 ± 15.86 years, with 28 (76.47%) being female. Twenty (58.82%) participants belonged to the group with 360 days of disease duration. The most prevalent symptoms were morning stiffness (28; 82.35%), arthralgia (22; 64.71%), and edema (16; 47.06%). In the comparison between the three groups of chronic patients with different disease durations (180, 360, and 720 days) and the control group, the biomarkers ANG-2, VCAM-1, and SYN-1 showed statistically significant differences (p = 0.007; p = 0.004; p < 0.001, respectively). Increased levels of ANG-2 (p = 0.037) were observed in patients with and without depression, as well as reductions in VCAM-1 (p = 0.047) and SYN-1 (p = 0.036) in cases with and without memory impairment. SYN-1 levels were increased in patients with fever (p = 0.041) and reduced in those with blurred vision (p = 0.019) and alopecia (p = 0.009), compared to those without these symptoms. Only the biomarkers ANG-2 and VCAM-1 showed a correlation with disease duration, with a moderate and positive correlation for ANG-2 (Rho = 0.456; p = 0.006) and a weak and negative correlation for VCAM-1 (Rho = -0.369; p = 0.034). ANG-2 was the only biomarker with good predictive performance in the AUC-ROC curve = 0.864 and 95% CI (0.725 - 1000), while VCAM-1 and SYN-1 presented, respectively, AUC-ROC = 0.605 and 95% CI (0.338 – 0.872); AUC-ROC = 0.519 and 95% CI (0.148 – 0.890). Conclusion: Increased levels of ANG-2 and reduced levels of VCAM-1 were associated with disease duration in the evaluated cases. SYN-1 may be related to the presence of symptoms such as fever, memory impairment, blurred vision, and alopecia in patients with chronic chikungunya. Tipo: Tese

Modelagem integrada de redes Multilayer, Análises Espaciais e Aprendizado de Máquina na investigação da disseminação de COVID-19 e de arboviroses (Dengue, Zika e Chikungunya) em Fortaleza

Wed, 01 Jan 2025 00:00:00 GMT

Título: Modelagem integrada de redes Multilayer, Análises Espaciais e Aprendizado de Máquina na investigação da disseminação de COVID-19 e de arboviroses (Dengue, Zika e Chikungunya) em Fortaleza Autor(es): Silva, Rôney Reis de Castro e Abstract: The rise of arboviral diseases—and, in particular, COVID-19—calls for approaches that integrate multiple territorial dimensions. This thesis adopts an integrated approach combining multilayer networks, statistical and spatial analyses, and interpretable machine learning to understand diffusion patterns of COVID-19, dengue, zika, and chikungunya in Fortaleza (CE), 2020–2024. Layers comprise epidemiological, socioeconomic/demographic, infrastructure, and political/HDI variables; intralayer relations are defined by neighborhood similarity, and interlayer relations by associations between variables. The COVID-19 dataset was built from weekly epidemiological bulletins, aggregated by month and neighborhood, prioritizing territorial patterns comparable across diseases. Spatially, we use global and local autocorrelation (Moran’s I, LISA) to identify clusters and local patterns; in the network domain, we compute centralities and apply community detection. Predictive models (Random Forest, XGBoost) and SHAP-based explanations assess the variables’ predictive power and contributions. K-means clustering synthesizes territorial profiles by combining structural and epidemiological characteristics. Findings reveal spatial heterogeneity and cross-layer differences, with territorial convergences and divergences that inform vulnerability assessment and prioritization. As a practical contribution, the thesis includes an Appendix: Methodological Enhancement Proposal (“Integrated Framework”) to guide future standardization and support municipal decision-making. Tipo: Tese

Impacto da volemia sobre a barreira funcional do epitélio intestinal em pacientes críticos com insuficiência cardíaca aguda

Wed, 01 Jan 2025 00:00:00 GMT

Título: Impacto da volemia sobre a barreira funcional do epitélio intestinal em pacientes críticos com insuficiência cardíaca aguda Autor(es): Monte Neto, Vicente Lopes Abstract: The regulation of blood volume (volemic homeostasis) depends on the interaction between the cardiovascular, renal, and intestinal systems, whose dynamics are not yet fully understood. In cases of Acute Heart Failure (AHF), these systems may be affected, particularly the intestinal barrier, which undergoes increased permeability. This phenomenon, poorly studied and with limited diagnostic tools, may compromise intestinal epithelial cells. The objective of this study was to investigate how acute changes in blood volume influence the integrity and function of the intestinal barrier in patients with AHF. This was a cross-sectional study, approved by the Research Ethics Committee of the Vale do Acaraú State University (CEP/CONEP), which evaluated intestinal barrier integrity in 80 individuals between March 2022 and January 2024. The sample consisted of 40 patients with AHF (clinical and echocardiographic diagnosis), 14 controls with Coronary Artery Disease (CAD), and 26 healthy controls. Intestinal permeability was measured using the lactulose/mannitol (L:M) urinary excretion ratio by HPLC-PAD. Patients with AHF presented a median L:M ratio of 0.1094 (IQR 25–75%: 0.0411–0.2732), representing an increase of 277.2% compared to healthy volunteers and 466.8% compared to the CAD group, with a statistically significant difference according to the Kruskal-Wallis test (P = 0.001). Kendall’s correlation was used to assess the association between the L:M ratio and Pro-BNP levels, as well as hemodynamic parameters obtained by echocardiography. Multiple regression was performed considering the L:M ratio as the dependent variable and clinical, therapeutic, and in-hospital prognostic characteristics as independent variables. Kendall’s correlation indicated a negative association between the Left Ventricular Outflow Tract (LVOT) Velocity-Time Integral (VTI) and L:M ratio, without statistical significance. Multiple regression did not show significant associations between L:M ratio and clinical, therapeutic, or prognostic variables. Conclusion: Patients with AHF presented increased intestinal permeability, reflected by elevated L:M ratio, suggesting epithelial barrier dysfunction and reduced effective absorptive area. These findings indicate a relevant interaction between cardiovascular dysfunction and intestinal integrity. Tipo: Tese