A5013617812- Acute Myocardial Infarction Research
- Coronary Interventions and Diagnostics
- Cardiac Imaging and Diagnostics
- Antiplatelet Therapy and Cardiovascular Diseases
- Chemotherapy-induced cardiotoxicity and mitigation
- Signaling Pathways in Disease
- Cardiovascular Function and Risk Factors
- Cerebrovascular and Carotid Artery Diseases
- Cardiac, Anesthesia and Surgical Outcomes
- Heart Failure Treatment and Management
- Atherosclerosis and Cardiovascular Diseases
- Thyroid Disorders and Treatments
- Cytokine Signaling Pathways and Interactions
- Cardiac Structural Anomalies and Repair
- Monoclonal and Polyclonal Antibodies Research
- Health Systems, Economic Evaluations, Quality of Life
- Metabolism, Diabetes, and Cancer
- Atrial Fibrillation Management and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Traumatic Ocular and Foreign Body Injuries
- Lipoproteins and Cardiovascular Health
- Cyclopropane Reaction Mechanisms
- Cardiac pacing and defibrillation studies
- Catalytic Alkyne Reactions
- Galectins and Cancer Biology
South Tees Hospitals NHS Foundation Trust
2018-2025
Newcastle University
2022-2025
James Cook University Hospital
2015-2025
United Lincolnshire Hospitals NHS Trust
2024
Northumbria Healthcare NHS Foundation Trust
2024
Freeman Hospital
2012-2024
Newcastle upon Tyne Hospitals NHS Foundation Trust
2012-2024
Charles R. Drew University of Medicine and Science
2017-2024
University of California, Los Angeles
2023-2024
California NanoSystems Institute
2019-2024
BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: this international registry-based, randomized, double-blind trial, without prior diabetes or chronic heart failure, presenting MI impaired left ventricular systolic function, were randomly assigned 10 mg dapagliflozin placebo, given once daily. The primary outcome was hierarchical composite death, hospitalization for...
BackgroundWhether a conservative strategy of medical therapy alone or plus invasive treatment is more beneficial in older adults with non–ST-segment elevation myocardial infarction (NSTEMI) remains unclear.MethodsWe conducted prospective, multicenter, randomized trial involving patients 75 years age NSTEMI at 48 sites the United Kingdom. The were assigned 1:1 ratio to best available an coronary angiography and revascularization therapy. Patients who frail had high burden coexisting...
The natural product rapamycin has been used to provide temporal and quantitative control of gene expression in animals through its ability interact with two proteins simultaneously. A shortcoming this approach is that an inhibitor cell proliferation, the result binding FKBP12-rapamycin-associated protein (FRAP). To overcome limitation, nontoxic derivatives bearing bulky substituents at C16-position were synthesized, each a single step. isosteric isopropoxy methallyl nonnatural...
Autoimmunity leads to the activation of innate effector pathways, proinflammatory cytokine production, and end-organ injury. Macrophage migration inhibitory factor (MIF) is an upstream activator response that mediates recruitment retention monocytes via CD74 associated chemokine receptors, it has a role in maintenance B lymphocytes. High-expression MIF alleles also are with damage different autoimmune diseases. We assessed therapeutic efficacy...
The identification of cellular targets has traditionally been the starting point for natural product mode action studies and led to understanding many biological processes. Conventional experimental approaches have depended on cell-based screening and/or affinity chromatography. Although both these techniques aid in discovery protein targets, a method that couples with gene isolation would be extremely valuable.A procedure direct cloning proteins, based their products, using cDNA phage...
Taxol (Paclitaxel) is an important natural product for the treatment of solid tumors. Despite a well documented tubulin-stabilizing effect, many side effects taxol therapy cannot be explained by cytoskeletal mechanisms. In present study submicromolar concentrations taxol, mimicking found in patients, induced cytosolic calcium (Ca(2+)) oscillations human neuronal cell line. These were independent extracellular and mitochondrial Ca(2+) but dependent on intact signaling via phosphoinositide...
While Ras activation has been shown to play an important role in signal transduction by the T-lymphocyte antigen receptor, mechanism of its T cells is unclear. Membrane localization guanine nucleotide exchange factor Sos, but not Vav or Dbl, was sufficient for Ras-mediated signaling lymphocytes. Activation Sos appears involve membrane recruitment and allosteric changes, because interaction with linking molecule Grb-2 required activation. To extend this analysis, we constructed a modified...
BACKGROUND Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy.Enalapril has been explored its potential to mitigate cardiotoxicity in patients.The dose-dependent effects of anthracyclines can be detected early through the biomarker cardiac troponin. OBJECTIVESThe PROACT (Preventing Cardiac Damage Patients Treated Breast Cancer and Lymphoma) clinical trial assessed effectiveness enalapril preventing cardiotoxicity, manifesting as myocardial injury function...
// David Austin 1 , Nalo Hamilton 2 Yahya Elshimali Richard Pietras 3, 4 Yanyuan Wu and Jaydutt Vadgama 1, Department of Medicine, Division Cancer Research Training, Charles Drew University School Medicine Science, Los Angeles, CA 90059, USA UCLA Nursing, California at 90095, 3 Johnson Comprehensive Center, Geffen Hematology-Oncology, Correspondence to: Vadgama, email: jayvadgama@cdrewu.edu Keywords: estrogen receptor-beta; triple negative breast cancer; insulin-like growth factor 2; DPN;...
<h3>Importance</h3> Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism patients with acute infarction is associated poor prognosis. <h3>Objective</h3> To evaluate the effect of levothyroxine treatment on left ventricular function and subclinical hypothyroidism. <h3>Design, Setting, Participants</h3> A double-blind, randomized clinical trial conducted 6 hospitals United Kingdom. Patients including ST-segment elevation non–ST-segment were...
A series of natural product analogues based on helioxanthin (2), with particular attention to modification the lactone ring and methylenedioxy group, were synthesized evaluated for their antiviral activities. Among them, lactam derivative 18 cyclic hydrazide 28 exhibited significant in vitro activity against hepatitis B virus (EC50 = 0.08 0.03 μM, respectively). Compound showed most potent C (55% inhibition at 1.0 μM). 12, an acid-hydrolyzed imide 9, was found exhibit broad-spectrum 0.8 μM),...
Over a nine-month period two hundred and thirteen referrals to the Department of Ophthalmology Leicester Royal Infirmary, England, for suspicion glaucoma were examined by single ophthalmologist. Ninety-nine percent resulted from findings at an opto-metric visit. Despite this, less than 32% confirmed as having 23% had ocular hypertension. Twenty-nine showed no abnormality. Of those with 19% advanced field loss in their worse eye. The guidelines relating referral practices result examinations...
Abstract Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8 + T-lymphocytes (CD8 T EMRA ) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use TA-65 to reduce cell in patients following Ninety MI aged over 65 years were either (16 mg daily) or placebo for 12 months....
Abstract Background Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the inhibition pathway. Methods performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines uncover essential nodes in IFNγ-mediated used transcriptomic profiling identify cell death pathways activated upon IFNγ exposure. Live...
The Src-like tyrosine kinases require membrane localization for transformation and probably their normal role in signal transduction. We utilized this characteristic to prepare that can be readily activated with the rationally designed chemical inducer of dimerization FK1012. Dimerization cytoplasmic was not sufficient signaling, but recruitment plasma led rapid activation transcription factors identical those regulated by crosslinking antigen receptor. Moreover, replaced signaling...
As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess impact patient-reported on treatment prognosis elderly early survivors non-ST-elevation acute syndrome (NSTE-ACS).
In eukaryotes, sequence-specific DNA-binding proteins activate gene expression by recruiting the transcriptional apparatus and chromatin remodeling to promoter through protein-protein contacts. many instances, connection between is established intermediacy of adapter known as coactivators. Here we describe synthetic molecules with low molecular weight that act We demonstrate a completely nonnatural activation domain in one such molecule capable stimulating transcription vitro vivo . The...
A stereocontrolled route to the deschloro cyclopentyl core of palau'amines and styloguanidines has been developed. This strategy makes use intramolecular Pauson-Khand cyclization an enyne with a "transient N-O tether" construct five-membered carbocycle in diastereoselective fashion. [reaction: see text]
The early use of automated external defibrillators (AEDs) improves outcomes in out-of-hospital cardiac arrest (OHCA). We investigated AED access across Great Britain (GB) according to socioeconomic deprivation. Cross-sectional observational study using location data from Circuit: the national defibrillator network led by British Heart Foundation partnership with Association Ambulance Chief Executives, Resuscitation Council UK and St John Ambulance. calculated street distances between all 1...
The aqueous extract of Scutellariae baicalensis Georgi has inhibitory activity against P-gp 170, a multiple drug resistant gene product. Baicalein, one the major flavones, was found to be responsible for this activity. hydroxyl groups A ring baicalein were systematically alkylated in order assess effect such modifications on 170. impact growth human nasopharyngeal cancer cell line KB and its 170 overexpressing KB/MDR also examined. results indicate that alkylation R5 does not have...
Chronic hepatitis B virus (HBV) infection continues to be an important worldwide cause of morbidity and mortality. All the currently approved therapeutic drugs have their limitations: interferon-α (IFN-α) has limited efficacy a high incidence adverse effects; nucleoside analogues are very efficient HBV DNA inhibitors, but resistance occurs eventually. Therefore, it is develop new non-nucleoside/nucleotide agents with different modes action that can used for antiviral combination therapy....