ABC2-Artigos (em revistas ou actas indexadas)
URI permanente para esta coleção:
Conteúdo: Artigos em revistas ou actas de conferências indexadas
a) incluídas na
a) incluídas na
- » Web of Science
- (v. www.webofknowledge.com)
- » ERIH
- (European Research Index for Humanities: erihplus)
- » Latindex
- (Sistema Regional de Información para Revistas Científicas de América Latina, Caribe, España y Portugal: latindex.org/latindex/)
- » Scielo
- (Scientific Electronic Library Online: www.scielo.org)
- » Scopus SJR
- (SCImago Journal & Country Rank: www.scimagojr.com)
Navegar
Percorrer ABC2-Artigos (em revistas ou actas indexadas) por Objetivos de Desenvolvimento Sustentável (ODS) "09:Indústria, Inovação e Infraestruturas"
A mostrar 1 - 10 de 39
Resultados por página
Opções de ordenação
- 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.
- 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.
- 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.
- Cold agglutinin syndrome in a patient with metastatic breast cancer: a Case reportPublication . Bandarra, Daniel; Rochate, Dina; Gosalbez, Beatriz; Ferreira, José; Cunha, Nidia Maltez; Carvalhal, SaraBackground: Cold agglutinin syndrome (CAS) is a form of autoimmune hemolytic anemia (AIHA), most often associated with lymphoproliferative disorders or infections. Its occurrence in breast cancer is rare and may be triggered by systemic treatment. Case presentation: We report the case of a woman in their fifties diagnosed with breast cancer in 2019. She underwent surgery followed by adjuvant chemotherapy and radiotherapy and subsequently received 3 years of endocrine therapy before developing bone and hepatic metastases. First-line treatment with ribociclib plus letrozole achieved partial response, and fulvestrant was administered at progression. Following further progression, paclitaxel was introduced as third-line metastatic therapy. After four weekly administrations, the patient was admitted to our hospital with severe anemia and diagnosed with CAS. Prompt management and a multidisciplinary approach resulted in partial hematological recovery. Nevertheless, paclitaxel was permanently discontinued, and subsequent therapies provided only transient benefit. The disease continued to progress, her performance status declined, and she ultimately transitioned to exclusive palliative care until death. Conclusion: This case illustrates a rare and severe immune complication of paclitaxel in metastatic breast cancer. The emergence of CAS not only limited systemic options but also reshaped the therapeutic trajectory, highlighting the need for close monitoring during cancer treatments. Early recognition, multidisciplinary approach, and prompt management can provide some improvement, although overall prognosis remains determined by the underlying malignancy.
- Fibrosis-related transcriptome unveils a distinctive remodelling matrix pattern in penetrating ileal Crohn’s diseasePublication . Sousa, Helena Tavares; Ferreira, Marta; Gullo, Irene; Rocha, Ana Mafalda; Pedro, Ana; Leitão, Dina; Oliveira, Carla; Carneiro, Fátima; Magro, FernandoBackground and Aims: Stricturing [B2] and penetrating [B3] ileal Crohn’s disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn’s disease. Methods: Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture[s] [B3s] and 12 without [B3o]. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes, a p-adjusted Results: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn’s disease localisa tion, perianal disease, and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn’s disease fibrogenesis, and eight differentially expressed genes were so in other organs. The most significantly active biological processes and pathways in penetrating disease were response to TGFβ and matrix organisation and degradation, as validated by immunohistochemistry. Conclusions: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn’s disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodelling.