Angiotensin II and VEGF are Involved in Angiogenesis Induced by Short-Term Exercise Training

Results from our laboratory have suggested a pathway involving angiotensin II type 1 (AT1) receptors and vascular endothelial growth factor (VEGF) in angiogenesis induced by electrical stimulation. The present study investigated if similar mechanisms underlie the angiogenesis induced by short-term exercise training. Seven days before training and throughout the training period, male Sprague-Dawley rats received either captopril or losartan in their drinking water. Rats underwent a 3-day treadmill training protocol. The tibialis anterior and gastrocnemius muscles were harvested under anesthesia and lightly fixed in formalin (vessel density) or frozen in liquid nitrogen (VEGF expression). In controls, treadmill training resulted in a significant increase in vessel density in all muscles studied. However, the angiogenesis induced by exercise was completely blocked by either losartan or captopril. Western blot analysis showed that VEGF expression was increased in the exercised control group, and both losartan and captopril blocked this increase. The role of VEGF was directly confirmed using a VEGF-neutralizing antibody. These results confirm the role of angiotensin II and VEGF in angiogenesis induced by exercise

Nanopartículas lipídicas na promoção da absorção oral de fármacos

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências FarmacêuticasÉ do conhecimento geral que a via oral é a preferida pelos doentes, conduzindo a uma maior adesão à terapêutica. No entanto, o recurso a esta via de administração apresenta limitações, relacionadas com as condições adversas do trato gastrintestinal (TGI) e com a baixa solubilidade aquosa de algumas moléculas, o que se pode traduzir na ineficácia dos tratamentos. Neste sentido, têm sido estudadas novas estratégias para promover a administração oral de fármacos, designadamente, o recurso a novos sistemas coloidais de transporte, como as nanopartículas lipídicas. Estas têm demonstrado resultados promissores, uma vez que os lípidos promovem a absorção oral dos fármacos, dado que sofrem os mesmos mecanismos fisiológicos de digestão dos lípidos provenientes dos alimentos. Adicionalmente, a encapsulação das moléculas em nanopartículas permite proteger as mesmas das condições adversas do TGI. Este trabalho tem como objetivo a revisão bibliográfica relativa ao estado da arte do uso de nanopartículas lipídicas para a administração oral de fármacos, bem como a análise do sucesso dos resultados obtidos até agora e as perspetivas futuras. It is well-known that the oral route is the most preferred by patients, leading to a high compliance during therapies. However, the use of this route of administration has limitations, related to the adverse conditions of the gastrointestinal tract (GIT) and the poor aqueous solubility of some molecules, which can originate an inefficacy of the treatments. Therefore, new strategies have been studied in order to improve oral administration of drugs, namely, the use of new colloidal systems of transport, such as lipid nanoparticles. These have shown promising results, since the lipids promote oral drug absorption, because they undergone the same physiological mechanisms of food lipids digestion. Additionally, the encapsulation of molecules in nanoparticles allows for protect them from the adverse conditions of the GIT. The aim of this work is to perform a bibliographic review regarding the state of the art of using lipid nanoparticles for oral drug delivery. The analysis of the success of the results obtained so far and the future prospects are also addressed

Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance

Resumo: A decisão da terapêutica hormonal no tratamento do cancro da mama baseiase na determinação do receptor de estrogénio alfa por imunohistoquímica (IHC). Contudo, a presença deste receptor não prediz a resposta em todas as situações, em parte devido a limitações do método IHC. Investigámos se a expressão dos genes ESR1 e ESR2, bem como a metilação dos respectivos promotores, pode estar relacionada com a evolução desfavorável de uma proporção de doentes tratados com tamoxifeno assim como com a perda dos receptores de estrogénio alfa (ERα) e beta (ERß). Amostras de 211 doentes com cancro da mama diagnosticado entre 1988 e 2004, fixadas em formalina e preservadas em parafina, foram utilizadas para a determinação por IHC da presença dos receptores ERα e ERß. O mRNA total do gene ESR1 e os níveis específicos do transcrito derivado do promotor C (ESR1_C), bem como dos transcritos ESR2_ß1, ESR2_ß2/cx, and ESR2_ß5 foram avaliados por Real-time PCR. Os promotores A e C do gene ESR1 e os promotores 0K e 0N do gene ESR2 foram investigados por análise de metilação dos dinucleotidos CpG usando bisulfite-PCR para análise com enzimas de restrição, ou para methylation specific PCR. Atendendo aos resultados promissores relacionados com a metilação do promotor do gene ESR1, complementamos o estudo com um método quantitativo por matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) suportado pelo software Epityper para a medição da metilação nos promotores A e C. Fez-se a avaliação da estabilidade do mRNA nas linhas celulares de cancro da mama MCF-7 e MDA-MB-231 tratadas com actinomicina D. Baixos níveis do transcrito ESR1_C associaram-se a uma melhor sobrevivência global (p = 0.017). Níveis elevados do transcrito ESR1_C associaram-se a uma resposta inferior ao tamoxifeno (HR = 2.48; CI 95% 1.24-4.99), um efeito mais pronunciado em doentes com tumores de fenótipo ERα/PgR duplamente positivo (HR = 3.41; CI 95% 1.45-8.04). A isoforma ESR1_C mostrou ter uma semi-vida prolongada, bem como uma estrutura secundária da região 5’UTR muito mais relaxada em comparação com a isoforma ESR1_A. A análise por Western-blot mostrou que ao nível da 21 proteína, a selectividade de promotores é indistinguivel. Não se detectou qualquer correlação entre os níveis das isoformas do gene ESR2 ou entre a metilação dos promotores do gene ESR2, e a detecção da proteína ERß. A metilação do promotor C do gene ESR1, e não do promotor A, foi responsável pela perda do receptor ERα. Estes resultados sugerem que os níveis do transcrito ESR1_C sejam usados como um novo potencial marcador para o prognóstico e predição de resposta ao tratamento com tamoxifeno em doentes com cancro da mama. Abstract: The decision of endocrine breast cancer treatment relies on ERα IHC-based assessment. However, ER positivity does not predict response in all cases in part due to IHC methodological limitations. We investigated whether ESR1 and ESR2 gene expression and respective promoter methylation may be related to non-favorable outcome of a proportion of tamoxifen treated patients as well as to ERα and ERß loss. Formalin-fixed paraffin-embedded breast cancer samples from 211 patients diagnosed between 1988 and 2004 were submitted to IHC-based ERα and ERß protein determination. ESR1 whole mRNA and promoter C specific transcript levels, as well as ESR2_ß1, ESR2_ß2/cx, and ESR2_ß5 transcripts were assessed by real-time PCR. ESR1 promoters A and C, and ESR2 promoters 0N and 0K were investigated by CpG methylation analysis using bisulfite-PCR for restriction analysis, or methylation specific PCR. Due to the promising results related to ESR1 promoter methylation, we have used a quantification method by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS) together with Epityper software to measure methylation at promoters A and C. mRNA stability was assessed in actinomycin D treated MCF-7 and MDA-MB-231 cells. ERα protein was quantified using transiently transfected breast cancer cells. Low ESR1_C transcript levels were associated with better overall survival (p = 0.017). High levels of ESR1_C transcript were associated with non-favorable response in tamoxifen treated patients (HR = 2.48; CI 95% 1.24-4.99), an effect that was more pronounced in patients with ERα/PgR double-positive tumors (HR = 3.41; CI 95% 1.45-8.04). The ESR1_C isoform had a prolonged mRNA half-life and a more relaxed 5’UTR structure compared to ESR1_A isoform. Western-blot analysis showed that at protein level, the promoter selectivity is undistinguishable. There was no correlation between levels of ESR2 isoforms or ESR2 promoter methylation and ERß protein staining. ESR1 promoter C CpG methylation and not promoter A was responsible for ERα loss. We propose ESR1_C levels as a putative novel marker for breast cancer prognosis and prediction of tamoxifen response

Authentic learning in a B2B context: cases involving undergraduate students from the University of Aveiro

This paper presents the results of an authentic learning project for undergraduate students, in a business to business (B2B) context, more specifically the case of the Information Technology (IT) cluster in Aveiro. The project was implemented between October 2021 and January 2022 with 93 undergraduate students from second and third year of the Bachelor in Marketing and Bachelor in Finance at University of Aveiro, which developed strategic plans and marketing plans for 18 companies belonging to the IT cluster in Aveiro. Results show that benefits overseeded the barriers.publishe

Surface activation strategy to improve PET functionality for cardiovascular applications

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Innovative approaches to teaching and learning: Project Based Learning (PBL) practices for good

The main goal of this paper is to describe a specific teaching-learning project implemented in two higher education courses – Bachelor in Marketing and Master in Competitiveness and Business Development, offered at a higher education institution. The project integrated Project Based Learning (PBL) methodologies and authentic learning, supported by technology, with Sustainable Development Goals (SDGs), studying real companies from different industries, and aiming to improve the quality of the learning experience, students’ motivation and academic success. A total of 300 students were involved in the 1st semester of the year 2022/2023. The idea of sustainable cocreation was at the base of this pedagogical innovation project, so that students may become aware and assume responsibility on the impact of marketing, strategy and competitiveness decisions in the contemporary society. Students were challenged to include in their works a proposal of actions that had positive impact and contributed to the SDGs defined by the United Nations and to reflect and measure the potential impact of these actions at the level of the community. From an operational perspective, students developed different activities in their academic works, in four different curricular units, in line with the educational level and syllabus of each curricular unit, always related to real companies from different industries and supported by different technologies, using different immersive learning experiences where students could combine authentic learning and SDGs analysis.publishe

Teoria e prática: importância da observação para a formação de docentes

Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014Observar é ver além do que se pode notar, é absorver informações para aprofundar sua pesquisa. É um método científico fundamentador da prática, relacionada com a teoria. No Projeto Institucional de Bolsa de Iniciação à Docência pode-se ir além da formação mínima do curso superior, promovendo uma maior aproximação com a realidade escolar. O Projeto relaciona a pesquisa com a observação, coleta de dados, discussão e análises para melhoria dos problemas possivelmente encontrados. Por meio das observações que foram feitas em escolas em parceria com o projeto, notou- se fatores importantes para compararmos a teoria com a prática. Espera-se que nas próximas etapas, o PIBID possa contribuir efetivamente para a formação dos docentes tanto em nível médio como superior, bem como para a prática pedagógica dos professores das escolas da rede pública envolvidas no program

Organic food purchase and the influence of personality traits: a study with Portuguese consumers

Consumer concerns with the quality of their diet and with the origins of food products is a current and important topic in marketing research. It is evident that consumers are increasingly purchasing organic products primarily for health and environmental reasons. However, this pattern of behavior is not homogeneous and may depend on demographic and psychographic variables. Presently, knowledge on Portuguese attitudes towards organic food is still scarce. This study aims to contribute to fill a gap in literature concerning the extent to which personality traits may affect Portuguese consumers’ predisposition to buy and consume organic food products. Specifically, it has two objectives (i) to describe the buying habits of organic products; (ii) to categorize personality traits that influence this purchasing decision. A quantitative methodology based on an online questionnaire to a sample of 375 respondents was adopted and multivariate analysis methods were used in the evaluation and collection of statistical data to clarify and explain relationships among the different variables. Main results suggest that the major indicators for buying organic food products are: local production, social responsibility, health and quality, diet options and consumer routines. Moreover, online stores are identified as the preferred place to purchase organic food products, and durability and cost play an important role regarding the selection of products to be purchased. Finally, the personality traits that seem to play a significant role in people who buy organic products are Conscientiousness, Extraversion and Agreeableness.publishe

Public procurement electronic platforms assessment: legal requirements

Electronic public procurement (EPP) has been considered an important tool for promoting competition, simplifying procedures, and ensuring transparency in decision-making processes. In Portugal, EPP replaced paper-based pre-contractual procedures for communication and processing. Addressing this general issue, the authors designed and proposed TrivPlat, a free access tool for monitoring, managing, and evaluating electronic platforms of public procurement. This paper presents the TrivPlat project, reporting its development so far: the identification and characterization of legal requirements that electronic platforms for public procurement are required to follow in Portugal. Legal requirements may be grouped into four types: general operating rules, functional requirements, technical requirements, and safety requirements. The first phase of the TrivPlat project diagnosis is expected to result in the development of an aggregate evaluation framework for public procurement platforms in order to reach the fundamental principles: equality of treatment, confidentiality, traceability, effectiveness, compatibility, interoperability, security and general availability.This work has been supported by FEDER funds through the Operational Program for Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the Project: no 031171 and by COMPETE: POCI-01-0145-FEDER-007043 and FCT - Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013