EM - Artigos Científicos
URI permanente para esta coleção:
Navegar
Percorrer EM - Artigos Científicos por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Biotecnologia Médica"
A mostrar 1 - 5 de 5
Resultados por página
Opções de ordenação
- Bioengineered baculovirus-derived extracellular vesicles loaded with of γ-carboxylated Gla-rich protein : dual modulation of inflammation and vascular calcificationPublication . Viegas, Carla; Pichard, Simon; Carreira, Joana; Ova, Adélia; Troffer-Charlier, Nathalie; Maia, Teresa M.; Edelweiss, Evelina; Macedo, Anjos L.; Matos, António; Faria, Tiago Q.; Calado, Sofia M.; Monico, Carina; Devos, Simon; Impens, Francis; Schaeffer-Reiss, Christine; Cianférani, Sarah; Peixoto, Cristina; Poterszman, Arnaud; Simes, DinaChronic inflammation and ectopic calcification are interrelated processes driving major chronic inflammatory diseases such as cardiovascular and chronic kidney diseases. Gla-rich protein (GRP), a vitamin K–dependent protein (VKDP) with dual anti-inflammatory and anti-calcific properties, has emerged as a promising therapeutic molecule. However, its biomedical development has been limited by difficulties in producing the γ-carboxylated (cGRP) form and by its poor solubility at physiological pH, constraining formulation and delivery. To address these challenges, we established a baculovirus expression vector system (BEVS) designed to couple GRP post-translational maturation with its secretion in extracellular vesicles (EVs). Co-expression of GRP with γ-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKOR), and the convertase Furin enabled efficient γ-carboxylation, propeptide removal, and secretion of mature cGRP. GGCX and VKOR were essential for γ-carboxylation, while Furin mediated propeptide processing. EVs were isolated by differential ultracentrifugation into 30 K and 100 K fractions and characterized by NTA, TEM, Western blot, ELISA, and proteomics. All vesicles displayed physical and molecular features resembling mammalian EVs, including canonical EV markers and distinct proteomic profiles, with GRP, GGCX, VKOR, and Furin preferentially enriched in the 30 K population. Functional assays demonstrated that the resulting EVs associated with human THP-1 macrophages and vascular smooth muscle cells (VSMCs) without inducing cytotoxicity, and both cGRP-EVs and uncarboxylated GRP-EVs reduced pro-inflammatory cytokine release while exerting dual anti-inflammatory and anti-mineralizing effects. This study establishes the first bioengineered platform capable of generating functional γ-carboxylated GRP and its vesicular formulation, providing a dual innovation for VKDP research and therapeutic biomaterial development.
- Facilitating “omics” for phenotype classification using a user-friendly AI-driven platform : application in cancer prognosticsPublication . Lima Filho, Uraquitan; Pais, Tiago Alexandre; Pais, Ricardo JorgePrecision medicine approaches often rely on complex and integrative analyses of multiple biomarkers from “omics” data to generate insights that can help with either diagnostic, prognostic, or therapeutical decisions. Such insights are often made using machine learning (ML) models that perform sample classification for a particular phenotype (yes/no). Building such models is a challenge and time-consuming, requiring advanced coding skills and mathematical modelling expertise. Artificial intelligence (AI) is a methodological solution that has the potential to facilitate, optimize, and scale model development. In this work, we developed an AI-based, user-friendly, and code-free platform that fully automated the development of predictive models from quantitative “omics” data. Here, we show the application of this tool with the development of cancer survival prognostics models using real-life data from breast, lung, and renal cancer transcriptomes. In comparison to other models, our generated models rendered performances with competitive sensitivities (72–85%), specificities (76–85%), accuracies (75–85%), and Receiver Operating Characteristic curves with superior Areas Under the Curve (ROC-AUC of 77–86%). Further, we reported the associated sets of genes (biomarkers) and their expression patterns that were predictive of cancer survival. Moreover, we made our models available as online tools to generate prognostic predictions based on the gene expressions of the biomarkers. In conclusion, we demonstrated that our tool is a robust, user-friendly solution for developing bespoke predictive tools from “omics” data, which facilitate precision medicine applications to the point-of-care.
- Multicriteria optimization of nanocellulose-reinforced polyvinyl alcohol and pyrrolidone hydrogelsPublication . Costa, Nuno; Lourenço, João; Cabalú, Joana; Branco, Ana; Figueiredo-Pina, Célio G.Developing new materials for human cartilage replacement is a hot research topic. These materials have multiple properties of interest, so selecting a new material (hydrogel) is a multi-attribute decision-making problem. A case study illustrates the application of a structured approach and tools to solve this problem type. Ten hydrogels, most of which are new formulations, were evaluated based on three attributes. The weights assigned to the attributes were identified using three methods from the literature, in addition to those previously assigned by an expert. Since the hydrogel properties showed some variability, Monte Carlo simulations were carried out using triangular distribution. Ten thousand decision matrices were built and 10,000 rankings were generated by each of the ten multicriteria decision-making methods employed in this study. Ranking similarity was evaluated through the PS index, whose values ensure consistency and reliability of the results achieved. Rank acceptability and pairwise indexes were used to identify the most promising hydrogels. Two hydrogels were identified as the most promising for further study, for any of the four sets of weights used. Both are annealed nanocellulose-reinforced polyvinyl alcohol and pyrrolidone hydrogels. The robustness of this result is supported on the values of acceptability and pairwise indexes.
- Point-of-care testing of nitrite in oral medicine : application and validation of an enzymatic biosensor in human salivaPublication . Gaspar, Sara Rodrigues; Proença, Luís; Alves, Ricardo; Almeida, Maria GabrielaPeriodontal disease (PD) is a chronic inflammatory condition triggered by bacterial biofilms and progresses through two main stages: gingivitis and periodontitis. The existing diagnostic methods remain time-consuming and require clinical expertise. Salivary nitrite, a stable end-product of nitric oxide produced during inflammation, has emerged as a promising biomarker for PD. However, its reliable quantification in saliva typically relies on laboratory-based assays that are unsuited to clinical workflows. This study aimed to test and validate a new nitrite point-of-care test (POCT) for oral medicine. Building on previous research, we developed a biosensing platform based on screen-printed carbon electrodes modified with a selective enzyme, the cytochrome c nitrite reductase. To adapt bioelectrodes for salivary analysis, they were further modified with a poly(vinyl) alcohol coating and a biochemical oxygen scavenger system (ascorbate oxidase and ascorbate). The nitrite biosensor achieved a suitable linear range of 5–300 μM, with a sensitivity of 0.015 μM−1, validated against the gold-standard Griess method. Unlike the Griess reaction, the biosensor was unaffected by sample turbidity, rendering centrifugation unnecessary. Additionally, we observed that sample freezing altered nitrite concentrations, increasing levels in non-centrifuged samples, while decreasing them in previously clarified samples. These findings highlight the need for real-time analysis and call into question the reliability of previously published data that overlooked these variables. Therefore, our results demonstrate the potential of the nitrite biosensor as a novel salivary POCT and emphasize the critical need for standardized sample-handling protocols.
- Polyhydroxyalkanoates : medical applications and potential for use in dentistryPublication . Abdeladhim, Rim Ben; Reis, José Alexandre; Vieira, Ana Maria; Almeida, Catarina Dias dePolyhydroxyalkanoates (PHAs) are promising biopolymers as an alternative to traditional synthetic polymers due to their biodegradability and biocompatibility. The PHA market is blooming in response to the growing demand for biodegradable and environmentally friendly plastics. These biopolyesters are produced and degraded by a variety of microorganisms, making them environmentally friendly, while offering benefits such as biocompatibility (when adequately processed) and biodegradability. Their versatility extends to various areas, from biomedicine to agriculture and composite materials, where they pave the way for significative innovations. In the field of regenerative medicine, some PHAs have key applications, namely in vascular grafts, oral tissue regeneration, and development of self-healing polymers. In addition, PHAs have the potential to be used in the creation of dental implant materials and dental medical devices. PHAs can also be used to encapsulate hydrophobic drugs, providing an approach for more targeted and effective treatments. To summarize, PHAs open new perspectives in the field of medicine by improving drug delivery and offering ecologically biocompatible solutions for medical devices. The aim of this review is to present the medical and dental applications of PHA, their advantages, disadvantages, and indications.