UA01-Teses
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- Qualidade de vida relacionada com a saúde e satisfação com a vida em idosos da Península IbéricaPublication . Encarnação, Ana Sofia Coelho; Ferreira, Lara Noronha; Botelho, Marta Cristina SoaresO envelhecimento demográfico tem vindo a ganhar notoriedade na Europa, devido aos desafios que coloca sobre os sistemas de saúde. A Qualidade de Vida Relacionada com a Saúde (QVRS) e da Satisfação com a Vida (SV) são indicadores importantes para avaliar a qualidade do envelhecimento e para auxiliar a gestão em saúde. Apesar destes indicadores serem influenciados por diferentes fatores, não existem estudos que comparem as populações idosas na Península Ibérica, em termos de QVRS e SV. O presente trabalho visa determinar e comparar a QVRS e a SV da população idosa portuguesa e espanhola, assim como identificar os fatores que contribuem para a QVRS e a SV nestas duas populações. Esta investigação pretende inclusive testar a hipótese da existência de uma relação em forma de U entre a SV e a idade e entre a autoperceção de saúde e a idade. O estudo utilizou dados relativos a 4379 participantes da 6ª vaga do projeto SHARE, que representam a população portuguesa e espanhola com pelo menos 65 anos. Para avaliar a QVRS e a SV, foram utilizadas duas variáveis referentes à autoperceção de saúde e à satisfação com a vida, para as quais foram construídos modelos de regressão ordinal. Os resultados obtidos indicam que os idosos espanhóis reportam níveis mais altos de QVRS e SV do que os idosos portugueses. Foram também identificados os fatores que contribuem para a QVRS e SV em Portugal e Espanha, sendo que o género, a ausência de cuidados informais e os baixos níveis de depressão foram os fatores que contribuíram positivamente para a QVRS e a SV em ambos os países. O rendimento não teve qualquer influência sobre a QVRS e a SV nos dois países. As conclusões deste estudo ajudam a identificar as áreas que permitem melhorar o bem-estar dos idosos.
- Study of chemical composition and biological activities of Euphorbia resinifera and Euphorbia officinarum and their honeysPublication . Boutoub, Oumaima; Miguel, Maria da Graça CostaEuphorbia officinarum and Euphorbia resinifera are two species found in Morocco. They have been used in traditional medicine. Reports indicate the use of Euphorbia officinarum for the treatment of wounds, skin infections and abscesses and the aerial parts of Euphorbia resinifera in combination with honey or extracts obtained by decoction have been used by patients in Morocco to treat cancer. The “Morocco Green Plan” has played an important in terms of sustainable development of the agricultural sector, helping to increase its benefit, through the promotion of specific products from different territories. One of these products is honey. Propolis (a natural substance produced by bees from plant resins, sap and other botanical sources) is beginning to attract the interest of Moroccan beekeepers thanks to its biological properties. This work does not focus on latex, but on the aerial parts of E. officinarum and E. resinifera, the inflorescence part called cyathium of E. resinifera, which do not secrete latex; monofloral honey of E. officinarum and E. resinifera; as well as propolis from E. officinarum and E. resinifera. The solvent for extracting the aerial parts of both species was water, because it is the liquid used by the population to treat their illnesses. The extraction temperature; extraction time; and plant/solvent ratio are the parameters chosen to obtain extracts with the highest quantities of phenols and with the best in vitro antioxidant properties, chelating activity and capacity to inhibit α-glucosidase activity using response surface methodology (RSM). The best extraction conditions detected were using 1 g/50 mL during 60 minutes at 30 ºC for E. resinifera and for E. officinarum; the best conditions were temperature of 50 ºC, using1 g/100 mL for 270 minutes. Euphorbia resinifera cyathium releases a nectar that bees collect and transform into honey, currently labeled as a Protected Geographical Indication, due to its qualities. Additionally, flower cyathium honey and water extracts have been used in traditional medicine in Morocco. Several compounds belonging to different metabolite classes were identified in the present investigation. Concerning the primary metabolites: in hexoses, glucose followed by fructose predominates; in organic acids, citrate and α-ketoglutarate were the most abundant; amino acids were also found in abundance, notably asparagine (Asn); and vitamins such as niacin, vitamin B3, threonate (a metabolite of vitamin C), and the antioxidants ascorbate and dehydroascorbate. Regarding secondary metabolites: lutein was dominant in the pigments identified; flavonoids were dominated by the flavonol glycosides quercetin, kaempferol and isorhamnetin; polyamines were also identified. The scavenging capacity of DPPH and superoxide radicals by the floral extracts corresponded to two thirds and half of the capacity of pure compounds used respectively as positive control. Out of seven honey samples, two were of floral origin from E. resinifera and after pollen analysis, the other five were found to have high percentages of E. officinarum pollen grains. The potassium (K) was the most important mineral element in in all samples with an average content of 409 mg/kg. The chromatographic profiles evaluated by liquid chromatography coupled to diode array detection and mass spectrometry (LC-DAD-MS) of Euphorbia honey extracts were quite different. In all samples, it was possible to detect gallic acid, 4-hydroxybenzoic acid and p-coumaric acid, although in different proportions. Naringenin was identified in all but one sample. Abscisic acid was detected in five of seven honey samples, being the major compound detected in in one E. resinifera honey. The antioxidant properties of E. officinarum and E. resinifera as well as their ability to inhibit acetylcholinesterase, lipoxygenase, tyrosinase, and xanthine oxidase enzymes were evaluated and compared. At the same time, the in vitro biological activities of the entire honey and the extracts obtained from the respective honey were also evaluated and compared. Generally, the methanolic extracts of the honey recorded better activities in all the biological activities, than the corresponding entire honey. The antioxidant properties and the capacity to inhibit some enzymatic activities of E. resinifera and E. officinarum aqueous extracts and honeys were assessed. The aqueous extracts were obtained by decoction and two extraction parameters were chosen: extraction time (1 h, 2 h, and 8 h); and PSR (plant solvent ratio) of 1 g/20 mL; 1 g/50 mL, and 1 g/100 mL. The physicochemical characteristics of the honey were also evaluated and were within the range of the quality standards, E. officinarum honey showed higher amounts of total phenols and better capacity for scavenging superoxide anion free radicals and DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals than E. resinifera honey, but poorer capacity for inhibiting lipoxygenase, acetylcholinesterase, tyrosinase, and xanthineoxidase. Moreover, the aqueous extracts had systematically higher in vitro activities than the respective honey samples. Concerning propolis samples, the study aimed to characterize the pollen type, the volatile compounds, the phenolic and mineral profiles of three Euphorbia propolis samples collected in Morocco. In addition, it was intended to evaluate its antioxidant and antimicrobial activities, as well has the enzymatic inhibition potential. Pollen analysis revealed that E. resinifera pollen dominated in the P1 sample (58%), while E. officinarum pollen dominated in the P2 and P3 samples (44%). The volatile compounds were primarily composed of monoterpenes hydrocarbons, with α-pinene being the major component. Calcium (Ca) was the predominant mineral element in all propolis samples. Higher levels of phenols, flavonoids, and dihydroflavonoids were detected in the E. officinarum which corresponded to superior antioxidant activity. This was determined by its ability to scavenge DPPH and nitric oxide (NO) free radicals, superoxide anion radicals, and to prevent lipid peroxidation. P1 and P3 exhibited the best inhibitory effects on glucosidase activity, while the P2 sample demonstrated the highest efficacy in inhibiting acetylcholinesterase, lipoxygenase, tyrosinase, and xanthine oxidase activities. Euphorbia propolis displayed the ability to inhibit quorum sensing in the biosensor Chromobacterium violaceum CV026 and disrupted bacterial biofilm formation, including that of resistant bacterial pathogens.
- Palynology of the Triassic - Jurassic of the Silves group in Portugal - its implications on a changing worldPublication . Boas, Ana Margarida Silva Vilas; Fernandes, Paulo; Pereira, Zélia; Cirilli, SimonettaThe biostratigraphy of the Lusitanian and Algarve basins is based on macrofossils and microfossils (foraminifers, nannofossils, and ostracods). Compared to these works, palynological studies are rare in these basins. Palynomorphs are a powerful biostratigraphic and paleoenvironmental tool, and their research could significantly contribute to the context of the two basins. In this project, the Upper Triassic and Lower Jurassic of the Lusitanian and Algarve basins were studied. In the Lusitanian Basin, twelve sections were sampled, all in Coimbra and Miranda do Corvo: Lamas I, Lamas II, Castelo Viegas I, Castelo Viegas II, IdealMed, Alto de São João, Parque de Campismo, Sobral Cid, Carvalhais, Redonda, Lordemão and Eiras. A total of 122 samples were collected in these sections and studied in detail. In the Algarve Basin, fifteen sections were sampled throughout the entire basin: Vale de Fuzeiros, Bengado, International Racetrack of Algarve, Marco, Loulé Rock Salt Mine, Santa Rita, Amorosa, Amado’s Beach, Rocha da Pena, Bodega, Barragem do Funcho, Santa Catarina Fonte do Bispo, Fonte da Pedra, Diapiro de Albufeira and Ayamonte. Full amount of 254 samples were collected in these sections and studied in detail. (...)
- All-inclusive hospitality dynamics - the case of the AlgarvePublication . Rassal, Carimo Hassam; Correia, Antónia de Jesus Henriques; Serra, Francisco Manuel DionisioThis reserach analyses the determinants of guest satisfaction and loyalty in the all-inclusive (AI) hotel sector in the Algarve to assess the dynamics and impacts of this activity in the region. From a methodological point of view, the research is based on Qualitative Comparative Analysis (fsQCA) to identify the multiple configurations that influence guest satisfaction in different hotel settings. (...)
- Establishment of a genetic resource bank for restocking management in Portuguese oyster (Crassostrea angulata) and striped venus clam (Chamelea gallina)Publication . Anjos, Catarina Miranda Castilho dos; Cabrita, Elsa; Matias, DomitíliaBivalves are essential for fisheries, aquaculture, and ecosystems, serving as nutrient-rich resources for human consumption. Despite their significance, many bivalve resources, including Crassostrea angulata (Portuguese oyster) and Chamelea gallina (striped venus clam) in Europe, evidence signs of depletion due to environmental change, anthropogenic impact, and overexploitation, requiring rehabilitation measures. One possible strategy involves establishing a genetic resource bank via cryopreservation. However, cryopreservation presents challenges, requiring optimization of freezing and thawing conditions, particularly the cryoprotectant solution, and understanding cryodamage. The present thesis aims to explore and establish conditions to store and preserve the genetic resources of C. angulata and C. gallina populations. Chapter 1 provides contextual background, on the current situation of bivalve production and the importance of these resources, with special attention on the endangered and valuable species for aquaculture/fisheries, C. angulata and C. gallina. The chapter addresses the fundamental principles of cryobiology and current knowledge on bivalve cryopreservation methodologies for sperm and larvae. This chapter discusses the value of cryodamage assessment tools, emphasizing “omics” molecular tools for high-potential analysis. Chapters 2 and 3 aim to optimize and develop new cryopreservation protocols for the target species. Chapter 2 investigates the effect of the cryoprotectant supplementation with sugars (trehalose and sucrose) on the post-thaw sperm quality of C. angulata. Several methodologies not commonly used in bivalve cryopreservation works were employed, including the determination of reactive oxygen species levels, acrosome integrity and the activity of antioxidant enzymes (superoxide dismutase - SOD, glutathione reductase - GR and glutathione peroxidase - GPX). Sugars supplementation, especially trehalose reduced lipid peroxidation and ROS levels having a positive effect in plasma membrane and acrosome integrity. Chapter 3 evaluates the larval quality of C. angulata and C. gallina exposed and cryopreserved with cryoprotectant solutions that differ in the permeant agent (dimethyl sulfoxide - DMSO and ethylene glycol - EG). The work aimed to understand the effects of cryoprotectant exposure and, cryopreservation on malformations, movement, and enzymatic activity compared with non-exposed larvae. The methodologies for cryopreserving D-larvae of both species were established for the first time. Chapter 4 investigates C. angulata D-larvae cryodamage during cryoprotectant exposure and cryopreservation, using RNA sequencing. This molecular approach was essential for providing evidence that the freezing process was the critical step rather exposure. Furthermore, identified 11 genes as relevant biomarkers of freezability for D-larvae quality assessment. This thesis presents strategies for cryopreserving the genetic material of C. angulata and C. gallina and for cryodamage evaluation.
- Intraspecific variation in response to marine heatwaves in two northeast Atlantic kelp speciesPublication . Barreto, Luís António de Matos; Serrão, Ester; Pearson, Gareth; Bartsch, InkaKelp forests, one of the most productive and biodiverse ecosystems are shifting their distributional ranges due to changing environmental conditions including marine heatwaves (MHWs). We tested two kelp sister species from thermally and phylogenetically differentiated clades, Laminaria hyperborea (cold-temperate) and Laminaria ochroleuca (warm-temperate) using populations across the latitudinal gradient of the species distribution in the northeast Atlantic. We specifically selected these ecological models because L. ochroleuca is expanding its northern distribution poleward while outcompeting the once dominant L. hyperborea which in turn is contracting at its southernmost distribution limits in the Iberian Peninsula. Local thermal regimes and long-term MHW metrics were performed to characterize the thermal exposure of each population and integrate temperature in the experimental design. L. ochroleuca, the effects of depth were also investigated on deep (-50 m) and shallow (-4 m) populations. We performed simulated MHWs (sMHWs) with field-collected adults, in vitro cultured gametophytes (microscopic sexual phase), and cultured F1 juvenile sporophytes derived from gametophyte crosses. L. hyperborea from the South warm edge population showed 100% mortality during recovery at 23 ºC sMHW, contrasting to the other regions. We analysed for the first time the genetic structure and diversity of L. hyperborea across its distribution, revealing high and unique genetic diversity in the less resilient ancient South populations. L. ochroleuca gametophytes showed population variation as onset of mortality in the North began at 23°C, while in the remaining populations mortality was only apparent at 27°C. The deep L. ochroleuca adult population (Az) was thermally inhibited by the highest sMHW temperatures but able to recover indicating photoinhibition that was not observed in the F1 juveniles (Me). F1 juvenile sporophytes from the North population were unable to fully recover photosynthetically (photodamage) from all sMHWs. This intraspecific variation may potentially be associated with reduced thermal tolerance in cooler northern regions.
- Maternal thyroid hormones role in zebra fish blood-hindbrain barrier developmentPublication . Trindade, Marlene Pacheco; Campinho, António do Nascimento Sequeira de JesusThyroid hormones (THs), thyroxine (T4) and 3,5,3’–triiodothyronine (T3), are key signalling molecules that regulate vertebrate development and physiology. In humans, an inadequate supply of THs during prenatal stages causes several neurological impairments, affecting a newborn’ psychomotor and cognitive development. The most severe condition results from mutations of the monocarboxylate transporter 8 (MCT8), leading to a rare X-linked neurodevelopmental disorder, the Allan-Herndon-Dudley syndrome (AHDS). In zebrafish, knockdown of the T3 exclusive membrane transporter Mct8 phenocopies the symptoms observed in AHDS patients. An impaired blood-hindbrain barrier (BHB) was observed in zebrafish but has not yet been confirmed in humans. This thesis aimed to understand how maternal T3 (MT3) through Mct8 coordinates the development of the vascular system of the zebrafish hindbrain. Transcriptome analysis of 25 hours post fertilisation (hpf) CTRMO vs MCT8MO zebrafish embryos revealed that expression of several genes of the important angiogenic Vegf pathway was significantly regulated by MT3. At the cellular level, specific vegfaa signalling juxtaposed to the developing central arteries (CtAs) was identified and vegfaa-165 mRNA rescues the majority of CtAs in MCT8MO zebrafish embryos. To identify the source of hindbrain vegfaa and, consequently, the cell identity dependent on MT3 signalling, neural cell markers were analysed. This revealed that pax8 inhibitory interneurons and cpne4 intrinsic digit-innervating motor neurons were under MT3 regulation but were not responsible for CtA development. pax6a neural progenitor cells (NPCs) were the source of hindbrain vegfaa, and a correlation between these cells and the migratory behaviour of the CtAs was found. Colocalisation analysis of pax6a NPCs with thraa, thrab and mct8 demonstrated that these cells were regulated in a cell-autonomous way and showed that the spatiotemporal expression could be an indicator of the timely sprouting of each CtA during BHB development. Finally, pax6a loss-of-function CRISPR/Cas9 zebrafish embryos had a similar hindbrain vascular impairment as the MCT8MO zebrafish embryos, confirming that pax6a NPCs were the cells responsible for CtA ingression into the hindbrain. In conclusion, MT3 via Mct8 is important for the survival and proliferation of pax6a NPCs, which are the instructing source of vegfaa necessary for the timely development of the BHB CtAs.
- Síntese de bisindolilmetanos via reações de ciclo-adição hetero Diels-Alder e as suas aplicações biológicas como antimicóticosPublication . Domingos, João Manuel Lopes; Lemos, Américo; Quintas, CéliaOs derivados indólicos associam-se a uma classe de alcalóides bioativos, caracterizados por apresentarem uma estrutura simples, baixa toxicidade e propriedades biológicas e farmacológicas de interesse, tais como antibacterianas, anticancerígenas, antioxidantes e anti-inflamatórias. Entre os diversos derivados, os bisindolilmetanos (BIMs) são compostos cujas origens na natureza predominam como agentes metabólitos bioativos, encontrados em ambiente terrestre e marinho, presentes em determinadas plantas e esponjas. A nível clínico, exibem uma extensa aplicação, como antibióticos contra uma diversidade de diferentes espécies (Vibrindole A) e anticancerígeno (Trisindolina). Nos últimos anos, tem-se descoberto novos BIMs que apresentam atividade antimicrobiana prometedora, podendo assim ser considerados como potenciais novos fármacos. O uso prolongado de determinados antifúngicos azólicos, em que está incluído o fluconazole, podem conduzir ao desenvolvimento de resistências em leveduras patogénicas, sendo necessário que se recorra a uma terapia combinada como forma de potencialmente superar esta inconveniência. Logo, investigações que possam conduzir a novos compostos que consigam eficazmente produzir uma atividade terapêutica sem que surjam problemas relacionados com resistência medicamentosa ou com reações adversas muito comuns entre eles, são cruciais. Presentemente, as vias de síntese mais prevalentes envolvem a reação de indoles com vários compostos carbonílicos ou equivalentes, catalisada por ácidos ou metais. Recentemente, a reações de ciclo-adição hetero-Diels-Alder, baseadas na dupla e consecutiva interseção de azo- e nitroso- alcenos conjugados com indoles provou ser uma alternativa de síntese versátil e de larga aplicação na preparação de BIMs. O objetivo desta monografia foi investigar a capacidade antimicótica de BIMs sintetizados, no âmbito deste estudo, com base em reações de ciclo-adição hetero-Diels-Alder. Assim os BIMs obtidos foram aplicados em ensaios biológicos, e comparada a sua eficácia contra três espécies de leveduras, Candida albicans (ATCC 90028 e 10231), Cryptococcus neoformans (YPO 186) e Saccharomyces cerevisiae (PYCC 3507) e três antimicóticos utilizados no tratamento de patologias originadas por estas leveduras (Anfotericina B, Nistatina e Fluconazole).
- Abordagem atual na seleção de medicamentos emergentes na Depressão ResistentePublication . Martins, Marta Sofia Tomé Vicente de Bastos; Silva, Isabel Maria Júlio daA depressão resistente ao tratamento é caracterizada pela falta de resposta adequada a, pelo menos, dois regimes antidepressivos de diferentes classes, afetando uma percentagem significativa de indivíduos diagnosticados com depressão major. Recentemente, alguns fármacos emergentes têm sido investigados como alternativas promissoras para a depressão resistente ao tratamento. Entre esses tratamentos, destacam-se a cetamina e a escetamina, antagonistas dos recetores NMDA, que oferecem alívio rápido dos sintomas, em doentes refratários ao tratamento. Outras substâncias psicadélicas, como a psilocibina e o MDMA, têm igualmente mostrado resultados positivos em ensaios clínicos, através da modulação dos circuitos neuronais envolvidos no humor e na cognição. As abordagens atuais focam-se em alternativas que vão, além dos mecanismos tradicionais de modulação de serotonina, noradrenalina e dopamina, permitindo uma investigação pormenorizada das vias relacionadas com o equilíbrio neuro químico e a plasticidade cerebral. A seleção dos medicamentos emergentes tem em consideração não apenas os medicamentos inovadores de ação, mas também a capacidade de proporcionar benefícios terapêuticos rápidos e uma melhoria significativa na qualidade de vida dos doentes. No entanto, apesar dos avanços, os desafios relacionados com a segurança a longo prazo, os efeitos adversos e a eficácia consistente precisam ainda de ser abordados em estudos adicionais. Assim sendo, os novos tratamentos representam uma mudança significativa na forma com a depressão resistente ao tratamento é tratada, proporcionando esperança e bem-estar aos doentes que não respondem às terapias convencionais.
- Fármacos de Platina no tratamento oncológico: mecanismos de resistênciaPublication . Guerreiro, Patrícia Maria dos Santos; Lourenço, João Paulo GilNa década de 1960, a descoberta da atividade anticancerígena da cisplatina e a sua eficácia clínica despertaram um grande interesse na investigação de compostos de coordenação para tratamento do cancro. Para além da cisplatina, surgiram outros complexos de platina, como a carboplatina e a oxaliplatina. Estes compostos são amplamente utilizados no tratamento de vários tipos de cancro, incluindo testicular, pulmonar, ovário e bexiga. O mecanismo de ação dos fármacos de platina é bastante complexo, sendo que a formação de adutos inter ou intracadeias com o ADN nuclear é uma das vias mais estudadas e reconhecidas. A formação destes adutos resulta na interrupção dos processos de replicação e trancrição do ADN, promovendo desta forma apoptose. No entanto, o ADN nuclear não é o único alvo, existem outros alvos celulares que contribuem para o efeito dos fármacos de platina. O complexo de cisplatina ataca as mitocôndrias e desencadeia a produção de espécies reativas de oxigénio, destruindo os lisossomas e por sua vez, induzindo a libertação de proteáses lisossomais que degradam o retículo endoplasmático. Estes complexos podem ainda, através da formação de adutos com grupos funcionais em proteínas, em particular com átomos de enxofre presentes nos resíduos de cisteína e metionina, alterar a função proteica contribuindo para a morte celular. Apesar da eficácia comprovada, a resistência aos fármacos de platina representa um grande desafio no meio oncológico. As células cancerígenas podem desenvolver resistência através de diversos mecanismos, como a alteração da captação/efluxo de fármaco, a inativação da cisplatina por moléculas contendo tiol, e a capacidade de regeneração do ADN danificado. Compreender estes mecanismos de resistência é crucial para o desenvolvimento de novas estratégias terapêuticas. Ao longo desta monografia são demonstrados diversos mecanismos de resistência, bem como formas de ultrapassar e otimizar o tratamento farmacoterapêutico.