Marine-inspired drugs and biomaterials in the perspective of pancreatic cancer therapies

Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.The authors would like to acknowledge the funding from the European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES (H2020-BG-01-2015-679849) and from the European Regional Development Fund, through INTERREG España-Portugal 2014-2020 under BLUEBIOLAB (0474_BLUEBIOLAB_1_E) project and through NORTE2020/PT2020 Programme under ATLANTIDA (Norte-01-0145-FEDER-000040) project

Evaluation of the impact of bottom-up and topdown approaches on daily activities in people with neglet – a systematic review

RESUMO | INTRODUÇÃO: Atualmente não existe um consenso entre quais as caraterísticas das abordagens (bottom-up ou top-down) mais eficazes na reabilitação das Atividades da Vida Diária (AVDs) em pessoas com Síndrome de Neglect (SN). OBJETIVO: Caracterizar as abordagens (bottom-up ou top-down) e o seu impacto nas AVDs em adultos e idosos com SN. MÉTODOS: Esta revisão sistemática foi realizada de acordo com a recomendação PRISMA - Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A pesquisa bibliográfica foi realizada nas bases de dados PubMed, Web of Science, PEDro e Cochrane. Foram considerados estudos experimentais em que pelo menos uma técnica das abordagens bottom-up e top-down fosse utilizada. A ferramenta Joanna Briggs Institute Critical Appraisal Checklist for RCTs foi utilizada para avaliar a qualidade metodológica dos estudos. Foi usada a seguinte combinação de palavras chave: Neglect Syndrome OR Unilateral Syndrome OR Neglect (…) AND Activities of Daily Living OR Daily (…) AND Treatment OR Intervention OR Technique (…). RESULTADOS: Foram incluídos 16 estudos, dos quais 9 incluem técnicas de abordagem bottom-up, 6 incluem técnicas de abordagem top-down e 1 artigo inclui técnicas das duas abordagens. As técnicas da abordagem bottom-up que aumentaram a independência nas AVDs foram Visuomotor Feedback Training, Smooth Pursuit Eye Movement Training e a combinação de Eye Patching com Constraint-induced Therapy. Na abordagem top-down as técnicas com os mesmos resultados foram Visual Scanning, Mental Practice, Continuous Theta Burst Stimulation e Transcranial Direct Current Stimulation. CONCLUSÃO: As abordagens bottom-up e top-down aumentam a independência nas AVDs e cada uma contém técnicas com significativo impacto positivo, como Visuomotor Feedback Training e Continuous Theta Burst Stimulation. O presente trabalho permitiu uma análise crítica à classificação das abordagens em bottom-up e top-down, uma vez que não são sensíveis à distinção dos mecanismos de reabilitação envolvidos.info:eu-repo/semantics/publishedVersio

Fucoidan from Fucus vesiculosus inhibits inflammatory response, both in vitro and in vivo

Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus, FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8–2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.This research received funding from project 0474_BLUEBIOLAB_1_E, financed by the European Regional Development Fund through INTERREG España-Portugal 2014–2020, and project ATLANTIDA (ref. NORTE-01-0145-FEDER-000040) supported by the Northern Portugal Regional Programme Norte 2020, under the Portugal 2020 Partnership Agreement. This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020) and LAQV-REQUIMTE (UIDB/50006/2020), financed by national funds of the Portuguese Foundation for Science and Technology (FCT)/MCTES. A. S. F. thanks FCT for the individual grant (SFRH/BD/102471/2014). This work was also funded by national funds (OE), through FCT, I.P., within the scope of the framework contract seen in numbers 4, 5 and 6 of article 23 of the Decree Law 57/2016, August 29, changed by Law 57/2017, July 19. The authors are also thankful to the financial support from the Natural Science Foundation of China (grant No. 32000936)

Adesão à terapêutica em diabéticos do tipo 2

Antecedentes/Objetivos: Atualmente regista-se um aumento significativo dos casos de Diabetes mellitus tipo 2 a nível mundial e em idades cada vez mais precoces (WHO, 2003; SPD, 2012). Segundo a SPD (2012), a prevalência desta patologia, em Portugal, em 2011, foi de 7,0%. Esta doença carateriza-se pelo aumento dos níveis de glicose no sangue, a hiperglicemia, que se deve, à insuficiente produção de insulina e/ou, à ação insuficiente da mesma (WHO, 2003; Nogueira et al, 2006; SPD, 2012). Na literatura a adesão terapêutica é retratada como o grau de concordância do comportamento do doente face às indicações do médico ou outro profissional de saúde, ao nível do cumprimento da prescrição médica e ao nível das indicações relativas ao estilo de vida e comportamentos saudáveis (WHO, 2003). Foram objetivos desta investigação determinar a adesão à terapêutica em diabéticos do tipo 2, utentes de uma farmácia comunitária localizada no concelho de Bragança, e identificar os motivos que mais contribuíram para a não adesão à terapêutica. Métodos: Estudo quantitativo transversal e analítico. A recolha de dados foi feita no período de janeiro a março de 2012 usando uma técnica de amostragem não probabilística acidental. Os utentes da farmácia foram abordados e convidados a participar, voluntariamente, no presente estudo aquando da dispensa de antidiabéticos orais (ADO). Na recolha de dados foi utilizado o teste de adesão ao tratamento (MAT), desenvolvido e validado para Portugal por Delgado & Lima (2001) e adaptado por Gimenes et al (2009). Participaram neste estudo 35 indivíduos com idades compreendidas entre os 48 e os 90 anos, sendo a maioria do género feminino (57,1%). Resultados: Relativamente à terapêutica medicamentosa, 91,4% dos utentes utilizam apenas antidiabéticos orais, 2,9% associam os antidiabéticos orais à insulina e 2,9% apenas utilizam insulina. Os resultados revelam que a esmagadora maioria (97,1%) adere à terapêutica medicamentosa. A hora da toma, seguido do esquecimento e do abandono da toma sem indicação médica foram os fatores que mais contribuíram para uma menor adesão à terapêutica. A dieta, o exercício físico e a toma de medicamentos associada a outras patologias mostram ser diferenciadoras do grau de adesão. Conclusiones: Esta investigação aponta para a necessidade do reforço das informações prestadas aos utentes com recurso a ferramentas que auxiliem o cumprimento das dosagens e horários. O uso de pictogramas, de informação escrita nas embalagens, a utilização de caixas multidose, entre outras medidas, são contributos, pouco dispendiosos e úteis, que ajudam a melhorar o grau de adesão à terapêutica medicamentosa

A National Wide Collaborative Study

INTRODUCTION: Even though the risk of COVID-19 in pregnancy may be increased, large-scale studies are needed to better understand the impact of the infection in this population. The aim of this study is to describe obstetric complications and the rate of vertical transmission in pregnant women with SARS-CoV-2 infection. MATERIAL AND METHODS: Detected cases of SARS-CoV-2 infection in pregnancy were registered in Portuguese hospitals by obstetricians. Epidemiological, pregnancy and childbirth data were collected. RESULTS: There were 630 positive cases in 23 Portuguese maternity hospitals, most at term (87.9%) and asymptomatic (62.9%). The most frequent maternal comorbidity was obesity. The rates of preterm birth and small-to-gestational-age were 12.1% and 9.9%, respectively. In the third trimester, 2.9% of pregnant women required respiratory support. There were eight cases (1.5%) of fetal death, including two cases of vertical transmission. There were five cases of postpartum respiratory degradation, but no maternal deaths were recorded. The caesarean section rate was higher in the first than in the second wave (68.5% vs 31.5%). RT-PCR SARS-CoV-2 positivity among newborns was 1.3%. CONCLUSION: SARS-Cov-2 infection in pregnancy may carry increased risks for both pregnant women and the fetuses. Individualized surveillance and the prophylaxis of this population with vaccination. is recommended in these cases.publishersversionepub_ahead_of_prin

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

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

Educação para a cidadania global em contexto português: possibilidades de integração curricular

Sem resumo disponível.publishe

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

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).info:eu-repo/semantics/publishedVersio

Meningite a Herpes zoster num adolescente – uma complicação rara da zona

A zona resulta da reativação do vírus varicela-zoster, latente na raíz dorsal dos gânglios sensitivos e nos gânglios dos nervos cranianos, após a resolução da varicela. Existem poucos estudos sobre as complicações da zona na população pediátrica. Enquanto que nos adultos está preconizada terapêutica antivírica específica contra o herpes zoster, nas crianças imunocompetentes o tratamento antivírico é questionável.Os adolescentes encontram-se entre estes dois grupos. O aciclovir é o único antivírico aprovado pela FDA para o tratamento da zona em crianças com menos de dois anos de idade. O valaciclovir, que apresenta uma maior biodisponibilidade, encontra-se aprovado como terapêutica contra a zona nos doentes entre os dois e os 17 anos. Descreve-se o caso de um adolescente, com zona, sem antecedentes patológicos de relevo, que sob terapêutica com aciclovir desenvolveu meningite a herpes-zoster. Questiona-se a abordagem clinica mais correta nos adolescentes imunocompetentes com zona