Novel photophysical and sequence based probes for DNA

THESIS 7451The aim of this research project was to develop novel DNA photophysical and sequence based probes. The sequence based probes were designed to target the diagnostic bcr/abl sequence of the Philadelphia chromosome that is present in 95 % of all cells affected by chronic myeloid leukaemia (CML). The photophysical probe examined was used to investigate the nature of calf thymus DNA

Recovery of cardiac function mediated by MSC and interleukin-10 plasmid functionalised scaffold

Journal articleStem cell transplantation has been suggested as a treatment for myocardial infarction, but clinical studies have yet to demonstrate conclusive, positive effects. This may be related to poor survival of the transplanted stem cells due to the inflammatory response following myocardial infarction. To address this, a scaffold-based stem cell delivery system was functionalised with anti-inflammatory plasmids (interleukin-10) to improve stem cell retention and recovery of cardiac function. Myocardial infarction was induced and these functionalised scaffolds were applied over the infarcted myocardium. Four weeks later, stem cell retention, cardiac function, remodelling and inflammation were quantified. Interleukin-10 gene transfer improved stem cell retention by more than five-fold and the hearts treated with scaffold, stem cells and interleukin-10 had significant functional recovery compared to the scaffold control (scaffold: -10+/-7%, scaffold, interleukin-10 and stem cells: +7 +/-6%). This improved function was associated with increased infarcted wall thickness and increased ratios of collagen type III/type I, decreased cell death, and a change in macrophage markers from mainly cytotoxic in the scaffold group to mainly regulatory in scaffold, stem cells and interleukin-10 group. Thus, treatment of myocardial infarction with stem cells and interleukin-10 gene transfer significantly improved stem cell retention and ultimately improved overall cardiac function. (C) 2011 Elsevier Ltd. All rights reserved

The vasoreparative function of myeloid angiogenic cells (macs) is impaired in diabetes through the induction of il1β

Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic-related ischemia. MACs were isolated from human peripheral blood and characterized alongside proinflammatory macrophages M (LPS+IFN) and proangiogenic macrophages M (IL4). Functional changes in MACs in response to high-d-glucose were assessed using an in vitro 3D-tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 proangiogenic characteristics, but can be distinguished by CD163(hi) expression. High-d-glucose treatment significantly reduced MACs proangiogenic capacity, which was associated with a significant increase in IL1 beta mRNA and protein expression. Inhibition of IL1 beta abrogated the antiangiogenic effect induced by high-d-glucose. IL1 beta was also significantly upregulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or nondiabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic-like conditions impair the proangiogenic and regenerative capacity of MACs, and this response is mediated by IL-1 beta

Delirium in hospitalised adults with acute burns – A systematic review

Introduction: Delirium is a potentially modifiable, acutely altered mental state, commonly characterised as a hospital-acquired complication. Studies of adult inpatients with acute burns with and without delirium identify causative risks related to the injury or treatment and outcomes related to the patient and healthcare system. We compare patients with and without delirium, providing a high-level quantitative synthesis of delirium risks and outcomes to inform guidelines and future research. Methods: A systematic review, meta-analysis and GRADE evaluation of risks and outcomes associated with delirium in adults with acute burns was conducted using PRISMA guidelines and PROSPERO protocol CRD42021283055. The Newcastle-Ottawa Scale was used to assess quality. Results: Investigators reviewed ten studies. ASA score ≥ 3, Total Body Surface Area Percentage (TBSA) \u3e 10%, surgery done, ICU admission, hospital and also Intensive Care Unit (ICU) lengths of stay all had statistically significant associations with delirium, with low-very low certainty on GRADE evaluation. Limitations were heterogeneous studies, review methodology and study bias. Conclusion: Delirium represents a significant risk to comorbid patients with burns that are hospitalised, receive ICU care, and surgery. Further research is indicated to precisely categorise delirium along the clinical journey to identify modifiable factors, prevention, and proactive therapy