A5086561677- MicroRNA in disease regulation
- Drug-Induced Hepatotoxicity and Protection
- Extracellular vesicles in disease
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Liver Disease and Transplantation
- Circular RNAs in diseases
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- thermodynamics and calorimetric analyses
- Drug Transport and Resistance Mechanisms
- Muscle and Compartmental Disorders
- Genomics, phytochemicals, and oxidative stress
- Biomedical and Chemical Research
- Circadian rhythm and melatonin
- High Altitude and Hypoxia
- Antifungal resistance and susceptibility
- Neuroscience and Music Perception
- Inflammatory Myopathies and Dermatomyositis
- Immune Response and Inflammation
- Cannabis and Cannabinoid Research
- Antimicrobial Resistance in Staphylococcus
- Zebrafish Biomedical Research Applications
MRC Centre for Regenerative Medicine
2016-2022
University of Edinburgh
2016-2022
Medical Research Council
2020-2021
University of Liverpool
2011-2020
University Hospital Coventry
2011
Harvard University Press
1979
Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated potential panel novel biomarkers (with enhanced liver expression or linked to mechanisms toxicity) identify patients with acetaminophen-induced acute injury (ALI) at first presentation when currently used markers are within normal range. In plasma sample from (n =...
•Primary BMDMs localised to liver and spleen within hours following intravenous injection in mice.•AAMs were highly phagocytic i.v. transfer elicited reductions necrotic area, HMGB1 translocation, hepatic neutrophil infiltration.•AAM reduced inflammatory mediators stimulated hepatocyte/endothelium proliferation injured liver.•Injection of clinical-grade human AAMs could partially recapitulate the efficacy murine immunocompetent mice. Background & AimFollowing acetaminophen (APAP) overdose,...
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
The role of the liver and endocrine pancreas in development hyperinsulinemia different types obesity remains unclear. Sedentary rats (160 g) were fed a low-fat-diet (LFD, chow 13% kcal fat), high-fat-diet (HFD, 35% or HFD+ 30% ethanol+ fructose (HF-EFr, 22% fat). Overnight-fasted culled after one, four eight weeks. Pancreatic hepatic mRNAs isolated for subsequent RT-PCR analysis. After weeks, body weights increased three-fold LFD group, 2.8-fold HFD 2.4-fold HF-EFr (p < 0.01). HF-EFr-fed...
Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) 4 (p4) produced proregenerative factors, strongly suppressing T cell responses the...
Background and Aims The transcription factor nuclear erythroid 2‐related 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role liver regeneration. We aimed test the hypothesis that pharmacological activation Nrf2 would enhance Approach Results Wild‐type null were administered bardoxolone methyl (CDDO‐Me), a potent activator has entered clinical development, then subjected two‐thirds partial hepatectomy. Using...
Journal Article A multicentre open clinical trial of teicoplanin in infections caused by Gram-positive bacteria Get access Peter Lewis, Lewis aDepartment Medical Research, Merrell Dow Research InstituteEgham, Surrey, UK Search for other works this author on: Oxford Academic PubMed Google Scholar Jean-Jacques Garaud, Garaud Francesco Parenti bLepetit Center, InstituteGerenzano, Italy Antimicrobial Chemotherapy, Volume 21, Issue suppl_A, 1988, Pages 61–67,...
Paracetamol is the commonest cause of acute liver failure in Western world and biomarkers are needed that report early hepatotoxicity. The liver-enriched microRNA (miRNA), miR-122, a promising biomarker currently being qualified humans. For development drug toxicity screening, zebrafish has advantages over rodents; however, blood acquisition this model remains technically challenging. We developed method for collecting from adult by retro-orbital (RO) bleeding compared it to commonly used...
Abstract Acetaminophen overdose is the leading cause of acute liver failure. One dose 10–15 g causes severe damage in humans, whereas repeated exposure to acetaminophen humans and animal models results autoprotection. Insight this process limited select proteins implicated toxicity cellular defence. Here we investigate hepatic adaptation from a whole proteome perspective, using quantitative mass spectrometry. In rat model, show response involves expression 30% all detected liver. Genetic...
There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, biomarker DILI in both rodent, human studies.To build on previous work within the field, we examined kinetics rat model acetaminophen (APAP)-induced to confirm sensitivity, specificity miR-122 glutamate dehydrogenase (GLDH).qRT-PCR standard enzymatic assay were used analysis.Both GLDH demonstrated be more...
BackgroundExtracellular microRNAs enter kidney cells and modify gene expression. We used a Dicer-hepatocyte-specific microRNA conditional-knock-out (Dicer-CKO) mouse to investigate transfer from liver kidney.MethodsDicerflox/flox mice were treated with Cre recombinase-expressing adenovirus (AAV8) selectively inhibit hepatocyte production (Dicer-CKO). Organ expression was measured in health following paracetamol toxicity. The functional consequence of hepatic determined by measuring the...
We read the letter from Qi et al. regarding use of endogenous normalizers for serum microRNAs with much interest. The authors describe a panel miRNAs (miR-374a, miR-374b, and let-7d) that appear to be expressed at consistent levels between healthy chronic disease groups. These may superior over currently used reference species. This is young evolving field, this contribution welcomed as it help define parameters most accurate quantification human circulating microRNAs. There no single...
<h3>Case history</h3> A 13 year old boy of African origin was admitted with an acute onset fever, cough and right leg swelling. He born in Malawi moved to UK at 3 years age. Findings on examination included a temperature 39°C, oral candidiasis, crepitations the side chest. His calf swollen, erythematous tender. There evidence proximal muscle weakness. started IV Cefuroxime for possible LRTI. Tests included: C reactive protein (345 mg/dl), normal doppler scan lower limbs, CD4 count (10...
Abstract Extracellular microRNAs have been demonstrated to the ability enter kidney tubular cells and modify gene expression. We used a Dicer-hepatocyte-specific microRNA conditional knock-out (Dicer-CKO) mouse investigate functional transfer from liver under physiological conditions in context of drug toxicity. Dicer-CKO mice time-dependent decrease hepatocyte-derived microRNA, miR-122, absence other changes. During hepatotoxicity, miR-122 increased cells; this was abolished mice. Depletion...