A5035312634- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Drug-Induced Hepatotoxicity and Protection
- Metabolism and Genetic Disorders
- Retinoids in leukemia and cellular processes
- Diet and metabolism studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Antioxidant Activity and Oxidative Stress
- Diet, Metabolism, and Disease
- Pancreatic and Hepatic Oncology Research
- Mitochondrial Function and Pathology
- Clinical Nutrition and Gastroenterology
- Liver physiology and pathology
- Immune Response and Inflammation
- Organ Transplantation Techniques and Outcomes
- Glycosylation and Glycoproteins Research
- Liver Diseases and Immunity
- Peptidase Inhibition and Analysis
- Hepatitis B Virus Studies
- Alcohol Consumption and Health Effects
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Cancer, Stress, Anesthesia, and Immune Response
The Royal Free Hospital
2014-2025
University College London
2016-2025
Instituto de Investigación Biomédica de Málaga
2024
Universidad de Málaga
2024
Roland Hill (United Kingdom)
2023
Charité - Universitätsmedizin Berlin
2021
National Research Council
2015
Istituto di Farmacologia Traslazionale
2015
Chiba University
2015
Ocera Therapeutics (United States)
2015
•In a first-in-man, randomized-controlled trial of DIALIVE vs. standard care, the primary endpoint safety was met.•DIALIVE achieved acceptable performance characteristics for albumin exchange and reduction in endotoxin.•DIALIVE significantly reduced time to resolution ACLF improved prognostic scores compared with care.•DIALIVE had greater impact on pathophysiologically relevant biomarkers associated ACLF. Background & AimsAcute-on-chronic liver failure (ACLF) is characterized by severe...
Retinoids are essential for the maintenance of epithelial differentiation. As such, they play a fundamental role in chemoprevention carcinogenesis and differentiation therapy. Physiological retinoic acid is obtained through two oxidation steps from dietary retinol, i.e. retinol-->retinal-->retinoic acid. The latter retinal-->retinoic step irreversible eventually marks disposal this nutrient, cytochrome P450-dependent oxidative steps. Mutant mice deficient aryl hydrocarbon receptor (AHR)...
Retinoids are essential for the maintenance of epithelial differentiation. As such, they play a fundamental role in chemoprevention carcinogenesis and differentiation therapy. Physiological retinoic acid is obtained through two oxidation steps from dietary retinol, i.e. retinol→retinal→retinoic acid. The latter retinal→retinoic step irreversible eventually marks disposal this nutrient, cytochrome P450-dependent oxidative steps. Mutant mice deficient aryl hydrocarbon receptor (AHR) accumulate...
The aims of this study were to determine the role cell death in patients with cirrhosis and acute decompensation (AD) on chronic liver failure (ACLF) using plasma‐based biomarkers. studied part CANONIC (CLIF Acute‐on‐Chronic Liver Failure Cirrhosis) (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable cirrhosis, a group 16 AD for histological studies. Caspase‐cleaved keratin 18 (cK18) (K18), which reflect apoptotic total death, respectively, cK18:K18 ratio...
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...
•We hypothesised that a TLR4 inhibitor, TAK-242, might mitigate the negative effects of G-CSF in ACLF.•G-CSF alone increases mortality and promotes inflammation rodent models ACLF.•The combination TAK-242 inhibits inflammation, hepatic regeneration prevents ACLF. Background & AimsAcute-on-chronic liver failure (ACLF) is characterised by high short-term mortality, systemic regeneration. Its treatment major unmet medical need. This study was conducted to explore whether combining Toll-like...
Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development wound healing. Factors secreted by senescent cells affect their microenvironment can induce spreading of locally. Acute severe liver disease hepatocyte frequently progresses to multi-organ failure. Why the latter occurs poorly understood. Here we demonstrate in extrahepatic organs organ dysfunction response using injury models genetic...
The main aim was to evaluate changes in urea cycle enzymes NAFLD patients and two preclinical animal models mimicking this entity. Seventeen liver specimens from were included for immunohistochemistry gene expression analyses. Three-hundred-and-eighty-two biopsy-proven genotyped rs1047891, a functional variant located carbamoyl phosphate synthetase-1 (CPS1) gene. Two employed analyse CPS1 by immunohistochemistry, choline deficient high-fat diet model (CDA-HFD) high fat LDLr knockout (LDLr...
We aimed to assess the role of FGF21 in metabolic dysfunction-associated steatotic liver disease (MASLD) at a multi-scale level.
Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) they lack diagnostic accuracy.Two-dimensional difference gel electrophoresis tandem mass spectrometry were used profile immunodepleted samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated healthy volunteers. The levels one candidate protein, leucine-rich α-2-glycoprotein...
Graphical abstractAbstractBackground & AimsIn acute liver failure, severity of injury and clinical progression disease are in part consequent upon activation the innate immune system. Endotoxaemia contributes to system detoxifying function albumin, critical recovery from injury, is irreversibly destroyed failure. University College London-Liver Dialysis Device a novel artificial extracorporeal assist device, which used with albumin infusion, achieve removal replacement dysfunctional...
Chronic liver disease is a predisposing factor for development of hepatocellular carcinoma (HCC). Toll-like receptors play crucial role in immunity against microbial pathogens and recent evidence suggests that they may also be important pathogenesis chronic disease. The purpose this study was to determine whether TLR7 TLR9 are potential targets prevention progression HCC.Tissue microarrays containing samples from patients with cirrhosis, viral hepatitis HCC were examined expression the data...
Objective Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 models and acute-on-chronic liver failure (ACLF) and, its safety tolerability clinical trial cirrhosis. Design Performance was evaluated vitro . Two-rat ACLF, (4 weeks, bile duct ligation or without lipopolysaccharide), receiving for 2 weeks; two-mouse...
Alterations in epithelial mucin expression are associated with carcinogenesis, but there few data biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as sensitive serological marker for BTC. We assessed (i) prospectively collected bile serum specimens from 72 patients obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) western blot analysis, (ii) 79 archived tissues (69 immunohistochemistry....
Abstract The lipopolysaccharide (LPS)– toll-like receptor-4 (TLR4) pathway plays an important role in liver failure. Recombinant alkaline phosphatase (recAP) deactivates LPS. aim of this study was to determine whether recAP prevents the progression acute and acute-on-chronic failure (ACLF). Eight groups rats were studied 4-weeks after sham surgery or bile duct ligation injected with saline LPS mimic ACLF. Acute induced Galactosamine-LPS both models animals treated prior administration. In...
Abstract Acute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis a form programmed lytic death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage domain-like (pMLKL) are key components. This study was performed to determine the role RIPK1 mediated ACLF. plasma levels hepatic expression RIPK1, RIPK3, pMLKL were measured healthy volunteers, stable patients with cirrhosis,...
Livers of aryl hydrocarbon receptor (AHR)-null mice have high levels retinoic acid (RA), retinol, and retinyl palmitate. Hepatic accumulation RA in these may be responsible part for the hepatic phenotype characterized by small liver size fibrosis. The increased due to decreased metabolism 4-hydroxyretinoic acid. To identify P450 isoform(s) involved metabolism, microsomes from AHR-null wild-type were subjected Western blotting probed with antibodies rat P450s that cross-react murine forms....