Proof-of-Concept Human Organ-on-Chip Study: First Step of Platform to Assess Neuro-Immunological Communication Involved in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) are complex chronic inflammatory disorders of the gastrointestinal (GI) tract. Recent evidence suggests that the gut-brain axis may be pivotal in gastrointestinal and neurological diseases, especially IBD. Here, we present the first proof of concept for a microfluidic technology to model bilateral neuro-immunological communication.

SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function.

The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective autophagy receptor family, are involved in Tax-mediated NF-κB signaling.

Hazard of a neonicotinoid insecticide on the homing flight of the honeybee depends on climatic conditions and Varroa infestation.

The paradigm for all toxicological bioassays in the risk assessment of pesticide registration reflects the principle that experimental conditions should be controlled to avoid any other factors that may affect the endpoint measures. As honeybee colonies can be frequently exposed to bio-aggressors in real conditions, often concomitantly with pesticides, co-exposure to pesticide/bio-aggressors is becoming a concern for regulatory authorities. We investigated the effects of the neonicotinoid insecticide thiamethoxam on the homing performances of foragers emerging from colonies differentiated by health status (infestation with Varroa destructor mites, microsporidian parasite Nosema spp.

Stability of HTLV-2 antisense protein is controlled by PML nuclear bodies in a SUMO-dependent manner.

Since the identification of the antisense protein of HTLV-2 (APH-2) and the demonstration that APH-2 mRNA is expressed in vivo in most HTLV-2 carriers, much effort has been dedicated to the elucidation of similarities and/or differences between APH-2 and HBZ, the antisense protein of HTLV-1. Similar to HBZ, APH-2 negatively regulates HTLV-2 transcription. However, it does not promote cell proliferation.

Inflammation of bronchial smooth muscle in allergic asthma.

Background: Recent observations in asthma suggest that bronchial smooth muscle is infiltrated by inflammatory cells including mast cells. Such an infiltration may contribute to airway remodelling that is partly due to an increase in smooth muscle mass. Whether muscle increase is the result of smooth muscle cell hypertrophy remains controversial and has not been studied by ultrastructural analysis.

A role for thrombin in liver fibrosis.

Background/aim: Several lines of evidence incriminate the serine proteinase thrombin in liver fibrogenesis either through its procoagulant function or its signaling via cell-surface receptors. The aim of this study was therefore to evaluate the effect of thrombin inhibition on experimental liver fibrosis.

Methods: Fibrosis was induced in rats by administration of CCl4 for either three or seven weeks.

Abnormal hepatic expression of fibrillin-1 in children with cholestasis.

Fibrillin-1, one of the main constituents of microfibrils, is present in normal adult liver and overexpressed in fibrotic area around cirrhotic nodules and hepatocellular carcinoma. In this work fibrillin-1 expression was studied by immunohistochemistry in liver samples from children with various cholestatic diseases corresponding to paucity of intrahepatic bile ducts, biliary atresia, congenital hepatic fibrosis, Byler's disease, mitochondrial cytopathy, sclerosing cholangitis, or choledochal cyst. As controls, histologically normal liver samples were used.

Inhibition of rat liver fibrogenesis through noradrenergic antagonism.

The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Two weeks of CCl4 induced an approximately 5-fold increase in the area of fibrosis as compared with controls.

Expression and cellular localization of fibrillin-1 in normal and pathological human liver.

Background: The expression and the distribution of fibrillin-1 and elastin were studied in normal and pathological human liver samples.

Methods: As controls, histologically normal/subnormal liver samples (n = 24) were used. Pathological samples corresponded to seven cirrhosis and eight hepatocellular carcinomas (HCC) developed on cirrhotic (four) or noncirrhotic (four) liver.

Deactivation of cultured human liver myofibroblasts by trans-resveratrol, a grapevine-derived polyphenol.

Liver myofibroblasts are major actors in the development of liver fibrosis and cancer progression. There is a large interest in drugs that might deactivate these cells. Many studies have shown that the grapevine-derived polyphenol, trans-resveratrol, and other stilbenes have therapeutic potential in some diseases.

Expression and cellular localization of the urokinase-type plasminogen activator and its receptor in human hepatocellular carcinoma.

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in tumour invasion. Previous studies have shown by RT-PCR that uPA and uPAR mRNAs are expressed in human hepatocellular carcinoma (HCC). Here, in situ hybridization, immunohistochemistry, and double immunofluorescence were used to identify the cells expressing uPA and uPAR in 26 HCCs.

Activation of cultured rat hepatic stellate cells by tumoral hepatocytes.

Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and it develops from hepatocytes. The stroma of HCC is infiltrated by myofibroblasts. In other settings, such as liver fibrosis, myofibroblasts are derived mainly from the activation of hepatic stellate cells (HSC).

Direct evidence that hepatocyte growth factor-induced invasion of hepatocellular carcinoma cells is mediated by urokinase.

Background/aims: We have shown that hepatocyte growth factor secreted by human hepatic myofibroblasts increased the in vitro invasion of the hepatocarcinoma cell line HepG2 through Matrigel. Our aim in this study was to evaluate the role of urokinase in this process.

Methods: Expression of urokinase in HepG2 cells was measured by Northern blot and zymography, and plasminogen activation was shown by a chromogenic substrate assay.

Aspirin and heparin prevent hepatic blood stasis and thrombosis induced by the toxic glycoprotein Bolesatine in mice.

Bolesatine is a toxic glycoprotein isolated from Boletus satanas Lenz, which inhibits protein synthesis in vivo and in vitro. The LD50 (24 h) is 1 mg /kg bw (i.p.

Characterization of a new human liver myofibroblast cell line: transcriptional regulation of plasminogen activator inhibitor type I by transforming growth factor beta 1.

Myofibroblasts (MF) are a major effector cell type in liver fibrogenesis, where they are thought to derive from the activation of hepatic stellate cells. Cultured human MF, grown from liver explants, retain most of the in vivo characteristics of liver MF but are in limited supply. A continuous MF cell line would therefore be valuable in studying human liver fibrogenesis.

Ultrastructure of human Kupffer cells maintained in culture.

Sinusoidal cells were isolated by collagenase perfusion and metrizamide gradient centrifugation, from liver resected for partial hepatectomy performed under warm ischemic conditions. Kupffer cells were then separated from this population by centrifugal elutriation. Isolated Kupffer cells showed good viability, with the typical features of Kupffer cells and were engaged in the endocytosis of foreign particles.

Transformation of sinusoids into capillaries in a rat model of selenium-induced nodular regenerative hyperplasia: an immunolight and immunoelectron microscopic study.

The oral administration of selenium (Se) to young rats induces, over a 2-month period, the formation of nodular regenerative hyperplasia with sinusoidal damage around nodules. Perinodular areas located in zone 1 comprise atrophic hepatocytes and capillarized sinusoids without fibrosis. We used this unique model of capillarization without fibrosis to investigate the temporal relationship between the process of capillarization and changes occurring in the deposition of components of the extracellular matrix.

Severe portal hypertensive gastropathy and antral vascular ectasia are distinct entities in patients with cirrhosis.

Background/aims: Whereas severe portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) have been separately defined in patients with cirrhosis, there is much confusion in the literature because they are both characterized by red spots at endoscopy. This prospective study compared clinical, biochemical, and pathological features of these syndromes.

Methods: Three groups of patients with cirrhosis and either GAVE (n = 14), severe portal hypertensive gastropathy (n = 14), or no gastric features at endoscopy (controls; n = 10) were included.

Lynxacarus radovskyi infestation in a cat.

An adult domestic short-hair cat from south Texas was examined because of excessive dandruff on the back, neck, thorax, and hind limbs. Removal of a few hairs for microscopic evaluation revealed Lynxacarus radovskyi, the cat fur mite. The small (< 0.

Nodular regenerative hyperplasia in the rat induced by a selenium-enriched diet: study of a model.

Weaned male rats were fed a 4 ppm selenium diet. Compared after 2 mo with a control group fed a 0.4 ppm diet, the rats' body weights had not significantly decreased and liver function was normal, but portal pressure was 1.

Characterization of liver-associated natural killer cells in patients with liver tumors.

The existence of a marginal lymphocyte population in rat liver sinusoids has already been demonstrated using the sinusoidal lavage method. We used the same technique to study the lymphocyte population in human liver obtained ex vivo after partial hepatectomy for benign or malignant tumors and compared it with peripheral and portal blood lymphocyte populations. Percentages of lymphocyte surface phenotypes were evaluated by flow cytometry.

Modifications of the sinusoidal barrier in a model of postsinusoidal hypertension in the rat. An ultrastructural study of endothelial cells.

Sinusoids and sinusoidal cells were examined by light and electron microscopy, using a rat model of postsinusoidal hypertension. One month after partial ligation of the vena cava (PLVC) above the hepatic veins, subcapsular hemorrhagic areas were visible with proliferation of hepatic veins; in non hemorrhagic areas, sinusoidal congestion was found. Postsinusoidal hypertension led to a significant increase in sinusoidal volume and to major abnormalities of the endothelium such as endothelial processes and pouches with numerous diaphragmed fenestrae; some red blood cells could be seen in these pouches.

Benign recurrent cholestasis: a light and electron microscopic study with emphasis on sinusoidal cells.

A liver biopsy was performed on a patient with benign recurrent cholestasis. Cholestasis was mainly centrolobular with infiltration by sinusoidal macrophages. There was no necrosis.

Removal of cellular debris formed in the Disse space in patients with cholestasis.

Using electron microscopy, we investigated how cellular debris, formed in the Disse space during cholestasis, was cleared. Ten patients with cholestasis of varied origin and severity were studied and compared with 10 controls without liver disease. In cholestatic patients, sinusoidal cells contained variable amounts of amylase PAS-positive material.