Anti-tumoral effects of an Iron and a Cobalt Scorpionate

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2020The World Health Organization (WHO) reports that cancer is the second leading cause of death globally and there have been several research attempts focused on finding more efficient treatments to deal with this disease, including the area of metal-based drugs for cancer chemotherapy. New transition metal complexes are being continuously designed and tested as anticancer agents, namely complexes obtained with the so called scorpionate ligands, which have provided significant contributions in the fields of catalysis and bioinorganic chemistry, and have also shown interesting antitumoral properties. This project was focused on the evaluation of the antiproliferative and antimigration effects of two scorpionate metal complexes as a preliminary approach to assess their anti-tumoral properties. An iron scorpionate, FeCl2Tpm (designated as S6), and a cobalt scorpionate, CoTpm2(OH)2 (termed S7) with tris(pyrazolyl)methane-derived ligands (Tpm), were tested in various representative cell lines, HCT116 (colorectal carcinoma), B16 (murine melanoma) and HaCaT (a non-tumoral line of spontaneously transformed skin keratinocytes), to evaluate their cytotoxic potential towards these cells and their capacity to inhibit cell migration, two features that would provide some insights regarding their anti-tumoral effects. The assessment of the cytotoxicity profile of the compounds S6 and S7 was conducted by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reduction assays, after confirmation of the purity of the complexes by HPLC (high-performance liquid chromatography). The evaluation of the effects of these scorpionates on cell migration was performed through scratch assays. Samples of cells exposed to S6 and S7 were also prepared and later submitted to metabolomic analyses, that could possibly identify alterations concerning metabolite levels and their respective metabolic pathways. Results revealed that S6 did not exhibit a significant toxicity towards the HCT116 and HaCaT cell lines under the tested conditions, but displayed the capacity to delay cell migration. S6 also led to an increase of the proliferation and migration of the B16 cell line. By contrast, S7 revealed a higher cytotoxic potential in the cell lines used, as well as the capacity to inhibit cell migration. The results obtained with the tested cell lines suggest that S7 could potentially be used as an anti tumoral agent, since this scorpionate complex revealed visible effects in two cellular processes that are particularly enhanced in tumoral cells (proliferation and migration). Further studies are needed to confirm these findings, which could involve testing their role in cell invasion in order to allow a better understanding of the anti-tumoral effects of these scorpionate complexes

The memory of iron stress in strawberry plants

Research ArticleTo provide information towards optimization of strategies to treat Fe deficiency, experiments were conducted to study the responses of Fe-deficient plants to the resupply of Fe. Strawberry (Fragaria ananassa Duch.) was used as model plant. Bare-root transplants of strawberry (cv. ‘Diamante’) were grown for 42 days in Hoagland's nutrient solutions without Fe (Fe0) and containing 10 mM of Fe as Fe-EDDHA (control, Fe10). For plants under Fe0 the total chlorophyll concentration of young leaves decreased progressively on time, showing the typical symptoms of iron chlorosis. After 35 days the Fe concentration was 6% of that observed for plants growing under Fe10. Half of plants growing under Fe0 were then Fe-resupplied by adding 10 mM of Fe to the Fe0 nutrient solution (FeR). Full Chlorophyll recovery of young leaves took place within 12 days. Root ferric chelate-reductase activity (FCR) and succinic and citric acid concentrations increased in FeR plants. Fe partition revealed that FeR plants expressively accumulated this nutrient in the crown and flowers. This observation can be due to a passive deactivation mechanism of the FCR activity, associated with continuous synthesis of succinic and citric acids at root level, and consequent greater uptake of Fe.info:eu-repo/semantics/publishedVersio

Obesidade no 1º ciclo : desenho e implementação de um programa de intervenção num estudo transversal

A obesidade é, nos dias de hoje, considerada uma doença epidémica sendo que nas crianças e jovens, é uma agravante, na medida em que, o seu crescimento e desenvolvimento será negativamente influenciado. Segundo WHO (2012) a obesidade mais do que duplicou desde 1980, sendo que em 2008, 1,4 biliões de pessoas acima de 20 anos têm excesso de peso, e destas, 200 milhões de homens e 300 milhões de mulheres são obesas. Em 2010 mais de 40 milhões de crianças menores que cinco anos têm excesso de peso. O objetivo do presente estudo é aplicar e verificar se um programa de intervenção de atividade física em crianças contribui para combater o sedentarismo e a obesidade. A amostra é constituída por crianças com idades compreendidas entre os 8 e 10 anos, que frequentam o 1º ciclo de duas escolas do concelho de Braga. Fazem parte desta amostra 200 crianças de ambos os sexos. O estudo baseia-se na aplicação de um programa de intervenção de atividade física estruturada e com o aconselhamento aos encarregados de educação sobre hábitos alimentares saudáveis. Este programa será aplicado ao grupo experimental, sendo que o segundo (grupo controlo) não será intervencionado. Pretende-se avaliar antes e depois da intervenção, a atividade física com aplicação de um questionário e a determinação da aptidão física com aplicação do FitnessGram. Pretendemos com este estudo, demonstrar a importância da atividade física estruturada na prevenção da obesidade, considerando o papel fulcral que a escola deve desempenhar e promover nesta epidemia. Neste contexto, professor de educação física, sendo um agente interveniente na formação dos alunos, deve ter um papel relevante nas estratégias e programas que incidam nesta problemática.CIEC - Centro de Investigação em Estudos da Criança, UM (UI 317 da FCT

Challenges for Deriving Hepatocyte-Like Cells from Umbilical Cord Mesenchymal Stem Cells for <em>In Vitro</em> Toxicology Applications

The in vitro toxicology field seeks for reliable human relevant hepatic models for predicting xenobiotics metabolism and for the safety assessment of chemicals and developing drugs. The low availability and rapid loss of the phenotype or low biotransformation activity of primary hepatocytes urged the stem cell differentiation into hepatocyte-like cells (HLCs). Umbilical cord-derived mesenchymal stem cells (UC-MSC), in particular, offer a highly available cell source, with few ethical issues and higher genetic stability. However, the dynamic and complex microenvironment of liver development, including the cell-ECM and cell–cell interactions, pressure gradients (oxygen and nutrients) and growth factor signaling that are critical for the differentiation and maturation of hepatocytes, challenges the progress of in vitro hepatic models. Promising strategies like (i) cytokine and growth factor supplementation mimicking the liver development; (ii) epigenetic modification; and (iii) bioengineering techniques to recreate the liver microphysiological environment are gaining increasing importance for the development of relevant in vitro liver models to address the need for higher predictivity and cost efficiency. In this context, this chapter reviews the existing knowledge and recent advances on the approaches for deriving HLCs from UC-MSC and their application for in vitro toxicology

Design of innovative clothing for pressure injury prevention: end-user evaluation in a mixed-methods study

The global relevance of pressure injury (PI) prevention technologies arise from their impact on the quality of life of people with limited mobility and the costs associated with treating these preventable injuries. The purpose of this mixed methods study is to evaluate the design of a prototype integrating Smart Health Textiles for PI prevention based on feedback from specialist nurses who care for individuals who are prone to or have PIs. This is a mixed methods study. A structured questionnaire was conducted as part of an evaluation of a prototype garment for the prevention of PIs. This questionnaire was applied during the evaluation of the prototype and afterwards focus group discussions were held with experts. Descriptive statistics techniques were used to analyze the data and thematic and integrated content analysis was conducted through concomitant triangulation. Nineteen nurses took part, aged 30 to 39 years (52.6%) and with 12.31 ± 8.96 years of experience. Participants showed that the prototype required more manipulation and physical effort, which interfered its usefulness, in addition to presenting difficulties with the openings and the material of the closure system, which interfered with the ease of use and learning. Overall satisfaction with the product was moderate, with some areas for improvement found, such as satisfaction, recommendations to colleagues, and pleasantness of use. It is concluded that areas for improvement have been found in all dimensions, including in the design of openings and the choice of materials. These findings supply significant insights for improving clothing to meet the needs of healthcare professionals and patients.The 4NoPressure project was co-financed by the Operational Program for Competitiveness and Internationalization (COMPETE 2020) under the PORTUGAL 2020 Partnership Agreement, with support from the European Regional Development Fund (ERDF), reference number POCI-01-0247- FEDER-039869

Cultura Material, Cultura Científica: Património Industrial para o Futuro

IH4Future (PTDC/FIS-aQM/30292/2017Material, Culture, Scientific Culture: Industrial Heritage for the Futurepublishersversionpublishe

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by 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).info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost