Saudi Cultural Missions Theses & Dissertations
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Item Restricted Modulation of scavenger receptor lectin-like oxidised low-density lipoprotein receptor -1 and plasmin inhibitor activities using Affimer technology, improves the hypofibrinolytic environment in high vascular-risk individuals(University of Leeds, 2023) Alsayejh, Basmah; Jawarneh, AhmedAtherothrombotic disease is a major cause of morbidity and mortality worldwide, with thrombus formation representing the final step in the pathophysiology, leading to end organ damage. Oxidised low-density lipoprotein (oxLDL) and its receptor Lectin-like oxidised low-density lipoprotein (LOX-1) play key roles in the pathogenesis of atherosclerosis and may have a role in thrombus formation but this remains controversial. In contrast, the antifibrinolytic protein plasmin inhibitor (PI) is well known to stabilise the fibrin network, which forms the backbone of the blood clot, through inhibition of the fibrinolytic process, protecting against excessive bleeding after vessel injury. However, there is a fine balance as excessive inhibition of fibrinolysis is associated with increased vascular thrombosis and adverse clinical outcomes. My hypothesis is that oxLDL affects fibrin clot formation and/or lysis and therefore represents a new therapeutic target to reduce thrombosis risk. I also hypothesise that PI activity can be modulated to reduce thrombosis risk and improve fibrinolysis in high- vascular risk conditions. Therefore, the aims of my work are to i) study the effects of oxLDL, with and without LOX-1, on clot structure/lysis to understand whether this pathway represents a new therapeutic target for reducing thrombosis risk, ii) use a new technology, employing small proteins called Affimers, to modulate PI activity and enhance the fibrinolytic process iii) probe into the mechanisms for Affimer-induced modulation of PI activity (if any).LDL was purified from plasma samples and oxidised using validated in vitro techniques. The effects of oxLDL on clot structure and lysis were studied using a turbidimetric assay in the absence and presence of sLOX-1. My results show that oxLDL, with and without sLOX-1, has no effects on clot structure/lysis using turbidimetric assays, indicating this is not a viable pathway for modulation of thrombosis risk. In the second part of my work, I show that the Affimer technology can be successfully used to modulate PI activity. One PI-specific Affimer shortened lysis of clots made from plasma samples and whole blood from healthy controls and also had similar effects across high vascular risk individuals, including patients with cardiovascular disease (CVD) and type 1 and type 2 diabetes (T1DM, T2DM). The mechanism of action of the PI-specific Affimer appears to be related to interference with plasmin generation with less of an effect on plasmin activity. In conclusion, my thesis demonstrates that oxLDL does not represent a credible target for reducing thrombosis risk. On the other hand, the affimer technology can be successfully employed to alter clot lysis by targeting the key anti-fibrinolytic protein, PI.7 0Item Restricted The Health Benefits of Probiotic Lactobacillus Plantarum: A systematic review and Meta-analysis(2023) Aljohani, Amal; Xiao, JinTo ensure effective implementation of probiotics in clinical practice, it is crucial to comprehend the specific strains and their association with human health. Therefore, our study aimed to evaluate the scientific evidence on the impact of Lactobacillus plantarum probiotic consumption on human health. We conducted a systematic review and meta-analysis by searching PubMed, Embase, Web of Science, and Cochrane Library in March 2022. Out of 11831 records, 135 studies were assessed qualitatively, and 18 studies were included in the meta-analysis. This systematic review provided evidence that probiotic supplementation, either in combination with L. plantarum or L. plantarum alone, can significantly benefit patients with specific pre-existing medical conditions by improving test results or alleviating symptoms, in the field of periodontal health, gastroenterological health, Mental health, Cardiovascular health, Endocrine health and Dermatological health. Understanding the strain-specific function and effect of probiotics is crucial to comprehending their potential therapeutic benefits for specific medical conditions. Our study's clinical significance highlights the importance of considering probiotic strain and their application to specific diseases when planning future studies and clinical interventions, emphasizing the need for further research in this area.27 0