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https://www.readbyqxmd.com/read/27918111/imatinib-accelerates-progenitor-cell-mediated-liver-regeneration-in-choline-deficient-ethionine-supplemented-diet-fed-mice
#1
András Rókusz, Edina Bugyik, Vanessza Szabó, Armanda Szücs, Sándor Paku, Péter Nagy, Katalin Dezső
Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline-deficient ethionine-supplemented diet (CDE)...
December 5, 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#2
Wei Xu, Nong-Rong Wang, Hua-Feng Wang, Qiong Feng, Jun Deng, Zhi-Qiang Gong, Jian Sun, Xiao-Liang Lou, Xue-Feng Yu, Lv Zhou, Jin-Ping Hu, Xiao-Feng Huang, Xiao-Qing Qi, Yan-Juan Deng, Rui Gong, Yan Guo, Meng-Meng Wang, Jia-Cheng Xiao, Huan Deng
BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection...
November 24, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27879410/triple-staining-including-foxa2-identifies-stem-cell-lineages-undergoing-hepatic-and-biliary-differentiation-in-cirrhotic-human-liver
#3
Charles E Rogler, Remon Bebawee, Joe Matarlo, Joseph Locker, Nicole Pattamanuch, Sanjeev Gupta, Leslie E Rogler
Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver...
November 22, 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27872855/partial-portal-vein-arterialization-attenuates-acute-bile-duct-injury-induced-by-hepatic-dearterialization-in-a-rat-model
#4
Jun Jiang, Jishu Wei, Junli Wu, Wentao Gao, Qiang Li, Kuirong Jiang, Yi Miao
Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27829832/members-of-the-cyr61-ctgf-nov-protein-family-emerging-players-in-hepatic-progenitor-cell-activation-and-intrahepatic-cholangiocarcinoma
#5
Qunfeng Wu, Marda Jorgensen, Joanna Song, Junmei Zhou, Chen Liu, Liya Pi
Hepatic stem/progenitor cells (HPC) reside quiescently in normal biliary trees and are activated in the form of ductular reactions during severe liver damage when the replicative ability of hepatocytes is inhibited. HPC niches are full of profibrotic stimuli favoring scarring and hepatocarcinogenesis. The Cyr61/CTGF/NOV (CCN) protein family consists of six members, CCN1/CYR61, CCN2/CTGF, CCN3/NOV, CCN4/WISP1, CCN5/WISP2, and CCN6/WISP3, which function as extracellular signaling modulators to mediate cell-matrix interaction during angiogenesis, wound healing, fibrosis, and tumorigenesis...
2016: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/27824131/infliximab-and-dexamethasone-attenuate-the-ductular-reaction-in-mice
#6
Stefaan Verhulst, Jan Best, Wing-Kin Syn, Hendrik Reynaert, Karine H Hellemans, Ali Canbay, Laurent Dolle, Leo A van Grunsven
Chronic hepatic injury is accompanied by a ductular response that is strongly correlated with disease severity and progression of fibrosis. To investigate whether anti-inflammatory drugs can modulate the ductular response, we treated mice suffering from a steatotic or cholestatic injury with anti-TNF-α antibodies (Infliximab) or glucocorticoids (Dexamethasone). We discovered that Dexamethasone and Infliximab can both modulate the adaptive remodeling of the biliary architecture that occurs upon liver injury and limit extracellular matrix deposition...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27796316/ductular-reaction-on-a-chip-microfluidic-co-cultures-to-study-stem-cell-fate-selection-during-liver-injury
#7
Amranul Haque, Pantea Gheibi, Gulnaz Stybayeva, Yandong Gao, Natalie Torok, Alexander Revzin
Liver injury modulates local microenvironment, triggering production of signals that instruct stem cell fate choices. In this study, we employed a microfluidic co-culture system to recreate important interactions in the liver stem cell niche, those between adult hepatocytes and liver progenitor cells (LPCs). We demonstrate that pluripotent stem cell-derived LPCs choose hepatic fate when cultured next to healthy hepatocytes but begin biliary differentiation program when co-cultured with injured hepatocytes. We connect this fate selection to skewing in production of hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β1 caused by injury...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27776008/key-histopathologic-features-of-liver-biopsies-that-distinguish-biliary-atresia-from-other-causes-of-infantile-cholestasis-and-their-correlation-with-outcome-a-multicenter-study
#8
Pierre Russo, John C Magee, Robert A Anders, Kevin E Bove, Catherine Chung, Oscar W Cummings, Milton J Finegold, Laura S Finn, Grace E Kim, Mark A Lovell, Margret S Magid, Hector Melin-Aldana, Sarangarajan Ranganathan, Bahig M Shehata, Larry L Wang, Frances V White, Zhen Chen, Catherine Spino
The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA...
December 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27774712/the-histological-quantification-of-alpha-smooth-muscle-actin-predicts-future-graft-fibrosis-in-pediatric-liver-transplant-recipients
#9
Sharat Varma, Xavier Stéphenne, Mina Komuta, Caroline Bouzin, Jerome Ambroise, Françoise Smets, Raymond Reding, Etienne M Sokal
Activated hepatic stellate cells express cytoplasmic ASMA prior to secreting collagen and consequent liver fibrosis. We hypothesized that quantifying ASMA could predict severity of future fibrosis after LT. For this, 32 pairs of protocol biopsies, that is, "baseline" and "follow-up" biopsies taken at 1- to 2-year intervals from 18 stable pediatric LT recipients, transplanted between 2006 and 2012 were selected. Morphometric quantification of "ASMA-positive area percentage" was performed on the baseline biopsy...
October 23, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27769530/inactivation-of-p120-catenin-in-mice-disturbs-intrahepatic-bile-duct-development-and-aggravates-liver-carcinogenesis
#10
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
December 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27755536/osteopontin-is-upregulated-in-human-and-murine-acute-schistosomiasis-mansoni
#11
Thiago Almeida Pereira, Wing-Kin Syn, Frederico Figueiredo Amâncio, Pedro Henrique Diniz Cunha, Julia Fonseca Morais Caporali, Guilherme Vaz de Melo Trindade, Elisângela Trindade Santos, Márcia Maria Souza, Zilton Araújo Andrade, Rafal P Witek, William Evan Secor, Fausto Edmundo Lima Pereira, José Roberto Lambertucci, Anna Mae Diehl
BACKGROUND: Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection...
October 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27752144/lps-tlr4-pathway-mediates-ductular-cell-expansion-in-alcoholic-hepatitis
#12
Gemma Odena, Jiegen Chen, Juan Jose Lozano, Jose Altamirano, Daniel Rodrigo-Torres, Silvia Affo, Oriol Morales-Ibanez, Hiroshi Matsushita, Jian Zou, Raluca Dumitru, Juan Caballeria, Pere Gines, Vicente Arroyo, Min You, Pierre-Emmanuel Rautou, Dominique Valla, Fulton Crews, Ekihiro Seki, Pau Sancho-Bru, Ramon Bataller
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27748735/apical-membrane-expression-of-distinct-sulfated-glycans-represents-a-novel-marker-of-cholangiolocellular-carcinoma
#13
Hitomi Hoshino, Makoto Ohta, Makoto Ito, Kenji Uchimura, Yasuhiro Sakai, Takeshi Uehara, Shulin Low, Mana Fukushima, Motohiro Kobayashi
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver neoplasm, followed by hepatocellular carcinoma. ICC can be further subclassified as (i) perihilar and (ii) peripheral types, the latter histologically resembling small-sized intrahepatic bile ducts, such as interlobular bile ducts, cholangioles/ductules and the canals of Hering. Cholangiolocellular carcinoma (CoCC), now classified by the World Health Organization as a subtype of combined hepatocellular-cholangiocarcinoma, is currently regarded as a subtype of peripheral-type ICC...
October 17, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27742301/long-time-choledochal-clamping-in-wistar-rats-causes-biliary-obstruction-progressing-to-hepatic-fibrosis
#14
G D L Jorge, R R Tártaro, C A F Escanhoela, I D F S F Boin
BACKGROUND: Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. METHODS: Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision...
September 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27713972/vascular-and-hepato-protective-effects-of-passion-fruit-seed-extract-containing-piceatannol-in-chronic-high-fat-diet-fed-rats
#15
Akira Ishihata, Hiroko Maruki-Uchida, Nozomi Gotoh, Sumika Kanno, Yoshitaka Aso, Satoshi Togashi, Masahiko Sai, Tatsuhiko Ito, Yumi Katano
The effects of chronic administration of piceatannol-enriched (9.5% w/w) passion fruit seed extract (PFSE) on the cardiovascular damage induced in a high-fat (HF) diet-fed model of Fischer 344 rats were evaluated. Rats were fed the control, HF, or HF diets containing PFSE (0.5% w/w) for 16 weeks, and the effects of the various diets on the tissue weight, serum lipid profile, hepatic fibrosis, hepatic ductular reaction, cardiac function and aortic ring reactivity were examined. HF diet-fed rats developed signs of cardiovascular disease with abnormal serum profiles compared to control diet-fed rats...
September 14, 2016: Food & Function
https://www.readbyqxmd.com/read/27681331/the-spectrum-of-histologic-findings-in-hepatic-outflow-obstruction
#16
Raul S Gonzalez, Michael A Gilger, Won Jae Huh, Kay Washington
Context .- Cardiac hepatopathy and Budd-Chiari syndrome are 2 forms of hepatic venous outflow obstruction with different pathophysiology but overlapping histologic findings, including sinusoidal dilation and centrilobular necrosis. Objective .- To determine whether a constellation of morphologic findings could help distinguish between the 2 and could suggest the diagnoses in previously undiagnosed patients. Design .- We identified 26 specimens with a diagnosis of cardiac hepatopathy and 23 with a diagnosis of Budd-Chiari syndrome...
September 28, 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27660679/contrast-enhanced-ultrasonographic-findings-of-serum-amyloid-a-positive-hepatocellular-neoplasm-does-hepatocellular-adenoma-arise-in-cirrhotic-liver
#17
Mariko Kumagawa, Naoki Matsumoto, Yukinobu Watanabe, Midori Hirayama, Takao Miura, Hiroshi Nakagawara, Masahiro Ogawa, Shunichi Matsuoka, Mitsuhiko Moriyama, Tadatoshi Takayama, Masahiko Sugitani
Hepatocellular adenoma (HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography (CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase...
September 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27643580/changes-in-liver-ganglioside-metabolism-in-obstructive-cholestasis-the-role-of-oxidative-stress
#18
V Šmíd, T Petr, K Váňová, J Jašprová, J Šuk, L Vítek, F Šmíd, L Muchová
Bile acids have been implicated in cholestatic liver damage, primarily due to their detergent effect on membranes and induction of oxidative stress. Gangliosides can counteract these harmful effects by increasing the rigidity of the cytoplasmic membrane. Induction of haem oxygenase (HMOX) has been shown to protect the liver from increased oxidative stress. The aim of this study was to determine the changes in the synthesis and distribution of liver gangliosides following bile duct ligation (BDL), and to assess the effects of HMOX both on cholestatic liver injury and ganglioside metabolism...
2016: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/27618307/macrophage-depletion-attenuates-extracellular-matrix-deposition-and-ductular-reaction-in-a-mouse-model-of-chronic-cholangiopathies
#19
Jan Best, Stefaan Verhulst, Wing-Kin Syn, Kimberly Lagaisse, Noemi van Hul, Femke Heindryckx, Jan-Peter Sowa, Liesbeth Peeters, Hans Van Vlierberghe, Isabelle A Leclercq, Ali Canbay, Laurent Dollé, Leo A van Grunsven
Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i...
2016: PloS One
https://www.readbyqxmd.com/read/27617400/ductular-reactions-in-the-liver-regeneration-process-with-local-inflammation-after-physical-partial-hepatectomy
#20
Yuji Suzuki, Hirokatsu Katagiri, Ting Wang, Keisuke Kakisaka, Kohei Kume, Satoshi S Nishizuka, Yasuhiro Takikawa
Partial hepatectomy models in mice have been widely used for liver regeneration studies. A typical procedure removes ~2/3 of the liver by lobular ligation without tissue dissection. However, hepatectomy in humans involves physical damage (ie, physical partial hepatectomy, PPHx). Therefore, the liver regeneration process after PPHx should involve reactions to acute local injury followed by systematic remodeling. To clarify the liver regeneration process after PPHx, we used a murine liver injury model that mimics the actual human surgical procedure...
September 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
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