377 research outputs found

    Benefits of pulse consumption on metabolism and health: a systematic review of randomized controlled trials

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    Pulses are nutrient-dense foods that have for a long time been empirically known to have beneficial effects in human health. In the last decade, several studies have gathered evidence of the metabolic benefits of pulse intake. However, it remains unclear at what amounts these effects may be attained. This study aimed to systematically review the scientific outputs of the last two decades regarding health benefits of pulse consumption and the amounts necessary for positive outcomes to be achieved. A PubMed search including keywords [(“dietary pulses”, “pulses”, “legumes”, “grain legumes”, “bean”, “chickpea”, “pea”, “lentil”, “cowpea”, “faba bean”, “lupin”) and (“inflammation”, “inflammatory markers”, “C-reactive protein”, “blood lipids”, “cholesterol”, “cardiometabolic health”, “cardiovascular disease”, “diabetes”, “glycaemia”, “insulin”, “HOMA-IR”, “body weight”, “body fat”, “obesity”, “overweight”, “metabolome”, “metabolic profile”, “metabolomics”, “biomarkers”, “microbiome”, “microbiota”, “gut”)] was performed. Only English written papers referring to human dietary interventions, longer than one day, focusing on whole pulses intake, were included. Most of the twenty eligible publications reported improvements in blood lipid profile, blood pressure, inflammation biomarkers, as well as, in body composition, resulting from pulse daily amounts of 150 g (minimum-maximum: 54-360 g/day; cooked). Concerns regarding methodological approaches are evident and the biochemical mechanisms underlying such effects require further investigation.N/

    Plantas na Medicina Tradicional de Cabo Verde

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    Neste trabalho apresenta-se o resultado de uma pesquisa pormenorizada sobre as plantas medicinais e aromáticas que se desenvolvem no arquipélago de Cabo Verde, apoiada na bibliografia actualmente disponível sobre o assunto. Indicam-se as famílias, nomes científicos e vernáculos, e distribuição no arquipélago, bem como os respectivos princípios activos, propriedades terapêuticas e as partes das plantas utilizadas na medicina popular tradicional. Foram identificados 157 táxones, pertencentes a 68 famílias, com interesse medicinal e aromático conhecido. Estas plantas são maioritariamente alóctones, introduzidas, subespontâneas, naturalizadas ou cultivadas. Cabo Verde, devido a diversos condicionalismos, nomeadamente, situação geográfica, humidade e altitude das diferentes ilhas, é rico em espécies endémicas com interesse medicinal mas cujas potencialidades são ainda pouco conhecidas. Neste estudo foram localizados 27 táxones com interesse medicinal, distribuídos por 21 famílias. Conclui-se que é necessário proceder a mais estudos sobre os endemismos, de forma a melhor avaliar o seu potencial interesse como plantas medicinais e aromáticas. No âmbito da medicina tradicional, urge realizar os seguintes estudos: (1) etnobotânicos; (2) composição química dos vários órgãos das plantas referidas com interesse, sobretudo, para combater as patologias para as quais ainda não foi encontrada resolução satisfatória; (3) distribuição geográfica e habitat precisos das plantas; (4) avaliação e experimentação do seu possível cultivo, de forma a evitar a extinção ou erosão genética motivada pela sua colheita excessiva; (5) propriedades terapêuticas; (6) toxicológicos, a fim de se conhecer os doseamentos eficientes e seguros e as respectivas contra-indicações

    Deep sequencing analysis reveals distinctive non-coding RNAs when comparing tumor multidrug-resistant cells and extracellular vesicles with drug-sensitive counterparts

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    This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was partially financed by the FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work is also a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT). The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of DS (SFRH/BD/98054/2013).Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-eux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, di erent studies have shown that extracellular vesicles (EVs) participate in the communication between MDR cells and drug-sensitive counterparts, promoting dissemination of the MDR phenotype. In the present work, we aimed to identify RNA species present in MDR cells and in EVs released by those cells, which may be associated with the MDR phenotype. The RNA content from two pairs (leukemia and lung cancer) of MDR (P-gp overexpressing) cells and their drug-sensitive counterparts, as well as from their EVs, was analyzed by deep sequencing. Our results showed distinctive transcripts for MDR cells and their EVs, when compared with their drug-sensitive counterparts. Remarkably, two pseudogenes (a novel pseudogene and RNA 5.8S ribosomal pseudogene 2) were found to be increased in EVs released by MDR cells in both leukemia and lung cancer models. Moreover, six miRs (miR-204-5p, miR-139-5p, miR-29c-5p, miR-551b-3p, miR-29b-2-5p, and miR-204-3p) exhibited altered levels in lung cancer MDR cells and their EVs. This study provides insights into the contribution of EVs to MDR.publishersversionpublishe

    Compounds from wild mushrooms with antitumor potential

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    For thousands of years medicine and natural products have been closely linked through the use of traditional medicines and natural poisons. Mushrooms have an established history of use in traditional oriental medicine, where most medicinal mushroom preparations are regarded as a tonic, that is, they have beneficial health effects without known negative side-effects and can be moderately used on a regular basis without harm. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of compounds which are modulators of tumour cell growth. Furthermore, they may have potential as functional foods and sources of novel molecules. We will review the compounds with antitumor potential identified so far in mushrooms, including low-molecular-weight (LMW, e.g. quinones, cerebrosides, isoflavones, catechols, amines, triacylglycerols, sesquiterpenes, steroids, organic germanium and selenium) and high-molecular-weight compounds (HMW, e.g. homo and heteroglucans, glycans, glycoproteins, glycopeptides, proteoglycans, proteins and RNA-protein complexes)

    Clitocybe alexandri extract induces cell cycle arrest and apoptosis in a lung cancer cell line: identification of phenolic acids with cytotoxic potential

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    Mushrooms are a possible rich source of biologically active compounds with potential for drug discovery. The aim of this work was to gain further insight into the citotoxicity mechanism of action of Clitocybe alexandri ethanolic extract against a lung cancer cell line (NCI-H460 cells). The effects on cell cycle profile and levels of apoptosis were evaluated by flow cytometry, and the effect on the expression levels of proteins related to cellular apoptosis was also investigated by Western blot. The extract was characterized regarding its phenolic composition by HPLC-DAD, and the identified compounds were studied regarding their growth inhibitory activity, by sulforhodamine B (SRB) assay. The effect of individual or combined compounds on viable cell number was also evaluated using the Trypan blue exclusion assay. It was observed that the Clitocybe alexandri extract induced an S-phase cell cycle arrest and increased the percentage of apoptotic cells. In addition, treatment with the GI50 concentration (concentration that was able to cause 50% of cell growth inhibition; 24.8 µg/ml) for 48h caused an increase in the levels of wt p53, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). The main components identified in this extract were protocatechuic, p-hydroxybenzoic and cinnamic acids. Cinnamic acid was found to be the most potent compound regarding cell growth inhibition. Nevertheless, it was verified that the concomitant use of the individual compounds provided the strongest decrease in viable cell number. Overall, we found evidence for alterations in cell cycle and apoptosis, involving p53 and caspase-3. Furthermore, our data suggests that the phenolic acids identified in the extract are at least partially responsible for the cytotoxicity induced by this mushroom extract

    Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective

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    Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR) cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic structure for mouse P-gp was obtained. However, for decades the design of new P-gp inhibitors employed mainly ligand-based approaches (SAR, QSAR, 3D-QSAR and phar macophore studies), and structure-based studies used P-gp homology models. However, some of those results are still the pillars used as a starting point for the design of potential P-gp inhibitors. Here, pharmacophore mapping, (Q)SAR, 3D-QSAR and homology modeling, for the discovery of P-gp inhibitors are reviewed. The importance of these methods for understanding mechanisms of drug resistance at a molecular level, and design P-gp inhibitors drug candidates are discussed. The examples mentioned in the review could provide insights into the wide range of possibilities of using CADD methodologies for the discovery of efficient P-gp inhibitors.info:eu-repo/semantics/publishedVersio

    Multidrug resistance reversal effects of aminated thioxanthones and interaction with cytochrome P450 3A4

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    Aminated thioxanthones have recently been described as dual-acting agents: growth inhibitors of leukemia cell lines and P-glycoprotein (P-gp) inhibitors. To evaluate the selectivity profile of thioxanthones as inhibitors of multidrug resistance (MDR), their interaction with other ABC transporters, which were found to have a strong correlation with multidrug resistance, such as multidrug resistant proteins 1 (MRP1), 2 (MRP2) and 3 (MRP3) and breast cancer resistance protein (BCRP) was also evaluated. The interaction of thioxanthones with cytochrome P450 3A4 (CYP3A4) together with the prediction of their binding conformations and metabolism sites was also investigated. Methods. The UIC2 monoclonal antibody-labelling assay was performed using P-gp overexpressing leukemia cells, K562Dox, incubated with eight thioxanthonic derivatives, in order to confirm their P-gp inhibitory activity. A colorimetric-based ATPase assay using membrane vesicles from mammalian cells overexpressing a selected human ABC transporter protein (P-gp, MRP1, MRP2, MRP3, or BCRP) was performed. To verify if some of the thioxanthonic derivatives were substrates or inhibitors of CYP3A4, a luciferin-based luminescence assay was performed. Finally, the in silico prediction of the most probable metabolism sites and docking studies of thioxanthones on CYP3A4 binding site were investigated. Results. Thioxanthones interacted not only with P-gp but also with MRP and BCRP transporters. These compounds also interfere with CYP3A4 activity in vitro, in accordance with the in silico prediction. Conclusion. Thioxanthonic derivatives are multi-target compounds. A better characterization of the interactions of these compounds with classical resistance mechanisms may possibly identify improved treatment applications.info:eu-repo/semantics/publishedVersio

    Caracterização fenólica e avaliação da atividade antiproliferativa de Fistulina hepatica e Suillus collinitus em linhas celulares tumorais humanas

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    Neste trabalho, avaliou-se a atividade antiproliferativa de extratos metanólicos, etanólicos e em água fervente de Fistulina hepatica e Suillus collinitus, dois cogumelos comestíveis do Nordeste de Portugal, em linhas celulares tumorais humanas. Determinaram-se ainda, cromatograficamente, os ácidos fenólicos presentes nos extratos metanólicos. Ao contrário dos extratos de Fistulina hepatica que não revelaram nenhuma atividade à máxima concentração testada (400 μg/mL), o extrato metanólico de Suillus collinitus foi bastante potente, particularmente em células MCF-7 (GI50 25,2±0,2 µg/mL), induzindo alterações no seu ciclo celular, aparentemente por um efeito mediado pela p53, e aumentando a percentagem de células apoptóticas
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