ABC2-Artigos (em revistas ou actas indexadas)
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- Immunomodulatory inhibition of osteoclastogenesis by a marine microalgal ethanol fraction targeting T-cells, antigen presentation, and macrophage fatePublication . Carletti, Alessio; Pes, Katia; Tarasco, Marco; Rosa, Joana; Poudel, Sunil; Pereira, Hugo; Louro, Bruno; Cancela, M. Leonor; Laizé, Vincent; Gavaia, PauloBackground: Targeting immune pathways to prevent bone loss represents a promising, yet underexplored therapeutic strategy. Methods: An ethanol-soluble fraction derived from the freeze-dried biomass of the marine microalga Skeletonema costatum (SKLT) was tested for its ability to modulate immune responses and inhibit osteoclastogenesis. Its effects were evaluated in a zebrafish model of bone regeneration, a medaka model of RANKLinduced osteoporosis, and in vitro using murine RAW 264.7 macrophages. Transcriptomic profiling of regenerating fin blastemas at 24 hours postamputation was performed to identify the affected molecular pathways. Results: In zebrafish, SKLT treatment suppressed the recruitment of osteoclast precursors and altered mineralization dynamics. Transcriptomic profiling revealed downregulation of genes involved in inflammation, antigen presentation, T-cell activation, and macrophage commitment towards osteoclastogenesis, accompanied by reduced expression of chemokines and cytokines that promote osteoclast precursor recruitment and fusion. In medaka, SKLT significantly reduced vertebral bone loss and enhanced neural arch mineralization in larvae with high RANKL expression. In vitro, SKLT inhibited proliferation and osteoclastic differentiation of murine RAW 264.7 macrophages exposed to RANKL without inducing cytotoxicity. Conclusion: These findings identify S. costatum as a source of bioactive immunomodulatory compounds capable of interfering with key osteoimmune mechanisms. Beyond providing proof of concept for their therapeutic potential in bone erosive disorders, this work opens avenues for isolating and characterizing the active molecules, optimizing their delivery, and evaluating their efficacy in preclinical mammalian models. Such strategies could expand the repertoire of safe, nutraceutical-based or adjuvant therapies for osteoporosis and other inflammation-driven skeletal diseases, complementing and potentially enhancing current antiresorptive and anabolic treatments.
- Comparing the diagnostic performance of ultrasound elastography and magnetic resonance imaging to differentiate benign and malignant breast lesions: a systematic review and meta-analysisPublication . Gomes, Ana Filipa; Justino, David; Tomás, Carina; Jesus, Diogo; Macedo, Ana; Pinto, Ezequiel; Leitao, HelenaObjective: The purpose of this systematic review and meta-analysis was comparing diagnostic performance of ultrasound elastography (UE), strain UE and shear wave elastography (SWE), with magnetic resonance imaging (MRI) in differentiating benign and malignant breast lesions. Methods: Literature search of MEDLINE, Web of Science, SCOPUS and Google Scholar was performed in June 2023. Included studies used Breast Imaging Reporting and Data System (BI-RADS) and histopathology as reference standard. A bivariate random-effects model was used to calculate sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios and area under the curve (AUC). Meta-regression subgroup analysis was performed. Results: Nine studies and 536 lesions were included. Pooled sensitivity was not different between MRI vs UE [MRI: 94% (95% CI: 88.2%-96.9%) vs UE: 90% (95% CI: 84.7%-93.1%); P=0.153] but a difference was found for specificity [UE: 78% (95% CI: 66.3%-86.4%) vs MRI: 71.3% (95% CI: 52.1%-85%); P=0.0065]. Strain UE showed higher specificity and similar sensitivity to SWE [strain UE: 0.85 (95% CI: 0.71-0.93) vs SWE: 0.72 (95% 0.58-0.83); P=0.017 and strain UE: 0.87 (95% CI 0.79-0.93) vs SWE: 0.91 (95% CI 0.85-0.95); P=0.311, respectively]. AUC was similar between MRI vs UE [0.91 (95% CI 0.87-0.95) vs 0.92 (95% CI 0.88-0.95); P=0.452, respectively] as was DOR [MRI: 38.083 (95% CI: 12.401-116.957) vs UE: 30.395 (95% CI: 16.572-55.75); P > 0.05]. Meta-regression analysis found no significant differences in the diagnostic accuracy between MRI, strain UE and SWE. Conclusion: Our results show that UE when compared to MRI has adequate performance in differentiating benign and malignant breast lesions.
- Editorial: advancing cancer therapy: innovative strategies targeting immune evasion and metabolic modulationPublication . Teotónio Fernandes, Mónica Alexandra; De Sousa-Coelho, Ana Luísa; Méndez-Lucas, AndrésCancer remains one of the leading causes of death worldwide, with both incidence and mortality continuing to rise despite advances in diagnosis and treatment (1). While early-stage cancers often respond to conventional therapies, advanced and recurrent tumors frequently develop resistance, limiting long-term therapeutic efficacy (2).Two fundamental hallmarks of cancer, immune evasion and metabolic reprogramming, enable tumors to thrive in hostile microenvironments (3, 4). Although immunotherapies have revolutionized cancer care, a significant proportion of patients either fail to respond or acquire resistance over time (5). In parallel, altered tumor metabolism is increasingly recognized as a promising therapeutic target, particularly for enhancing responses to immunotherapy (7).This Research Topic highlights recent advances that move beyond traditional treatment. Collectively, the nine featured articles provide valuable insights into the interplay between immunity and metabolism in cancer, exploring strategies to overcome therapeutic resistance and improve clinical outcomes across diverse cancer types.
- Long-term predictive accuracy of the ‘mild cognitive impairment due to Alzheimer's disease’ criteriaPublication . Cardoso, Sandra; Montalvo, Alexandre; Maroco, João; Silva, Dina; Alves, Luísa; Guerreiro, Manuela; Mendonça, Alexandre deBackground: The development and clinical use of biomarkers has dramatically changed the framework of Alzheimer’s disease (AD) management, allowing the diagnosis at the mild cognitive impairment (MCI) stage. In 2015 we compared the prevalence and prognosis of AD at the MCI stage according to different criteria available at that time, and we found that the National Institute of Aging-Alzheimer Association (NIA-AA) criteria provided higher predictive accuracy for AD dementia after 3 years. Since then, we adopted these criteria in clinical practice. Objective: To evaluate the long-term predictive accuracy of the ‘MCI due to AD - high likelihood’ criteria by taking advantage from an extended follow-up in a memory clinic setting. Methods: Patients were diagnosed according to the ‘MCI due to AD - high likelihood’ criteria and followed up until conversion to dementia. Results: One hundred and fourteen patients with ‘MCI due to AD - high likelihood’ were enrolled in the study and followed-up for 3.0±1.8 [0.4–8.3] years. During the follow-up 106 (93.0%) patients progressed to dementia, 2 (1.8%) had stroke, 6 (5.3%) died, and none remained in MCI or reverted to normal cognitive status. The average survival time remaining in MCI, analyzed with Kaplan-Meier curve, was 3.2 (95% CI 2.9–3.6) years. Using a multivariate Cox proportional hazards regression model, patients with higher Mini-Mental State Examination kept the MCI status longer. Conclusions: The diagnostic criteria of NIA-AA ‘MCI due to AD - high likelihood’ have an excellent long-term predictive accuracy in a memory clinic setting.
- Molecular detection of multiple antimicrobial resistance genes in helicobacter pylori-positive gastric samples from patients undergoing upper gastrointestinal endoscopy with gastric biopsy in Algarve, PortugalPublication . Nunes, Francisco José Viegas Cortez; Aguieiras, Catarina; Calhindro, Mauro; Louro, Ricardo; Peixe, Bruno; Queirós, Patrícia; Castelo-Branco, Pedro; Mateus, Teresa LetraBackground/Objectives: Helicobacter pylori (H. pylori) is a common gastric pathogen linked to gastritis, gastroduodenal ulcers, and gastric cancer. Rising antimicrobial resistance (AMR) poses challenges for effective treatment and has prompted the WHO to classify H. pylori as a high-priority pathogen. This study aimed to detect the prevalence of AMR genes in H. pylori-positive gastric samples from patients in Algarve, Portugal, where regional data is scarce. Methods: Eighteen H. pylori-positive gastric biopsy samples from patients undergoing upper gastrointestinal endoscopy were analyzed. PCR and sequencing were used to identify genes associated with resistance to amoxicillin (Pbp1A), metronidazole (rdxA, frxA), tetracycline (16S rRNA mutation) and clarithromycin (23S rRNA). Sequence identity and homologies were verified using tBLASTx and the Comprehensive Antibiotic Resistance Database (CARD). Results: Out of the 18 H. pylori-positive samples, 16 (88.9%) contained at least one AMR gene. The most frequent genes were rdxA (83.3%) and frxA (66.7%) for metronidazole resistance, and the 16S rRNA mutation (66.7%) for tetracycline. Resistance to amoxicillin and clarithromycin was detected in 27.8% and 16.7% of cases, respectively. Most samples (72.2%) had multiple resistance genes. A significantly strong association was found between female sex and the presence of the rdxA gene (p = 0.043). Conclusions: The study reveals a high prevalence of H. pylori resistance genes in Algarve, particularly against metronidazole and tetracycline. These findings highlight the need for local surveillance and tailored treatment strategies. Further research with larger populations is warranted to assess regional resistance patterns and improve eradication efforts.
- Targeting trypanothione synthetase and Trypanothione reductase: development of common inhibitors to tackle Trypanosomatid diseasePublication . Augusto, André; Costa, Inês; Conceição, Jaime; Cristiano, Maria de LurdesNeglected Tropical Diseases (NTDs) encompass a range of disorders, including infectious diseases caused by viruses, bacteria, parasites, fungi, and toxins, mainly affecting underprivileged individuals in developing countries. Among the NTDs, those caused by parasites belonging to the Trypanosomatidae family are particularly impacting and require attention, since the lack of financial incentives has led to constraints on the development of novel drugs to tackle them effectively. To circumvent the minor advances in drug discovery in this area, academic research emerges as a crucial player, namely through the identification and validation of new drug targets, thereby contributing to the development of more efficient, safe, and less expensive therapies against Trypanosomatidae infections. Noteworthy, this is a matter of utmost urgency since these diseases are endemic in countries with low socioeconomic standards. This review provides a comprehensive understanding of the current paradigm of NTDs caused by parasites belonging to the Trypanosomatidae family, addressing the ongoing limitations and challenges associated to the current chemotherapy solutions for these diseases and discussing the opportunities unravelled by recent research that led to the identification of new biomolecular targets that are common to Trypanosomatidae parasites. Among these, the unique properties of Trypanothione Synthetase (TryS) and Trypanothione Reductase (TryR), two key protozoan enzymes that are essential for the survival of Trypanosoma and Leishmania parasites, will be emphasised. In addition to a critical analysis of the latest advances in the discovery of novel molecules capable of inhibiting TryS and TryR, the possibility of dual targeting through a combination of TryS and TryR inhibitors will be addressed.
- An integrative review of potential diagnostic biomarkers for complex regional pain syndromePublication . Lopes, Revelino; Santos, André; Gomes, Teresa; Ribeiro, Júlia; Rodrigues, Ivone; Paiva, Bruno; Nzwalo, Isa; Catamo Vaz, Deise Haua da Silva; Baco, Jamal; Buque, Helena Agostinho; Botelho, Marta; Pais, Sandra; Nzwalo, HipólitoBackground: Complex regional pain syndrome (CRPS) is a rare, chronic, painful, neurological, debilitating disorder. Despite the substantial impact on quality of life, diagnosis remains challenging due to its complex pathophysiology and subjective clinical criteria. This integrative review aims to synthesize current research on potential diagnostic biomarkers for CRPS. Methods: A systematic search was conducted using the PubMed and Scopus databases to identify relevant studies published until January 2025. Inclusion criteria focused on adult CRPS patients, with studies examining diagnostic or predictive biomarkers. Results: Key findings highlight the role of inflammatory and immune-related biomarkers, such as elevated levels of cytokines (IL-6, TNF-alpha), immune cell infiltration, and specific autoantibodies. Neuropeptides, including substance P and calcitonin gene-related peptide, were associated with pain sensitization in acute phases, though their levels normalized in chronic stages. Additionally, genetic and epigenetic markers, brain imaging, and neurophysiological alterations provided insights into CRPS pathogenesis, emphasizing the dynamic nature of these biomarkers across disease stages. Conclusions: This review underscores the need for further research to integrate these biomarkers into diagnostic frameworks, which could enhance early diagnosis and treatment strategies for CRPS.
- Advanced therapy medicinal products development - from guidelines to medicines in the marketPublication . Frederico, Catarina; Vieira da Conceição, André Filipe; Nóbrega, Clévio; Mendonça, Liliana S.In Europe, Advanced Therapy Medicinal Products (ATMPs) include medicines based on gene therapy, somaticcell therapy, tissue-engineered products, and combined ATMPs. ATMPs constitute an emerging and innovative class of medicines used to treat multiple pathologies and are particularly relevant in pathologies where therapeutic options are limited and require high medical needs. These therapies act, among others, through the insertion of recombinant nucleic acids, including genes, to promote a therapeutic effect and through the restoration of cell functions, and repairing or replacing damaged cells and tissues impaired in pathological conditions. Despite their unique potential, these therapies face challenges related to scientific complexity, production processes, regulatory approval, and market access that hinder their development and availability. Based on official European guidelines, the present review explores the current regulatory framework for the non-clinical and clinical development of advanced therapies. We aimed to discuss the regulations applied to the different types of ATMPs, as well as the challenges associated with their development until these therapies reach the market. Accordingly, topics such as the implementation of proof-of-concept studies to provide evidence supporting the potential clinical effect; biodistribution studies to evaluate tissue distribution and persistence; and toxicology studies to assess potential undesirable effects, integration potential of viral vectors, tumorigenicity, and germline transmission, are discussed. This work also covers some of the ATMPs available to patients on the EU market.
- Green surgery: a systematic review of the environmental impact of laparotomy, laparoscopy, and roboticsPublication . Cunha, Miguel F.; Neves, João Cunha; Roseira, Joana; Pellino, Gianluca; Castelo-Branco, PedroSurgery is the most energy-intensive healthcare sector, but data on the environmental impact of abdominal surgical techniques are limited. This systematic review aims to identify the most sustainable approach among open, laparoscopic, and robotic surgeries. We searched MEDLINE, Cochrane, and Web of Science databases (inception to March 2024) for studies on the carbon footprint of abdominal surgery, focusing on carbon dioxide equivalents (CO2e) or CO2 emissions. The Joanna Briggs Institute checklist was used to assess bias. (PROSPERO: 298486). Of 2155 records, eight cohort studies were included, showing low to moderate risk of bias but high heterogeneity. Two studies on hysterectomy found robotic surgery had the highest carbon footprint (12.0-40.3 kgCO2e) compared to laparoscopic (10.7-29.2 kgCO2e) and open surgery (7.1-22.7 kgCO2e). Another study found laparoscopic prostatectomy produced more emissions than robotic surgery (59.7 vs. 47.3 kgCO2e) due to higher disposable devices, surgery time and length of stay. Single-use devices in laparoscopic cholecystectomy emitted more CO2e than hybrid devices (7.194 vs. 1.756 kgCO2e). CO2 used in minimally invasive surgery had negligible environmental effects (0.9 kgCO2e). Qualitative subgroup analyses revealed significant differences between surgery types and measurement methodologies, contributing to data heterogeneity. Minimally invasive surgeries often have higher carbon footprints due to disposable tools and waste. However, one study showed robotic surgery may reduce the overall environmental impact by shortening hospital stays. Due to methodological heterogeneity across studies, definitive conclusions remain limited. Standardized life-cycle assessment methodologies and inclusion of clinical outcomes in future studies are urgently needed to clarify the environmental sustainability of surgical practices.
- Comparing the outcomes of digital and traditional cardiac rehabilitation practices: a systematic review and meta-analysisPublication . Ansari, Sumbul; Nadar, Bhuvaneshwari G; Estêvão, Maria Dulce da Mota Antunes de Oliveira ; Aguiar, Débora R.; Ejeh, Jude; Khan, ZahidThis systematic review and meta-analysis aimed to evaluate the effects of digital cardiac rehabilitation (DCR) encompassing application-based telehealth compared to traditional cardiac rehabilitation on major adverse cardiovascular events (MACE), rehospitalisation, costs, quality of life (QoL), and physical activity levels in patients with coronary artery disease (CAD). From 2014 to May 2024, a systematic search of the MEDLINE, PubMed, Web of Science, and Scopus databases was conducted using relevant keywords to identify randomised controlled trials (RCTs) or randomised cross-over trials. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database (PEDro) scale and risk of bias tool. The included articles were then subjected to qualitative synthesis and meta-analysis. Thirteen studies involving 1850 participants were included in the study. Meta-analysis revealed statistically significant improvements in QoL (mean deviation (MD) = 0.10, 95% CI: 0.05-0.15, p = 0.0002). DCR compared with centre-based rehabilitation (CBR). These improvements in QoL likely translated to enhanced daily functioning, such as the increased ability to perform activities of daily living. However, no significant differences were found for physical activity levels (MD = 1.69, 95% CI: 1.49-4.87, p = 0.30), rehospitalisation (relative risk (RR) = 0.86, 95% CI: 0.66-1.11, p = 0.25) or MACE (RR = 0.67, 95% CI: 0.42-1.07, p = 0.09). High heterogeneity was observed in QoL, likely due to variations in DCR modalities, study populations, and intervention content. The results of this study, therefore, must be interpreted with caution. DCR may offer significant benefits in terms of improving the QoL in patients with CAD. While promising trends were observed for rehospitalisation and MACE, further research is needed to confirm these findings. Potential reasons for the observed benefits of DCR over centre-based rehabilitation plausibly include improved accessibility, enhanced patient engagement, and greater flexibility. However, it is important to acknowledge the presence of heterogeneity among the included studies and potential gender imbalances within the study populations, which may have influenced the results. Future research should prioritize long-term outcomes, cost-effectiveness, real-world effectiveness in diverse populations, and the development of standardized DCR protocols.