A5003819252- Galectins and Cancer Biology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Macrophage Migration Inhibitory Factor
- Pulmonary Hypertension Research and Treatments
- Cystic Fibrosis Research Advances
- COVID-19 Clinical Research Studies
- Systemic Sclerosis and Related Diseases
- SARS-CoV-2 and COVID-19 Research
- Protein Tyrosine Phosphatases
- Child Nutrition and Feeding Issues
- Extracellular vesicles in disease
- Inhalation and Respiratory Drug Delivery
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- Autophagy in Disease and Therapy
- Magnesium Alloys: Properties and Applications
- Breastfeeding Practices and Influences
- Genetics and Neurodevelopmental Disorders
- Pharmacological Receptor Mechanisms and Effects
- Sinusitis and nasal conditions
- Phagocytosis and Immune Regulation
- Sepsis Diagnosis and Treatment
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of Edinburgh
2007-2024
Centre for Inflammation Research
2014-2024
Mission Therapeutics (United Kingdom)
2023
The Queen's Medical Research Institute
2020-2022
Queen's Medical Centre
2016-2022
University Hospital Llandough
2007
Galveston College
1984
Wilmington VA Medical Center
1981
The University of Sydney
1925
Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 novel potent small-molecule inhibitor Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess safety, tolerability, pharmacokinetics pharmacodynamics inhaled 36 healthy subjects 24 patients with IPF. Six dose cohorts six were evaluated (4:2 TD139:placebo ratio) single...
Abstract Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid sustained suppression NF-κB signalling in macrophage through unique regulatory relationship which is independent apoptosis. The reduction activation occurs blockade transforming growth factor β-activated kinase 1 (TAK1) IKKβ activation. As consequence, (p65) phosphorylation reduced, its translocation nucleus inhibited NF-κB-mediated inflammatory...
BackgroundMany repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate.MethodsWe present the findings a phase Ib/IIa open label, platform randomised controlled trial intravenous hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly standard care (SoC), or an alternative therapy. Nafamostat was administered as...
Abstract Mutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson’s disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN PINK1, mutated autosomal recessive PD, regulate preferential autophagic clearance dysfunctional mitochondria (“mitophagy”) by inducing ubiquitylation proteins, process counteracted deubiquitylation via USP30....
High circulating galectin-3 is associated with poor outcomes in patients coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside inhibitor antiinflammatory and antifibrotic actions, would be safely effectively delivered COVID-19 pneumonitis.
Rationale: Galectin-3 (Gal-3) drives fibrosis during chronic lung injury, however, its role in acute injury (ALI) remains unknown. Effective pharmacological therapies available for ALI are limited; identifying novel concepts treatment is essential. GB0139 a Gal-3 inhibitor currently under clinical investigation the of idiopathic pulmonary fibrosis. We investigate and evaluate whether inhibition with offers protective role. The effect on was explored vivo vitro.Methods: pharmacokinetic...
Rationale: Galectin-3 (Gal-3) is an immune regulator and important driver of fibrosis in chronic lung injury, however, its role acute injury (ALI) remains unknown. Previous work has shown that global deletion galectin-3 reduces collagen deposition a bleomycin-induced pulmonary model (MacKinnon et al., Am. J. Respir. Crit. Care Med., 2012, 185, 537–46). An inhaled Gal-3 inhibitor, GB0139, undergoing Phase II clinical development for idiopathic (IPF). This aims to elucidate the myeloid...
Monophosphoryl lipid A (MPLA) is a lipopolysaccharides (LPS) derivative associated with neutrophil‐dependent anti‐inflammatory outcomes in animal models of sepsis. Little known about the effect MPLA on neutrophil function. This study sought to test hypothesis that would reduce release cytotoxic mediators from neutrophils without impairing bacterial clearance. Neutrophils were isolated whole blood healthy volunteers. The effects and LPS autologous serum‐opsonised Pseudomonas aeruginosa...
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease, with high mortality. Currently, the aetiology and pathology of IPF are poorly understood, both innate adaptive responses previously being implicated in disease pathogenesis. Heat shock proteins (Hsp) antibodies to Hsp patients have been suggested as therapeutic targets prognostic biomarkers, respectively. We aimed study relationship between expression Hsp72 anti-Hsp72 BAL fluid serum Aw progression IPF....
Immunoblastic lymphadenopathy was diagnosed in a 71-year-old white man who had weakness, with weight loss, fever, cough, and generalized lymphadenopathy. The patient long occupational history of shipyard work. Diagnosis asbestosis made clinically by chest x-ray, ferruginous bodies were found the lung at autopsy. Recent reports have suggested possible association between asbestos exposure lymphoproliferative neoplasms. Chronic antigenic stimulation could predispose one to immunoproliferative...
Abstract Introduction: A clear and detailed clinical history is essential in the assessment of patients with balance symptoms. The aim this study was to assess usefulness open-ended questionnaires specialist clinic. Methods: Fifty-four consecutive new completed an questionnaire, prior a consultation which taken using standardised proforma. results two were compared. Results: provided patient-centred data, did not provide clinicians sufficient data for diagnosis. Patients more likely respond...
ABSTRACT Despite the success of vaccines and selected repurposed treatments, COVID-19 is likely to remain a global health problem further chemotherapeutics are required. Many drugs have progressed rapidly Phase 2 3 trials without characterisation Pharmacokinetics (PK)/Pharmacodynamics (PD) including safety in COVID-19. One such drug Nafamostat Mesylate (Nafamostat), synthetic serine protease inhibitor with anticoagulant anti-inflammatory properties. Preclinical data has demonstrated that it...
Background: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is Nafamostat Mesylate.Methods: We present the findings a phase Ib/II open label, platform randomised controlled trial intravenous hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly standard care (SoC), or an alternative therapy. was administered as infusion at...
Background: Blockage of autophagic pathways had been reported in IPF. Exosomes are microvesicles that mediate a variety biological functions. Compromised autophagy can modify cellular exosomes release. Aims: We aimed to study alveolar macrophage (AMo) and the BALf patients with fibrotic interstitial lung disease (ILD). hypothesized impaired …