A5046436059- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Nanoparticles: synthesis and applications
- Air Quality and Health Impacts
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Electrochemical Analysis and Applications
- Graphene and Nanomaterials Applications
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Pediatric health and respiratory diseases
- Nanoparticle-Based Drug Delivery
- Energy and Environment Impacts
- Lung Cancer Treatments and Mutations
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Congenital Diaphragmatic Hernia Studies
- Extracellular vesicles in disease
- Pulmonary Hypertension Research and Treatments
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Air Quality Monitoring and Forecasting
- Lung Cancer Diagnosis and Treatment
- Advanced Nanomaterials in Catalysis
- Child Nutrition and Water Access
- Hedgehog Signaling Pathway Studies
- Protein Degradation and Inhibitors
Duke University
2021
University College London
2021
Imperial College London
2009-2020
Novartis (United States)
2020
Novartis Institutes for BioMedical Research
2019
Novartis (Switzerland)
2019
Lung Institute
2010-2016
National Institutes of Health
2011-2015
British Lung Foundation
2008-2012
Royal Brompton & Harefield NHS Foundation Trust
2004
Chronic obstructive pulmonary disease (COPD) is a common lung with cigarette smoking as the major etiological factor, but only 15% of smokers develop COPD. Destruction elastin observed in COPD mediated by many enzymes, including cysteine, serine, and matrix metalloproteinases (MMP). The contribution these enzymes to elastolytic load, released from alveolar macrophages collected nonsmokers, healthy smokers, patients, was examined radiolabeled substrate presence specific enzyme inhibitors....
Abstract Bacterial colonization is a secondary feature of many lung disorders associated with elevated cytokine levels and increased leukocyte recruitment. We hypothesized that, alongside macrophages, the epithelium would be an important source these mediators. investigated effect LPS (0, 10, 100, 1000 ng/ml LPS, up to 24 h) on primary human macrophages alveolar type II epithelial cells (ATII; isolated from resected tissue). Although produced higher cytokines TNF-α IL-1β (p < 0.0001),...
Rationale: Patients with idiopathic pulmonary fibrosis (IPF), a progressive disease dismal prognosis, exhibit an unexplained disparity of increased alveolar epithelial cell (AEC) apoptosis but reduced fibroblast apoptosis.Objectives: To examine whether the failure patients IPF to up-regulate cyclooxygenase (COX)-2, and thus antifibrotic mediator prostaglandin (PG)E2, accounts for this imbalance.Methods: Fibroblasts primary type II AECs were isolated from control fibrotic human lung tissue....
The ability to manipulate the size and surface properties of nanomaterials makes them a promising vector for improving drug delivery efficacy. Inhalation is desirable route administration as preferentially deposit in alveolar region, large area absorption. However, yet, mechanisms by which particles translocate across epithelial layer are poorly understood. Here we show that human type I cells internalize nanoparticles, whereas II do not, nanoparticles monolayer but unable penetrate tight...
The respiratory epithelium is a significant target of inhaled, nano-sized particles, the biological reactivity which will depend on its physicochemical properties. Surface-modified, 50 and 100 nm, polystyrene latex nanoparticles (NPs) were used as model particles to examine effect particle size surface chemistry transformed human alveolar epithelial type 1-like cells (TT1). Live images TT1 exposed amine-modified NPs taken by hopping probe ion conductance microscopy revealed severe damage...
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Studies in patients and experimental animals provide compelling evidence of the involvement major thrombin receptor, proteinase-activated receptor-1 (PAR(1)), potent chemokine, chemokine (CC motif) ligand-2 (CCL2)/monocyte chemotactic protein-1, pathogenesis idiopathic pulmonary fibrosis (IPF). PAR(1) knockout mice are protected from bleomycin-induced lung inflammation this protection is associated with marked attenuation CCL2 induction.The aim study was to determine which cell types...
It is widely believed that the alveolar epithelium unresponsive to LPS, in absence of serum, due low expression TLR4 and CD14. Furthermore, responsiveness TLR-2 ligands also poorly understood. We hypothesised human type I (ATI) II (ATII) epithelial cells were responsive TLR2 (MALP-2 LPS respectively), expressed necessary TLRs co-receptors (CD14 MD2) released distinct profiles cytokines via differential activation MAP kinases. Primary ATII macrophages an immortalised ATI cell line (TT1)...
Experimental data on dynamic interactions between individual nanoparticles and membrane processes at nanoscale, essential for biomedical applications of nanoparticles, remain scarce due to limitations imaging techniques. We were able follow single 200 nm carboxyl-modified particles interacting with identified structures the rate 15 s/frame using a scanning ion conductance microscope modified simultaneous high-speed topographical fluorescence imaging. The approach demonstrated here opens new...
Silver nanowires (AgNWs) are being developed for use in optoelectronics. However before widespread usage, it is crucial to determine their potential effects on human health. It accepted that Ag nanoparticles (AgNPs) exert toxic by releasing Ag+ ions, but much less known about whether reacts with compounds, or any downstream bioactive of transformed AgNPs. Analytical high-resolution transmission electron microscopy has been employed elucidate cellular uptake and reactivity AgNWs inside...
// Franco Conforti 1,2,* , Elizabeth R. Davies Claire J. Calderwood 1 Thomas H. Thatcher 3 Mark G. Jones 1,2 David E. Smart Sumeet Mahajan 4 Aiman Alzetani 5 Tom Havelock 2,5 Toby M. Maher 6,7 Philip L. Molyneaux Andrew Thorley 7 Teresa D. Tetley Jane A. Warner 1,2,4 Graham Packham 8 A. Ganesan 9 Paul Skipp Benjamin Marshall Luca Richeldi 1,2,5 Patricia Sime Katherine M.A. O'Reilly 2,10,11 and Donna The Brooke Laboratory, Clinical Experimental Sciences, University of Southampton Faculty...
Abstract Background Multimorbidity has been identified as a research priority in recent years, fibrosis (progressive organ scarring) is one mechanism which may underpin multimorbidity. Some studies suggest hypertension could be fibrotic, particularly severe (uncontrollable with medications), however it not currently known whether associated fibrotic conditions. Objective To investigate treatment resistant Methods We used the Clinical Practice Research Datalink (CPRD) Aurum primary care...
Inhalation of antigenic matter stimulates rapid recruitment dendritic cells (DCs) into the lung. Recent studies propose that chemokine CCL20 (macrophage inflammatory protein-3alpha) may play an important role in DC recruitment. We previously showed primary human alveolar type II epithelial (ATII) are a rich source chemokines and so hypothesized ATII cell produces might therefore be key regulator Here, we show cells, but not macrophages, produce both constitutively (403.5 +/- 85.4 pg/ml; 24...
Gold nanoparticles (AuNPs) have emerged as promising drug delivery candidates that can be leveraged for cancer therapy. Lung (LC) is a heterogeneous disease imposes significant burden on society, with an unmet need new therapies. Chemotherapeutic drugs such afatinib (Afb), which clinically approved the treatment of epidermal growth factor receptor positive LC, hydrophobic and has low bioavailability leading to spread around body, causing severe side effects. Herein, we present novel...
Uptake and translocation of short functionalized multi-walled carbon nanotubes (short-fMWCNTs) through the pulmonary respiratory epithelial barrier depend on physicochemical property cell type. Two monoculture models, immortalized human alveolar type 1 (TT1) cells primary 2 (AT2), which constitute barrier, were employed to investigate uptake transport 300 700 nm in length, poly(4-vinylpyridine)-functionalized, (p(4VP)-MWCNTs) using quantitative imaging spectroscopy techniques. The...