LSRE-LCM - Artigos em Revistas Nacionais e de Circulação Internacional
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- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Publication . Samhan-Arias, Alejandro K.; Poejo, Joana; Marques-da-Silva, Dorinda; Martínez-Costa, Oscar H.; Gutierrez-Merino, CarlosLipid membrane nanodomains or lipid rafts are 10–200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.
- Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations*Publication . Onoufriadis, A.; Cabezas, A.; Ng, J. C. F.; Canales, J.; Costas, M. J.; Ribeiro, J. M.; Rodrigues, J. R.; McAleer, M. A.; Castelo‐Soccio, L.; Simpson, M. A.; Fraternali, F.; Irvine, A. D.; Cameselle, J. C.; McGrath, J. A.Background: Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven. A better understanding the aetiology of loose anagen hair may improve prevention and treatment strategies. Objectives: To identify a possible genetic basis of loose anagen hair using next-generation DNA sequencing and functional analysis of variants identified. Methods: In this case study, whole-exome sequencing analysis of a pedigree with one affected individual with features of loose anagen hair was performed. Results: The patient was found to be compound heterozygous for two single-nucleotide substitutions in TKFC resulting in the following missense mutations: c.574G> C (p.Gly192Arg) and c.682C> T (p.Arg228Trp). Structural analysis of human TKFC showed that both mutations are located near the active site cavity. Kinetic assays of recombinant proteins bearing either of these amino acid substitutions showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity reduced to just 10% of wildtype catalytic activity. Conclusions: TKFC missense mutations may predispose to the development of loose anagen hairs. Identification of this new biochemical pathobiology expands the metabolic and genetic basis of hypotrichosis.
- Cardiolipin Membranes Promote Cytochrome c Transformation of Polycyclic Aromatic Hydrocarbons and Their In Vivo MetabolitesPublication . Lopes, João; Marques-da-Silva, Dorinda; Videira, Paula A.; Samhan-Arias, Alejandro K.; Lagoa, RicardoThe catalytic properties of cytochrome c (Cc) have captured great interest in respect to mitochondrial physiology and apoptosis, and hold potential for novel enzymatic bioremediation systems. Nevertheless, its contribution to the metabolism of environmental toxicants remains unstudied. Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with impactful diseases, and animal models have unveiled concerning signs of PAHs’ toxicity to mitochondria. In this work, a series of eight PAHs with ionization potentials between 7.2 and 8.1 eV were used to challenge the catalytic ability of Cc and to evaluate the effect of vesicles containing cardiolipin mimicking mitochondrial membranes activating the peroxidase activity of Cc. With moderate levels of H2O2 and at pH 7.0, Cc catalyzed the oxidation of toxic PAHs, such as benzo[a]pyrene, anthracene, and benzo[a]anthracene, and the cardiolipin-containing membranes clearly increased the PAH conversions. Our results also demonstrate for the first time that Cc and Cc–cardiolipin complexes efficiently transformed the PAH metabolites 2-hydroxynaphthalene and 1-hydroxypyrene. In comparison to horseradish peroxidase, Cc was shown to reach more potent oxidizing states and react with PAHs with ionization potentials up to 7.70 eV, including pyrene and acenaphthene. Spectral assays indicated that anthracene binds to Cc, and docking simulations proposed possible binding sites positioning anthracene for oxidation. The results give support to the participation of Cc in the metabolism of PAHs, especially in mitochondria, and encourage further investigation of the molecular interaction between PAHs and Cc.
- 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.
- Enhancing human gut health: Global innovations in dysbiosis managementPublication . Lagoa, Ricardo; Reda El Boukhari; Maima Matin; Latifa Bouissane; Michał Ławiński; Oleh Lushchak; Rajeev K. Singla; Michel‐Edwar Mickael; Jordi Mayneris‐Perxachs; Maria Eleni Grafakou; Shuhua Xu; Bowen Liu; Jiayi Guan; Andrzej Półtorak; Arkadiusz Szpicer; Agnieszka Wierzbicka; Nikolay T. Tzvetkov; Maciej Banach; Jarosław Olav Horbańczuk; Artur Jóźwik; Marco Cascella; Bairong Shen; Vasil Radoslavov Pirgozliev; Dongdong Wang; Olena Litvinova; Olga Adamska; Agnieszka Kamińska; Marcin Łapiński; Artur Stolarczyk; Ioana Berindan‐Neagoe; Luigi Milella; Andy Wai Kan Yeung; Prashanth Suravajhala; Anupam Bishayee; Ronan Lordan; Laszlo Barna Iantovics; Monika Michalczuk; Jivko Stoyanov; A. Douglas Kinghorn; Banaz Jalil; Wolfram Weckwerth; Bey Hing Goh; Meng‐Yao Li; Gyaneshwer Chaubey; Gian Luigi Russo; Sara Frazzini; Luciana Rossi; Maurizio Battino; Wei Jia; Qi Su; Xiaoqiang Ma; Judith M. Rollinger; Simon K.‐M. R. Rittmann; Helen Sheridan; John J. Walsh; Gérard Lizard; Tomasz M. Karpiński; Ana Sanches Silva; Jakub Piwowarski; Liwei Xie; Tai‐Ping Fan; Francesca Giampieri; Adil El Midaoui; Ka‐Hing Wong; Ren‐You Gan; Ahmed Fatimi; Atanas G. AtanasovTo the Editor, The gut microbiota represents all the microorganisms, mainly bacteria, that coexist in the digestive system and are mostly beneficial. In adulthood, the gut microbiota composition, which varies from person to person, generally remains stable with a particular density in each part of the digestive system. However, a microbial community imbalance within the body, particularly in the gut, is sometimes observed, causing dysbiosis characterized by reduced microbial diversity, loss of beneficial bacteria, and increased pathogenic microorganisms. [...]
- Food literacy among Portuguese adults with skeletal dysplasia: insights from a cross-sectional studyPublication . Guerra, Beatriz; Alves, Inês; Costa, Ricardo; Dias, Valter; Jesus, Pedro; Pereira, Cidália D.; Soliman, NeveenPurpose Skeletal dysplasias are a heterogeneous group of 771 rare diagnoses, that present short stature as a common feature. Despite the importance of nutrition in health management, food literacy in this population remains largely unexplored. This study aimed to assess the level of food literacy among Portuguese adults with skeletal dysplasia. Methods A cross-sectional observational study was conducted among adults (> 18 years) with skeletal dysplasia (n = 43, 30 female). Data were collected through an online questionnaire comprising two sections: sociodemographic and clinical information and the Portuguese version of the Food Literacy Scale (FLS). The FLS covers three dimensions: literacy about the nutritional composition of food, literacy about labelling and food choices, and literacy about healthy eating practices. Food literacy scores were calculated as percentage indices. Descriptive statistics with 95% confidence intervals and subgroup comparison by sex and age were performed. Results Mean overall food literacy score was 60.8% (CI 95%: 54.7–66.9). Among the three dimensions, the highest mean score was observed for healthy eating practices, 62.0% (CI 95%: 56.4–67.6), and the lowest for labelling and food choices, 59.0% (CI 95%: 51.1–66.9). No statistically significant differences were found in overall food literacy or in any of its dimensions according to sex or age. Participants reported greater difficulty with recommended protein amounts, interpreting and using food labels, adhering to the Mediterranean diet, and recommended portion sizes. Conclusions Adults with skeletal dysplasia in Portugal showed modest food literacy scores, mainly in domains related to food labelling and food choices. Tailored nutrition education strategies and more easily accessible food-related guidance may help address the specific literacy gaps identified in this population.
- Health-promoting and medicinal properties of Zingiberaceae family plants: A minireview with a special focus on galangal, turmeric, cardamom, and gingerPublication . Lagoa, Ricardo; Maima Matin; Rajeev K. Singla; Artur Jóźwik; Jarosław Olav Horbańczuk; Natalia Ksepka; Kamil Wysocki; Thadiyan Parambil Ijinu; Neenthamadathil Mohandas Krishnakumar; Sreejith Pongillyathundiyil Sasidharan; Ifeoma C. Ezenyi; John Igoli; Fabio Fusi; Sara Frazzini; Luciana Rossi; Michel-Edwar Mickael; Abhishek Joshi; Olga Adamska; Artur Stolarczyk; Esra Capanoglu; Deniz Gunal-Koroglu; Shi-Hui Cheng; Omar M. Atrooz; Kiran Kharat; Ibrahim M. Abu-Reidah; Neeraj Rani; Atul Kabra; Ruchika Kabra; Dama Sreedhar Preethidan; Prathyusha Surendran; Emad Mohamed Abdallah; Seetha Harilal; Rajesh Kumar; Syed Abidullah; Hemanth Kumar Boyina; Vimal Arora; Prasanna Srinivasan Ramalingam; Sujatha Elangovan; Sivakumar Arumugam; Tanveer Alam; Edlira Aruci; Elena González-Burgos; Isabel Ureña-Vacas; Visitación López-Miranda; Esperanza Herradón; Rupesh Kumar Gautam; Rajat Goyal; Shah Alam Khan; Logesh Rajan; Joel Ojogbane Onoja; Sharad Vats; Akinleye Akinrinde; Smith B. Babiaka; Conrad V. Simoben; Doris E. Enow; Kennedy O. Abuga; Priti Talwar; Palaniyandi Ravanan; Reda El Boukhari; Ahmed Fatimi; Fabien Schultz; Ren-You Gan; Jean Noël Nyemb; Gaetan Bayiha Ba Njock; Constant Anatole Pieme; Goh Bey Hing; Nikolay T. Tzvetkov; Farhan Bin Matin; Antonello Santini; Jaya Arora; Aswathy Chankaramkandath Vasu; Suraj Kadunganattil; Abeer Essam Noman; Luay M Alsubhi; Indra Lasmana Tarigan; Shafaat Yar Khan; Ali Zarrabi; Hefa Mangzira Kemung; Kavitha Raj Varadaraju; Tomasz M. Karpiński; Md. Mohaiminul Islam; Shaikh Jamal Uddin; Carmela Fimognari; Hari Prasad Devkota; Ivana Carev; Dongdong Wang; Kenneth Anchang Yongabi; Luther Bob Mbeku; Sohini Chakraborty; Sourav S. Patnaik; Shanmugam Thangapandiyan; Bikash Baral; Siva Sai Chandragiri; Eliana B. Souto; Gérard Lizard; Fatiha Brahmi; Farid Khallouki; Adil El Midaoui; Ronan Lordan; Anupam Bishayee; Meng-Yao Li; Monika Szymańska-Czerwińska; Krzysztof Niemczuk; Manik Chandra Shill; Michał Ławiński; Oleh Lushchak; Iwona Wojtasik-Kalinowska; Agnieszka Wierzbicka; Thomas Jakschitz; Mathew Dan; Imen Ghzaiel; Leila Rezig; Anne Vejux; Amira Zarrouk; Ahmad Ali; Andy Wai Kan Yeung; Günther K. Bonn; Bairong Shen; Atanas G. AtanasovThe Zingiberaceae family, including among others, galangal (Alpinia galanga), turmeric (Curcuma longa), cardamom (Elettaria cardamomum), and ginger (Zingiber officinale), has been widely used in traditional medicine and culinary practices worldwide due to its diverse health-promoting properties. This mini-review aims to provide a concise overview of Zingiberaceae species’ medicinal potential and identify key areas for further research to facilitate their integration into modern medicine. Herein we summarize the existing research on the pharmacological activities of these species, with a focus on their antioxidant, anti-inflammatory, antimicrobial, anticancer, cardiovascular, digestive, and metabolic effects. Aside from the reported biological effects of traditional formulations and phytopharmaceutical preparations, emphasis is given to the primary bioactive compounds identified in these plants including diverse phenolics, terpenes, and various other secondary metabolites. Mechanisms contributing to therapeutic benefits. Moreover, highlighted is the promise of these plants for future development of drugs and nutraceuticals despite current challenges, particularly bioavailability issues and the need for more clinical studies.
- 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.
- Influence of commensal bacteria on the proteolytic and antigenic profiles of INFOGEST-like digested wheat gliadinPublication . Pereira-Costa, Flávio; Domingues, Vanessa S.; Roque, Ana; Almeida, Zaida L.; Cruz, Pedro F.; Cordeiro, Rachel; Trindade, Daniela; Moura, Carla; Melo, Joana B.; Pereira, Sónia G.; Vaz, Daniela C.Introduction: Celiac disease (CeD) is a chronic autoimmune enteropathy developed by genetically predisposed individuals when exposed to gluten. Gluten gliadins, along with gut microbiota, may influence CeD onset and progression through mechanisms that remain unclear. Methods: Gliadin-degrading bacterial isolates obtained from CeD patients, and their 1st-degree relatives’ stool and blood were identified (Bacillus tropicus, Enterococcus faecalis, Micrococcus sp., Cronobacter sakazakii, Pseudomonas aeruginosa, and Serratia marcescens) and used in an INFOGEST-like protocol to simulate gliadin digestion after 4 h (digested gliadin, d-gliadin). The d-gliadin digesta were analyzed by fast protein liquid chromatography (FPLC), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), fluorescence spectroscopy, and polyclonal and monoclonal (R5 and G12) enzyme-linked immunosorbent assays (ELISA). Results and discussion: In the absence of the bacterial isolates, gliadin is poorly digested and self-assembles within 1 day into intermediate and large protein oligomers/aggregates, enriched in β-sheet structure (FTIR amide I band between 1,600 and 1,700 cm−1) and able to bind thioflavin T and Congo red. Conversely, in the presence of the bacterial isolates, gliadin is further digested, leading to an increase in protein fragments. After 4 h, the P. aeruginosa, C. sakazakii, and B. tropicus d-gliadin digesta presented a mixture of d-gliadin peptides and aggregates that showed higher antigenicity (associated with the exposure of the 5-amino acid QQPFP and 6-amino acid QPQLPY epitopes, present in the 25-mer and 33-mer, respectively) than control digestions (without bacteria), while E. faecalis led to lower antigenicity. In turn, within 24 h of incubation, all bacterial isolates led to the formation of undigested material with lower antigenicity, either due to fewer 33-mers and 25-mers in solution, or to fragment aggregation into amorphous material, not exposing antigenic sequences. Hence, intestinal flora may enhance or diminish the antigenicity of gliadin, thereby modulating the immunogenic response to gliadin/gluten.
- Low-Protein Diets, Malnutrition, and Bone Metabolism in Chronic Kidney DiseasePublication . Pereira, Cidália D.; Guimarães, Carla; Ribeiro, Vânia S.; Vaz, Daniela C.; Martins, Maria JoãoChronic kidney disease (CKD) has a high prevalence worldwide, with increasing incidence in low- and middle-income countries, and is associated with high morbidity and mortality, particularly from cardiovascular disease. Protein-restricted diets are one of the most widely used non-pharmacological approaches to slow the progression of CKD and prevent associated metabolic abnormalities. However, some concerns have been raised about the long-term safety of these diets, particularly with regard to patients’ nutritional status and bone and mineral disorders. Therefore, the aim of this article is to review the most recent scientific evidence on the relevance of using protein-restricted diets (with or without keto-analogue supplementation) and, in particular, their relationships with malnutrition and mineral and bone disorders in people with CKD without kidney replacement therapies. Although protein-restricted diets, especially when supplemented with keto-analogues and highly personalized and monitored, do not appear to be associated with malnutrition, research on their effects on bone and mineral disorders is scarce, deserving further investigation.