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https://www.readbyqxmd.com/read/28919113/hepatic-tmem30a-deficiency-causes-intrahepatic-cholestasis-by-impairing-expression-and-localization-of-bile-salt-transporters
#1
Leiming Liu, Lingling Zhang, Lin Zhang, Fan Yang, Xudong Zhu, Zhongjie Lu, Yeming Yang, Haiqi Lu, Lifeng Feng, Zhuo Wang, Hui Chen, Sheng Yan, Lin Wang, Zhenyu Ju, Hongchuan Jin, Xianjun Zhu
Mutations in ATP8B1 or ATP11C (members of P4-type ATPases) cause progressive familial intrahepatic cholestasis type 1 (PFIC1) in human or intrahepatic cholestasis in mice. Transmembrane protein 30A (TMEM30A), as a β-subunit, is essential for the function of P4-type ATPases including ATP8B1 and ATP11C, however, its role in the etiology of cholestasis remains poorly understood. To investigate the function of TMEM30A in bile salt homeostasis, we developed Tmem30a liver-specific knockout (LKO) mice. Tmem30a LKO mice suffered from hyperbilirubinaemia, hypercholanaemia, inflammatory infiltration, ductular proliferation and liver fibrosis...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28889961/analysis-of-the-reversibility-of-biliary-cirrhosis-in-young-rats-submitted-to-biliary-obstruction
#2
Maria Julia de Aro Braz, Leonardo Ervolino Corbi, Ana Cristina Aoun Tannuri, Maria Cecília Mendonça Coelho, Josiane Oliveira Gonçalves, Suellen Serafini, Uenis Tannuri
BACKGROUND/PURPOSE: Biliary atresia and other liver biliary obstructions are relevant conditions in pediatric surgery due to their progression to biliary cirrhosis and indication for liver transplantation. It is known that the period during which biliary obstruction persists determines the development of cirrhosis and its reversibility after a biliary drainage procedure. However, no time or histological markers of biliary cirrhosis reversibility have been established. MATERIALS AND METHODS: One hundred and twenty-nine young Wistar rats underwent surgery for ligation of the common bile duct and were maintained until 8weeks...
August 24, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28888832/ageing-sensitized-by-ipla2%C3%AE-deficiency-induces-liver-fibrosis-and-intestinal-atrophy-involving-suppression-of-homeostatic-genes-and-alteration-of-intestinal-lipids-and-bile-acids
#3
Li Jiao, Hongying Gan-Schreier, Xingya Zhu, Wang Wei, Sabine Tuma-Kellner, Gerhard Liebisch, Wolfgang Stremmel, WaleeChamulitrat
Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA2β is a homeostatic PLA2 by playing a role in phospholipid metabolism and remodeling. Global iPLA2β(-/-) mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887231/therapeutic-activity-of-superoxide-dismutase-containing-enzymosomes-on-rat-liver-ischaemia-reperfusion-injury-followed-by-magnetic-resonance-microscopy
#4
Paulo Marcelino, H Susana Marinho, Maria Celeste Campos, Ana Rita Neves, Carla Real, Filipa S Fontes, Alexandra Carvalho, Gabriel Feio, M Bárbara F Martins, M Luísa Corvo
Liver ischaemia-reperfusion injury (IRI) may occur during hepatic surgery and is unavoidable in liver transplantation. Superoxide dismutase enzymosomes (SOD-enzymosomes), liposomes where SOD is at the liposomal surface expressing enzymatic activity in intact form without the need of liposomal disruption, were developed with the aim of having a better insight into its antioxidant therapeutic outcome in IRI. We also aimed at validating magnetic resonance microscopy (MRM) at 7T as a tool to follow IRI. SOD-enzymosomes were characterized and tested in a rat ischaemia-reperfusion model and the therapeutic outcome was compared with conventional long circulating SOD liposomes and free SOD using biochemical liver injury biomarkers, histology and MRM...
September 6, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28862262/centrilobular-ductular-reaction-correlates-with-fibrosis-stage-and-fibrosis-progression-in-non-alcoholic-steatohepatitis
#5
Lei Zhao, Maria Westerhoff, Rish K Pai, Won-Tak Choi, Zu-Hua Gao, John Hart
There is increasing interest in the role of ductular reaction as part of the pathogenesis and characteristic histology of non-alcoholic steatohepatitis. However, earlier studies did not separately assess the contribution of periportal and centrilobular zone ductular reaction over the spectrum of non-alcoholic steatohepatitis, and their clinical significance remains unclear. We herein analyzed the character of ductular reaction in each hepatic zone in non-alcoholic steatohepatitis biopsies and for the first time evaluated the prognostic value of ductular reaction in baseline biopsies as a predictor of progression of fibrosis in subsequent biopsies...
September 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#6
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28777941/cholangiocytes-no-longer-cinderellas-to-the-hepatic-regenerative-response
#7
Malcolm R Alison
Biliary ductal cells proliferate from the portal areas of chronically damaged livers, but their significance to regeneration has been controversial. A recent article in Nature by Raven et al. (2017) now shows that blocking hepatocyte replication is essential for the hepatic differentiation of ductular cells after liver damage.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28769978/ultrastructural-characteristics-of-rat-hepatic-oval-cells-and-their-intercellular-contacts-in-the-model-of-biliary-fibrosis-new-insights-into-experimental-liver-fibrogenesis
#8
Joanna Maria Lotowska, Maria Elzbieta Sobaniec-Lotowska, Dariusz Marek Lebensztejn, Urszula Daniluk, Piotr Sobaniec, Krzysztof Sendrowski, Jaroslaw Daniluk, Joanna Reszec, Wojciech Debek
PURPOSE: Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL). METHODS: The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks. RESULTS: Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28714273/%C3%AE-catenin-regulation-of-farnesoid-x-receptor-signaling-and-bile-acid-metabolism-during-murine-cholestasis
#9
Michael D Thompson, Akshata Moghe, Pamela Cornuet, Rebecca Marino, Jianmin Tian, Pengcheng Wang, Xiaochao Ma, Marc Abrams, Joseph Locker, Satdarshan P S Monga, Kari Nejak-Bowen
Cholestatic liver diseases result from impaired bile flow and are characterized by inflammation, atypical ductular proliferation (ADP), and fibrosis. The Wnt/β-catenin pathway plays a role in bile duct development, yet its role in cholestatic injury remains indeterminate. Liver-specific β-catenin knockout (KO) mice and wild-type (WT) littermates were subjected to cholestatic injury via bile duct ligation or short-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Intriguingly, KO exhibit a dramatic protection from liver injury, fibrosis, and ADP, which coincided with significantly decreased total hepatic bile acids (BA)...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28709963/animal-models-of-biliary-injury-and-altered-bile-acid-metabolism
#10
REVIEW
Valeria Mariotti, Mario Strazzabosco, Luca Fabris, Diego F Calvisi
In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28700576/cholangiocytes-act-as-facultative-liver-stem-cells-during-impaired-hepatocyte-regeneration
#11
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J Forbes
After liver injury, regeneration occurs through self-replication of hepatocytes. In severe liver injury, hepatocyte proliferation is impaired-a feature of human chronic liver disease. It is unclear whether other liver cell types can regenerate hepatocytes. Here we use two independent systems to impair hepatocyte proliferation during liver injury to evaluate the contribution of non-hepatocytes to parenchymal regeneration. First, loss of β1-integrin in hepatocytes with liver injury triggered a ductular reaction of cholangiocyte origin, with approximately 25% of hepatocytes being derived from a non-hepatocyte origin...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28688656/notch-signaling-promotes-ductular-reactions-in-biliary-atresia
#12
Jessica A Zagory, William Dietz, Alex Park, Michael Fenlon, Jiabo Xu, Sarah Utley, Nirmala Mavila, Kasper S Wang
BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative disease of the extrahepatic biliary tree and the most common cause of end-stage liver disease in children. BA is characterized by extensive intrahepatic proliferating ductular reactions that may contribute to biliary fibrosis. Lineage tracing during experimental cholestasis indicates that cells within ductular reactions derive from PROM1-expressing hepatic progenitor cells. Given the role of Notch signaling in normal biliary development, we hypothesize that activated Notch signaling promotes the formation of ductular reactions in BA...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28687948/role-of-hepatobiliary-scintigraphy-and-preoperative-liver-biopsy-for-exclusion-of-biliary-atresia-in-neonatal-cholestasis-syndrome
#13
Ankur Mandelia, Richa Lal, Nijagal Mutt
All diagnostic algorithms for Neonatal Cholestasis Syndrome (NCS) focus on differentiating numerous medical causes from Biliary Atresia (BA). No preoperative diagnostic algorithm has 100% diagnostic accuracy for BA and yet, timely diagnosis is crucial to optimize surgical outcome. Markers for high index of clinical suspicion for BA are: a "usually" well thriving infant with conjugated hyperbilirubinemia, raised gamma glutamyl transpeptidase, persistently "acholic" stools, firm hepatomegaly with dysmorphic, hypoplastic gall bladder...
July 8, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28652608/high-resolution-3d-visualization-of-ductular-proliferation-of-bile-duct-ligation-induced-liver-fibrosis-in-rats-using-x-ray-phase-contrast-computed-tomography
#14
Lili Qin, Xinyan Zhao, Jianbo Jian, Yuqing Zhao, Mengyu Sun, Chunhong Hu
X-ray phase-contrast computed tomography (PCCT) can provide excellent image contrast for soft tissues with small density differences, and it is particularly appropriate for three-dimensional (3D) visualization of accurate microstructures inside biological samples. In this study, the morphological structures of proliferative bile ductules (BDs) were visualized without contrast agents via PCCT with liver fibrosis samples induced by bile duct ligation (BDL) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group, 2-week and 6-week post-BDL groups...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637362/spindle-cell-mucoepidermoid-carcinoma-of-the-palatine-tonsil-with-crtc1-maml2-fusion-transcript-report-of-a-rare-case-in-a-17-year-old-boy-and-a-review-of-the-literature
#15
Giap Hean Goh, Chwee Ming Lim, Tomas Vanacek, Michal Michal, Fredrik Petersson
Mucoepidermoid carcinoma (MEC) with a predominant spindle cell composition occurring in the palatine tonsil is exceedingly rare. We present a case of a 17-year-old boy with an uncommon spindle cell variant of MEC arising in the palatine tonsil. Histologically, the tumor showed a solid, noncystic architecture and was composed of a predominant population of bland spindle to fusiform cells arranged in organoid nests with interspersed goblet cells and focal areas of ductular structures. Reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed the presence of a t(11;19) CRTC1-MAML2 gene fusion in this rare variant of MEC...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#16
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28627210/lactobacillus-rhamnosusgg-reduces-hepatic-fibrosis-in-a-model-of-chronic-liver-disease-in-rats
#17
Thais Ortiz Hammes, Renata Leke, Thayssa Dalla Costa Escobar, Laisa Beduschi Fracasso, Fabiola Schons Meyer, Michael Éverton Andrades, Themis Reverbel da Silveira
BACKGROUND: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. AIM: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. METHODS: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups)...
June 5, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/28614208/il-8-expression-in-granulocytic-epithelial-lesions-of-idiopathic-duct-centric-pancreatitis-type-2-autoimmune-pancreatitis
#18
Yuna Ku, Seung-Mo Hong, Kohei Fujikura, Sung Joo Kim, Masayuki Akita, Shiho Abe-Suzuki, Hideyuki Shiomi, Atsuhiro Masuda, Tomoo Itoh, Takeshi Azuma, Myung-Hwan Kim, Yoh Zen
Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0...
August 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28572084/ductular-and-proliferative-response-of-esophageal-submucosal-glands-in-a-porcine-model-of-esophageal-injury-and-repair
#19
Leandi Krüger, Liara M Gonzalez, Tiffany A Pridgen, Shannon J McCall, Richard J von Furstenberg, Ivan Harnden, Gwendolyn E Carnighan, Abigail M Cox, Anthony T Blikslager, Katherine S Garman
Esophageal injury is a risk factor for diseases such as Barrett's esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28562206/lipopolysaccharide-induces-the-differentiation-of-hepatic-progenitor-cells-into-myofibroblasts-via-activation-of-the-hedgehog-signaling-pathway
#20
Xiao-Rong Pan, Ying-Ying Jing, Wen-Ting Liu, Zhi-Peng Han, Rong Li, Yang Yang, Jing-Ni Zhu, Xiao-Yong Li, Pei-Pei Li, Li-Xin Wei
Normally, hepatic progenitor cells (HPCs) are activated and differentiate into hepatocytes or bile ductular cells to repair liver damage during liver injury. However, it remains controversial whether the abnormal differentiation of HPCs occurs under abnormal conditions. Lipopolysaccharide (LPS), a component of the microenvironment, promotes liver fibrosis. In the present study, HPCs promoted liver fibrosis in rats following carbon tetrachloride (CCl4) treatment. Meanwhile, the LPS level in the portal vein was elevated and played a primary role in the fate of HPCs...
July 18, 2017: Cell Cycle
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