A5072161259- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Advanced MRI Techniques and Applications
- Cardiac Ischemia and Reperfusion
- Advanced Neuroimaging Techniques and Applications
- Cardiovascular Function and Risk Factors
- Cancer-related Molecular Pathways
- MRI in cancer diagnosis
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Cardiac Imaging and Diagnostics
- Cardiac Arrest and Resuscitation
- Muscle metabolism and nutrition
- Medical Imaging Techniques and Applications
- Adipose Tissue and Metabolism
- Diabetes Treatment and Management
- Cancer, Lipids, and Metabolism
- Cancer Research and Treatments
- Heart Failure Treatment and Management
- Traditional Chinese Medicine Analysis
- Cytokine Signaling Pathways and Interactions
- Hepatitis B Virus Studies
- Cardiac electrophysiology and arrhythmias
- Metabolism and Genetic Disorders
Molecular Oncology (United States)
2023
University of Oxford
2015-2021
British Heart Foundation
2021
Centre for Human Genetics
2016-2021
University College London
2012-2014
Cardiovascular Institute of the South
2012-2013
Roche (United States)
2009
University of Bristol
2004
The dipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin and Vildagliptin lower blood glucose by augmenting endogenous levels of glucagon-like peptide-1 (GLP-1), an incretin which also confers cardioprotection. As such, we hypothesized that treatment with DPP-4 are cardioprotective. In ex vivo experiments: Male Sprague–Dawley rats were randomized to receive oral gavage either (20 mg/kg/day), (100 or water for 2 weeks. Excised hearts Langendorff-perfused buffer containing 5 mmol/L 11...
AimsOld age and diabetes are risk factors that often coexist increasing the vulnerability of heart to lethal effects ischaemia–reperfusion injury (IRI). However, our knowledge, no investigations have examined IRI cardioprotective signalling in animal models bearing these co-morbidities concomitantly. The ability recover following is greatly dependent on its innate potential, which a central role played by Akt. We aimed investigate an aging diabetic rat model, susceptibility IRI,...
The binding affinity of four palm and thumb site representative non-nucleoside inhibitors (NNIs) HCV polymerase NS5B to wild-type resistant proteins was determined, the influence RNA on NNI investigated. NNIs with high potently inhibited activity replicon replication. Among compounds tested, HCV-796 showed slow kinetics NS5B. increased 27-fold over a 3-h incubation period an equilibrium <i>K<sub>d</sub></i> 71 ± 2 nm. Slow driven by dissociation from <i>k</i><sub>off</sub> 4.9 0.5 ×...
Abstract Cardiac architecture is fundamental to cardiac function and can be assessed non-invasively with diffusion tensor imaging (DTI). Here, we aimed overcome technical challenges in ex vivo DTI order extract fine anatomical details provide novel insights the 3D structure of heart. An integrated set methods was implemented rat hearts, including dynamic receiver gain adjustment, gradient system scaling calibration, prospective adjustment gradients, interleaving diffusion-weighted...
Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively. Cardiac DTI enables inference of cell and sheetlet orientations, which are altered under pathological conditions. However, affected by many factors, therefore robust validation critical. Existing histological intrinsically flawed, since it requires further processing leading sample distortion, routinely limited in field-of-view reconstruction three-dimensional volumes from two-dimensional images. In...
Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of at times high demand. We hypothesized that elevating MtCK would be beneficial ischaemia-reperfusion (I/R) injury.Mice were created over-expressing sarcomeric gene with αMHC promoter Rosa26 locus (MtCK-OE) and compared wild-type (WT) littermates. activity was 27% higher than WT, no change other CK...
Diabetes mellitus is a major risk factor for ischemic heart disease (IHD). Patients with diabetes and IHD experience worse clinical outcomes, suggesting that the diabetic may be more susceptible to ischemia-reperfusion injury (IRI). In contrast, animal data suggests either more, equally, or even less IRI. The conflicting due choice of and/or IRI model. Ischemic conditioning, phenomenon in which protected against by one brief nonlethal periods ischemia reperfusion, provide novel...
Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) kidney catalyses both first step biosynthesis as well homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have whole body creatine-deficiency. We hypothesized that would develop cardiac dysfunction and rescue by dietary imply causality.Withdrawal of provided...
Purpose Diffusion MRI requires acquisition of multiple diffusion‐weighted images, resulting in long scan times. Here, we investigate combining compressed sensing and a fast imaging sequence to dramatically reduce times cardiac diffusion MRI. Methods Fully sampled prospectively undersampled tensor data were acquired five rat hearts at acceleration factors between two six using spin echo (FSE) sequence. Images reconstructed framework, enforcing sparsity by means decomposition adaptive...
The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and cytoplasmic CKM CKB. We hypothesized that augmenting in vitro would preserve cell viability function sought determine efficacy of various isoforms. open reading frame each isoform was cloned into pcDNA3.1, followed by transfection stable selection human embryonic kidney cells (HEK293). CKMT2- CKM- CKB-HEK293 had...
Abstract Hypoxia-inducible factor 1α is a key regulator of the hypoxia response in normal and cancer tissues. It well recognized to regulate glycolysis target for therapy. However, how tumor cells adapt grow absence HIF1α poorly understood an important concept understand developing targeted therapies flexibility metabolic via alternative pathways. We analyzed pathways that allow survive hypoxic stress HIF1α, using HCT116 colon cell line with deleted versus control. Spheroids were used...
Purpose The diffusion tensor model assumes Gaussian and is widely applied in cardiac MRI. However, biological tissue deviates from a profile as result of hindrance restriction cell microstructure, may be quantified better by non‐Gaussian modeling. aim this study was to investigate healthy hypertrophic hearts. Methods Thirteen rat hearts (five healthy, four sham, hypertrophic) were imaged ex vivo. Diffusion‐weighted images acquired at b‐values up 10,000 s/mm 2 . Models fit the data ranked...
Aims Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however majority of laboratory research uses young, healthy animal models. Several recent workshops focus meetings have highlighted importance using clinically relevant models to help aid translation realistic patient populations. We previously shown that mice over-expressing creatine transporter (CrT-OE) elevated intracellular levels are protected against ischaemia-reperfusion...
Aims Adenylate kinase 1 (AK1) catalyses the reaction 2ADP ↔ ATP + AMP, extracting extra energy under metabolic stress and promoting energetic homeostasis. We hypothesised that increased AK1 activity would have negligible effects at rest, but protect against ischaemia/reperfusion (I/R) injury. Methods Results Cardiac-specific overexpressing mice (AK1-OE) had 31% higher ( P = 0.009), with unchanged total creatine citrate synthase activities. Male AK1-OE exhibited mild in vivo dysfunction...
<h3>Rationale</h3> In adult cardiomyocytes there are known to be 3 different sub-populations of mitochondria: Subsarcolemmal (SS), Interfibrillar (IF), and Perinuclear (PN), which appear have distinctive properties shapes. Here, we investigate the mitochondrial morphology these subgroups examine effect ischaemia on parameters. <h3>Methodology</h3> We investigated in rodent hearts at baseline response ischemia using electron microscopy (x3000 magnification). six randomly selected micrographs...
Biophysical models are a promising means for interpreting diffusion weighted magnetic resonance imaging (DW-MRI) data, as they can provide estimates of physiologically relevant parameters microstructure including cell size, volume fraction, or dispersion. However, their application in cardiac mapping (CMM) has been limited. This study proposes seven new two-compartment with combination restricted cylinder and tensor to represent intra- extracellular spaces, respectively. Three extended...
An effective mechanism for interfering with prolactin signalling would provide a powerful tool clarifying the importance of in breast cancer, as well investigating functions other tissues. Based on our previous identification dominant-negative mutation growth hormone receptor that causes familial short stature, we investigated potential using similar truncated mutant (PRLR1-242). Like receptor, PRLR1-242 exerts an exceptionally effect. A probable explanation strong activity this class is...
<h3></h3> The dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin in combination with metformin has been suggested to significantly improve glycaemic control compared either monotherapy type 2 diabetes (T2D). In addition, and other DPP-4 inhibitors have shown protect against ischemic injury clinical experimental studies. We therefore hypothesised that chronic treatment may the T2D heart myocardial infarction. Moreover, metformin, an enhanced effect be achieved. Goto-Kakizaki (GK-a model of...
<p>S8. WTN, KON, WTH, and KOH HCT116 cell proliferation after 5 days in two O2 conditions,21% 1% for cells knocked down GTR3, GTR14 , HIF2α</p>
<p>S1. Blocking O-GlcNAcylation in vivo by inducing shOGT or alloxan treatment qualitatively reduces EZH2 immunoreactivity after irradiation.</p>