Saudi Cultural Missions Theses & Dissertations
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Item Restricted The effects of different nutritional strategies on markers of inflammation, oxidative stress and gastrointestinal stress after exercise(Saudi Digital Library, 2025) Alhebshi, Abrar Hamzah; Clifford, TomThesis abstract Exercise elicits a transient physiological stress response, involving inflammation, oxidative stress, and gastrointestinal (GI) disturbances. Regular, moderate-intensity training is associated with low-to-moderate elevations in reactive oxygen and nitrogen species (RONS) and inflammatory mediators, which play a pivotal role in cellular signalling and adaptive responses in skeletal muscle. However, prolonged or unaccustomed high-intensity exercise can provoke a more pronounced acute-phase inflammatory reaction, oxidative stress and compromise GI barrier integrity that can be detrimental to both immune and muscular recovery processes. Hence, there is a growing body of research exploring the potential of numerous nutritional approaches for modulating inflammation, oxidative stress, and gut integrity. These interventions may provide a practical advantage in athletic settings where recovery windows are limited. Among these, (poly)phenols—bioactive compounds in plant-based foods—have attracted considerable scientific attention for their potential health-promoting effects. Within this group, curcumin, a pleiotropic compound derived from turmeric, has gained particular attention due to its ability to interact with multiple antioxidant and inflammatory signalling pathways as well as its gastroprotective properties. Besides these concentrated supplements, an increasing focus has shifted toward lower-dose (poly)phenol-rich meals that are thought to deliver a complex matrix of phenolic and non-phenolic constituents, which may enhance overall bioefficacy through additive or synergistic mechanisms. While curcumin and these high (poly)phenol diets have been extensively studied in vitro or in clinical populations, evidence from human exercise studies remains limited. Accordingly, the overarching aim of this thesis was to investigate whether specific nutritional strategies—including dietary proteins and (poly)phenol-based interventions—could attenuate exercise-induced markers of inflammation, oxidative stress, and GI disturbances during the immediate hours post-exercise in healthy humans. Chapter 3 systematically evaluated the evidence from high-quality randomized controlled trials examining the effects of whole protein and commonly consumed amino acid-based supplements on biomarkers associated with inflammation and oxidative stress following exercise. The concluded evidence regarding the modulatory impact of dietary protein and amino acid supplementation on exercise-induced inflammation and oxidative stress remains insufficient and inconsistent. Consequently, the future experimental Chapters focused on exploring alternative nutritional approaches that are hypothesized to exert stronger anti-inflammatory effects. Chapter 4 aimed to explore whether short-term intake of an innovative formulation of curcumin supplementation could modify markers of inflammation and oxidative stress after intense exercise, and if this novel formulation was bioavailable. This study found that curcumin may, to some extent, modify the immune response by attenuating elevated systemic neutrophil concentrations. However, despite significantly higher plasma curcumin metabolites, the data suggested that curcumin exerted limited and inconsistent effects on other markers of inflammation and oxidative stress post-exercise, as evidenced by elevated granulocytes colony stimulating factor (G-CSF), vascular cell adhesion protein (VCAM)-1, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in curcumin group. Chapter 5 builds upon the data from Chapter 4, by evaluating specific markers of GI disturbance or integrity post-intense exercise after acute curcumin supplementation. The findings indicated that acute curcumin supplementation may have elevated GI damage markers immediately following exercise. Chapter 6 aimed to examine whether 4 days consumption of (poly)phenols, this time whole foods breakfast, prior to muscle-damaging exercise positively influences post-exercise inflammatory and oxidative stress markers. This study reported no consistent trend in the markers measured to suggest that increasing plasma (poly)phenol levels through whole foods effectively mitigates post-exercise changes in oxidative stress and inflammation, as reflected by low glutathione peroxidase (GPX) activity and higher 8-OHdG concentrations in the supplemented group. Collectively, the findings in this thesis indicate that the ability of dietary protein, curcumin, or (poly)phenol-rich foods to modify exercise-induced markers of inflammation, oxidative stress, or GI stress (curcumin only) in humans is both limited and inconsistent. The potential benefits of these interventions in addressing post-exercise biological responses remains uncertain, and future research is needed to clarify their effectiveness in athletic populations and therefore efficacy to support recovery.6 0Item Restricted Novel Pharmacological Strategies to Treat Cigarette Smoking-induced Atherogenesis in Chronic Obstructive Pulmonary Disease(Saudi Digital Library, 2025) Almerdasi, Suleman; Vlahos, Ross; Chan, Stanly; Selemidis, StavrosChronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterised by persistent airflow limitation and chronic lung inflammation, primarily driven by exposure to noxious particles and gases such as cigarette smoke (CS). Repeated CS exposure induces oxidative stress and disrupts pulmonary barrier integrity, leading to the “spill-over” of inflammatory mediators into the systemic circulation. This systemic inflammation contributes to vascular dysfunction and platelet activation, which are key drivers of cardiovascular disease (CVD) - a major comorbidity in COPD. This thesis investigated the mechanistic links between CS-induced oxidative stress, systemic inflammation, and vascular pathology using a validated preclinical model of COPD. It further evaluated the therapeutic potential of antioxidant and lifestyle-based interventions, including apocynin, carnosine supplementation, and exercise intervention, with a focus on sex-specific responses. In Chapter 3, apocynin - a NADPH oxidase inhibitor - was shown to attenuate CS-induced airway inflammation, preserve endothelial-dependent vasodilation, and reduce platelet activation, highlighting oxidative stress as a modifiable trait in COPD. Chapter 4 demonstrated that carnosine supplementation or exercise alone reduced airway inflammation and partially restored vascular function, while Chapter 5 revealed that their combination produced synergistic benefits. The combined intervention significantly preserved body weight, improved endothelial function, and prevented platelet activation, outperforming either treatment alone. Chapter 6 explored sex-specific responses to CS and intervention. Males exhibited heightened neutrophilic inflammation, vascular dysfunction, and platelet adhesion, whereas females showed greater lymphocytosis and epithelial thickening. The combined therapy mitigated these effects in both sexes, though the magnitude and mechanisms of response varied, underscoring the importance of sex as a biological variable in COPD research. In conclusion, this thesis provides mechanistic evidence that CS-induced oxidative stress and systemic inflammation drive vascular dysfunction and platelet activation in COPD. It establishes that combining carnosine supplementation with exercise offers a promising strategy to protect vascular integrity and reduce systemic inflammation. The observed sex differences further support the need for personalised therapeutic approaches in COPD management.21 0Item Restricted Targeting cell-cell communication systems of Streptococcus pneumoniae by molecularly imprinted polymers(Saudi Digital Library, 2025) Baqasi, Aisha Mohammad; Yesilkaya, HasanStreptococcus pneumoniae communicates through quorum sensing systems (QSS), which coordinate bacterial behaviour via pheromone signalling. Among peptide-mediated QSS, the regulatory gene family glycosyltransferase (Rgg) plays a crucial role in biofilm formation, virulence, bacteriocin production, and oxidative stress resistance, though its role in virulence and the possibility of being a drug target remain underexplored. This study investigated Rgg144 and Rgg1518, examining their regulatory interactions using isogenic mutants in growth studies, biochemical assays, and reporter gene analyses. The findings indicate that both Rggs contribute to mannose and galactose metabolism, as mutants exhibit attenuated growth and both systems were specifically induced by these sugars. Furthermore, full induction of each pathway required the presence of the other, indicating the inter-regulatory interactions between the two systems. Additionally, both Rggs play a significant role in protection against oxidative stress as evidence by the reduced expression of genes coding for superoxide dismutase (sodA) and thiol peroxidase (tpxD) in mutant strains and increased sensitivity to hydrogen peroxide and paraquat. Rgg144 and Rgg1518 were also implicated in pneumococcal colonisation and virulence, as mutant strains showed attenuated phenotypes in vivo. To disrupt pneumococcal communication, peptide-specific nano-molecularly imprinted polymers (nano-MIPs), shp144MIP and shp1518MIP, were synthesised. These nano-MIPs exhibited no toxicity in vivo (Galleria mellonella) or in vitro (S. pneumoniae growth) and effectively reduced disease progression, nasopharyngeal colonisation in a murine model, gene expression in reporter strains, and galactose utilisation. This study highlights the critical roles of Rgg144 and Rgg1518 in pneumococcal metabolism, oxidative stress response and colonisation, and introduces nano-MIPs as a promising therapeutic strategy to interfere with quorum sensing in Gram-positive bacterial infections, particularly S. pneumoniae.13 0Item Restricted RISK FACTORS, BEHAVIOURS, AND MISCONCEPTIONS CONTRIBUTING TO PHOTOAGEING(King's College Lomdon, 2024) Almusalami, Mustafa; Novakovic, LjubomirPhotoageing, distinct from intrinsic ageing, results from prolonged exposure to ultraviolet (UV) radiation, leading to premature skin ageing. This study investigates the risk factors, behaviours, and misconceptions contributing to photoageing, highlighting the impacts of UVB and UVA radiation. It also explores the roles of visible light and infrared radiation in photoageing, emphasizing comprehensive photoprotection strategies. The study examines environmental and individual factors, such as geographic location, lifestyle, and skin type, influencing UV exposure and photoageing severity. Behavioural factors, including intentional tanning and inadequate sunscreen use, further increase the risk. The research underscores the importance of public education to promote effective sun protection and dispel common misconceptions about sunscreen and UV exposure.19 0Item Restricted Modulation of Autistic-Related Factors in Hippocampal Neurons: Role of Oxytocin(2023-04-24) Alfaifi, Hassan; Castejon, AnaBackground: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with dysregulation of several cellular processes. Accumulating evidence links ASD to the abnormality of cellular growth and programmed cell death (apoptosis). According to many postmortem and animal studies, abnormalities of several apoptotic signaling pathways have been linked to the induction of ASD, such as the ERK and p53 signaling pathways. Besides, the participation of neuroinflammation and oxidative stress in ASD induction and perpetuation has been identified. It has been reported that the levels of ROS and interleukin-1β are abnormally increased in neuronal brain cells in individuals with ASD. Therefore, agents that can improve cellular growth, regulate apoptosis, and reduce oxidative stress and neuroinflammation, like the neuropeptide oxytocin (OXT), may be effective in managing ASD. Objective: Our main goal was to investigate the effects of OXT on autistic-related factors, including cellular growth, oxidative stress, and neuroinflammation, as well as the intracellular signaling pathways involved in these effects. Methodology: We evaluated the effect of OXT on cell growth and death by performing cell counting (hemocytometer), MTT assay, and Bresto blue assay in hippocampal neurons (mHippoE-2). The proliferative effect mechanisms were evaluated using western blotting and MTT assay. In the survival experiments, viability was assessed by MTT assay in cells incubated in the presence or absence of OXT 1000 nM and/or 1000nM OXTA with oxidative stress inducers (H2O2, DMNQ, and CPT) and neuroinflammatory inducer (LPS). The mechanisms of the protective effect were evaluated using western blotting, ELISA. Also, we used the DCFDA kit to evaluate the antioxidant effect of OXT. Moreover, we employed the immunocytochemistry technique to assess the effect of 1000 nM OXT and/or 1000 nM OXTA against the induced morphological alterations. v Results: This study revealed that OXT significantly induced cell growth in hippocampal neurons (mHippoE-2). The OXTA (L-371,257) significantly reduced cell growth. The proliferative effect of OXT is mediated through MEK/ERK signaling pathway. In addition, treatment with 1000 nM OXT significantly reduced the reduction in cell viability induced by oxidative stress inducers (H2O2, CPT, and DMNQ) but not inflammatory inducer (LPS). In addition, OXT significantly reduced ROS generation when the cells were exposed to H2O2 and DMNQ but not CPT. The western blotting technique demonstrated that OXT significantly reduced the protein levels of p53-caspase 3 and increased the levels of Mdm2 induced by H2O2 and DMNQ, but not CPT. Our morphological studies showed that OXT countered the reduction in cellular projection length induced by H2O2, CPT, and DMNQ. Furthermore, OXT significantly reduced the protein levels of PI3K and p-AKT but not the NLRP3-caspase 1 signaling pathway. Conclusion: Our results indicate that OXT has a proliferative effect by activating the ERK signaling pathway. Furthermore, we revealed that the protective effect of OXT was mediated through the modulation of oxidative stress and mitochondrial apoptosis pathway. Moreover, OXT decreased the levels of some inflammatory-mediated proteins. On the other hand, these effects were lacking in the presence of OXTA. These results will contribute to a better understanding of OXT’s potential role in autistic-related factors associated with cell loss, oxidative stress, and neuroinflammation.6 0