👤 Roberto Barbosa Morais

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that, through the activation of its full length receptor, TrkB-FL, plays a pivotal role in neuroprotection, namely against neuronal toxicity mediated by amyloid-β peptide (Aβ). In astrocytes, the increase of calcium (Ca Show less

The incorporation of selenium into tacrine derivatives has been explored as a novel strategy to enhance therapeutic efficacy while minimizing toxicity in the treatment of neurodegenerative diseases such as Alzheimer's. This study utilized computational and experimental approaches, including Density Functional Theory (DFT), molecular docking, pharmacokinetic profiling, and toxicological predictions, to evaluate the potential of these derivatives. The selenium-modified compounds demonstrated improved electronic properties, such as narrower HOMO-LUMO gaps and optimized electronegativity, resulting in enhanced stability and reactivity. Pharmacokinetic analyses revealed favorable absorption, distribution, and blood-brain barrier penetration, while toxicological assessments indicated reduced hepatotoxicity and skin sensitization risks compared to tacrine. Molecular docking and dynamic simulations highlighted strong and stable interactions of the derivatives with critical enzymes, including acetylcholinesterase (AChE) and beta-secretases (BACE1 and BACE2). Compounds Show less

Oral squamous cell carcinoma (OSCC) remains a challenging malignancy with poor 5-year survival rates due to diagnosis at an advanced stage and a high likelihood of recurrence and metastasis. These aggressive traits may be influenced by cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). This study investigated the prognostic significance of the CSC marker CD44 and EMT-related proteins (Snail1, Snail2, E-cadherin, N-cadherin) in 132 OSCCs using immunohistochemistry. The comprehensive survival analysis included univariate and multivariate (stepwise method) Cox regression for disease-specific survival (DSS) and disease-free survival (DFS), Kaplan-Meier curves based on log-rank testing, and receiver operating characteristic (ROC) analysis to assess the predictive accuracy of the markers. High CD44 expression independently predicted worse DSS (HR = 2.74, 95% CI 1.44-5.23, p = 0.003) and DFS (HR = 2.22, 95% CI 1.16-4.23, p = 0.01), and Snail1 was significantly associated with poor DSS (HR = 2.62, 95% CI 1.37-5.03, p = 0.004). The combined expression of CD44 and Snail1 improved the discrimination of worse outcomes compared to markers individually. The presence of lymphovascular invasion (HR = 8.68, 95% CI 3.81-19.75, p < 0.0001) and a positive surgical margin (< 5 mm; HR = 4.45, 95% CI 1.99-9.96, p = 0.0003) were also independently associated with DSS. The results of this study highlight the prognostic significance of CD44 and Snail1 in OSCC, emphasizing their potential interplay in tumor aggressiveness. Show less

Urea cycle disorders (UCD) are inborn errors of metabolism caused by deficiency of enzymes required to convert nitrogen from ammonia into urea. Current paradigms of treatment focus on dietary manipulations, ammonia scavenger drugs, and liver transplantation. The aim of this study was to describe the characteristics and indication of liver transplantation in UCD in a tertiary hospital. We performed a retrospective study of children with UCD seen in the period 2000-2021. Data was collected on clinical onset, hyperammonemia severity, evolution and liver transplantation. There were 33 patients in the study period, whose diagnosis were: ornithine transcarbamylase (OTC, Show less

Cancer cells produce abnormal levels of reactive oxygen species (ROS) that contribute to promote their malignant phenotype. In this framework, we hypothesized that the change in ROS concentration above threshold could impair key events of prostate cancer cells (PC-3) progression. Our results demonstrated that Pollonein-LAAO, a new L-amino acid oxidase obtained from Bothrops moojeni venom, was cytotoxic to PC-3 cells in two-dimensional and in tumor spheroid assays. Pollonein-LAAO was able to increase the intracellular ROS generation that culminates in cell death from apoptosis by both intrinsic and extrinsic pathways due to the up-regulation of TP53, BAX, BAD, TNFRSF10B and CASP8. Additionally, Pollonein-LAAO reduced mitochondrial membrane potential and caused G0/G1 phase to delay, due to the up-regulation of CDKN1A and the down-regulation of the expression of CDK2 and E2F. Interestingly, Pollonein-LAAO inhibited critical steps of the cellular invasion process (migration, invasion and adhesion), due to the down-regulation of SNAI1, VIM, MMP2, ITGA2, ITGAV and ITGB3. Furthermore, the Pollonein-LAAO effects were associated with the intracellular ROS production, since the presence of catalase restored the invasiveness of PC-3 cells. In this sense, this study contributes to the potential use of Pollonein-LAAO as ROS-based agent to enhance the current understanding of cancer treatment strategies. Show less

The aim of the present study was to investigate the role of SNAIL1, E-cadherin, and N-cadherin immunoexpression in oral tongue carcinogenesis. In addition, we evaluated in vitro the impact of silencing of the nuclear transcription factor SNAIL1 on the viability, apoptosis, proliferation, migration, and invasion of SCC-9 and HSC-3 cells. Immunohistochemical analysis of SNAIL1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia (OED) and 41 oral tongue squamous cell carcinoma (OTSCC). The suppression of SNAIL1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of SNAIL1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. Significant differences were observed in the expression of SNAIL1, E-cadherin, and N-Cadherin between OTSCC and OED. A low membrane expression of E-cadherin was strongly associated with poor overall survival in patients with OTSCC (P < .05), but the association did not withstand the Cox multivariate survival analysis. SNAIL1 silencing played a key role in the suppression of epithelial-mesenchymal transition and inhibited migration and invasion of HSC-3 cells (P < .0001, P < .01, respectively). In SCC-9 cells, SNAIL1 silencing promoted a significant reduction in the proliferation (P < .0001) and invasion (P < .0001). The epithelial-mesenchymal transition is present in different stages of oral tongue carcinogenesis, and SNAIL1 plays a key role in this process, although the underlying mechanisms still need to be elucidated. Thus, SNAIL1 might be a promising therapeutic target in OTSCC. Show less

Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression. Show less