ABC-RI
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Àcerca do Centro de Investigação Biomédica do Algarve => ABC-RI
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Percorrer ABC-RI 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.
- 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.
- 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.
- 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.
- Delays in the stroke care pathway in a low-income setting: an audit study from MozambiquePublication . Buque, Helena Agostinho; Smith, Lee; Lopes, Dino; Pizzol, Damiano; Lorenzo, Elder; Arroz, Nachan; Bacallau, Lazara; Sidat, Mohsin; Bauaze, Evangelina Namburete; Nzwalo, HipólitoBackground: The burden of stroke is on the rise in low-income countries (LICs). Organized stroke care (OSC) is crucial for improving outcomes in LICs and is the very first step to reducing delays in diagnosis and treatment. We aim to evaluate delay times (DT) in accessing OSC at the national reference hospital of Mozambique, a LIC from southern Africa. Methods: An observational study based on consecutive case series of 59 stroke patients confirmed by computed tomography (CT) scans over a period of 3 months (May–July 2023). The total DT (from stroke onset to inward hospitalization) was the main outcome. Other specific DTs were analyzed including initial symptoms to arrival and admission (DT0), arrival to CT scans (DT1), arrival of laboratory results (DT2), and arrival to inward hospitalization (DT3). Results: The mean age was 61.9 (min 30–max 90) and 45.8% were female. The median total DT was 20 h. The median time DT0 was 10.6 h (interquartile range (IQR): 16.48). The median DT1 and DT2 were 4 h (IQR: 3.5) and 5 h (IQR: 2.6), respectively. The median DT3 was 10 h (IQR: 4). None of the patients were treated under a stroke code. Conclusions: This study reveals an unacceptable prehospital and in-hospital DT. Waiting for the CT scan contributed to a large proportion of the total DT, which among other factors can be explained by the absence of a stroke code and limited imaging capacity. These findings mirror disparities in stroke care seen in other LICs, where late presentation, scarce imaging, and limited specialized protocols are common. The urgent implementation of organized prehospital and in-hospital stroke pathways is needed in Maputo to improve outcomes.
- Drug-related glomerular phenotypes: a global pharmacovigilance perspectivePublication . Baptista, Alexandre; Macedo, Ana; Marreiros, Ana; Coelho, André; Perazella, Mark A.Abstract: Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors’ knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as ‘potential nephrotoxins’ (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as ‘non-nephrotoxic’, a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.
- The immune tumor microenvironment in gliomas: may CITED2 play a role?Publication . Teotónio Fernandes, Mónica AlexandraGliomas are the most common brain cancers, resulting from transformed glial cells. CITED2 is a co-transcriptional regulator previously implicated in several types of cancer, affecting both cellintrinsic processes and the microenvironment. Because in breast cancer it was shown to contribute to the recruitment of macrophages and their polarization to an immunosuppressive phenotype, a potential similar role was explored in gliomas. By analyzing publicly available databases using a set of bioinformatics tools, it was found that CITED2 is overexpressed in higher-grade gliomas and contributes to an adverse prognosis. In addition, CITED2 expression correlates with macrophage infiltration and a M2 phenotype.