A5014545439- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- IL-33, ST2, and ILC Pathways
- Respiratory and Cough-Related Research
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Muscle metabolism and nutrition
- Nutrition and Health in Aging
- Eosinophilic Esophagitis
- Neuroscience of respiration and sleep
- Muscle Physiology and Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genetics and Physical Performance
- Bioinformatics and Genomic Networks
- Advanced Glycation End Products research
- Eicosanoids and Hypertension Pharmacology
- Sulfur Compounds in Biology
- Inflammation biomarkers and pathways
- Melanoma and MAPK Pathways
- Calcium signaling and nucleotide metabolism
- Redox biology and oxidative stress
- Herbal Medicine Research Studies
- Ion Channels and Receptors
- Immune Cell Function and Interaction
Imperial College London
2014-2024
Lung Institute
2013-2022
Royal Brompton & Harefield NHS Foundation Trust
2014-2022
Interface (United States)
2022
NIHR Southampton Biomedical Research Centre
2019
University of Southampton
2019
British Airways (United Kingdom)
2015-2016
Kyorin University
2013
Aristotle University of Thessaloniki
2012
National Institutes of Health
2011
Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms.Using transcriptomic profiling of airway tissues, we sought to define the molecular phenotypes severe asthma.The transcriptome derived from bronchial biopsies epithelial brushings 107 subjects with moderate asthma were annotated gene set variation analysis using 42 signatures relevant asthma, inflammation, immune function. Topological data clinical histologic was performed derive clusters, nearest...
Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis chronic obstructive pulmonary disease (COPD). The object this study was identify molecular mechanism underlying increase MMP9 expression, and here we show that oxidative stress-dependent reduction a protein deacetylase, SIRT1, known as putative antiaging enzyme, causes expression. A sirtuin inhibitor, splitomycin, SIRT1 knockdown by RNA interference led an expression human monocytic...
Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro vivo. However the efficacies current macrolides relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior clinical use. The (SOL) on lipopolysaccharide-induced TNF<i>α</i> (tumor necrosis factor <i>α</i>) and/or CXCL8 (C-X-C motif chemokine ligand 8;...
Severe asthma patients with a significant smoking history have airflow obstruction reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of and ex-smoking severe molecular phenotypes. The U-BIOPRED cohort patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers healthy was examined. Blood sputum cell counts, fractional exhaled nitric oxide spirometry were obtained. Exploratory proteomic supernatants transcriptomic bronchial brushings,...
Corticosteroid insensitivity is a major therapeutic problem for some inflammatory diseases including chronic obstructive pulmonary disease (COPD), and it known to be induced by reduced histone deacetylase (HDAC)-2 activities via activation of the phosphoinositide 3-kinase (PI3K) pathway. The aim this study evaluate effects novel macrolide/fluoroketolide, solithromycin (SOL, CEM-101), on corticosteroid sensitivity oxidative stress.Corticosteroid was determined IC50/EC50 dexamethasone (Dex)...
Rationale: Mast cells (MCs) play a role in inflammation and both innate adaptive immunity, but their involvement severe asthma (SA) remains undefined. Objectives: We investigated the phenotypic characteristics of U-BIOPRED (Unbiased Biomarkers for Prediction Respiratory Diseases Outcomes) cohort by applying published MC activation signatures to sputum cell transcriptome. Methods: Eighty-four participants with SA, 20 mild/moderate (MMA), 16 healthy without were studied. calculated enrichment...
Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids, which has been linked oxidative stress. Here we that the long-acting β(2) -agonist formoterol (FM) reversed corticosteroid insensitivity under stress via inhibition of phosphoinositide-3-kinase (PI3K) signalling.Responsiveness corticosteroids dexamethasone (Dex), budesonide (Bud) and fluticasone propionate (FP) was determined, as IC(50) values on TNF-α-induced interleukin 8 release, in U937...
There is a potential for silver nanowires (AgNWs) to be inhaled, but there little information on their health effects and chemical transformation inside the lungs in vivo. We studied of short (S-AgNWs; 1.5 μm) long (L-AgNWs; 10 instilled into Sprague-Dawley rats. S- L-AgNWs were phagocytosed degraded by macrophages; was no frustrated phagocytosis. Interestingly, both AgNWs internalized alveolar epithelial cells, with precipitation Ag2S surface as secondary nanoparticles. Quantitative serial...
Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Using endothelial colony-forming-cells (ECFC), we have demonstrated accelerated in smokers patients with COPD compared non-smokers. Subgroup analysis suggests that ECFC from on inhaled corticosteroids (ICS) (n=14; eight ICS) exhibited significantly reduced (Senescence-associated-beta galactosidase activity, p21 CIP1 ), markers DNA damage response (DDR)...
Over the past decade, there has been a significant rise in use of vaping devices, particularly among adolescents, raising concerns for effects on respiratory health. Pressingly, many recent vaping-related lung injuries are unexplained by current knowledge, and overall implications health poorly understood. This study investigates effect hydrophobic liquid chemicals pulmonary surfactant biophysical function. We focus commonly used flavoring benzaldehyde its byproduct, propylene glycol acetal....
<h3>Objectives</h3> Hydrogen sulfide (H<sub>2</sub>S) is a gas produced by respiratory cells including smooth muscle and may play role as cellular gasotransmitter. We evaluated whether H<sub>2</sub>S levels in serum or sputum could represent new biomarker of COPD cross-sectional study. <h3>Methods</h3> samples were measured using sulfide-sensitive electrode 64 patients with stable (S-COPD), 29 subjects during acute exacerbation (AE-COPD), 14 healthy smokers 21 non-smokers. <h3>Results</h3>...
In chronic obstructive pulmonary disease (COPD), oxidative stress regulates the inflammatory response of bronchial epithelium and monocytes/macrophages through kinase modulation has been linked to glucocorticoid unresponsiveness. Glycogen synthase-3β (GSK3β) inactivation plays a key role in mediating signaling processes upon reactive oxygen species (ROS) exposure. We hypothesized that GSK3β is involved stress-induced insensitivity COPD. studied levels phospho-GSK3β-Ser9, marker inactivation,...
Introduction Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key finding effective therapies. Variants the bradykinin receptor 2 (BDKRB2) have been linked athletic performance. The rs1799722–9 rs5810761 T alleles shown be overrepresented in endurance athletes, possibly due increased transcriptional rates receptor. These variants rarely studied older people or with sarcopenia. Methods We performed a post hoc sub-study Leucine ACE (LACE)...
Chronic cough is associated with airway inflammation and remodelling. Abnormal smooth muscle cell (ASMC) function may underlie mechanisms of chronic cough. Our objective was to examine the transcriptome focused secretome ASMCs from patients healthy non-cough volunteers. ASMC gene expression profiling performed at baseline and/or after stimulation polyinosinic:polycytidylic acid (poly(I:C)) mimic viral infection. Supernatants were collected for multiplex analysis. results showed no...
Background Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity proposed as a method inhibit The LACE clinical trial was designed determine whether ACE inhibition would reduce further loss in individuals with sarcopenia but suffered from low recruitment and returned negative result. Polymorphic variation the promoter (I/D alleles) associated differences physiology range of conditions. This aim this...