ABC2-Artigos (em revistas ou actas indexadas)
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Percorrer ABC2-Artigos (em revistas ou actas indexadas) por Objetivos de Desenvolvimento Sustentável (ODS) "03:Saúde de Qualidade"
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- Activity induced genes expression is impaired in polyglutamine spinocerebellar ataxiasPublication . Torquato Afonso, Inês; Vilhena Catarino Brito, David; Bading, Hilmar; Nóbrega, ClévioPolyglutamine Spinocerebellar ataxias (SCAs) are a group of 6 incurable genetic disorders, caused by an expansion of the trinucleotide cytosine-adenine-guanine in their causative genes, which produces a protein with an expanded glutamine region. This project focuses on the study of Spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) (1), which are rare dominantly inherited disorders that primarily impair the cerebellum therefore leading to motor ataxia. Activity-induced inhibitor of death (AID), are a group of pro-survival 9 genes which were found to be neuroprotector in several neurological disorders, including stroke, glaucoma, AD, HD, and ALS (2). In this project, we aim to investigate about the relevance of the expression of AID genes for cerebellum function and whether their expression levels are impaired in SCA2 and SCA3
- Annexin A2 regulates AKT upon H2O2-dependent signaling activation in cancer cellsPublication . Castaldo, Stéphanie Anais; Ajime, Tom; Serrão Fernandes, Lina Gisela; Anastácio, Fábio; Rosa, Joana Teixeira; Giacomantonio, Carman Anthony; Howarth, Alison; Hill, Richard; Madureira, PatriciaHydrogen peroxide (H2O2) is a main second messenger in oncogenic signaling networks including the Ras and the growth factor receptor pathways. This is achieved predominantly through the oxidation of redox-sensitive cysteine (Cys) residues in proteins resulting in changes to their structure and function. We previously identified annexin A2 (ANXA2) as a redox regulatory protein that plays an important cellular role during oxidative stress and also promoting tumorigenesis. Here we investigated the role of ANXA2 in the regulation of H2O2-dependent signaling that drives tumor progression. We show that depletion of ANXA2 leads to the enhanced activation of AKT following either EGF/EGFR stimulation or oncogenic Ras transformation. The phosphatase and tensin homologue (PTEN) protein negatively regulates the PI3K/AKT pathway. We demonstrate that ANXA2 via its reactive Cys-8 residue, binds to PTEN and that the co-expression of PTEN and ANXA2, but not ANXA2 Cys-8-Ala mutant, inhibits AKT phosphorylation on Ser 473. These results indicate that ANXA2 is important for PTEN regulation within the PI3K/AKT signaling cascade. Furthermore, we also reveal that ANXA2 inversely regulates the expression of the peroxidase, peroxiredoxin 2, in a reactive oxygen species dependent manner.
- Antimicrobial and antioxidant activities of natural compounds: enhance the safety and quality of foodPublication . Faleiro, Maria Leonor; Miguel, Maria da GraçaNature has offered us a tremendous diversity of natural compounds, for which antimicrobial and antioxidant properties have been intensively explored and nowadays are plenty recognized. During the last decades both the antimicrobial action of natural compounds (preventing and limiting microbial growth) and their antioxidant properties (reducing the oxidation of fats and limiting the ripening and browning of fruit and vegetables after harvesting) have been intensively investigated, particularly in the food packaging sector, evidencing that they may represent an effective eco-friendly approach to enhance the safety and quality of food products, without an environmentally deleterious impact.
- Association of epigenetic age and outcome in critically Ill patientsPublication . Sharma-Oates, Archana; Sullivan, Jack; Pestana, Daniel; Santos, Claudia C. dos; Binnie, Alexandra; Lord, Janet M.OBJECTIVES: DNA methylation can be used to determine an individual’s biological age, as opposed to chronological age, an indicator of underlying health status. This study aimed to assess epigenetic age in critically ill patients with and without sepsis to determine if higher epigenetic age is associated with admission diagnosis or mortality. DESIGN: Secondary analysis of whole blood DNA methylation data generated from a nested case–control study of critically ill septic and nonseptic patients. SETTING: Four tertiary care hospitals in Canada. INTERVENTIONS: None. PATIENTS: Critically ill patients with and without sepsis. MEASUREMENTS AND MAIN RESULTS: Epigenetic age was derived from DNA methylation data using the Hannum and PhenoAge algorithms and deviation from the patient’s chronological age in years was determined. Of the 66 patients with sepsis, 34 were male (51.5%), the mean age was 65.03 years and 25 patients (37.8%) died before discharge. Of the 68 nonseptic patients, 47 were male (69.1%), the mean age was 64.92 years and 25 (36.7%) died before discharge. Epigenetic age calculated using the PhenoAge algorithm showed a significant age acceleration of 4.97 years in septic patients (p = 0.045), but no significant acceleration in nonseptic patients. Epigenetic age calculated using the Hannum algorithm showed no significant acceleration in the septic or nonseptic patients. Similarly, in the combined septic and nonseptic cohorts, nonsurvivors showed an epigenetic age acceleration of 7.62 years (p = 0.004) using the PhenoAge algorithm while survivors showed no significant age acceleration. Survivor status was not associated with age acceleration using the Hannum algorithm.
- Basal progenitors as drivers of neocortical expansionPublication . Barao, Soraia; Müller, UlrichThe diversification and expansion of distinct progenitor cell subtypes during embryogenesis are essential to form the sophisticated brain structures present in vertebrates. In particular, the emergence of highly proliferative basal progenitors contributed to the evolutionary enlargement of the mammalian neocortex. Basal progenitors are at the center of indirect neurogenesis and can be divided into two main subtypes: the classical TBR2-positive intermediate progenitor cells and the outer radial glial cells, which are especially abundant in gyrencephalic species. While the function of some transcriptomic regulators is conserved across the mammalian clade, recent studies have identified human-specific genes and enhancers that uniquely affect progenitor biology, possibly driving the increased neocortical complexity and disease-susceptibility of the human brain. Here, we review the evolution of basal progenitors, highlighting species-specific traits, molecular drivers of proliferation, and how imbalances in neurogenesis contribute to human brain disorders.
- Biological therapies for metastatic colorectal cancer: literature reviewPublication . Almeida, Maria Patricia; Condinho, MónicaColorectal cancer is among the most prevalent and lethal malignancies worldwide. Its initially asymptomatic nature contributes to a high incidence of metastatic cases. Although predominantly diagnosed in older adults, the incidence among younger populations is rising at an alarming rate. Historically, treatment has relied on antineoplastic agents such as 5-fluorouracil, irinotecan, and oxaliplatin. While these agents remain in use, their effectiveness is limited, particularly in metastatic disease, with modest improvements in overall survival and progressionfree survival. Moreover, their low target specificity results in significant systemic toxicity. This underscores the urgent need formore selective and less toxic therapeutic strategies, such as monoclonal antibodies. Monoclonal antibodies targeting Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor Receptor (EGFR), and immune checkpoints have become integral to the management of metastatic colorectal cancer. Notable examples include bevacizumab (anti-VEGF), cetuximab and panitumumab (anti-EGFR), and the immune checkpoint inhibitors pembrolizumab, nivolumab, and ipilimumab. Their clinical success especially when guided by molecular tumour profiling highlights their contribution to improved patient outcomes. In addition, other targeted therapies distinct from monoclonal antibodies are currently under investigation.
- Biopotential of sea cucumbers (echinodermata) and tunicates (chordata) from the western coast of portugal for the prevention and treatment of chronic illnessesPublication . Carletti, Alessio; Cardoso, Carlos; Juliao, Diana; Arteaga, Jorge L.; Chainho, Paula; Dionísio, Maria Ana; Sales, Sabrina; Gaudêncio, Maria J.; Ferreira, Inês; Afonso, Cláudia; Lourenço, Helena; Cancela, M. Leonor; Bandarra, Narcisa M.; Gavaia, PauloIn the present work, we aimed to explore the potential of two groups of marine invertebrates—sea cucumbers (Echinodermata) and ascidians (Chordata)—as sources of antiinflammatory, anti-oxidant, and osteogenic compounds with potential to be used as pharmaceuticals and nutraceuticals for the treatment and prevention of chronic diseases. 24 extracts (ethanol, water, and ethyl acetate) from 4 species of sea cucumbers and 4 species of tunicates were produced and screened in vitro for their anti-inflammatory and anti-oxidant activities and in vivo for osteogenic activity through an assay using zebrafish larvae. Our results showed that ethanolic extracts presented anti-oxidant and anti-inflammatory activity, which revealed to be stronger in the ascidians. The osteogenic activity, which provides evidence of the bioactive potential of these organisms in preventing chronic disorders causing low bone density, was found to be strong in one species of ascidians and 3 of holothurians. This study demonstrates the high potential of extracts from these marine organisms for using as nutraceuticals in the prevention of chronic bone disorders.
- The burden of COVID-19 care in community and academic intensive care units in Ontario, Canada: a retrospective cohort studyPublication . Pestana, Daniel; Joshi, Divya; Duan, Erick; Fowler, Robert; Tsang, Jennifer; Binnie, AlexandraDuring the COVID-19 pandemic, neighbourhoods with high material deprivation and high proportions of racialized Canadians were disproportionately affected by COVID-19. Many of these neighbourhoods were served by community hospitals. We sought to compare the burden of COVID-19 care in community and academic intensive care units (ICUs) in Ontario, Canada. We included all adult patients admitted to Ontario ICUs with COVID-19 between 1 March 2020 and 31 July 2021 in a retrospective cohort study. We compared patient volumes, demographics, interventions, and outcomes between community hospital corporations (CHCs) and academic hospital corporations (AHCs). During the first three waves of the pandemic, 9,651 adult ICU admissions for COVID-19 were reported across 72 hospital corporations in Ontario: 6,902 (71.5%) in CHCs and 2,749 (28.5%) in AHCs. Days of ICU care per baseline ICU bed were highest in large CHCs ([ 10 baseline ICU beds) relative to AHCs and small CHCs (median [interquartile range], 73.7 [53.8–110.6] vs 42.2 [32.7–71.8] vs 21.4 [7.2–40.3]; Kruskal–Wallis test, P \ 0.001). Among direct ICU admissions, CHC patients had greater severity of illness whereas among transfer ICU admissions, AHC patients were more severely ill. In a multivariable logistic regression model, mortality was similar among patients with index admission to a CHC or AHC; however, patients with index admission to an AHC were more likely to receive extracorporeal membrane oxygenation (adjusted odds ratio, 6.16; 95% confidence interval, 4.72 to 8.11). During the pandemic, Ontario’s large CHCs provided significantly more days of ICU COVID-19 care per baseline ICU bed compared with AHCs and small CHCs. Equipping large CHCs to handle ICU surges during future emerging disease outbreaks should be a priority for pandemic preparedness.
- Chemical and health risks of swimming pool maintenance workersPublication . Silva, Adriana; Pinto, Ezequiel; Braz, Nídia Maria Dias Azinheira RebeloSwimming pool maintenance workers are exposed to occupational hazards, as it involves the regular handling of toxic chemicals. These exposures can result in acute reactions or chronic complications. The present study, still in the design phase, aims to describe the chemical and biological exposure of workers of a swimming pool maintenance company and to verify its compliance with the safety standards in force. A quantitative questionnaire will identify the use of personal protective equipment, chemical agents, and handling procedures, particularly regarding the time and frequency of use.
- Chromenone derivatives as CRM1 inhibitors for targeting glioblastomaPublication . Princiotto, Salvatore; Jiménez, Lucía; Domínguez, Lucía; Sequeira, João G. N.; Mourato Paulo, Cristiana Isabel; Orea-Soufi, Alba; da Silva Santos, Bruno Filipe; Dallavalle, Sabrina; Machuqueiro, Miguel; Ferreira, Bibiana; Link, WolfgangGlioblastoma (GBM) is one of the most aggressive and deadly cancers. Due to the complexity and redundancy within signaling networks in GBM, targeted inhibitors of specific pathways have shown only limited success. The nuclear export receptor chromosome region maintenance 1 (CRM1) has recently emerged as a promising therapeutic target, as its inhibition can simultaneously disrupt multiple key oncogenic drivers. Herein, whether chromenone derivatives, known for detecting thiol-containing molecules, can function as CRM1 inhibitors is explored. Several chromenonebased derivatives are synthesized and it is demonstrated that they inhibit CRM1-driven nuclear export in a structure- and dose-dependent manner. A preliminary structure–activity relationship is established, providing a rationale for selective CRM1 binding based on molecular docking studies. Additionally, it is showed that the active chromenone derivatives effectively inhibit the nuclear export of endogenous nuclear export signal-containing substrates in GBM cells. Several of these compounds exhibit selective cytotoxicity againstGBM cell lines, highlighting their potential as targeted therapies for GBM.