A5047246563- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Gut microbiota and health
- Gastrointestinal motility and disorders
- Pulmonary Hypertension Research and Treatments
- Mast cells and histamine
- Dermatology and Skin Diseases
- Occupational and environmental lung diseases
- Eosinophilic Disorders and Syndromes
- Pleural and Pulmonary Diseases
- Microbial metabolism and enzyme function
- Asthma and respiratory diseases
- Tissue Engineering and Regenerative Medicine
- Fibroblast Growth Factor Research
- Neonatal Respiratory Health Research
- Mesenchymal stem cell research
- Heat shock proteins research
- Neuroendocrine regulation and behavior
- Occupational exposure and asthma
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Diet and metabolism studies
- Inhalation and Respiratory Drug Delivery
- Eosinophilic Esophagitis
- Autophagy in Disease and Therapy
- Cellular Mechanics and Interactions
- Extracellular vesicles in disease
McMaster University
2016-2025
Population Health Research Institute
2022-2025
Digestive Health Research Institute
2020-2024
St. Joseph’s Healthcare Hamilton
2015-2019
Shimane University
2009-2013
Institute for Respiratory Health
2013
Rationale: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant vivo context pulmonary fibrosis.Objectives: To explore effect stress on TGF-β1 and its signaling pathway rat human fibrotic lung tissue using a novel ex model.Methods: Rat fibrosis induced transient gene expression active TGF-β1. Lungs were harvested at Day 14 or 21 submitted to various bath equipped with force...
The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal patients with IBS, and this was accompanied by changes the decreased urinary histamine concentrations. Here, we used germ-free mice colonized fecal from IBS to investigate role bacteria neuroactive mediator visceral hypersensitivity. Germ-free who...
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated role of GRP78, main UPR regulator, in an experimental model injury fibrosis. Grp78(+/-) , Chop(-/-) wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation lungs examined at days 7 21. We demonstrate here that strongly protected from bleomycin-induced fibrosis, as...
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibroblast and myofibroblast proliferation, extensive deposition of extracellular matrix (ECM). Fibroblast growth factor-1 (FGF-1) belongs to the FGF family has been shown inhibit collagen production differentiation into myofibroblasts, revert epithelial–mesenchymal transition inhibiting TGF-β1 signalling pathways. However, precise role FGF-1 in not yet elucidated. In this study, we explore mechanisms underlying...
Accumulating evidence suggests the microbiota is a key factor in Disorders of Gut-Brain Interaction (DGBI), by affecting host immune and neural systems. However, underlying mechanisms remain elusive due to their complexity clinical heterogeneity patients with DGBIs. We aimed identify neuroimmune pathways that are critical microbiota-gut-brain communication during de novo gut colonization. employed combination gnotobiotic state-of-the-art microbial tools, behavioral analysis, pharmacological...
Background The role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown. Objectives We investigated the effect fibrotic extracellular matrix (ECM) on experimental and human fibrosis. Results In IPF lungs, cell numbers were increased correlated with disease severity (control vs 60%<FVC<90%, mean difference=-222.7, 95% CI −386.3 to −59.2, p=0.004; control FVC<60%, difference=−301.7, difference −474.1 −129.34, p=0.0001; FVC>90% difference=−189.6,...
The major role of mast cells in wound healing process has not been identified. In this study, we used cell-deficient W/W(V) mice and their congenic control (+/+) to examine the scald healing.The size wound, thickness dermis, collagen deposition, vascularization, number chymase activity were measured before at 3, 7, 14 21 days after inducing injury.Although closure re-epithelialization was markedly different between +/+ mice, degree fibrous proliferation edge vascularization proliferative...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with an unknown cause. Two drugs, nintedanib and pirfenidone, have been shown to slow, but not stop, progression. Pulmonary hypertension (PH) frequent complication in IPF patients associated poor prognosis. Macitentan dual endothelin receptor antagonist that approved for arterial treatment. We hypothesised using macitentan treat animals induced by adenoviral vector encoding biologically active transforming growth factor-β1...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM slowly overtakes normal tissue, disturbing gas exchange and leading to respiratory failure death. cross-linking subsequent stiffening thought be major contributor progression also promotes activation transforming growth factor (TGF)-β1, one main profibrotic factors. Lysyl oxidase-like (LOXL) 1 belongs enzyme family has been...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity through worsening dyspnoea and overall functional decline. IPF characterised by apoptosis-resistant myofibroblasts, which are major source for excessive production extracellular matrix (ECM) overtaking normal tissue. We sought to study role heat shock protein (HSP) isoforms HSP90α HSP90β, whose distinct roles in fibrogenesis remain elusive. determined level circulating patients...
Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic co-localized with neurons were higher mice colonized compared those healthy control (HC) microbiota. In situ hybridization showed presence IBS, but not microbiota, lamina propria RNAscope demonstrated frequent co-localization bacteria cells. TLR4 H4 receptor expression was...
Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology poorly understood. Accumulating evidence suggests that microbiota modulates gut function, but underlying mechanisms unknown. We therefore investigated pathways by which gastrointestinal motility in different sections of alimentary tract.
Abstract Background Bacterial translocation is defined as migration of bacteria or bacterial fragments from the intestinal lumen into extraintestinal tissues; this process has been implicated in pathophysiology gastrointestinal disorders and central nervous system disorders. However, direct causal relationship between behavioral changes, well mechanism remains unclear. In previous study, we showed that commensal microbes can cross barrier access deeper layers gut distal organs restraint...
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation hMSC infusion, while the controls (n=5) had OA, an infusion vehicle control. were infused 1h after administration OA. The...
Recent findings suggest the importance of mast cells in pathogenesis rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with potent membrane-stabilizing effect on wide range anti-inflammatory effects, thus may be advantageous treatment arthritis. Here, we have evaluated effects tranilast progression collagen-induced mice.Tranilast (400 mg.kg(-1).day(-1)) was orally administered for 8 weeks to mice established Arthritis assessed by...
Rationale Extracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) important modulators of biological processes. Fibrocytes circulating bone marrow-derived cells that migrate into the injured lungs contribute to fibrogenesis. The question whether miRNAs derived from fibrocytes able regulate pulmonary fibrosis has not been addressed yet. Methods Pulmonary was induced in rats by intratracheal administration an adenoviral gene vector encoding active transforming...
The authors investigated the role of leukotrienes (LTs) in pathogenesis silica-induced pulmonary fibrosis mice during progression from acute to chronic phases. Intratracheal instillation silica particles induced progressive fibrosis. tissue content cysteinyl (Cys) LTs and LTB(4) was markedly increased phase after instillation, concurrently with up-regulation receptor, transforming growth factor (TGF)-beta1, tumor necrosis (TNF)-alpha, along down-regulation CysLT type 2 receptor. Importantly,...