Biomedical potential of fucoidan, a seaweed sulfated polysaccharide: from a anticancer agent to a building block of cell encapsulating systems for regenerative medicine

Marine macroalgae or seaweeds synthesize a wide variety of polymers and smaller compounds with several bioactivities, among which the sulfated polysaccharides acquire greater relevance not only due to the reported antioxidant, antiviral and anticancer[1] activities, but also to the resemblance of extracellular matrix glycosaminoglycans found in the human body[2]. In this study, the potential of fucoidan (Fu) isolated from brown seaweed Fucus vesiculosus for therapeutical use has been evaluated, focusing in its performance as antitumoral agent (bioactive role) or as building block of cell encapsulating systems (structural role). Materials and Methods: The anticancer activity of Fu extracts was assessed by evaluating the cytotoxic behavior over two human breast cancer cell lines (MCF-7 and MDA-MB-231) in in-vitro culture, using human fibroblasts and endothelial cells (HPMEC-ST1 and MRC-5, respectively) as reference. Regarding the structural role, Fu was modified by methacrylation reaction (MFu) using methacrylic acid and further crosslinked using visible radiation and triethanolamine and eosin-y as photoinitiators. The photocrosslinking was performed on MFu solution droplets placed in a silica-based superhydrophobic surface[3], allowing the formation of particles[4] (since natural Fu is highly soluble in water and ion gelation is not effective). Biological performance of the developed particles was assessed by in vitro culture of fibroblasts and pancreatic cells (L929 and 1.1B4, respectively) in contact with MFu particles, up to 7 days. The ability of the developed materials to support adhesion and proliferation of cells was evaluated for both types of cells. Results and Discussion: The tested anticancer activity is not ubiquitous on Fu extracts, being dependent on its chemical features, with molecular weight (Mw) representing a particular role. Specifically, Mw values around 60 kDa exhibited cytotoxic effects to human breast cancer cell lines, while not affecting normal fibroblasts or endothelial cells (which represent the cells of the healthy tissue that would be closer to the tumor in a real situation). A concentration range of 0.2 to 0.3 mg mL-1 from the selected Fu extract could be considered as the therapeutic window for further studies. Regarding fucoidanâ s role on innovative biomaterials, the developed MFu particles could support the proliferation of fibroblasts (L929), but also of human pancreatic beta cells (1.1B4), which tend to form pseudo-islets after 7 days in culture (Fig. 1). This pancreatic cells could be also successfully encapsulated, opening a new route for a diabetes mellitus type 1 therapeutic approach. Fig. 1: Confocal microscopy images of 1.1B4 cells cultured in the presence of fucoidan-based particles and organized in pseudo-islets (red â actin; blue â nuclei). Conclusion: The present work establishes fucoidan as a high performance building block for the development of advanced therapies for cancer (targeted therapy) or tissue and organ regeneration. It shed light on the relation between chemical structure and biological activity towards anti-cancer effect and proposes novel beta cell laden particles as injectable insulin producing systems to tackle diabetes.Funding from projects 0687_NOVOMAR_1_P (co-funded by INTERREG 2007-2013 / POCTEP), CarbPol_u_Algae (EXPL/MAR-BIO/0165/2013, funded by the Portuguese Foundation for Science and Technology, FCT), POLARIS (FP7-REGPOT-CT2012-316331) and ComplexiTE (ERC-2012-ADG 20120216-321266), funded by the European Union’s Seventh Framework Programme for Research and Development is acknowledged. ASF, SSS, NMO and DSC are also thankful to FCT for their individual fellowships

Cognitive differentiation during childhood: A study on cognitive profiles of 5, 7, and 9-year-old children

No seio do debate sobre se a inteligência é mais bem definida por um fator geral ou por aptidões específicas, ganha relevância a hipótese da diferenciação cognitiva. Análises recentes enfatizam o interesse dessa questão para a investigação e alertam para a relevância das suas implicações na área educativa. Este estudo analisou a possibilidade de a diferenciação das aptidões cognitivas ocorrer já na infância e também o efeito moderador do Quociente de Inteligência na magnitude da relação entre as habilidades cognitivas. Aplicou-se uma bateria de provas que avaliam várias funções cognitivas a uma amostra de 231 crianças com 5, 7 e 9 anos, distribuídas por três grupos de desempenho cognitivo. Os resultados de uma análise de clusters hierárquica e de uma análise de variância apontam para a não diferenciação das funções cognitivas na infância. Contudo, uma análise mais cuidadosa aponta para alguma diferenciação suportada pela heterogeneidade dos perfis cognitivos junto dos alunos com Quociente de Inteligência elevado.Within the debate about whether intelligence is best defined by a general factor or specific skills, the hypothesis of cognitive differentiation gains relevance. Recent analyses have emphasized the importance of this issue in the investigation of cognitive skills and have highlighted its implications in education. This study examined the possibility that the differentiation of cognitive abilities may occur during childhood and investigated the moderating effect of Intelligence Quotient on the magnitude of the relationship between cognitive abilities. A battery of tests for assessing cognitive function was administered to 231 children aged 5, 7, and 9 years old, who were divided into three cognitive performance groups. The results of hierarchical cluster analysis and variance analysis indicate the lack of differentiation of cognitive functions during childhood. However, a more careful analysis suggests some differentiation supported by the heterogeneity of cognitive profiles among students with high Intelligence Quotient.FCT -Fundação para a Ciência e a Tecnologia(SFRH/BD/84153/2012

Sensitive method for determination of piplartine, an alkaloid amide from Piper species, in rat plasma samples by liquid chromatography-tandem mass spectrometry

Piplartine (PPTN) is an alkaloid amide found in Piper species that presents different activities. PPTN determination in rat plasma is necessary to better understand its biological effects. The aim of this study was to develop a sensitive LC-MS/MS method for the determination of PPTN in rat plasma. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, and stability have been assessed and were within the recommended guidelines. The validated method proved to be suitable in a pilot study of PPTN kinetic disposition in rat plasma after a single intraperitoneal dose, and represents an appropriate tool to further pharmacokinetic studies

Desenvolvimento do self e processos de hiperindividualização: interrogações à Psicologia Dialógica

Resumo: Em psicologia, à perspectiva dialógica estão associadas teorias do self, em especial a Teoria do Self Dialógico (TSD). Embora avanços consistentes venham sendo alcançados no que se refere à compreensão da organização dinâmica da estrutura do self no tempo microgenético, a teoria carece de estudos que se aprofundem na compreensão do desenvolvimento do self, tomando-se por base os distintos níveis temporais e suas relações. Este estudo propõe explorar essa lacuna, tomando por ponto de partida a tríade epistemológica da abordagem dialógica, a saber, suas bases semiótico-culturais, fenomenológicas e construcionistas. Em seguida, apresentará um estudo de caso em que serão analisadas as transições de desenvolvimento de um adolescente, considerando-se os complexos semióticos de gênero, raça e religião e seu papel nas transformações vividas em termos da organização temporal do self

Downregulation of RKIP Is Associated with Poor Outcome and Malignant Progression in Gliomas

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear