Therapeutic Options in Neuro-Oncology

One of the biggest challenges in neuro-oncology is understanding the complexity of central nervous system tumors, such as gliomas, in order to develop suitable therapeutics. Conventional therapies in malignant gliomas reconcile surgery and radiotherapy with the use of chemotherapeutic options such as temozolomide, chloroethyl nitrosoureas and the combination therapy of procarbazine, lomustine and vincristine. With the unraveling of deregulated cancer cell signaling pathways, targeted therapies have been developed. The most affected signaling pathways in glioma cells involve tyrosine kinase receptors and their downstream pathways, such as the phosphatidylinositol 3-kinases (PI3K/AKT/mTOR) and mitogen-activated protein kinase pathways (MAPK). MAPK pathway inhibitors include farnesyl transferase inhibitors, Ras kinase inhibitors and mitogen-activated protein extracellular regulated kinase (MEK) inhibitors, while PI3K/AKT/mTOR pathway inhibitors are divided into pan-inhibitors, PI3K/mTOR dual inhibitors and AKT inhibitors. The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.This work was funded by the Portuguese Foundation for Science and Technology (FCT), Portugal: grant numbers PTDC/MED-ONC/29402/2017, UIDP/04138/2020 and UIDB/04138/2020.info:eu-repo/semantics/publishedVersio

Effect of 6% maltodextrin intake on capillary lactate concentration in soccer players

Communication abstract: Proceedings of the 5th International Congress of CiiEM - Reducing inequalities in Health and Society, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from June 16th to 18th, 2021.This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Recent literature suggests that ergogenic substances may play a beneficial role in intermittent exercise. Maltodextrin supplementation has been investigated in soccer players, but few studies have been reported. The aim of this study was to evaluate the effect of 6% maltodextrin supplementation on capillary lactate in soccer players. The study was carried out during soccer training, which was characterised by intense activity (90 min). Participants (n = 24) were randomly allocated in control (water) and intervention (6% maltodextrin solution) groups. Capillary lactate levels were evaluated at pre-exercise (0 min—t0), exercise (45 min—t1), and post-exercise (90 min—t2) moments. At t1, the mean capillary lactate concentration value was significantly higher in players not supplemented with 6% maltodextrin (5.47 mmol/L) than in supplemented players (4.79 mmol/L).info:eu-repo/semantics/publishedVersio

Behind Brain Metastases Formation: Cellular and Molecular Alterations and Blood Brain Barrier Disruption

Breast cancer (BC) brain metastases is a life-threatening condition to which accounts the poor understanding of BC cells’ (BCCs) extravasation into the brain, precluding the development of preventive strategies. Thus, we aimed to unravel the players involved in the interaction between BCCs and blood–brain barrier (BBB) endothelial cells underlying BBB alterations and the transendothelial migration of malignant cells. We used brain microvascular endothelial cells (BMECs) as a BBB in vitro model, under conditions mimicking shear stress to improve in vivo-like BBB features. Mixed cultures were performed by the addition of fluorescently labelled BCCs to distinguish individual cell populations. BCC–BMEC interaction compromised BBB integrity, as revealed by junctional proteins (β-catenin and zonula occludens-1) disruption and caveolae (caveolin-1) increase, reflecting paracellular and transcellular hyperpermeability, respectively. Both BMECs and BCCs presented alterations in the expression pattern of connexin 43, suggesting the involvement of the gap junction protein. Myosin light chain kinase and phosphorylated myosin light chain were upregulated, revealing the involvement of the endothelial cytoskeleton in the extravasation process. β4-Integrin and focal adhesion kinase were colocalised in malignant cells, reflecting molecular interaction. Moreover, BCCs exhibited invadopodia, attesting migratory properties. Collectively, hub players involved in BC brain metastases formation were unveiled, disclosing possible therapeutic targets for metastases prevention.This work was funded by the Portuguese Foundation for Science and Technology (FCT), Portugal, grant numbers PTDC/MED-ONC/29402/2017, UIDP/04138/2020 and UIDB/04138/2020. We also acknowledge FCT financial support of J.G.-P. (SFRH/BD/145522/2019) and of A.R.G. (2020.07115.BD). We acknowledge the Faculty of Sciences of the University of Lisbon’s Microscopy Facility, a node of the Portuguese Platform of BioImaging (PPBI-POCI-01-0145-FEDER-022122). We also acknowledge Luís Marques (Faculty of Sciences, University of Lisbon) for the excellent technical support with image acquisition.info:eu-repo/semantics/publishedVersio

Effect of Cinnamon Tea on Postprandial Glucose Concentration

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period

The choroid plexus in health and in disease: dialogues into and out of the brain

This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150 mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer's disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer's disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder Alzheimer's disease), and how sex-differences may relate to disease susceptibility.The work at ICVS/3B's has the support of Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). JCS, FM and JAP have the support of a fellowship from Bial Foundation through Grant 217/12. Fernanda Marques is a recipient of a FCT Investigator award (IF/ 00231/2013) of the Fundação para a Ciência e Tecnologia (FCT, Portugal). The work by JP has been financed by the following grants: Deutsche Forschungsgemeinschaft DFG PA930/9, DFG PA930/12; VIAA Latvia NFI/ R/2014/023; Leibniz Society SAW-2015-IPB-2; HelseSØ No: 2016062; Norsk forskningsrådet: NFR251290, NFR246392, NFR248772, JPND NeuroGEM NFR247179, JPND PROP-AD NFR260786. The work by CS has been supported by the Portuguese Foundation for Science and Technology (FCT, Portugal – hrrp://www.fct.pt) project grants (PTDC/SAU-NEU/114800/2009); and by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT - Foundation for Science and Technology (Project UID/ Multi/00709). The work by AB at Faculty of Pharmacy, Universidade de Lisboa, was funded, in part, by iMed.ULisboa (UID/DTP/04138/2013) from Fundação para a Ciência e a Tecnologia (FCT), Portugal.info:eu-repo/semantics/publishedVersio

Forget How We Got Here? Newspaper Coverage of the Royal Charter Deal

When Leveson published his Report at the end of November our research showed that the press presented the story as one mainly about freedom of the press and the struggle by hacking victims for vindication and protection in the future. Slightly less prominent but also present was a narrative of the politico-media complex or ties between big media and politicians. Our latest study of newspaper coverage before and after the Royal Charter agreement for implementing Leveson’s recommendations showed that the struggle of the victims of press wrongdoings has all but disappeared from the story

Portuguese Pinus nigra J.F. Arnold populations: genetic diversity, structure and relationships inferred by SSR markers

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Useful Molecular and Cytogenetic Approaches in Population Genetics Studies of Pine Species

In the last decade, we characterised Portuguese populations of Pinus sylvestris L., Pinus nigra Arnold and Pinus pinaster Aiton by using different molecular and cytogenetic approaches. DNA markers helped assess intra- and inter-population genetic variability, extrapolation of phylogenies, provenances and/or infraspecific taxonomy. Quantitative real-time polymerase chain reaction (qRT-PCR), Classical Cytogenetics techniques and/or Comet assay were valuable to assign origins, infraspecific taxa or populations more tolerant to water stress. Seed germination tests coupled with the cytogenetic analysis of root cell division provided clues about the impact of fire recurrence on the natural regeneration ability and root growth, respectively. Molecular Cytogenetics contributed to detecting chromosomal anomalies commonly detected in individuals from peripheral populations relative to the species’ natural distribution area. The studies briefly described in this chapter integrated multidisciplinary R&D projects whose assembled results allowed inferences about the adaptive potential of the analysed Pinus spp. and relevant information for the definition of strategies concerning germplasm conservation, management, use, and, ultimately, genetic improvement