Teses de Doutoramento
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Browsing Teses de Doutoramento by Field of Science and Technology (FOS) "Ciências Médicas::Biotecnologia Médica"
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- Anticancer prodrug nanoscale platform using low-generation dendrimers and/or platinum derivatives. Synthesis, cytotoxicity and synergetic effectsPublication . Camacho, Cláudia; Rodrigues, João Manuel Cunha; Tomás, Helena Maria Pires Gaspar
- Metallodendrimers as HIV antiviral and anticancer agentsPublication . Maciel, Dina Maria Sousa; Rodrigues, João Manuel Cunha; Muñoz-Fernándes, Maria Ángeles
- Multi-user Touch Surfaces to Promote Social Participation and Self-efficacy in Upper-limb Stroke RehabilitationPublication . Pereira, Fábio Dinis Silva; Cameirão, Mónica da SilvaThis thesis addresses the growing incidence of stroke and its impact on long-term disability, emphasizing the importance of post-stroke rehabilitation. Predicting a 34% increase in stroke cases by 2025, this work focuses on factors affecting post-stroke motor rehabilitation, such as depressive symptoms, while recognizing the role of social participation and self-efficacy in modulating these outcomes. To tackle these challenges, we propose the use of a multi-user interactive table for upper limb rehabilitation. This innovative approach involves detecting objects of various sizes and shapes as interfaces for serious games, fostering collective therapeutic activities targeting motor rehabilitation, depressive symptoms, social participation, and self-efficacy. Four exploratory studies informed the development of the interactive table. The studies determined game mechanics, object types, and game features. Three game modes (competitive, co-active, and collaborative) were explored, with the collaborative mode showing higher social engagement and more positive outcomes. Subsequent studies involving stroke survivors confirmed the effectiveness of collaborative gameplay. Feasibility, engagement, and usability were tested using objects of different sizes and shapes, revealing insights into task performance, grasping, and task complexity adjustments. The developed interactive table accommodates up to four participants, using top down object shape tracking and a multi-touch panel. Four serious games were designed to target specific upper limb skills, played in collaborative mode with incorporated features to enhance the overall experience. A pilot study with 12 stroke survivors over four weeks demonstrated significant improvements in motor outcomes, including range of motion, dexterity, strength, and coordination. The participants reported high enjoyment and interest in the system, with good usability scores. The study suggests that a group-based holistic motor rehabilitation approach, as presented, holds potential for enhancing motor outcomes by promoting social interaction and self-efficacy. These results indicate the viability of the proposed system as a promising solution for stroke rehabilitation.
- Non-invasive, innovative and promising strategy for breast cancer diagnosis based on metabolomic profile of urine, cancer cell lines and tissuePublication . Silva, Catarina Grace Sousa Luís; Câmara, José de Sousa; Tomás, Helena Maria Pires GasparThe work presented in this thesis aimed to establish the metabolomic profile of urine and breast cancer (BC) tissue from BC patients (samples cordially provided by Funchal Hospital), in addition to BC cell lines (MCF-7, MDA-MB-231, T-47D) as a powerful strategy to identify metabolites as potential BC biomarkers, helping on the development of non-invasive approaches for BC diagnosis and management. To achieve the main goal and obtain a deeper and comprehensive knowledge on BC metabolome, different analytical platforms, namely headspace solid-phase microextraction (HSSPME) combined with gas chromatography-quadrupole mass spectrometry (GC-qMS) and nuclear magnetic ressonance (1H NMR) spectroscopy were used. The application of multivariate statistical methods - principal component analysis (PCA) and orthogonal partial least square – discriminant analysis (OPLS-DA), to data matrix obtained from the different target samples allowed to find a set of highly sensitive and specific metabolites metabolites, namely, 4-heptanone, acetic acid and glutamine, able to be used as potential biomarkers in BC diagnosis. Significant group separation was observed in OPLS-DA score plot between BC and CTL indicating intrinsic metabolic alterations in each group. To attest the robustness of the model, a random permutation test with 1000 permutations was performed with OPLS-DA. The permutation test yielded R2 (represents goodness of fit) and Q2 values (represents predictive ability) with values higher than 0.717 and 0.691, respectively. Several metabolic pathways were dysregulated in BC considering the analytical approaches used. The main pathways included pyruvate, glutamine and sulfur metabolisms, indicating that there might be an association between the metabolites arising from the type of biological sample of the same donor used to perform the investigation. The integration of data obtained from different analytical platforms (GC-qMS and 1H NMR) for urinary and tissue samples revealed that five metabolites (e.g., acetone, 3-hexanone, 4-heptanone, 2methyl-5-(methylthio)-furan and acetate), were found significant using a dual analytical approach.
- Nutraceuticals and functional foods for diabetes and obesity controlPublication . Spínola, Vítor Agostinho Rodrigues; Castilho, Paula Cristina Machado FerreiraThe aim of this work was to study the anti-diabetic potential of different berry-producing plants. Their mineral and phytochemical composition was studied by inductively coupled plasma - mass spectrometry and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry analysis, respectively. A static model to simulate gastrointestinal digestion was employed to analyse the stability of phenolic compounds from targeted species. The mechanism of hypoglycaemic activity was evaluated in terms of in vitro inhibitory action on key digestive enzymes linked to type-2 diabetes (α-,β-glucosidases and α-amylase) and obesity (pancreatic lipase). Additionally, the inhibitory effect towards human aldose reductase and protein glycation, associated with long-term diabetic complications, was determined. The antioxidant activity of methanolic extracts was investigated using four different free radicals (ABTS•+, DPPH•, NO• and O2•-). Finally, the cytotoxicity of analysed species was assessed in Caco-2 cells by the resazurin reduction fluorescence method. Berry species proved to be good sources of essential minerals, some of which, are known to possess hypoglycaemic effects. Analysed extracts showed diverse phytochemical profiles, anthocyanins, hydroxycinnamic acids, flavonols, flavan-3-ols and ellagitannins being the dominant compounds. Extracts showed a stronger inhibition towards glucosidases and were moderate inhibitors of α-amylase and pancreatic lipase. Potent inhibitory effects were observed in aldose reductase assay and towards formation of advanced glycation end-products. Additionally, good antioxidant activities were observed. Preliminary cytotoxicity measurements revealed that plant extracts can be considered safe for human consumption. The phenolic content and biological activities were substantially affected by the simulated in vitro digestion. Still, positive health effects were verified for digested samples. The generated data about these berry-producing plants and their potential effect on the management/control of type-2 diabetes and prevention of associated complications may be useful in designing future dietary/nutraceutical strategies aimed at alleviating hyperglycaemia.