A5042479811- S100 Proteins and Annexins
- Gut microbiota and health
- Barrier Structure and Function Studies
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Stress Responses and Cortisol
- Nuclear Receptors and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Birth, Development, and Health
- Neonatal Respiratory Health Research
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Biomarkers in Disease Mechanisms
- Neuroendocrine regulation and behavior
- Neuropeptides and Animal Physiology
- Protease and Inhibitor Mechanisms
- Tryptophan and brain disorders
- Estrogen and related hormone effects
- Connexins and lens biology
- Amyotrophic Lateral Sclerosis Research
- Growth Hormone and Insulin-like Growth Factors
- Neurological diseases and metabolism
- Biochemical Analysis and Sensing Techniques
- Receptor Mechanisms and Signaling
- Inflammation biomarkers and pathways
Queen Mary University of London
2013-2024
William Harvey Research Institute
2012-2020
University of Westminster
2015-2016
Hammersmith Hospital
2003-2015
Imperial College London
2006-2015
University College London
2012
Queen's University Belfast
2012
Brf (Brazil)
1993
Gut microbiota composition and function are symbiotically linked with host health altered in metabolic, inflammatory neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, blood-brain barrier (BBB) also contribute to axis. Propionate, produced...
Significance Inflammation is a crucial host defense response but can cause chronic disease if unregulated. Several endogenous anti-inflammatory and proresolving circuits balance modulate inflammation, including mechanism centered on the formyl peptide receptor (FPR) family. One receptor, ALX/FPR2, recognizes both proinflammatory signals. We have investigated this unusual molecular finding that anti-inflammatory, not signals, activate homodimers of receptor. This triggers intracellular...
Communication between the gut microbiota and brain is primarily mediated via soluble microbe-derived metabolites, but details of this pathway remain poorly defined. Methylamines produced by microbial metabolism dietary choline L-carnitine have received attention due to their proposed association with vascular disease, effects upon cerebrovascular circulation hitherto not been studied.
The brain microenvironment is continuously monitored by microglia with the detection of apoptotic cells or pathogens being rapidly followed their phagocytosis to prevent inflammatory responses. protein annexin A1 (ANXA1) key leukocytes during peripheral resolution, but pathophysiological significance its expression in CNS that restricted almost exclusively unclear. In this study, we test hypothesis ANXA1 important microglial clearance neurons both noninflammatory and conditions. We have...
The blood–brain barrier (BBB), a critical guardian of communication between the periphery and brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting inappropriate passage molecules leukocytes into brain. Here we show that glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) expressed brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1 −/− mice exhibit significantly increased permeability result...
Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering molecular and cellular processes required tissue repair. Macrophages play a central role in regulation inflammation, resolution, repair/regeneration. Using model skeletal muscle injury repair, herein we identified annexin A1 (AnxA1) as extracellular trigger macrophage skewing toward pro-reparative phenotype. Brought into injured initially by migrated neutrophils, then overexpressed...
Significance Sepsis defines a syndrome with poor clinical management characterized by overlapping phases of excessive inflammation temporally aligned an immunosuppressed state. We define endogenous pathway centered on formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—that protects the host against polymicrobial sepsis. Using null mice and proof-of-concept experiments peptide–agonist, we demonstrate how engagement Fpr2/3 is crucial enact nonredundant...
Annexin A1 (AnxA1) is an effector of the resolution inflammation and highly effective in terminating acute inflammatory responses. However, its role chronic settings less investigated. Because changes AnxA1 expression within adipose tissue characterize obesity mice humans, we queried a possible for pathogenesis nonalcoholic steatohepatitis (NASH), disease commonly associated with obesity. NASH was induced wild-type (WT) knockout (AnxA1 KO) C57BL/6 by feeding methionine-choline deficient...
Abstract Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse atherosclerosis Alzheimer’s disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by protein annexin A1 (ANXA1), found abundance inflammatory exudates. Using primary human blood from healthy donors, we identified ANXA1 a potent CD14+CD16− monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed p38 MAPK-mediated...
The sequential activity of gut microbial and host processes can exert a powerful modulatory influence on dietary components, as exemplified by the metabolism amino acids tyrosine phenylalanine to p-cresol microbes, then glucuronide (pCG) enzymes. Although such conjugates are classically thought be biologically inert, there is accumulating evidence that this may not always case. We investigated pCG, studying its interactions with cerebral vasculature brain in vitro vivo. Male C57Bl/6 J mice...
Sleep disorders may increase neurodegenerative diseases risks and alter gut microbiota composition. Saffron (Crocus sativus) supplementation has been linked to sleep improvements microbiome changes, but its effect on quality through microbiota-brain axis modulation remains unexplored. A randomised, placebo-controlled pilot study of saffron (30mg/day for 4-weeks) was conducted with 52 older adults (55-85 years) experiencing complaints. Subjective objective were measured using validated...
Abstract Early exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological ‘programming’ are unclear. This study tested hypothesis that inappropriate glucocorticoid stress hormones (GCs) during critical periods of development permanently alters mesencephalic dopaminergic populations ventral tegmental area (VTA) substantia nigra pars compacta (SNc). Using a rat model, synthetic GC...