A5064614262- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- NF-κB Signaling Pathways
- Total Knee Arthroplasty Outcomes
- Endoplasmic Reticulum Stress and Disease
- Connective Tissue Growth Factor Research
- Phagocytosis and Immune Regulation
- Lipid metabolism and biosynthesis
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer, Stress, Anesthesia, and Immune Response
- 3D Printing in Biomedical Research
- Digestive system and related health
- Epigenetics and DNA Methylation
- Mathematical Biology Tumor Growth
- Pediatric Hepatobiliary Diseases and Treatments
- Adipose Tissue and Metabolism
- Cancer Cells and Metastasis
- Dermatologic Treatments and Research
- Proteoglycans and glycosaminoglycans research
- Adipokines, Inflammation, and Metabolic Diseases
- Liver Disease and Transplantation
- Neuropeptides and Animal Physiology
- Inflammasome and immune disorders
- Organ Transplantation Techniques and Outcomes
- Glycosylation and Glycoproteins Research
Newcastle University
2017-2025
John Wiley & Sons (United States)
2019
Precision cut liver slices (PCLSs) retain the structure and cellular composition of native represent an improved system to study fibrosis compared two‐dimensional mono‐ or co‐cultures. The aim this was develop a bioreactor increase healthy life span PCLSs model fibrogenesis. were generated from normal rat human liver, fibrotic cultured in our bioreactor. PCLS function quantified by albumin enzyme‐linked immunosorbent assay (ELISA). Fibrosis induced transforming growth factor beta 1 (TGFβ1)...
In nonalcoholic fatty liver disease (NAFLD), fibrosis is the most important factor contributing to NAFLD-associated morbidity and mortality. Prevention of progression reduction in are main aims treatment. Even early stages NAFLD, hepatic systemic hyperammonemia evident. This due reduced urea synthesis; as ammonia known activate stellate cells, we hypothesized that may be involved NAFLD.In a high-fat, high-cholesterol diet-induced rodent model observed progressive stepwise expression activity...
Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between DNA-mehyltransferases like G9a DNMT1 common theme gene expression regulation. We aimed study the efficacy of CM272, first-in-class dual reversible G9a/DNMT1 inhibitor, halting fibrogenesis.G9a were analysed cirrhotic human livers, mouse models liver fibrosis cultured HSC. was...
Background and Aims NAFLD is the most common hepatic pathology in western countries no treatment currently available. characterized by aberrant hepatocellular accumulation of fatty acids form lipid droplets (LDs). Recently, it was shown that liver LD degradation occurs through a process termed lipophagy, autophagy. However, molecular mechanisms governing lipophagy are elusive. Here, we aimed to ascertain key players regulate their importance NAFLD. Approach Results We analyzed formation...
Chronic liver injury characterized by unresolved hepatitis leads to fibrosis, potentially progressing cirrhosis and hepatocellular carcinoma. Effective treatments for halting or reversing fibrosis are currently lacking. This study investigates the potential of HDAC6 as a therapeutic target in fibrosis. We synthesized two selective inhibitors, DR‐3 FDR2, assessed their effects on hepatic stellate cell (HSC) activation using human precision cut slices (hPCLS). Molecular docking, deacetylation...
Age-related chronic inflammation promotes cellular senescence, disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease tumorigenesis. We used an established model spontaneous inflammaging, steatosis, cancer (
ABSTRACT Chronic pain and restricted knee motion is a significant problem following the total arthroplasty (TKA). The molecular pathogenesis of post‐TKA not known no targeted therapeutic intervention available. aim this study was to investigate whether pro‐inflammatory mediators are elevated in revision patients, indicating an active, ongoing inflammatory process that may contribute pain. Twelve key markers (pro‐inflammatory cytokines granulocyte‐macrophage colony‐stimulating factor...
<b><i>Introduction:</i></b> Heparin sulphate proteoglycans in the liver tumour microenvironment (TME) are key regulators of cell signalling, modulated by sulfatase-2 (SULF2). SULF2 overexpression occurs hepatocellular carcinoma (HCC). Our aims were to define nature and impact HCC TME. <b><i>Methods:</i></b> In biopsies from 60 patients with HCC, expression localization analysed associated clinical parameters outcome. Functional mechanistic...
NF-κB regulates genes that control inflammation, cell proliferation, differentiation and survival. Dysregulated signalling alters normal skin physiology deletion of cRel limits bleomycin-induced fibrosis. This study investigates the role in modulating fibroblast phenotype context SSc.Fibrosis was assessed histologically mice challenged with bleomycin to induce lung or RNA sequencing pathway analysis performed on wild type Rel-/- murine dermal fibroblasts. Functional assays examined migration...
Disease modelling is vital for improving knowledge of disease mechanisms and development new therapeutic molecules strategies. Modelling the intact living tumour microenvironment (TME) increasingly considered to be not only gaining a better understanding biology cancer but examining efficacy novel oncology drugs. To date, pre-clinical mouse models have represented mainstay methodology studying evolving TME determining effects potential on evolution growth. Regarding drug screening, in vivo...
Summary box What is already known about this subject? Currently there are no effective anti-fibrotic drugs to treat liver fibrosis and an urgent unmet need increase our knowledge of the disease process develop better tools for drug discovery. Preclinical in vitro cell cultures animal models widely used study test drugs, but have shortfalls; culture lack relevant complex cell-cell interactions only reproduce some features human disease. Precision Cut Liver Slices (PCLS) structurally...