Percorrer por autor "Fernandes, Silvia"
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- Betulinic acid modulates adipocyte differentiation and secretome activity: Downstream effects on Glioblastoma cell migrationPublication . Gouveia, Afonso; Ferraz, Ricardo; Prudêncio, Cristina; Fernandes, Silvia; Fernandes, SílviaBetulinic acid (BA) has been recognized for its po-tential to modulate tumor progression and adipocyte function, yet its effects on adipocyte secretome re-modeling and the downstream consequences for glio-blastoma behavior remain incompletely understood1-4. In this study, we investigated the influence of BA on adipocyte secretory activity and its functional impact on glioblastoma cell migration. Direct exposure of U251 glioblastoma cells to BA significantly reduced cell migration, confirming its intrinsic anti-migratory potential. To further explore microenvironmental in-teractions, adipocyte-conditioned media (ACM) de-rived from BA-treated adipocytes was evaluated for its effects on glioblastoma behavior. Secretome anal-ysis demonstrated that BA altered matrix metallopro-teinase (MMP) expression and reduced gelatinolytic activity, indicating significant modulation of extracel-lular matrix–related proteolytic pathways. Functional assessment using wound healing assays revealed that ACM from BA-treated adipocytes did not consistent-ly suppress glioblastoma migration. Intermediate BA concentrations were associated with increased migratory behavior relative to basal conditions, although differences compared with control ACM were not statistically significant. Additionally, transwell migra-tion assays did not demonstrate significant differ-ences between treatment conditions, suggesting that BA-induced alterations in adipocyte secretome com-position do not uniformly translate into measurable changes in glioblastoma migratory capacity across dif-ferent experimental models. These findings indicate that modulation of gelatinolytic pathways alone is insufficient to predict glioblastoma cell migration and support the contribution of additional adipocyte-de-rived signalling mechanisms in regulating tumor be-havior. Overall, BA induces substantial remodelling of adipocyte secretory function, producing complex and non-linear downstream effects on glioblastoma cells. This study highlights the importance of tumor micro-environment crosstalk and underscores the need to evaluate multiple regulatory pathways when consid-ering the therapeutic potential of BA and related bio-active compounds.
- Enhancing antifungal activity against Candida albicans using novel organic compoundsPublication . Alves, Beatriz; Silva, Rui; Vieira, Mónica; Ferraz, Ricardo; Fernandes, Silvia; Teixeira, Vitor; Pereira, Clara; Almeida Vieira, Mónica Andreia; Fernandes, SílviaCandida albicans is the predominant cause of inva-sive candidiasis, a major global health threat [1 The increasing emergence of resistance to commonly used antifungals (ex.:iazoles and polyenes) demonstrates an urgent need for alternative therapeutic strategies. The objective of this study was to evaluate the antifungal activity of novel organic derivatives from bioactive natural compound, including Naphthalene, Betulinic Acid (BA) [2]; Protocatechuic Acid (PCA) and Gallic Acid (GA), alone, or in combination with conventional antifungals to investigate synergistic effects that en-hance their efficacy. Antifungal susceptibility assays were performed in C. albicans ATCC 10231 using the broth microdilution method, according to CLSI M27 guidelines, to determine Minimum Inhibitory Concen-trations (MICs) and Minimum Fungicidal Concentra-tions (MFC). The interaction between BA derivatives and amphotericin B was assessed by checkerboard assay and fractional inhibitory concentration index (FICI). Naphthalene, PCA and GA derivatives showed low antifungal activity, falling within the moderate to weak bioactivity range (MIC ≥ 100 μg mL−1; [3]). Among BA derivatives, BA-4 and BA-5 exhibited the best antifungal activity, with MIC values of 0,95 and 1,91 μg mL−1, respectively, achieving 99% fungicidal activity at the same concentration. Furthermore, in combination assays, both compounds enhanced Am-photericin B activity, showing synergistic effects (FICI = 0.50), resulting in a decrease in MIC. Although most newly synthesized compounds exhibited limited anti-fungal potential, BA-4 and BA-5 demonstrated very strong bioactivity and fungicidal effects against C. albicans. The observed synergy with amphotericin B highlights their potential role as antifungal adjuvants and supports the further exploration of betulinic acid derivatives as viable approaches to overcoming anti-fungal resistance.