Fisiopatologia do envelhecimento cerebral e mecanismos anti-aging

A idade é o principal fator de risco para as doenças crónicas, como o cancro, as doenças cerebrocardiovasculares e as doenças neurodegenerativas. Existe um défice cognitivo com a idade condicionado por vários fatores: redes neuronais, reserva cognitiva prévia, fatores genéticos, fatores anatomopatológicos, fatores vasculares, entre outros. Recentemente, surgiram estudos com novas estratégias para prevenir doenças relacionadas com a idade. O principal objetivo desta monografia é descrever e analisar o envelhecimento cerebral, assim como os mecanismos com potencial de interferir no mesmo. É necessária uma melhor compreensão da base biológica do envelhecimento e de como o envelhecimento incrementa o risco de doenças, procurando mecanismos de prevenção. A metodologia usada neste trabalho foi a pesquisa bibliográfica nas bases de dados PubMed e Google Scholar. Foram também consultados alguns livros de referência. Na pesquisa utilizaram-se estas palavras-chave: “aging” associada a “brain”, “decline”, “cognitive”, “neurodegeneration”, “rejuvenation”, “model” and “organism”. O envelhecimento produz alterações no sistema nervoso central, como alterações neuroanatómicas, alterações na neurotransmissão e alterações neurofisiológicas. As doenças mais relevantes associadas ao envelhecimento cerebral são: doença de Alzheimer, doença de Parkinson e acidente vascular cerebral. São recomendadas estratégias preventivas: incentivar a educação, aumentar as atividades intelectuais e de lazer, boa higiene do sono, alimentação saudável, prática regular de exercício físico, evitar traumatismos cranianos e modificar os fatores de risco vascular. Novas abordagens têm sido investigadas: miméticos da restrição calórica; terapia celular com células estaminais; terapia genética e epigenética. Resultados concretos têm sido alcançados em modelos animais. O grande desafio é replicar os resultados em humanos.Age is the main risk factor for chronic diseases, such as cancer, cerebrovascular diseases and neurodegenerative diseases. There is a cognitive deficit with age conditioned by several factors: neuronal networks, cognitive reserve, genetic factors, anatomopathological factors, vascular factors, among others. Recently, studies have emerged with new strategies to prevent age-related diseases. The main objective of this monograph is to describe and analyze the aging brain as well as the mechanisms with potential to interfere with it. A better understanding of the biological basis of aging and how aging increases the risk of disease is necessary, looking for prevention mechanisms. The methodology used in this work was the bibliographic research in the PubMed and Google Scholar databases. Some reference books were also consulted. In the research, these keywords were used: "aging" associated with "brain", "decline", "cognitive", "neurodegeneration", "rejuvenation", "model" and "organism". Aging produces changes in the central nervous system, such as neuroanatomical changes, changes in neurotransmission and neurophysiological changes. The most relevant diseases associated with the aging brain are: Alzheimer's disease, Parkinson's disease and stroke. Preventive strategies are recommended: encouraging education, increasing intellectual and leisure activities, good sleep hygiene, healthy diet, regular physical exercise, avoiding head injuries and modifying vascular risk factors. New approaches have been investigated: calorie restriction mimetics; cell therapy with stem cells; gene and epigenetic therapy. Concrete results have been achieved in animal models. The big challenge is to replicate the results in humans

Antecedentes do comprometimento afetivo com automóveis de luxo

Mestrado em GestãoEsta dissertação propõe estudar a imagem da marca, a qualidade percebida, a satisfação global e a confiança, como antecedentes do comprometimento afetivo de marcas de automóveis de luxo de determinados segmentos. Considera-se ainda a qualidade e a satisfação como mediadores entre a imagem, e a confiança e o comprometimento afetivo. Os resultados mostram que efetivamente a qualidade e a satisfação podem atuar como mediadores. A personalidade da marca, as atitudes positivas face à marca e a satisfação global podem exercer um efeito mais forte na construção do comprometimento afetivo com a marca de carros de luxo dos segmentos considerados, do que a qualidade percebida.This dissertation aims to study brand image, perceived quality, overall satisfaction and trust as antecedents of affective commitment of luxury car brands in certain segments. Quality and satisfaction act as mediators between image, and trust and affective commitment. The results show that quality and satisfaction can really act as mediators. Brand personality, brand attitude and overall satisfaction may have a stronger effect on affective commitment with the luxury car brand, than perceived quality

Techno-economic and life-cycle assessments of small-scale biorefineries for isobutene and xylo-oligosaccharides production: a comparative study in Portugal and Chile

ABSTRACT: This work presents a comparative simulation study involving the techno-economic and environmental assessment of lignocellulosic-based small-scale biorefineries, integrated with a piggery waste-based anaerobic digestion platform (ADB), located in Portugal and Chile. Two main products are obtained: isobutene and xylo-oligosaccharides (XOS). The bioproduction of isobutene using a genetically engineered organism (Escherichia coli), coupled with the removal and purification of high added-value XOS, obtained after a feedstock hydrothermal pre-treatment, was evaluated. Two lignocellulosic agricultural wastes were used: corn stover in the Portuguese case study and wheat straw in Chilean case study. Both processes were simulated using the Aspen Plus modeling software tool, while the Aspen Process Economic Analyzer was used to carry out the economic evaluation. The simulation results were validated with experimental data from the laboratory and the literature. An economic assessment was performed considering the different locations of both biorefineries. A life-cycle analysis (LCA) was also applied to evaluate the differences in environmental impacts on both locations. The results showed that the isobutene / XOS biorefinery concept was economically viable in both Portugal and Chile, mainly due to the high market value of XOS. The biorefinery has lower production costs for isobutene and XOS (1 US$/kg of isobutene and 1.18 US$/kg of XOS) when located in Portugal, as compared with Chile (1.14 US$/kg of isobutene and 1.56 US$/kg of XOS). Conversely, it leads to less environmental impact when located in Chile: 48.8 kg(CO2eq.)/GJ(isobutene), in comparison to 60.7 kg(CO2eq.)/GJ(isobutene) in Portugal.info:eu-repo/semantics/publishedVersio

Endothelial progenitor cells in diabetic patients with myocardial infarction – Can statins improve their function?

The effect of statins on endothelial progenitor cells (EPCs) function derived from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown. In this study we assess the response of early and late EPCs from diabetic versus non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10 diabetic and 10 age-matched non-diabetic male patients with AMI. For each patient, cultures of early and late EPCs were performed under 4 different conditions: normal glucose concentration (control); high glucose concentration; normal glucose concentration with atorvastatin supplementation and normal glucose concentration with pravastatin supplementation. To compare the effect of these treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC colony-forming units (CFU) assay; cell cycle analysis; viability assessment and expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those of NDMpts (1.4±0.8 vs 2.6±1.2 CFU/well, P=0.021). When early EPCs from DMpts were cultured in the presence of statins, CFU capacity was restored, surmounting that of NDMpts under control conditions. Statins significantly improved viability of early EPCs and delayed the onset of late EPCs senescence, even in cells from DMpts. In addition, statins induced approximately a 2-fold increase in the proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a beneficial effect on both early and late EPCs from DMpts with AMI. Despite the functional impairment of EPCs from DMpts, they exhibit similar responsiveness to statins as equivalent cells from NDMpts

Análise do impacto do processo organosolv para pré-tratamento de biomassa lenhocelulósica na redução das emissões de gases com efeito de estufa (GEE)

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMO: No âmbito do projeto H2020 AMBITION, foram desenvolvidos processos de pré-tratamento inovadores e energeticamente eficientes, a fim de serem integrados num conceito de melhoria do processamento da biomassa para a produção de correntes líquidas de açúcares e derivados de lenhina para aplicações em bioenergia e produtos de valor acrescentado. O objetivo deste trabalho consiste em analisar os impactos ambientais do pré-tratamento organosolv de biomassa (palha de trigo e resíduos de eucalipto) utilizando misturas etanol/água, a fim de avaliar a sua integração num processo multiproduto de modo a originar elevados rendimentos de açúcares e recuperar lenhina de alta qualidade num conceito de biorrefinaria. O processo foi simulado em SuperPro Designer (Intelligen Inc.) para determinar os balanços de massa e energia, bem como para desenvolver o Inventário de Ciclo de Vida (LCI). A Avaliação do Ciclo de Vida (ACV) foi realizada utilizando o software SimaPro 9.0 (PRé Consultants BV) com a base de dados Ecoinvent 3.5, sendo comparada com os processos clássicos de pré-tratamento à escala industrial (e.g. explosão com vapor). O processo organosolv com etanol e para uma razão líquido-sólido (RLS) padrão de 10, apresenta resultados em termos de emissões de GEE (numa abordagem gate-to-gate) ligeiramente superiores aos obtidos para a explosão com vapor, concluindo-se posteriormente que na tecnologia organosolv, só a redução da RLS pode conduzir a melhorias significativas em termos ambientais.ABSTRACT: Within the H2020 AMBITION project, innovative and energy efficient pre-treatment processes were developed in order to be integrated in a biomass processing improvement concept that would produce liquid streams of sugars and lignin derivatives for applications in bioenergy and added-value products. The objective of this work is to analyse the environmental impacts of organosolv pre-treatment of biomass (wheat straw and eucalyptus residues) using ethanol/water mixtures in order to assess its integration in a multi-product process to produce high sugar yields and recover high quality lignin in a biorefinery concept. The process was modelled in SuperPro Designer (Intelligen Inc.) to determine mass and energy balances as well as to develop the Life Cycle Inventory (LCI). The Life Cycle Assessment (LCA) was performed using SimaPro 9.0 software (PRé Consultants BV) with the Ecoinvent 3.5 database and compared with classical industrial scale pre-treatment processes (e.g. steam explosion). The organosolv process with ethanol with a standard liquid-to-solid ratio (LSR) of 10, presents, in terms of GHG emissions (in a gate-to-gate approach), slightly higher GHG emissions than those obtained for the steam explosion, leading to the conclusion that a reduction in the solid-liquid ratio in organosolv technology causes significant environmental improvements.info:eu-repo/semantics/publishedVersio

EQUIPAMENTOS PARA EVENTOS EM BONITO/MS E O PAPEL DO CONVENTION BUREAU

Em uma tentativa estratégica que possui como objetivo principal o aumento do contingente turístico em baixa temporada, o Convention Bureau em parceria com o poder público, desempenham um papel fundamental no desenvolvimento de atividades que apoiam a captação e realização de eventos indutores de fluxo turístico. O presente trabalho teve o objetivo de identificar a estrutura da oferta turística para eventos no município de Bonito. Como procedimentos metodológicos, utilizou-se pesquisas bibliográficas, pesquisa de campo e entrevistas. Como resultados, percebeu-se que entre os principais eventos locais, com grande alcance de público são o Festival de Inverno de Bonito/MS e o Festival da Guavira, além dos eventos técnico-científicos que ocorrem na cidade. Verificou-se ainda que a cidade de Bonito/MS é detentora de uma sólida estrutura de hospedagem, com capacidade de acolher os visitantes e ao mesmo tempo servir como infraestrutura de eventos, e que o Centro de Convenções e o Convention Bureau tem papel fundamental na promoção da cidade enquanto destino turístico não apenas de natureza, mas de eventos também

Frequency and functional activity of Th17, Tc17 and other T-cell subsets in Systemic Lupus Erythematosus

To compare frequency and functional activity of peripheral blood (PB) Th(c)17, Th(c)1 and Treg cells and the amount of type 2 cytokines mRNA we recruited SLE patients in active (n = 15) and inactive disease (n = 19) and healthy age- and gender-matched controls (n = 15). The study of Th(c)17, Th(c)1 and Treg cells was done by flow cytometry and cytokine mRNA by real-time PCR. Compared to NC, SLE patients present an increased proportion of Th(c)17 cells, but with lower amounts of IL-17 per cell and also a decreased frequency of Treg, but with increased production of TGF-b and FoxP3 mRNA. In active compared to inactive SLE, there is a marked decreased in frequency of Th(c)1 cells, an increased production of type 2 cytokines mRNA and a distinct functional profile of Th(c)17 cells. Our findings suggest a functional disequilibrium of T-cell subsets in SLE which may contribute to the inflammatory process and disease pathogenesis

CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis

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Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis

Abstract Objective MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. Methods The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells. Results 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes. Conclusions Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc

Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting.

Background and objective S ystemic sclerosis (SSc) is a severe autoimmune disease, in which the pathogenesis is dependent on both genetic and epigenetic factors. Altered gene expression in SSc monocytes, particularly of interferon (IFN)-responsive genes, suggests their involvement in SSc development. We investigated the correlation between epigenetic histone marks and gene expression in SSc monocytes. Methods C hromatin immunoprecipitation followed by sequencing (ChIPseq) for histone marks H3K4me3 and H3K27ac was performed on monocytes of nine healthy controls and 14 patients with SSc. RNA sequencing was performed in parallel to identify aberrantly expressed genes and their correlation with the levels of H3K4me3 and H3K27ac located nearby their transcription start sites. ChIP-qPCR assays were used to verify the role of bromodomain proteins, H3K27ac and STATs on IFNresponsive gene expression. Results 1046 and 534 genomic loci showed aberrant H3K4me3 and H3K27ac marks, respectively, in SSc monocytes. The expression of 381 genes was directly and significantly proportional to the levels of such chromatin marks present near their transcription start site. Genes correlated to altered histone marks were enriched for immune, IFN and antiviral pathways and presented with recurrent binding sites for IRF and STAT transcription factors at their promoters. IFN\u3b1 induced the binding of STAT1 and STAT2 at the promoter of two of these genes, while blocking acetylation readers using the bromodomain BET family inhibitor JQ1 suppressed their expression. Conclusion SS c monocytes have altered chromatin marks correlating with their IFN signature. Enzymes modulating these reversible marks may provide interesting therapeutic targets to restore monocyte homeostasis to treat or even prevent SSc