A5061474320- Drug Transport and Resistance Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Pediatric Hepatobiliary Diseases and Treatments
- Pharmacological Effects of Natural Compounds
- Inflammatory Bowel Disease
- COVID-19 Clinical Research Studies
- Cystic Fibrosis Research Advances
- Drug Solubulity and Delivery Systems
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Peroxisome Proliferator-Activated Receptors
- Pancreatitis Pathology and Treatment
- Immune Response and Inflammation
- Natural product bioactivities and synthesis
Royal College of Surgeons in Ireland
2019-2023
Beaumont Hospital
2020-2023
Increased epithelial permeability is a key feature of IBD pathogenesis and it has been proposed that agents which promote barrier function may be therapeutic benefit. We have previously reported the secondary bile acid, ursodeoxycholic acid (UDCA), to protective in mouse model colonic inflammation its bacterial metabolism required for beneficial effects. The current study aimed compare effects UDCA, LCA, non-metabolizable analog 6-methyl-UDCA (6-MUDCA), on mucosal inflammation. Bile acids...
Activation of the nuclear bile acid receptor, farnesoid X receptor (FXR), specifically upregulates ACE2 expression in undifferentiated colonic epithelial cells and inhibits virus-induced proinflammatory cytokine release. By virtue these actions FXR represents a promising target for development new approaches to prevent intestinal manifestations SARS-CoV-2 infection.
Bile acids classically known for their roles in dietary fat absorption are now recognized as hormones critical to regulating intestinal and metabolic function, including mucosal immune responses, epithelial proliferation/apoptosis, transepithelial transport barrier function. Downregulation of the nuclear bile acid receptor, farnesoid X receptor (FXR), epithelium occurs inflammatory bowel disease colorectal cancer, whereas FXR activation prevents progression pre-clinical models. Thus...
Introduction The nuclear bile acid receptor, farnesoid x receptor (FXR), plays an important role in the enterohepatic circulation (EHC) of acids. Dysregulation EHC signalling is associated with a number intestinal disorders including inflammatory bowel disease, colorectal cancer and chronic diarrhoeal diseases, however mechanisms involved are not clearly understood. Limitations currently‐available cell culture or animal models, necessitates development more physiologically relevant models to...
Introduction: The nuclear bile acid receptor, farnesoid X receptor (FXR), is expressed on intestinal epithelial cells where its potential as a new drug target for treatment of and metabolic disorders, such chronic diarrhoea, colitis, colon cancer, obesity diabetes, has been well-established. We have previously shown that pentacyclic triterpenes (PCTs), class dietary phytochemical, enhance the expression activity colonic FXR. Here, we investigated if another common polyunsaturated fatty acids...
Background: Increased epithelial cell death leading to compromised intestinal barrier function is a key contributor the pathogenesis of inflammatory bowel disease. Previously published studies suggest that nuclear bile acid receptor, farnesoid X receptor (FXR), promotes and protective against colonic inflammation. Here, we investigated potential mechanisms involved. Methods: Mucosal inflammation was induced in mice by adding 2.5% dextran sulfate sodium (DSS) their drinking water, either with...
Introduction: While better known for its pulmonary symptoms, SARS-CoV-2 also adversely affects the gastrointestinal tract, causing diarrhoea with evidence of inflammation. The nuclear bile acid receptor, farnesoid x receptor (FXR), is expressed in colonic epithelial cells and has been previously shown to inhibit cytokine production promote barrier function, thereby preventing inflammatory responses gut. In current studies, we set out investigate a potential role FXR modulating SARS-CoV-2....
Background Increased apoptosis and loss of epithelial barrier function are hallmark features in the pathogenesis inflammatory bowel disease. While bile acids classically known for their roles facilitating digestion absorption fats, they have more recently become appreciated as a family enterocrine hormones that regulate many aspects intestinal function. However, even though changes luminal closely associated with IBD pathogenesis, regulating still largely unknown. Lithocholic acid (LCA) is...
Introduction and Aims The intestinal epithelium functions to transport nutrients, fluid electrolytes, while at the same time acting as a barrier entry of harmful substances. CFTR is transmembrane Cl − channel important in regulating implicated pathogenesis number diseases. Bile acids, classically known for their roles lipid digestion, are now also recognised enteric hormones that regulate many aspects epithelial function. Indeed, it thought bile acid metabolism primary mechanism by which...
CFTR, a Cl- channel important in regulating intestinal fluid and electrolyte secretion, is implicated the pathogenesis of number disorders. We have previously shown that bile acids, acting via nuclear receptor, farnesoid X receptor (FXR), inhibit colonic epithelial CFTR expression. Dietary phytochemicals been reported to capacity modulate FXR signalling. Here, we set out investigate mechanisms underlying regulation expression, potential for therapeutically targeting with dietary...
The intestinal epithelium forms the interface between body and luminal contents, facilitating fluid electrolyte transport, while also acting as a barrier to harmful pathogens. Dysregulation of transport function is associated with pathogenesis number conditions, including chronic diarrhoeal inflammatory bowel diseases (IBD). Previous studies from ours, other laboratories, have identified nuclear bile acid receptor, farnesoid x receptor (FXR), an excellent target for development new...