Percorrer por autor "Videira, Paula A."
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- Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridinePublication . Mendo, Ana Soraia; Figueiredo, Sara; Roma-Rodrigues, Catarina; Videira, Paula A.; Ma, Zhen; Diniz, Mário; Larguinho, Miguel; Costa, Pedro M.; Lima, João C.; Pombeiro, Armando J. L.; Baptista, Pedro V.; Fernandes, Alexandra R.Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4′-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.
- A Community-Based Participatory Framework to Co-Develop Patient Education Materials (PEMs) for Rare Diseases: A Model Transferable across DiseasesPublication . Falcão, Marta; Allocca, Mariateresa; Rodrigues, Ana Sofia; Granjo, Pedro; Francisco, Rita; Pascoal, Carlota; Rossi, Maria Grazia; Marques-da-Silva, Dorinda; Magrinho, Salvador C. M.; Jaeken, Jaak; Castro, Larisa Aragon; Freitas, Cláudia de; Videira, Paula A.; Andrés-Aguayo, Luísa de; Ferreira, Vanessa dos ReisAt least 50% of chronic disease patients don’t follow their care plans, leading to lower health outcomes and higher medical costs. Providing Patient Education Materials (PEMs) to individuals living with a disease can help to overcome these problems. PEMs are especially beneficial for people suffering from multisystemic and underrecognized diseases, such as rare diseases. Congenital disorders of glycosylation (CDG) are ultra-rare diseases, where a need was identified for PEMs in plain language that can clearly explain complex information. Community involvement in the design of PEMs is extremely important for diseases whose needs are underserved, such as rare diseases; however, attempts to involve lay and professional stakeholders are lacking. This paper presents a community-based participatory framework to co-create PEMs for CDG, that is transferable to other diseases. A literature review and questionnaire were performed, and only four articles describing the development of PEMS for rare diseases have been found, which demonstrates a lack of standardized approaches. The framework and PEMs were co-developed with CDG families and will be crucial in increasing health literacy and empowering families. We will close a gap in the creation of PEMs for CDG by delivering these resources in lay language in several languages.
- New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric ApproachPublication . Francisco, Rita; Pascoal, Carlota; Marques da Silva, Dorinda; Brasil, Sandra; Pimentel-Santos, Fernando M.; Altassan, Ruqaiah; Jaeken, Jaak; Grosso, Ana Rita; Ferreira, Vanessa dos Reis; Videira, Paula A.Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations’ prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general “healthy” population. Two-hundred and nine CDG patients/caregivers and 349 healthy participants were included in this study. PMM2-CDG was the most represented CDG (n = 122/209). About half of these participants (n = 65/122) described relevant infections with a noteworthy prevalence of those affecting the gastrointestinal tract (GI) (63.1%, n = 41/65). Infection burden and QoL impact were shown as infections correlated with more severe clinical phenotypes and with a set of relevant non-immune PMM2-CDG signs. Autoimmune diseases had only a marginal presence in PMM2-CDG (2.5%, n = 3/122), all being GI-related. Allergy prevalence was also low in PMM2-CDG (33%, n = 41/122) except for food allergies (26.8%, n = 11/41, of PMM2-CDG and 10.8%, n = 17/158, of controls). High vaccination compliance with greater perceived ineffectiveness (28.3%, n = 17/60) and more severe adverse reactions were described in PMM2-CDG. This people-centric approach not only confirmed literature findings, but created new insights into immunological involvement in CDG, namely by highlighting the possible link between the immune and GI systems in PMM2-CDG. Finally, our results emphasized the importance of patient/caregiver knowledge and raised several red flags about immunological management.
- Oxidative Stress and Inflammatory Response of Skin Fibroblasts Exposed to ChlorpyrifosPublication . Silva, Zélia; Almeida, Danielle; Marques-da-Silva, Dorinda; Lagoa, Ricardo; Videira, Paula A.Chlorpyrifos (CPF) is a widely used insecticide. The aim of this work was to study the effect of CPF in skin fibroblasts exposed to concentrations detected in human skin and unleash underlying cellular mechanisms. Fibroblasts were exposed to different concentrations (0.36–250 µM) of CPF pure alone or in a commercial CPF mixture (Lethal 20) for 6 days. In conclusion, prolonged exposure to 250 µM of CPF pure and 125 µM of Lethal 20 caused a significant loss of the fibroblast´s viability. Moreover, the toxicity of this pesticide in fibroblasts is evidenced by the induction of oxidative stress and stimulation of the production of interleukin (IL)-6.
- Use of Lipid Vesicles for Revealing the Potential Contribution of Cytochrome C in the Metabolism of Environmental ToxicantsPublication . Lopes, João M.; Marques-da-Silva, Dorinda; Videira, Paula A.; Lagoa, RicardoCytochrome c (Cc) is well-known as an electron carrier at mitochondria but can also catalyze peroxidase-like reactions. Although the reported catalytic abilities are low, the role of Cc in transforming environmental toxicants requires additional studies. We employed cardiolipin vesicles to stimulate the enzymatic activity of Cc and tested the catalytic system towards the dye methyl orange and the polycyclic aromatic hydrocarbons (PAHs) benzo[b]fluoranthene and benzo[a]pyrene. The results showed that cardiolipin-containing vesicles promoted dye decolorization and the oxidation of both PAHs by Cc, indicating that lipid membranes can be useful to further investigate Cc–mediated metabolism of toxicants.