Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

This deposit is composed by the main article, and it hasn't any supplementary materials associated.The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/92860/2013, PTDC/BIM-MEC/4665/2014); European Research Council grants: (ERC-2014-CoG 647888-iPROTECTION).info:eu-repo/semantics/publishedVersio

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness

Modelo de gestão de identidade corporativa: da teoria à aplicação (Ambial)

Relatório de projeto apresentado à Escola Superior de Artes Aplicadas do Instituto Politécnico de Castelo Branco e à Faculdade de Arquitetura da Universidade Técnica de Lisboa para obtenção do Grau de Mestre em Design GráficoTudo indica que muitos gestores empresariais, nomeadamente em Portugal, não vêm ainda o design como uma disciplina estratégica para as suas empresas, mas sim uma área secundária de não retorno. Não compreendendo, portanto, o contributo deste e muito menos os gastos implícitos na sua concepção e aplicação. Com este projeto, pretende-se ajudar a demonstrar que o design e os seus processos de gestão, são um contributo essencial para o sucesso de qualquer empresa; mais especificamente naquelas de pequena e média dimensão. Para tal, irá reformular-se a identidade corporativa da Ambial; uma pequena empresa especializada em controlo de pragas, segurança alimentar e venda de produtos / equipamentos de higienização. A metodologia implementada ao longo deste projeto servirá para demonstrar as formas e as mais-valias da gestão de identidade corporativa, assim como reafirmar e fundamentar a presença desta disciplina no tecido empresarial contemporâneo. Além do mencionado, este trabalho terá também o intuito de sensibilizar os empreendedores, os empresários e os próprios designers para a inclusão do design na estratégia de topo empresarial, desmistificando a perceção geral e ainda atual de que esta disciplina e as suas variantes são consideradas apenas processos finais, de mera execução técnica.ABSTRACT Everything indicates that most business managers, particularly in Portugal, do not see design as a strategic discipline for their companies, but a secondary area of no payback. By not understanding therefore its contribution and much less the spending implicit in its conception and implementation. With this project, it is intended to demonstrate that design and its management processes, are an essential contribution to the success of any company, more specifically those of small and medium size. Therefore, Ambial’s corporate identity will reshape itself; a small company specialized in plague’s control, food security and product /equipment hygiene selling. The implemented methodology throughout this project will serve to demonstrate the ways and gains in corporate identity’s management, as well as to reaffirm and justify this discipline’s presence among nowadays business web. Besides the already mentioned, this work will also aim to raise awareness among entrepreneurs, businessmen and designers themselves for design inclusion in the top business strategy, demystifying general perception, still current nevertheless, that this discipline and its variants are considered final steps, of mere technical execution

Sistema transfere de 3 eixos servomecanizados

Mestrado em Engenharia MecânicaO projeto apresentado tem como objetivo a conceção de um sistema modular de manipulação programável a três eixos. Este tipo de equipamento, está bastante difundido na área de alimentação/extração de peças em prensas mecânicas. Uma vez que as prensas mecânicas atuais já possuem este equipamento há uma carência na implementação em prensas obsoletas no qual este projeto pretende abraçar. Para além de ser um equipamento importante a aplicar em prensas obsoletas pretende-se implementar no mercado um equipamento constituído por peças modulares e normalizados tornando-se mais competitivo no mercado e que a sua manutenção não seja complexa. Este projeto baseia-se na análise de diferentes soluções em função da viabilidade técnica e económica baseadas em patentes. O projeto inclui as seguintes fases do ciclo de desenvolvimento de um equipamento industrial: análise de mercado, especificação do produto, conceção e materialização. Todos os componentes existentes no projeto existem no mercado. Foram ainda definidos os requisitos iniciais para a unidade manipuladora de peças conformadas em prensas mecânicas: o manipulador possui um deslocamento vertical de 100mm em altura, e um deslocamento horizontal de prensa para prensa de 800mm. O movimento deste manipulador possui uma velocidade máxima de 0.1ms-1 e no momento antes de este parar começa a desacelerar havendo a formação de uma rampa linear. Por fim o manipulador de peças tem de desimpedir a zona de trabalho da prensa, após este realizar a tarefa de introdução da chapa na prensa.The Project here submitted has as main goal to propose the modular design of transfer system manipulator operating in a 3-axes kinematics. This equipment is quite defunded in feeding operations of metal sheet in forming equipment, as drawing, stamping, blanking or bending presses. A sequence of automated tasks as inserting, positioning and extracting constitute the essential operations of transfer systems. Nowadays practically all sheet metal forming systems operate with automated feed/extraction transfer systems; however, old design presses have to be equipped with such systems in order to increase their productivity. This project for a transfer system proposes a system compatible with current design presses, promoting the easier assembling and mechanical compatibility with the press architecture. The maintenance of such equipment must be competitive with the most recently developed ones. The project development was carried out on consulting the up to date patents and products available for the purpose on analysis. All the accessories and parts included in this project are available in the market. Essential characteristics are: Vertical stroke: 100mm and a maximum transverse displacement of 800mm between adjacent presses. The movement of this manipulator has a mean carrier speed: 0.1m/s sustained after accelerating from 0 to 100mm/s. Also, a linear deceleration is obtained at the slowing step. Finally, the manipulator must clear the mechanical press working area once the correct sheet metal position in achieved

The adaptive evolution of the mammalian mitochondrial genome

<p>Abstract</p> <p>Background</p> <p>The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.</p> <p>Results</p> <p>Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome <it>b </it>in species with more-specialized metabolic requirements (such as adaptation to low energy diet <it>or </it>large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation to unusual oxygen requirements, for example diving in cetaceans, flying in bats, and living at high altitudes in alpacas). Signatures of adaptive variation in the NADH dehydrogenase complex were restricted to the loop regions of the transmembrane units which likely function as protons pumps. Evidence of adaptive variation in the cytochrome <it>c </it>oxidase complex was observed mostly at the interface between the mitochondrial and nuclear-encoded subunits, perhaps evidence of co-evolution. The ATP8 subunit, which has an important role in the assembly of F₀, exhibited the highest signal of adaptive variation. ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas.</p> <p>Conclusion</p> <p>Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation. We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.</p

Influência das bebidas desportivas na saúde oral

Objetivos: os objetivos deste trabalho são perceber o efeito das bebidas desportivas na saúde oral dos atletas, identificar os principais malefícios e benefícios das mesmas e quais os problemas a nível bucal. Metodologia: A metodologia baseou-se na pesquisa de publicações científicas para a construção de uma revisão de literatura, através da pesquisa em bases científicas: Scielo Portugal, Google Scholar, PubMed e b-on. As palavras-chave utilizadas foram “oral health” “sport drinks” “athletes”. Os critérios utilizados para a inclusão neste tema foram publicações científicas publicadas maioritariamente nos últimos dez anos; escritos em Língua Portuguesa, Espanhola e Inglesa, de consulta gratuita. Como critérios de exclusão consideraram-se publicações que não fossem realizadas em seres humanos e publicações que não estivessem escritas nas línguas anteriormente mencionadas. Descrição: Em geral nos artigos apresentados os atletas consumem bebidas desportivas com um índice elevado de hidratos de carbono e bebidas ácidas o que aumenta a prevalência de problemas orais.Objectives: The objectives of this study are to understand the effect of sports drinks on the oral health of athletes, to identify the main harms and benefits of them and what problems at the oral level. Methodology: The methodology was based on the research of scientific publications for the construction of a literature review, through research in scientific bases: Scielo Portugal, Google Scholar, PubMed and b-on. The keywords used were "oral health" "sport drinks" "athletes". The criteria used for inclusion in this topic were scientific publications published mostly in the last ten years; written in Portuguese, Spanish and English, free consultation. Exclusion criteria were considered to be non-human publications and publications that are not written in the above-mentioned languages. Description: In general, in the articles presented athletes consume sports drinks with a high carbohydrate and acidic beverages, which increases the prevalence of oral problems

Influência das bebidas desportivas na saúde oral

Objetivos: os objetivos deste trabalho são perceber o efeito das bebidas desportivas na saúde oral dos atletas, identificar os principais malefícios e benefícios das mesmas e quais os problemas a nível bucal. Metodologia: A metodologia baseou-se na pesquisa de publicações científicas para a construção de uma revisão de literatura, através da pesquisa em bases científicas: Scielo Portugal, Google Scholar, PubMed e b-on. As palavras-chave utilizadas foram “oral health” “sport drinks” “athletes”. Os critérios utilizados para a inclusão neste tema foram publicações científicas publicadas maioritariamente nos últimos dez anos; escritos em Língua Portuguesa, Espanhola e Inglesa, de consulta gratuita. Como critérios de exclusão consideraram-se publicações que não fossem realizadas em seres humanos e publicações que não estivessem escritas nas línguas anteriormente mencionadas. Descrição: Em geral nos artigos apresentados os atletas consumem bebidas desportivas com um índice elevado de hidratos de carbono e bebidas ácidas o que aumenta a prevalência de problemas orais.Objectives: The objectives of this study are to understand the effect of sports drinks on the oral health of athletes, to identify the main harms and benefits of them and what problems at the oral level. Methodology: The methodology was based on the research of scientific publications for the construction of a literature review, through research in scientific bases: Scielo Portugal, Google Scholar, PubMed and b-on. The keywords used were "oral health" "sport drinks" "athletes". The criteria used for inclusion in this topic were scientific publications published mostly in the last ten years; written in Portuguese, Spanish and English, free consultation. Exclusion criteria were considered to be non-human publications and publications that are not written in the above-mentioned languages. Description: In general, in the articles presented athletes consume sports drinks with a high carbohydrate and acidic beverages, which increases the prevalence of oral problems

Effects of metoclopramide on the expression of metalloproteinases and interleukins in left colonic anastomoses : an experimental study

PURPOSE: To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS: Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS : On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION: Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

Introduction: Ankylosing spondylitis (AS) is typically characterized by focal bone over-growth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, and in vitro osteoclast differentiation in AS patients. Methods: Patients with active AS without any ongoing therapy and age-and gender matched healthy donors were recruited. Receptor activator of nuclear factor-K13 (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations were assessed. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and quantitative reverse transcription real-time PCR for OC-specific genes were performed. Results: Pro-and anti-inflammatory cytokine serum levels were higher in AS patients than in controls. RANKL neutrophil expression was higher in AS patients when compared to healthy donors, but CD51/CD61 expression was lower in the classical monocyte subpopulation. Concerning osteoclastogenesis, we found no differences in the in vitro osteoclast differentiating potential of these cells when compared to healthy donors. However, we observed low expression of CSF1R, RANK, and NFATc1 in AS OCPs. Conclusion: Despite the high levels of pro-inflammatory cytokines present in AS patients, no differences in the number of OC or resorbed area were found between AS patients and healthy donors. Moreover, we observed that OCPs have low OC specific gene expression. These findings support our hypothesis of an impaired response of OCPs to pro-osteoclastogenic stimuli in vivo in AS patients.Peer reviewe