ABC2-Artigos (em revistas ou actas indexadas)
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- Antibody–drug conjugates: pharmacotherapeutic properties and future perspectivesPublication . Augusto, André; Cristiano, Maria de Lurdes; Conceição, JaimeBackground: The clinical landscape for antibody–drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensive description of currently approved ADCs, with a particular focus on their pharmacotherapeutic properties, mechanisms of action, therapeutic indications, and safety profiles. By integrating currently available clinical data and pharmacological properties, it is possible to identify key translational gaps between ADC design and their real-world performance. This article also evaluates how the structural components contribute to both efficacy and toxicity of ADCs, offering a framework for rational molecular optimizations. Conclusions: Beyond the current oncology-centric paradigm, this review highlights the imminent pivot toward non-oncology applications, including targeted therapies for autoimmune, infectious, and neurodegenerative diseases. Importantly, this article highlights emerging innovations shaping the next generation of ADCs, including bispecific antibodies, novel cytotoxic payloads with improved therapeutic indices, and advanced linker technologies enabling more precise payload release. Despite current limitations, ongoing advances in ADC development, along with a rapidly expanding clinical pipeline, position these drugs in a dynamic therapeutic class with the potential to transform multiple complex diseases and improve the quality of life of patients who have them.
- Disease modification in advanced parkinson’s disease: a review and roadmap for paving the way for next-generation interventionsPublication . Groppa, Sergiu; Fasano, Alfonso; Urso, Daniele; Yang, Xinjie; Popescu, Bogdan; Klivenyi, Peter; Laar, Teus van; Jost, Wolfgang; Garcia-Ruiz, Pedro J.; Bhidayasiri, Roongroj; Outeiro, TiagoParkinson’s disease (PD) exhibits highly heterogeneous clinical trajectories, yet “advanced PD” (aPD) lacks a standardized definition. Current reliance on clinical milestones (e.g., motor fluctuations, cognitive decline) is limited by non-linear progression and the absence of objective measures. Although biomarkers like aggregated α-synuclein, MRI, and PET are under investigation, their correlation with clinical progression remains modest. Robust, reproducible endpoints are urgently needed to evaluate disease-modifying therapies across diverse phenotypes, accounting for genetic background, age of onset, co-pathologies, and motor/autonomic/cognitive domains. Given this complexity, single-target interventions are likely insufficient. We propose a multi-domain therapeutic framework for aPD that integrates: (A) simultaneous targeting of key pathological cascades, including α-synuclein aggregation, mitochondrial dysfunction, oxidative stress, proteostasis imbalance, neuroinflammation, and the gut–brain axis; (B) biology-driven patient stratification using emerging biomarkers to match subgroups with targeted interventions; and (C) systematic management of comorbidities and lifestyle factors, such as cardiovascular health and exercise, to enhance neuroresilience. Finally, advancing aPD care requires addressing systemic determinants, including global healthcare inequities, and prioritizing caregiver well-being. Mechanistically informed, patient-centered strategies that combine multi-target therapies with precision stratification and holistic support will be essential to modify disease progression and improve long-term outcomes.
- The benefits of using exosomes in professional cosmetic products: from theory to practicePublication . Costa, Gabrielle; Silva, Elisa; Silva, Fátima; Casas, Ana; Bastos, Bernardo; Oliveira, Maria Beatriz P. P.; Nóbrega, Clévio; Almeida, HugoThe integration of exosomes into professional cosmetics marks a significant paradigm shift from traditional passive formulations to advanced regenerative esthetics. Rather than being defined solely by their nanometric dimensions or classical association with endosomal biogenesis, these vesicles function as highly targeted intercellular messengers capable of delivering complex bioactive payloads to modulate tissue repair and collagen synthesis. While robust preclinical and clinical trials validate their remarkable potential in skin rejuvenation, hair restoration, and hyperpigmentation management, significant translational barriers remain. A critical analysis of the current literature reveals that successful clinical outcomes frequently rely on physical penetration enhancers, such as microneedling or fractional lasers, making it challenging to isolate the autonomous efficacy of topical vesicles from the trauma-induced regenerative response. Furthermore, commercial viability is dictated by stringent regulatory frameworks. In the European Union, Regulation (EC) No 1223/2009 strictly prohibits human-derived biologicals, while the US Food and Drug Administration (FDA) aggressively monitors the unsubstantiated marketing of cellular therapies. To navigate these biosafety and legal constraints, the aesthetic industry is increasingly pivoting toward non-human and legally compliant alternatives. Consequently, Plant-Derived Extracellular Vesicles (PDEVs), microbiome-derived exosomes (such as those obtained from bacterial fermentation), and bioengineered synthetic analogues have become the focal point of market innovation. A practical evaluation of the MCCM Medical Cosmetics portfolio illustrates this strategic shift, demonstrating the clinical versatility of botanical sources. To secure the long-term credibility of exosome technology, the industry must overcome current manufacturing heterogeneity by aligning with international standardization frameworks, such as the MISEV2023 guidelines, thereby ensuring reliable delivery systems, batch-to-batch consistency, and uncompromised consumer safety. This review provides a comprehensive overview of the biological mechanisms, clinical efficacy, and translational challenges associated with exosome-based cosmetics.
- Lewy bodies are not associated with neuronal or synaptic loss in dementia with lewy bodiesPublication . Hawksworth, Jade I.; Kirkby‐Geddes, Eddie; Thom, Searlait; O'Neill, Joe; Ikwue, Amelia; Wood, Lucy; Outeiro, Tiago; Erskine, DanielAims: The misfolding and accumulation of the protein α-synuclein (αSyn) into cytoplasmic inclusions termed Lewy bodies (LBs) and Lewy neurites is the defining neuropathological feature of LB diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The loss of neurons and/or synapses has been postulated to underlie the clinical syndrome of DLB. The present study sought to elucidate the relationship between LB burden and neuronal and synaptic loss in DLB. Methods: Post-mortem brain tissue from the cingulate gyrus and inferior temporal gyrus, two regions vulnerable to LB pathology, was obtained from DLB (N=20) and control cases (N=20). Formalin-fixed paraffin-embedded tissue was stained to quantify LB, Alzheimer-type pathology and a neuronal marker. Frozen tissue from the contralateral hemisphere was processed for immunoblotting to compare the abundance of synaptic markers across cases. Results: Across both regions, no evidence of reduced total neuronal density was observed, but a modest reduction in parvalbumin interneurons was observed in the cingulate gyrus, and there were only modest reductions in some synaptic markers in DLB. LB burden was markedly variable across DLB cases but was not associated with any synaptic marker abundance or neuronal density. Conclusions: Taken together, these findings do not support an association between LB density and neuronal or synaptic loss in DLB, even in regions with particularly high burdens of LBs, such as the cingulate gyrus. These findings suggest that the link between αSyn proteinopathy and disease requires further investigation.
- Holisticscape dimensions of the tourism experience in wellness spas: Evidence from PortugalPublication . Valente Pedro, Cristina; de Matos, Nelson Manuel da Silva; Pinto, PatríciaThe present study examines how tourists’ experiences in wellness spas promote holistic health through the Holisticscape framework from both tourists’ and other stakeholders’ perspectives, an extension of the servicescape that encompasses the ambience, social, activity, body, mind, and spirit dimensions. An ex-ploratory, multi-stakeholder qualitative design was employed, with 20 in-depth interviews conducted inwellness spas in Portugal. Thematic analysis revealed that ambience, social relations, activity, body, mind, and spiritual stimuli support tourists’ holistic health. These findings extend existing research on servicescape and experiencescape by demonstrating how multidimensional experiential stimuli interact to produce holistic health in wellness spa settings. The study offers practical implications for designing immersive and health-oriented environments, enhancing service customisation, and integrating cultural and natural resources intowellness spa offerings. Given its exploratory and context-bound nature, it is recommended that further research be conducted to validate Holisticscape dimensions across a range of wellness spas at distinct destinations. Furthermore, the development of measurement tools for future quantitative investigations is recommended.
- Autoantibodies against myelin oligodendrocyte glycoprotein in a subgroup of patients with psychotic symptomsPublication . Burgt, Nikita A. van de; Kulsvehagen, Laila; Mané-Damas, Marina; Lutz, Luc; Lecourt, Anne-Catherine; Monserrat, Clara; Vinke, Anita M.; Küçükali, Cem İ.; Zong, Shenghua; Hoffmann, Carolin; González-Vioque, Emiliano; Arango, Celso; Leibold, Nicole K.; Losen, Mario; Molenaar, Peter C.; Tüzün, Erdem; Beveren, Nico J. M. van; Mané, Anna; Rouhl, Rob P. W.; Amelsvoort, Therese A. M. J. van; Pröbstel, Anne-Katrin; Martinez-Martinez, PilarThe presence of autoantibodies against myelin oligodendrocyte glycoprotein (MOG) is a hallmark of MOG antibody-associated disease (MOGAD), a recently defined demyelinating disease entity presenting with core clinical features of optic neuritis, myelitis, and acute disseminated encephalomyelitis. Although MOG antibodies have also been described in a small number of patients with other conditions, including mental disorders, their prevalence and clinical specificity in patients with isolated psychotic symptoms remain unclear. Here, we screened sera from 262 patients with at least one psychotic episode and 166 control subjects for the presence of MOG antibodies of the immunoglobulin G (IgG) isotype with a live cell-based assay. Serum reactivity to additional antigens was assessed by immunohistochemistry. Four patients, representing 1.5% of the patient cohort, and one control individual, representing. 0.6% of the healthy control cohort, were seropositive for MOG-IgG antibodies. Of the four MOG-IgG seropositive patients, three experienced visual hallucinations. Overall, MOG antibodies were detected at a low frequency in patients with psychotic episodes. While we cannot exclude the possibility of false-positive results or seroconversion due to secondary myelin damage, the association with visual hallucinations in three out of four MOG-IgG seropositive patients may point toward an underlying autoimmune etiology.
- Telehealth for integrated cardiovascular and diabetes management: a scoping reviewPublication . Estêvão, Maria Dulce da Mota Antunes de Oliveira ; Teotónio Fernandes, Mónica Alexandra; De Sousa-Coelho, Ana Luísa; Neto Espírito-Santo, Margarida de Fátima; Nascimento, Tânia; Alfredo CaturanoCardiovascular disease (CVD) and diabetes mellitus represent major global health challenges, frequently co-occurring and mutually exacerbating. Telehealth interventions offer a promising approach for their management, with potential to improve patient outcomes, enhance access to care, and increase cost-effectiveness. This review synthesized existing evidence from randomized controlled trials (RCTs) and observational studies to evaluate the effectiveness of telehealth interventions for the management of diabetes, focusing on CVD risk, and to identify critical research gaps. A systematic literature search was conducted across major databases (PubMed, Web of Science, and Scopus) to identify studies meeting predefined eligibility criteria, considering digital tools for remote monitoring, consultation, education, and medication management. After the screening of 3041 articles, six studies met the inclusion criteria. Telehealth interventions utilized a range of digital health tools, including mobile applications, artificial intelligence–powered clinical decision aids, electronic consultations, and integrated remote monitoring platforms. Although direct assessment of composite cardiovascular risk was largely absent, the included studies reported several clinical parameters associated with cardiovascular health, namely, blood pressure, lipid profile, and glycated hemoglobin. Telehealth interventions implemented for individuals with Type 2 diabetes mellitus demonstrated promising potential in improving glycemic control and supporting self-management. However, their effectiveness in managing broader cardiovascular risk factors remains less clear due to inconsistent reporting and heterogeneous intervention designs.
- How artificial intelligence can enable personalized mesenchymal stem cell–based therapeutic strategies in systemic lupus erythematosusPublication . Kumar, Sushmitha Rajeev; He, Khor Kai; Lokanathan, Yogeswaran; Gaurav, Anand; Yusoff, Khatijah; Macedo, M. Fatima; Bhassu, SubhaMesenchymal Stromal Cells (MSCs) are increasingly recognized as promising candidates for treating Systemic Lupus Erythematosus (SLE) due to their immunomodulatory and regenerative properties. However, their therapeutic efficacy remains inconsistent, largely due to the heterogeneity of MSC origins, culture conditions, cell quality, host immune interactions, and the influence of immunosuppressive treatments. Artificial Intelligence (AI) offers powerful tools to address these challenges by optimising MSC modification and application. This review explores how AI can identify optimal genetic and epigenetic targets, predict MSC behaviour under different environmental and priming conditions, and design personalise therapies tailored to individual patients. Moreover, AI enables the analysis of extensive datasets to refine dosing strategies and improve the integration of MSC therapy with immunosuppressants. By enhancing the precision, consistency, and personalisation of MSC-based interventions, AI has the potential to significantly improve therapeutic outcomes in SLE, advancing the field toward more effective and patient-centred autoimmune disease management.
- Characterization of knowledge, attitudes, comfort, and perception of discrimination regarding sexual and/or gender minoritized people: comparison between two cohorts of medical students - 2018–2023Publication . Macedo, Ana; Ferreira, João; Gutierrez, Ana Rita; Gato, JorgeObjectives: Despite progress made in the medical field to address the health concerns ofsexual and gender minoritized identities, LGBTQIAþ individuals continue to experience dis-crimination in healthcare. This study aims to evaluate the effects of incorporating a seminaron gender identity and sexual orientation into the medical curriculum of a PortugueseMedical School, after 5 years. The study’s main objective was to compare the changes in stu-dents’ knowledge, attitudes, comfort, and perception of discrimination against LGBTQIAþ,pre and post-intervention.Methods: A total of 313 students in their third, fourth, fifth, and sixth year at a PortugueseMedical School were assessed in 2018 (pre-intervention) and 2023 (post-intervention). Thedata collected were analyzed regarding age, gender identity, sexual orientation, number offriends or family members who identify themselves as LGBTQIAþ, and level of religiosity.Results: The overall knowledge regarding LGBTQIAþ people specific health aspects improvedfrom the 2018 cohort to the 2023 cohort, with significant differences in questions regardinggender identity (OR ¼ 2.0, p ¼ .007), sexual orientation (OR ¼ 2.9, p <.001), and mentalhealth (OR ¼ 3.2, p <.001). The perceived discrimination against homosexual patients wassimilar in both cohorts, with approximately 60% of respondents from both groups agreeingthat homosexual patients were discriminated against in healthcare.Conclusion: Although the perception of discrimination against LGBTQIAþ people in health-care remained high across the two cohorts, positive changes were observed regarding stu-dents’ overall knowledge of LGBTQIAþ individuals’ health, clinical preparation and comfortin treating LGBTQIAþ people, and attitudes toward lesbian women and gay men. Theseresults reinforce the need to develop training and information strategies targeting medicalstudents, promoting greater knowledge and, above all, increasing contact and clinical prac-tice with LGBTQIAþ people, since relationships and personal contact are the most differenti-ating aspects for nondiscrimination.
- Editorial: Endocrine regulation and physiological adaptation of stress response in aquatic organisms, volume IIPublication . Li, Yi-Feng; Li, Yiming; Campinho, Marco António; Fuentes, JuanAt the individual level, organisms develop many complex morphological and physiological adaptations to maintain homeostasis, of which endocrine regulation is the key. By adjusting physiological mechanisms, organisms adapt their response to the external environment, enabling the acquisition of new homeostatic equilibrium that allows survival. The physiological adaptative mechanism plays an important role in maintaining homeostasis and adapting to changes in the external environment. Well-known environmental factors such as ambient temperature, pH, ammonia nitrogen, salinity, and exposure to new pollutants can disrupt homeostasis, resulting in growth and physiological and endocrine disorders. Thus, in a rapidly changing climate, it is important to explore the biological adaptive regulation mechanism and endocrine regulation strategy under stress, which has an important impact on the protection of aquatic ecology. The main purpose of the Research Topic is to explore and discuss these potential physiological and molecular mechanisms to provide new insights for developing new green ecological activities.