School of Interprofessional Health Studies
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The School of Interprofessional Health Studies develops and teaches the core interdisciplinary papers in the Faculty of Health and Environmental Sciences degree programmes.
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- ItemEffect of Bone Marrow Mesenchymal Stem Cells-derived Exosomes on Diabetes-induced Retinal Injury: Implication of Wnt/ B-catenin Signaling Pathway(Elsevier BV, 2022-10) Ebrahim, N; El-Halim, HEA; Helal, OK; El-Azab, NE-E; Badr, OAM; Hassouna, A; Saihati, HAA; Aborayah, NH; Emam, HT; El-wakeel, HS; Aljasir, M; El-Sherbiny, M; Sarg, NAS; Shaker, GA; Mostafa, O; Sabry, D; Fouly, MAK; Forsyth, NR; Elsherbiny, NM; Salim, RFBackground Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. Methods Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). Results Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. Conclusion Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.
- ItemMechanism of Resveratrol Dimers Isolated from Grape Inhibiting ¹O₂ Induced DNA Damage by UHPLC-QTOF-MS² and UHPLC-QQQ-MS² Analyses(MDPI AG, 2021) Kong, Q; Zeng, Q; Yu, J; Xiao, H; Lu, J; Ren, XResveratrol dimers have been extensively reported on due to their antioxidative activity. Previous studies revealed that resveratrol dimer has been shown to selectively quench singlet oxygen (1O2), and could protect DNA from oxidative damage. The mechanism of resveratrol dimers protecting DNA against oxidative damage is still not clear. Therefore, in this project, the reactants and products of resveratrol dimers protecting guanine from oxidative damage were qualitatively monitored and quantitatively analyzed by UHPLC-QTOF-MS2 and UHPLC-QQQ-MS2. Results showed that when guanine and resveratrol dimers were attacked by 1O2, mostly resveratrol dimers were oxidized, which protected guanine from oxidation. Resveratrol dimers’ oxidation products were identified and quantified at m/z 467.1134 [M-H]− and 467.1118 [M-H]−, respectively. The resorcinol of resveratrol dimers reacted with singlet oxygen to produce p-benzoquinone, protecting guanine from 1O2 damage. Therefore, it is hereby reported for the first time that the resorcinol ring is the characteristic structure in stilbenes inhibiting 1O2 induced-DNA damage, which provides a theoretical basis for preventing and treating DNA damage-mediated diseases.
- ItemEffectiveness of Psilocybin on Depression: A Qualitative Study(Modestum Publishing Ltd, 2021-04-27) Alshaikhli, H; Al-Naggar, RA; Erlam, GIntroduction: Psilocybin mushroom use is well documented in spiritual and religious ceremonies globally. This drug is now the most popular in Europe and the USA. Objective: The objective of this study is to explore the experiences and effects of psilocybin on patients with depression and anxiety. Method: A qualitative study was conducted interviewing ten participants currently taking psilocybin while experiencing depression and/or anxiety. Ethical approval was obtained from the University ethics committee. Participants were recruited via social media and groups are known to have used psilocybin for the treatment of anxiety and/or depression. Participants were informed of study aims and consent was obtained before interviews commenced. Confidentiality was maintained throughout this study. Interviews began with informing participants that psilocybin may be effective in the management of depression. Initially, information around the way treatment with psilocybin was obtained was sought. This was followed by queries around the effects of the drug in terms of experiences both during and after treatment. Finally, participants were asked to outline the positive effects of psilocybin on their lives. Results: The data were thematically coded using Grounded Theory as an underpinning philosophical paradigm. Emerging themes included enhancement of smell, vision, hearing, and taste sensations. Another theme emerging was the experience of being ‘connected with the universe’ while on the drug. Additionally, participants reported a stabilization of mood, an increase in optimism and emotional control, and a healthier emotional connection with others. Most also felt an increase in comfort, peace and calmness. Another theme that emerged centered on the mechanism of action of psilocybin. Participants stated that this substance seemed to ‘make new connections in their brain,’ resulting in new perspectives. Some participants felt this resulted in a calming influence on the mind and body. This aligns with research showing that psilocybin works by changing the thinking and improving information processing. Conclusion: Psilocybin has promising effects on the patients with depression/anxiety even after a single dose. Psilocybin is safe but the administration should be guided by a health professional to yield safe and positive outcomes.
- ItemRelationships Between Hyperinsulinaemia, Magnesium, Vitamin D, Thrombosis and COVID-19: Rationale for Clinical Management(BMJ, 2020) Cooper, ID; Crofts, CAP; DiNicolantonio, JJ; Malhotra, A; Elliott, B; Kyriakidou, Y; Brookler, KHRisk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.
- ItemCovalently Immobilized Battacin Lipopeptide Gels With Activity Against Bacterial Biofilms(MDPI AG, 2020) De Zoysa, GH; Wang, K; Lu, J; Hemar, Y; Sarojini, VNovel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.