36 research outputs found

    Phenotypic Effects of Wild-Type and Mutant SOD1 Expression in N9 Murine Microglia at Steady State, Inflammatory and Immunomodulatory Conditions

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    Accumulation of mutated superoxide dismutase 1 (mSOD1) in amyotrophic lateral sclerosis (ALS) involves injury to motor neurons (MNs), activation of glial cells and immune unbalance. However, neuroinflammation, besides its detrimental effects, also plays beneficial roles in ALS pathophysiology. Therefore, the targeting of microglia to modulate the release of inflammatory neurotoxic mediators and their exosomal dissemination, while strengthening cell neuroprotective properties, has gained growing interest. We used the N9 microglia cell line to identify phenotype diversity upon the overexpression of wild-type (WT; hSOD1WT) and mutated G93A (hSOD1G93A) protein. To investigate how each transduced cell respond to an inflammatory stimulus, N9 microglia were treated with lipopolysaccharide (LPS). Glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS), known to exert neuroprotective properties, were tested for their immunoregulatory properties. Reduced Fizz1, IL-10 and TLR4 mRNAs were observed in both transduced cells. However, in contrast with hSOD1WT-induced decreased of inflammatory markers, microglia transduced with hSOD1G93A showed upregulation of pro-inflammatory (TNF-α/IL-1β/HMGB1/S100B/iNOS) and membrane receptors (MFG-E8/RAGE). Importantly, their derived exosomes were enriched in HMGB1 and SOD1. When inflammatory-associated miRNAs were evaluated, increased miR-146a in cells with overexpressed hSOD1WT was not recapitulated in their exosomes, whereas hSOD1G93A triggered elevated exosomal miR-155/miR-146a, but no changes in cells. LPS stimulus increased M1/M2 associated markers in the naïve microglia, including MFG-E8, miR-155 and miR-146a, whose expression was decreased in both hSOD1WT and hSOD1G93A cells treated with LPS. Treatment with GUDCA or VS led to a decrease of TNF-α, IL-1β, HMGB1, S100B and miR-155 in hSOD1G93A microglia. Only GUDCA was able to increase cellular IL-10, RAGE and TLR4, together with miR-21, while decreased exosomal miR-155 cargo. Conversely, VS reduced MMP-2/MMP-9 activation, as well as upregulated MFG-E8 and miR-146a, while producing miR-21 shuttling into exosomes. The current study supports the powerful role of overexpressed hSOD1WT in attenuating M1/M2 activation, and that of hSOD1G93A in switching microglia from the steady state into a reactive phenotype with low responsiveness to stimuli. This work further reveals GUDCA and VS as promising modulators of microglia immune response by eliciting common and compound-specific molecular mechanisms that may promote neuroregeneration

    The impact of IL-10 dynamic modulation on host immune response against visceral leishmaniasis

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    Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sulfate administration (pMT-10). We addressed the role of IL-10 during the initial stages of L. donovani infection by analyzing the parasite burden in the spleen and liver of the infected pMT-10 and WT mice as well as the histopathological alterations upon IL-10 induction. Furthermore, the profile of cytokines expressed by T cells was assessed. Our results demonstrate that an increase in IL-10 production has an impact early but not later after infection. This specific temporal role for IL-10-mediated susceptibility to VL is of interest.Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) and the Fundação para a Ciência e Tecnologia (FCT) (contracts SFRH/BD/120127/2016 to IM, PD/BDE/127830/2016 to CF, SFRH/BD/120371/2016 to AMB, IF/01147/2013 to RDO, IF/01390/2014 to ET, IF/00735/2014 to AC, SFRH/BPD/96176/2013 to CC and IF/00021/2014 to RS), and Infect-Era (project INLEISH). JE also thanks the Canada Research Chair program for financial assistanceinfo:eu-repo/semantics/publishedVersio

    Improvements chemical processes to obtain Fenitoin

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    Foram otimizados os processos para obtenção de Fenitoína (5,5-difenil-2,4-imidazolidinadiona), fármaco utilizado no grande mal da epilepsia psicomotora. Os processos poderão ser adaptados para escala piloto visando suprir a demanda do Rio Grande do Sul, que foi de 1.395 kg e 8.690 kg no Brasil, em 1990.Improvements were made with the chemical processes to obtain Fenitoin, a drug used in the psicomotor eplepsia treatment. The processes can be adapted to "pilot plant scale" in order to achieve the demand of fenitoin in Rio Grande do Sul. In 1990 the consumption on fenitoin in Brazil was 8.650 Kg and in Rio Grande do Sul 1.395 Kg

    Comparison of zinc oxide nanoparticle integration into non-woven fabrics using different functionalisation methods for prospective application as active facemasks

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    The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP content and distribution within the textile fibres by morphological and chemical analysis, the samples were evaluated regarding their antimicrobial properties. The functionalised fabrics obtained via dip-pad-dry unveiled the most promising data, with 0.017 ± 0.013wt% ZnO NPs being mostly located at the fibre’s surface and capable of total eradication of Staphylococcus aureus and Escherichia coli colonies within the tested 24 h (ISO 22196 standard), as well as significantly contributing (**** p < 0.0001) to the growth inhibition of the bacteriophage MS2, a surrogate of the SARS-CoV-2 virus (ISO 18184 standard). A three-layered structure was assembled and thermoformed to obtain facemasks combining the previously chosen NWF, and its resulting antimicrobial capacity, filtration efficiency and breathability (NP EN ISO 149) were assessed. The developed three-layered and multiscaled fibrous structures with antimicrobial capacities hold immense potential as active individual protection facemasks.FCT -Fundação para a Ciência e a Tecnologia(LA/P/0029/2020)info:eu-repo/semantics/publishedVersio

    Mortality from COVID-19 in Brazil : analysis of death’s civil registry from 2020 January to 2021 February

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    Objetivo: analisar a evolução da mortalidade por COVID-19 no período de janeiro de 2020 a fevereiro de 2021 no Brasil. Métodos. Dados sobre todos os óbitos foram obtidos do Portal da Transparência, alimentado continuamente pelos cartórios civis do país. Foi considerado óbito por COVID-19 quando havia citação de COVID-19, coronavírus ou novo coronavírus como causa de óbito. As taxas de mortalidade por COVID-19 foram padronizadas por sexo e faixa etária, conforme estimativa populacional para 2020. Mortalidade por COVID-19 proporcional foi calculada por faixa etária e região, conforme o sexo. Mortalidade geral proporcional foi calculada por local de falecimento e região, conforme causa do óbito. Resultados. Dos 1.596.130 óbitos registrados, 16% tiveram COVID-19 como causa básica, a taxa de mortalidade no Brasil foi de 119,9 por 100 mil habitantes, chegando a 410,5 em Roraima para o sexo masculino. Altas taxas foram encontradas principalmente na região Norte e as menores na região Nordeste. A maior proporção foi entre 70 e 79 anos de idade. A morte por COVID-19 em domicílio atingiu 3,8% dos óbitos na região Norte e 3,4% no Nordeste. Conclusões. O uso de dados do registro civil é de grande importância para o monitoramento atualizado da mortalidade por COVID-19, demonstrando que o país enfrenta, em 2021, aumento de óbitos e agravamento da pandemia.Objective: to analyze the evolution of mortality due to COVID-19 in the period from January 2020 to February 2021 in Brazil. Methods. Data on all deaths were obtained from the transparency portal, continuously fed by the country's civil registry offices. It was considered death by COVID-19 when there were citations of COVID-19, coronavirus or new coronavirus in the cause of death. Mortality rates for COVID-19 were standardized by sex and age group, according to a population estimate for 2020. Proportional COVID-19 mortality was calculated by age group and region, according to sex. General proportional mortality was calculated by place of death and region, according to the cause of death. Results. Of the 1,596,130 deaths recorded, 16% had COVID-19 as a basic cause, the mortality rate in Brazil was 119.9 per 100 thousand inhabitants, reaching 410.5 in Roraima for men. High rates were found mainly in the North and lowest in the Northeast. The highest proportion was between 70 and 79 years of age. Death by COVID-19 at home reached 3.8% of deaths in the North and 3.4% in the Northeast. Conclusions. The use of civil registry data is of great importance for a timely monitoring of COVID-19 mortality, thus showing the country faces, in 2021, an increase in deaths, worsening the pandemic

    Unrevealing the interactive effects of climate change and oil contamination on lab-simulated estuarine benthic communities

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    There is growing concern that modifications to the global environment such as ocean acidification and increased ultraviolet radiation may interact with anthropogenic pollutants to adversely affect the future marine environment. Despite this, little is known about the nature of the potential risks posed by such interactions. Here, we performed a multifactorial microcosm experiment to assess the impact of ocean acidification, ultraviolet radiation B (UV-B) and oil hydrocarbon contamination on sediment chemistry, the microbial community (composition and function) and biochemical marker response of selected indicator species. We found that increased ocean acidification and oil contamination in the absence of UV-B will significantly alter bacterial composition by, among other changes, greatly reducing the relative abundance of Desulfobacterales, known to be important oil hydrocarbon degraders. Along with changes in bacterial composition, we identified concomitant shifts in the composition of aromatic hydrocarbons in the sediment and an increase in oxidative stress effects on our indicator species. Interestingly, our study identifies UV-B as a critical component in the interaction between these factors, since its presence alleviates harmful effects caused by the combination of reduced pH and oil pollution. The model system used here shows that the interactive effect of reduced pH and oil contamination can adversely affect the structure and functioning of sediment benthic communities, with the potential to exacerbate the toxicity of oil hydrocarbons in marine ecosystems

    EAIR 41st Annual Forum in Leiden, The Netherlands 25 till 28 August 2019

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    Trabalho apresentado em EAIR 41st Annual Forum, 25-28 agosto 2019, Leiden, Países Baixos.Polytechnic Institutes in Portugal: research on the impact of twelve institutes on the local economy Higher Education Institutions are recognized as important actors in regional development. The Portuguese higher education system comprises both Universities and Polytechnic Institutes, which face an increasing pressure to demonstrate that their presence has an impact on the surrounding communities contributing to their economic development. This paper presents the estimation of the economic impact of twelve Polytechnic Institutes, located in quite diverse regions, based on a shared model so that comparisons have a collective framework of analysis. The main results obtained show that the economic impact ranged from 1.8% to 10.6% of the local GDP and that these Institutes are major local employers.info:eu-repo/semantics/publishedVersio

    Arbustus unedo essence: morphological and genetic characterization of the strawberry tree of Castelo de Paiva

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    O medronheiro é um arbusto da região mediterrânica que pode ser encontrada por todo o país. Ao contrário do que verifica na região sul do país, no concelho de Castelo de Paiva é atribuída uma reduzida importância económica a esta espécie. Com o intuito de preservar e potenciar a produção desta espécie e contribuir para a dinamização da economia do concelho, procedeu-se à caracterização morfológica e genética de uma amostra da população de medronheiros de Castelo de Paiva. A caracterização morfológica e genética foi realizada para um total de 10 genótipos. Para tal recolheram-se 70 folhas aleatoriamente em cada árvore. Em 40 folhas mediu-se o comprimento, largura, comprimento do pedúnculo, peso fresco, peso seco e determinou-se a área foliar. Dos caracteres morfológicos analisados, aqueles que se revelaram mais úteis na distinção dos vários genótipos foram: comprimento do pedúnculo, peso fresco e peso seco. As restantes 30 folhas foram utilizadas para a caracterização genética. Esta caracterização foi realizada recorrendo a um marcador de DNA, ISSR. Os 5 primeiros exemplaresutilizados na técnica de ISSR demonstraram-se polimórficos. Os resultados da caracterização genética sugerem que a variabilidade genética na população é média a alta.The strawberry tree is a shrub native in the Mediterranean region and it can be found throughout Portugal. Unlike the case in the southern region of the country, in Castelo de Paiva a minor economic importance is given to this species. In order to preserve, to enhance the production of this species and to contribute to the boosting of the economy of the region, we proceeded to the characterization of a small sample population of this fruit tree of Castelo de Paiva in what concerns to its morphology and genetics. The morphological and genetic characterization was performed for a total of 10 genotypes. For this, 70 leaves were randomly collected from each tree. For 40 leaves, it was measured the length, the width, the peduncle length, the wet weight, the dry weight and determined the leaf area. Of the morphological characteristics analyzed, the ones that proved most useful in distinguishing the various genotypes were: the length peduncle, the wet weight and the dry weight. The remaining 30 leaves were used in the genetic characterization. This characterization was performed using a DNA marker, the ISSR. The 5 primers used in the ISSR technique proved to be polymorphic. The results from the genetic characterization suggest that variability in population genetics is medium to high
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