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- 2024 Annual meeting of the international network on ectopic calcification (INTEC)—abstract proceedingsPublication . Cancela, M. Leonor; Alouane, Ahmed; Bertelli, Pietro M.; Camacho, Antonio; Derudder, Robbe; Forlino, Antonella; Harris, Matthew P.; Jacinto, Marta; Lengyel, Imre; Link, Wolfgang; Murshed, Monzur; Pasch, Andreas; Kaliya-Perumal, Arun-Kumar; Quaglino, Daniela; Qin, Zihan; Sabbagh, Yves; Seminari, Elena; Villar, Marcos M.; Winkler, Christoph; Vanakker, Olivier M.The 3rd Annual Meeting of the International Network on Ectopic Calcification (INTEC) was held in Faro, Portugal on 12–13 September 2024. This hybrid meeting brought together researchers and clinicians focused on the molecular, (patho)physiological, and clinical aspects of ectopic calcification in hereditary and acquired conditions, as well as in aging. The findings presented in this year’s meeting emphasised the complexity of the field, offering new insights into both mechanistic pathways and translational hurdles. The abstracts of this year’s meeting are collected in this conference paper, with permission from the corresponding authors.
- Advanced nanotherapeutic strategies transforming diabetic wound healingPublication . Ramos, Filipa; Kumar, Girish; Virmani, Tarun; Sharma, Abhishek; Duarte, Sofia O. D.; Fonte, PedroDue to their high recurrence rates and slow healing, diabetic wounds are becoming a greater public health concern [Citation1]. Each year, 1.6 million cases of diabetic wounds occur in the United States alone, affecting approximately 18.6 million people worldwide [Citation2]. Because of poor cellular regeneration, increased inflammation, and reduced angiogenesis, traditional treatments like debridement, antibiotics, and dressings usually do not work [Citation3]. To overcome the limitations of traditional treatments, there is now a significant demand for advanced therapeutic modalities that promise accurate, efficient, and rapid healing processes [Citation4]. These include microneedles (MNs), exosomes, tetrahedral framework nucleic acids (tFNAs), three-dimensional scaffolds, gene therapy, oxygen-releasing biomaterials, phototherapies, and nanozymes.
- Anthropogenic particles ingestion by fish larvae in important nursery areas of Iberia (South Europe)Publication . Zeri, Giulia; Baptista, Vânia; Teodosio, Maria; Cruz, JoanaMicroplastics (MPs) are now widespread in the marine environment, and their levels are expected to rise as larger plastic debris continues to break down and new plastic waste enters the ocean. Microplastics ingestion has been documented in fish larvae, which are already particularly vulnerable to predation, environmental stressors, and starvation. This study examines for the first time MPs ingestion by wild fish larvae in Southern Iberia, focusing on two key nursery ecosystems of Portugal: the Ria Formosa coastal lagoon and the Guadiana River estuary. Fish larvae collected monthly from surface water, between April 2023 and March 2024, exhibited encounter rates (ER - Total number of ingested particles/ Total number of organisms analysed *100) of 12.99% in Ria Formosa and 11.54% in the Guadiana estuary. No significant differences were observed in ER among taxa and locations. The ingested particles ranged in size from 20 μm to 2 mm and were predominantly made of rayon, transparent and in the form of fibres. No correlation was found between the size of the larvae and that of the ingested particles. Although larval size had a positive effect on MP ingestion, this effect was not significant. There were no differences in polymer type ingestion among taxa. Our results underline the role of nursery areas as exposure spots and the underestimated pressure of the textile industry on marine ecosystems. Further research is needed to assess the potential consequences of this exposure for larval survival, recruitment success, and the health of adult fish populations.
- Antibacterial activity of PDDA-stabilized GO-AgNP nanocompositesPublication . Sadoq, Badr-Edine; Elamine, Youssef; Leal, Inês; Bouajaj, Adel; Britel, Mohammed Reda; Maurady, Amal; Power, Deborah MaryGraphene oxide (GO)-silver nanoparticle (AgNP) nanocomposites are widely studied for their antimicrobial synergy. In this study, the antibacterial activity of GO– AgNP nanocomposites prepared with poly(diallyldimethylammonium chloride) (PDDA) as a stabilizing linker was investigated. The composites were characterized by UV–Vis spectroscopy, FTIR, zeta potential analysis, XRD, TGA, and MPAES. GO–PDDA–AgNPs exhibited a strong surface plasmon resonance band at ~ 420 nm, new C–H stretching bands at 2865–3012 cm⁻¹ from PDDA, and a high positive zeta potential (+ 57.5 mV) compared to bare GO (–40 mV), confirming successful functionalization and improved colloidal stability. Antibacterial activity was evaluated against E. coli and S. aureus using disk diffusion assays, growth curves, and MIC determination. GO and AgNPs alone showed no inhibition at concentrations up to 20 µg/mL, whereas PDDA alone produced inhibition zones of 6–11.5 mm against S. aureus (2.5–100 µg/mL) and induced selective bacterial aggregation. The minimum inhibitory concentration (MIC) of PDDA was between 6.25 and 12.5 µg/mL for S. aureus and between 25 and 50 µg/mL for E. coli, indicating greater potency toward Gram-positive bacteria. The GO–PDDA–AgNP composite inhibited S. aureus with zones of 8.5–10 mm at 10–20 µg/mL, while no significant inhibition was observed for E. coli at the tested concentrations. Molecular docking simulations examining interactions between PDDA and quorum-sensing regulatory proteins AgrA in S. aureus and LsrR in E. coli predicted higher binding affinity to AgrA (–5.11 kcal/mol) than LsrR (–3.76 kcal/mol). While in vitro assays using a Chromobacterium violaceum CV026 biosensor showed no inhibition of AHL-mediated signalling, it should be noted that this model differs mechanistically from the Gram-positive agr system, leaving the predicted AgrA interaction as a potential target for future investigation. Ultimately, this study demonstrated that PDDA is the primary antibacterial component of the GO–PDDA–AgNP composite, exhibiting potent activity against Gram-positive bacteria through a mechanism involving selective bacterial aggregation.
- 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.
- The antithyroid drug methimazole as an emerging aquatic contaminant: physiological and reproductive disruption in female goldfish (Carassius auratus) and partial mitigation by thyroxinePublication . Abdollahpour, Hamed; Karimzadeh, Milad; Jafari Pastaki, Naghmeh; Zamani, HosseinaliThyroxine (T4), a key thyroid hormone, plays a crucial role in regulating growth, metabolism, and reproduction in fish, whereas methimazole (MMI), a thyroid peroxidase inhibitor, can disrupt these processes by inducing hypothyroidism. This study investigates thyroid-modulating compounds' physiological and reproductive effects on the growth and development of mature female goldfish (Carassius auratus). A total of 240 adult female goldfish were divided into four treatment groups: control (coconut oil), T4, MMI, and T4+MMI (combined). The fish were acclimatized for four weeks before receiving injections of the respective compounds. Growth performance, blood biochemistry, thyroid hormone (THs) levels, oocyte development, and liver histology were evaluated over a 28-day experimental period. Results indicated significant differences in growth indices, with the T4 group showing the highest weight gain, specific growth rates, and lowest feed conversion ratio (P < 0.05), while the MMI group exhibited the lowest growth parameters. Blood glucose, triglyceride, and total protein levels were significantly elevated in the T4-treated group, whereas cholesterol was reduced (P < 0.05). Plasma T3 and T4, were highest in the T4 group and lowest in the MMI group. Histological analysis revealed advanced oocyte maturation in the T4 group, with a higher proportion of oocytes at the O4 stage, while the MMI group showed delayed development, with most oocytes remaining at the O2 stage. The T4+MMI group exhibited intermediate effects, with some improvement in oocyte development relative to the MMI group. Hepatic histopathology demonstrated normal liver structure in the control and T4 groups, while severe hepatic alterations, including necrosis and vacuolation, were observed in the MMI group. The T4+MMI group displayed intermediate liver damage. These findings demonstrate that the pharmaceutical methimazole, an emerging aquatic contaminant, acts as a potent endocrine disruptor, inducing hypothyroidism that severely impairs growth, metabolic homeostasis, and reproductive maturation in fish. The partial mitigation by thyroxine suggests potential complex interactions in environments contaminated with multiple bioactive compounds. This study underscores the significant ecological risk of antithyroid drugs in aquatic ecosystems and contributes critical data for environ mental risk assessment.
- Assessing the bioactive potential of Lysimachia atropurpurea extracts using HPLC-MS/MS, in vitro and in silico analysisPublication . Ak, Gunes; Nilofar, Nilofar; Saka, Enver; Uba, Abdullahi Ibrahim; Rodrigues, Maria João; Fernandes, Eliana; Custódio, Luísa; Yildiztugay, Evren; Yapıcı, Ismail; Gulcin, Ilhami; Mahmoud, Orchid A.; Eldahshan, Omayma A.; Singab, Abdel Nasser B.; Wu, Yimao; Li, Meng-Yao; Zengin, GokhanThe genus Lysimachia is of great interest to the scientific community, especially in terms of its potential anticancer effects. In this study, the aerial parts and roots of Lysimachia atropurpurea L. were collected and extracted by maceration using solvents of ethyl acetate (EA), ethanol (EtOH), ethanol/water, and water. The biological activities of the extracts, including antioxidant, enzyme inhibition, and anticancer effects, were evaluated using various assays. High-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) analysis revealed a total of 32 compounds in the extracts of L. atropurpurea. The roots showed significantly the highest antioxidant activity compared to the aerial part. In case of cholinesterase inhibition, the aerial parts of the EtOH extract showed the highest acetylcholinesterase (AChE) inhibition activity, measuring 3.05 mg galatamine equivalent (GALAE)/g. The EtOH and EtOH/water extracts exhibited the strongest cytotoxicity, reducing the viability of human neuroblastoma (SH-SY5Y) and human hepatocarcinoma (HepG2) cancer cells to as low as 4.86–6.33 %. The results of network pharmacology and molecular docking suggest that the extract of L. atropurpurea exerts inhibitory effects on hepatocellular carcinoma through the modulation of SRC, PI3K, and HSP90, while it demonstrates potential inhibitory activity against neuroblastoma by targeting SRC, PI3K, HSP90, ESR1, AKT, and other related targets. In conclusion, the L. atropurpurea extracts showed potential antioxidant, enzyme inhibition, and selective anticancer effects, which support their potential for further research as therapeutic agents in drug development.
- 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.
- Bioprospecting of natural products from medicinal plantsPublication . Rodrigues, Maria JoãoThe exploration of natural products derived from medicinal plants that provide an abundance of bioactive compounds has long been a cornerstone of scientific discovery, revolutionizing fields such as medicine, agriculture, and biotechnology [1]. Notable examples include artemisinin, a life-saving antimalarial derived from Artemisia annua [2], and taxol, a chemotherapeutic agent sourced from the Pacific yew tree [3], both of which highlight the immense potential of medicinal plants to address global health challenges. Over the past decade, rapid advancements in analytical techniques, omics technologies, and bioinformatics have significantly improved our ability to uncover and characterize these natural products. Despite these strides, critical challenges persist in the field, including the sustainable utilization of plant resources, the discovery of novel compounds with unique modes of action, and the translation of these findings into practical, real-world applications.