Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver.

Objective: Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid.

C. G. Jung and intuition: from the mindscape of the paranormal to the heart of psychology.

Intuition is central in the work, practice, and philosophical legacy of C. G. Jung.

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism.

Type I interferon signaling in systemic immune cells from patients with alcoholic cirrhosis and its association with outcome.

Background & Aims: In immune cells, constitutively and acutely produced type I interferons (IFNs) engage autocrine/paracrine signaling pathways to induce IFN-stimulated genes (ISGs). Enhanced activity of IFN signaling pathways can cause excessive inflammation and tissue damage. We aimed to investigate ISG expression in systemic immune cells from patients with decompensated alcoholic cirrhosis, and its association with outcome.

Mitochondrial DNA maintenance is regulated in human hepatoma cells by glycogen synthase kinase 3β and p53 in response to tumor necrosis factor α.

During chronic liver inflammation, up-regulated Tumor Necrosis Factor alpha (TNF-α) targets hepatocytes and induces abnormal reactive oxygen species (ROS) production responsible for mitochondrial DNA (mtDNA) alterations. The serine/threonine Glycogen Synthase Kinase 3 beta (GSK3β) plays a pivotal role during inflammation but its involvement in the maintenance of mtDNA remains unknown. The aim of this study was to investigate its involvement in TNF-α induced mtDNA depletion and its interrelationship with p53 a protein known to maintain mtDNA copy numbers.

Subcellular localization of iron and heme metabolism related proteins at early stages of erythrophagocytosis.

Background: Senescent red blood cells (RBC) are recognized, phagocytosed and cleared by tissue macrophages. During this erythrophagocytosis (EP), RBC are engulfed and processed in special compartments called erythrophagosomes. We previously described that following EP, heme is rapidly degraded through the catabolic activity of heme oxygenase (HO).

Influence of garlic or its main active component diallyl disulfide on iron bioavailability and toxicity.

Garlic is regularly consumed and is known to have diverse biologic activities, particularly due to its antioxidant properties. In this study, we hypothesized that crude garlic can prevent iron-mediated oxidative stress in a rat model of nutritional iron overload, and we used an in vitro model to confirm the results. For the in vivo studies, rats received a basal diet supplemented with or without carbonyl iron (3%) and were fed distilled water or garlic solution (1g/kg body weight) by gavage for 3 weeks.

Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia.

Objective: Anemia in critically ill patients is frequent and consists of chronic disease associated with blood losses. These two mechanisms have opposite effects on iron homeostasis, especially on the expression of the iron regulatory hormone hepcidin. We developed a mouse model mimicking the intensive care anemia to explore iron homeostasis.

Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression.

Tissue macrophages play an essential role in iron recycling through the phagocytosis of senescent RBCs (red blood cells). Following haem catabolism by HO1 (haem oxygenase 1), they recycle iron back into the plasma through the iron exporter Fpn (ferroportin). We previously described a cellular model of EP (erythrophagocytosis), based on primary cultures of mouse BMDMs (bone-marrow-derived macrophages) and aged murine RBCs, and showed that EP induces changes in the expression profiles of Fpn and HO1.

A physiological model to study iron recycling in macrophages.

Following erythrophagocytosis (EP) of senescent red blood cells (RBCs), heme iron is recycled to the plasma by tissue macrophages. This process is critical for mammalian iron homeostasis but remains elusive. We characterized a cellular model using artificially-aged murine RBCs and murine bone marrow-derived macrophages (BMDMs) and study mRNA and protein expression of HO-1, ferroportin and ferritin after EP.

Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin.

Ferroportin, the only mammalian iron exporter identified to date, is highly expressed in duodenal enterocytes and in macrophages. Several lines of evidence indicate that in enterocytes the iron export mediated by ferroportin occurs and is regulated at the basolateral cell surface, where the transporter is strongly expressed. By contrast, in macrophages, ferroportin has been shown in intracellular vesicles.