FCB2-Artigos (em revistas ou actas indexadas)
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- Impact of bariatric and metabolic surgery on sarcopenia-related parameters according to the EWGSOP2 consensus criteria in persons living with obesityPublication . Cardoso, Paulo Alexandre e Castro; Santos, Tânia V.; Ramon-Krauel, Marta; Pais, Sandra; De Sousa-Coelho, Ana LuísaAlthough bariatric and metabolic surgery (BS) has proved effective in the treatment of obesity based on the reduction in fat mass and the remission of comorbidities, there is also loss of lean mass after BS which could compromise muscle functionality. According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia is a disease associated with loss of muscle mass, strength, and function. Through a comprehensive review of the literature, we identified a range of studies focusing on evaluating sarcopenia-related parameters according to the EWGSOP2 consensus criteria, before and after BS. Although most studies reported reductions in skeletal muscle mass and absolute muscle strength after surgery, improvements in muscle functionality were generally achieved, independent of the type of BS.
- Unveiling inter- and intra-patient sequence variability with a multi-sample coronavirus target enrichment approachPublication . Lado, Sara; Thannesberger, Jakob; Spettel, Kathrin; Arapović, Jurica; Ferreira, Bibiana; Lavitrano, Marialuisa; Steininger, ChristophAmid the global challenges posed by the COVID-19 pandemic, unraveling the genomic intricacies of SARS-CoV-2 became crucial. This study explores viral evolution using an innovative high-throughput next-generation sequencing (NGS) approach. By taking advantage of nasal swab and mouthwash samples from patients who tested positive for COVID-19 across different geographical regions during sequential infection waves, our study applied a targeted enrichment protocol and pooling strategy to increase detection sensitivity. The approach was extremely efficient, yielding a large number of reads and mutations distributed across 10 distinct viral gene regions. Notably, the genes Envelope, Nucleocapsid, and Open Reading Frame 8 had the highest number of unique mutations per 1000 nucleotides, with both spike and Nucleocapsid genes showing evidence for positive selection. Focusing on the spike protein gene, crucial in virus replication and immunogenicity, our findings show a dynamic SARS-CoV-2 evolution, emphasizing the virus–host interplay. Moreover, the pooling strategy facilitated subtle sequence variability detection. Our findings painted a dynamic portrait of SARS-CoV-2 evolution, emphasizing the intricate interplay between the virus and its host populations and accentuating the importance of continuous genomic surveillance to understand viral dynamics. As SARS-CoV-2 continues to evolve, this approach proves to be a powerful, versatile, fast, and cost-efficient screening tool for unraveling emerging variants, fostering understanding of the virus’s genetic landscape.
- Insights into cockayne syndrome type B: what underlies its pathogenesis?Publication . Afonso Reis, Ricardo António; Madeira, Cristiana; Vilhena Catarino Brito, David; Nóbrega, ClévioCockayne Syndrome (CS) is an autosomal recessive disorder arising from mutations in either of two disease-associated genes, ERCC6 or ERCC8. CS patients exhibit cutaneous photosensitivity, neuropathological abnormalities, severe growth retardation, a distinctive facial appearance with pronounced sunken eyes, musculoskeletal anomalies, sensory impairment, and dental decay. Approximately 70% of all CS cases carry ERCC6 mutations; therefore, this review will focus solely on Cockayne Syndrome complementation group B (CS-B). CS-B exhibits several hallmarks of aging, including genomic instability, epigenetic modifications, loss of proteostasis, and mitochondrial failure. CS-B is proposed to result from the accumulation of DNA damage and the resulting transcription impairment. However, the main pathophysiological mechanisms underlying the severe cellular impairments observed in CS-B remain unclear. Here, we review the current literature to elucidate ERCC6-related mechanisms, highlighting the key and emerging pathological mechanisms underlying CS-B, as well as their putative interactions. Considering the mechanisms that heavily rely on ERCC6, we propose that CS-B pathogenesis arises from a combination of DNA damage accumulation, transcriptional dysregulation, and mitochondrial dysfunction. Furthermore, we argue that these molecular features influence each other, rather than acting as isolated mechanisms. This suggests that the crosstalk between mechanisms is a key factor for CS-B pathogenesis. Although efforts have been made to unveil CS-B pathogenesis, research is still lacking, hindering progress in understanding this deadly disease. Future work will prove crucial to determine the main contributor to CS-B pathogenesis and identify new interactions between CS-B-affected mechanisms.
- Serum biomarkers of extracellular matrix remodeling in ulcerative colitis—one step closer to fibrosis biomarkers in inflammatory bowel diseasePublication . Sousa, Helena Tavares; de Oliveira, RaquelFibrosis is a serious complication of both Crohn's disease (CD) and ulcerative colitis(UC) and is currently the major unmet need in inflammatory bowel disease (IBD) management [1]. Although much less prevalent in UC, strong evidence supports severity and chronicity of inflammation are the main drivers of excessive extracellular matrix (ECM) deposition in the submucosa and muscularis mucosae [2], leading to increased wall stiffness, and ultimately to motility and anorectal dysfunction, rectal urgency and incontinence.
- Prevalence and diagnostic comparison of helicobacter pylori and non-helicobacter pylori helicobacter infections in patients undergoing upper gastrointestinal endoscopy with gastric biopsy in Algarve, PortugalPublication . Mateus, Teresa Letra; Aguieiras, Catarina; Louro, Ricardo; Peixe, Bruno; Calhindro, Mauro; Nunes, Francisco José Viegas Cortez; Queirós, Patrícia; Castelo-Branco, PedroH. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori.
- Inhalable N-acetylcysteine-loaded lactose-coated PLGA nanoparticles for tuberculosis treatmentPublication . Chaudhary, Kabi Raj; Mestre Viegas, Cláudia Sofia; Pirela, Paola; Atalaia, Mariana; Ruivinho, Beatriz Lourenço; Arora, Sanchit; Singh, Arti; Brandão, Pedro; Singh, Charan; Fonte, PedroObjective Glutathione (GSH), known for having mucolytic, anti-inflammatory, and antioxidant activities, is used in clinical practice in several pathologies, including tuberculosis (TB). N-acetylcysteine (NAC) has been primarily used to treat lung conditions and paracetamol-induced liver toxicity. However, NAC exhibits potential antimycobacterial activity through several mechanisms including immunomodulation, enhancement of GSH levels, and direct antimycobacterial effect. In this work, we aim to develop an effective drug delivery system for NAC for inhalable formulations. Methods Herein, we report the development of lactose-coated NAC-loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NAC-PLGA NPs) obtained by double emulsion methodology. Lactose has a double role, as a cryoprotectant agent and dispersant for inhalable formulations. The physicochemical properties of lactose-coated NAC-PLGA NPs were examined in terms of particle size, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency, and morphology. The in vitro release and lung deposition studies were assessed. Results The physicochemical characterization studies revealed the compatibility of the drug with the selected excipients. Moreover, lactose-coated NAC-PLGA NPs showed particle size of 310±3 nm, PdI of 0.15±0.01, and of -11.5±0.4 mV. The in vitro release study suggested a biphasic release profile. Likewise, in vitro lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, in vitro studies for antimycobacterial activity exhibited superior antibacterial activity against Mycobacterium Tuberculosis (MTB) H37Rv. Conclusions These preliminary findings suggest that lactose-coated NAC-PLGA NPs can open the door to new therapeutic options against one of the most drug-refractory and drug-resistant infectious diseases, TB.
- Importance of axial kidney scans in ultrasound screening in prehospital assessment for renal colicPublication . Miravent, Sérgio; Gomes, Carla Marisa; Vaz, BrunaRenal screening sonography or renal point-of-care ultrasonography (POCUS) plays a crucial role in evaluating conditions such as renal colic in nephrolithiasis. When an obstructive cause such as a stone lodged in the urinary tract is not visualized sonographically during renal colic assessment, the presence of hydronephrosis and perirenal fluid becomes significant. These sonographic signs are often associated with more severe cases,1 prompting the need for further investigation by urology and radiology specialists. Definitive diagnosis and management may require conventional sonography or the gold standard, computed tomography (CT). However, both imaging modalities and specialists are unavailable in peripheral prehospital settings, as are hematological and urine analyses.
- Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in micePublication . Ferreira-Marques, Marisa; Carmo-Silva, Sara; Pereira, Joana; Botelho, Mariana; Nóbrega, Clévio; López‐Otín, Carlos; Almeida, Luís Pereira de; Aveleira, Célia A.; Cavadas, CláudiaThe hypothalamus has been recognized as a regulator of whole-body aging. Neuropeptide Y (NPY), highly abundant in the central nervous system and produced by the hypothalamus, enhances autophagy in this brain region and mediates autophagy triggered by caloric restriction, suggesting a potential role as a caloric restriction mimetic and an aging regulator. Considering that hypothalamic NPY levels decline during aging, we investigated if reestablishment of NPY levels mitigate aging phenotype, using a mouse model of premature aging – Zmpste24−/− mouse. The results show that reestablishing hypothalamic NPY levels delayed aging-associated features, including lipodystrophy, alopecia, and memory. Moreover, these results suggest that strategies that promote maintenance of hypothalamic NPY levels might be relevant to counteract aging progression and age-related deteriorations.
- 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.
- Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes in contemporaneous clinical practicePublication . Costa, Hugo; Espírito-Santo, Miguel; Fernandes, Raquel; Bispo, João; Guedes, João; Azevedo, Pedro; Carvalho Silva, Daniela; Vinhas, Hugo; Gonçalves, Rui Baptista; Mimoso, JorgeBACKGROUND Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes (NSTE-ACS) during hospitalization is still a matter of contention within the cardiology community. Our aim was to analyze in-hospital and one-year follow-up outcomes of patients with NSTE-ACS pretreated with dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT). METHODS A retrospective study was carried out with NSTE-ACS patients who planned to undergo an invasive strategy and were included in the Portuguese Registry of ACS between 2018 and 2021. A composite primary outcome (in-hospital re-infarction, stroke, heart failure, hemorrhage, death) was compared regarding antiplatelet strategy (DAPT versus SAPT). Secondary outcomes were defined as one-year all-cause mortality and one-year cardiovascular rehospitalization. RESULTS A total of 1469 patients were included, with a mean age of 66 12 years, and 73.9 % were male. The DAPT regime was used in 38.2 % of patients and SAPT in 61.8 % of patients. NSTE myocardial infarction was the most frequent presentation (88.5 %). Revascularization was performed within 24 h in 55.2% of patients. Time until revascularization >24 h occurred in 44.8% of patients, with 16.5% of these between [24 h–48 h], 10.6% in [48 h–72 h] and 17.6% > 72 h. The primary outcome was more frequently observed in the SAPT group (10.4 %, p ¼ 0.033), mainly driven by more ischemic events. Time until revascularization >72 h and the SAPT regime were independent predictors of the primary outcome (OR 3.09, p ¼ 0.005, and OR 2.03, p ¼ 0.008, respectively).