Percorrer por autor "Marques-da-Silva, Dorinda"
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- Ação antimicrobiana e antioxidante da epicatequina em óleos de pinhãoPublication . Marques-da-Silva, Dorinda; Lagoa, Ricardo; Santos Ribeiro, Vânia
- Alginate films encapsulating polyphenols for nutraceutical and biomedical applicationsPublication . Lagoa, Ricardo; Vanat, Pavlo; Ferreira, Stefanie; Silva, João; Marques-da-Silva, Dorinda; Vaz, Daniela C.; Barreiros, Fátima; Rodrigues, Joaquim Rui; Santos Ribeiro, Vânia
- Anthocyanins, effects in mitochondria and metabolismPublication . Marques-da-Silva, Dorinda; Rodrigues, Joaquim Rui; Lagoa, RicardoAlterations in mitochondrial function, cellular redox signaling, and metabolism participate in the etiology and progression of different pathological conditions, such as diabetes, cancer, cardiovascular, and neurodegenerative diseases. Epidemiological, preclinical, and clinical studies indicate that anthocyanins afford therapeutic benefits for these pathologies. It is thus important to revise the effects of anthocyanins on mitochondria and metabolism that hold potential for the development of novel health protective methods. The studies available support the ability of certain anthocyanins to prevent damage to mitochondria and to sustain its function. Evidence is more compelling for cyanidin and delphinidin compounds, but promising data could also be found for malvidin, pelargonidin, and protocatechuic acid. Additionally, berry extracts also demonstrated positive outcomes in different models of neurodegeneration, endothelial dysfunction, myocardial damage, metabolic disorders, longevity, and cancer. At the molecular level, major anthocyanins can modulate the expression and activity of mitochondrial proteins, apoptotic and biogenesis factors, antioxidant defenses, inflammation, and the AMPK pathway. Noteworthy, anthocyanins could balance abnormalities in ROS production, respiration, and mitochondrial fragmentation in cells exposed to toxicants or oxidizing agents.
- Biochemical and anatomical basis of brain dysfunctions caused by cytochrome b5 reductase deficiency or dysregulationPublication . Samhan-Arias, Alejandro; López-Sánchez, Carmen; Marques-da-Silva, Dorinda; Lagoa, Ricardo; Garcia-Lopez, Virginio; García-Martínez, Virginio; Gutierrez-Merino, Carlos
- 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.
- Comparison of cytochrome c with conventional biocatalysts in the degradation of environmental toxicantsPublication . Lagoa, Ricardo; Lopes, João M.; Rodrigues, J. Rui; Marques-da-Silva, DorindaPeroxidases and laccases are amongst the most attractive enzymes for the degradation of concerning pollutants like polycyclic aromatic hydrocarbons (PAHs) and organic dyes. In spite of the availability of high activity enzymes, their applicability is hindered by specificity and stability limitations in real environmental conditions, so more suitable biocatalysts are demanded. Cytochrome c (Cc) is best known as a protein electron carrier at mitochondria, but it also displays (pseudo-)peroxidase activity. In this work, we aimed to evaluate the potential of Cc as biocatalyst of PAHs’ and azo dyes’ degradation and compare it with two more conventional enzymes - plant peroxidases and fungi laccases. The studies were carried out with Cc from horse heart, horseradish peroxidase (HRP) and laccase from Trametes versicolor. The enzymes were tested with two major PAHs, anthracene and benzo[a]pyrene (BaP), and with methyl orange (MO) as a model azo dye. The enzyme-catalyzed oxidation of PAHs was determined by HPLC, and MO decolorization was followed in spectrophotometric kinetic assays. Several degradation studies were performed to assess the catalytic capacity at different pH and the effect of the redox mediator ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)). Peroxidase reactions of HRP and Cc were initiated with 100 μM H2O2 (in media containing 100 μM DTPA as metal chelator). In pH 5 acetate buffer, the specific ABTS-oxidizing activity of Cc was much lower than that of laccase and HRP. However, these two enzymes lost almost all activity at pH 7, while Cc exhibited catalytic activity even at pH 8 (phosphate buffer). Decolorization assays showed laccase alone to be a weak catalyst of MO degradation, although addition of ABTS to the reaction media greatly accelerated the transformation. On the contrary, both HRP and Cc directly catalyzed MO decolorization, including at neutral pH, and the redox mediator offered no advantage. As for the PAHs, HRP and laccase catalysis benefited from the presence of ABTS in the media, but again Cc oxidized anthracene and BaP directly. Indeed, 24h incubation of BaP (1 mg/L) with Cc (0.1 mg/mL) resulted in the transformation of 70±4% of the PAH and generation of major reaction products different of the BaP quinones produced by laccase- and HRP-ABTS systems. This work disclosed catalytic properties of Cc different from laccase and HRP that are relevant for the design of new enzymatic remediation processes.
- Comparison of Laccases and Hemeproteins Systems in Bioremediation of Organic PollutantsPublication . Lopes, João M.; Marques-da-Silva, Dorinda; Videira, Paula Q.; Lagoa, Ricardo L.Aim: Laccases and peroxidases have attracted great interest for industrial and environmental applications. These enzymes have a broad substrate range and a robust oxidizing ability. Moreover, using mediators or co-oxidants makes it possible to increase their catalytic activity and extend their substrate scope to more resistant chemical structures. Background: Fungal laccases and ligninolytic peroxidases, mainly lignin and manganese peroxidases, are the privileged oxidoreductases for bioremediation processes. Nonetheless, an increasing diversity of laccases and peroxidase-type enzymes has been proposed for environmental technologies. Objective: This article aims to provide an overview of these enzymes and compare their applicability in the degradation of organic pollutants. Methods: Fundamental properties of the proteins are covered and applications towards polycyclic aromatic hydrocarbons (PAHs) and pesticides are specially focused. Results: Laccases are multicopper oxidases initially studied for applications in the pulp and paper in-dustry but able to oxidize a variety of environmentally concerning compounds. Relying on O2, laccases do not require peroxides nor auxiliary agents, like Mn2+, although suitable redox mediators are needed to attack the more recalcitrant pollutants (e.g., PAHs). True and pseudo-peroxidases use a stronger oxi-dant (H2O2) and the redox chemistry at the heme site generates high potential species that allow the oxidation of dyes and some pesticides. Conclusion: Lately, research efforts have been directed to enzyme discovery, testing with micropollu-tants, and improving biocatalysts’ stability by immobilization and protein engineering. Further under-standing of the effects of natural media components and solvents on the enzymes might lead to compet-itive enzymatic treatments of highly toxic media.
- An Electronic Questionnaire for Liver Assessment in Congenital Disorders of Glycosylation (LeQCDG): A Patient-Centered StudyPublication . Marques-da-Silva, Dorinda; Francisco, R.; Ferreira, V. dos Reis; Forbat, L.; Lagoa, Ricardo; Videira, P. A.; Witters, P.; Jaeken, J.; Cassiman, D.Congenital disorders of glycosylation (CDG) are ultra-rare diseases showing a great phenotypic diversity ranging from mono-to multi-organ/multisystem involvement. Liver involvement, mostly nonprogressive, is often reported in CDG patients. The main objectives of this work were (1) to better understand liver involvement in CDG patients through a liver electronic questionnaire targeting CDG families (LeQCDG) and (2) to compare responses from LeQCDG participants with literature review regarding the prevalence of liver disease and the occurrence of liver symptoms in CDG patients. The network of patient advocacy groups, families and professionals (CDG & Allies – PPAIN) developed the LeQCDG by adapting validated published questionnaires. The LeQCDG was approved by an ethics committee, and the recruitment of patients and caregivers proceeded through social media platforms. Participants were asked to report past or present liver-related symptoms (e.g. hepatomegaly, liver fibrosis and cirrhosis) and laboratory results (e.g. biochemical and/ or radiological). From 11 December 2016 to 22 January 2017, 155 questionnaires were completed. Liver disease was present in 29.9% of CDG patients. Main symptoms reported included hepatomegaly, increased levels of serum transaminases, fibrosis, steatosis and cirrhosis. The data obtained in this online survey confirm findings from a recent literature review of 25 years of published evidence (r ¼ 0.927, P ¼ 0.02). Our questionnaire collected large amounts of meaningful, clinical and patient-oriented data in a short period of time without geographic limitations. Internet-based approaches are especially relevant in the context of ultra-rare diseases such as CDG.
- Humic acid aggregates with laccase and decreases the performance of the enzyme catalytic systems through various mechanismsPublication . Lopes, João; Marques-da-Silva, Dorinda; Peralta, Cláudia; Rodrigues, Joaquim Rui; Vaz, Daniela; Lagoa, RicardoLaccases are among the best-rated enzymes for industrial and environmental applications, yet their use in bioremediation is limited by interference from environmental components like humic acid (HA). This study evaluated HA impact on the oxidation of 2,2 ′-azino-bis-(3-ethylbenzothiazoline-6-sulphonate (ABTS) and two model pollutants — anthracene and methyl orange — by laccase( mediator) systems. HA consistently diminished conversion rates, with EC50 values between 5 and 51 mg/L suggesting diverse inhibitory mechanisms. We investigated potential mechanisms including substrate sequestration, radical quenching, and chelation of laccase coppers by HA. Incubations with free and immobilized HA showed that adsorption can impede anthracene degradation, at least at high concentrations, but not methyl orange. Using chemically generated ABTS radical and azide-blocked enzyme, it was demonstrated that HA scavenges free radicals produced by laccase, though this alone did not fully explain the observed interference with catalysis. Further assays with metal chelator and added copper or calcium ruled out HA binding to the laccase metal centers. Instead, data from molecular docking, f luorescence, light scattering, and microscopy revealed that HA forms micrometer-scale aggregates with laccase that encapsulate the enzyme. This newly identified mechanism likely applies broadly to laccase-based systems and must be considered in applications involving aqueous media containing humic substances.
- Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenolsPublication . Lagoa, Ricardo; Marques-da-Silva, Dorinda; Diniz, Mário; Daglia, Maria; Bishayee, AnupamHuman exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been sug-gested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by poly- phenols. Plant-derived polyphenols, such as epigallocatechin-gallate, resveratrol, curcumin and anthocyanins reduce the incidence of cancer and can be useful nutraceuticals for alleviating the detrimental outcomes of harmful pollutants. However, development of therapies based on polyphenol administration requires further studies to validate the biological efficacy, identifying effective doses, mode of action and new delivery forms. Innovative microphysiological testing models are presented and specific proposals for future trials are given. Merging the current knowledge of multifactorial actions of specific polyphenols and chief environmental toxi- cants, this work aims to potentiate the delivery of phytochemical-based protective treatments to individuals at high-risk due to environmental exposure.