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https://www.readbyqxmd.com/read/29751359/bone-morphogenetic-protein-9-as-a-key-regulator-of-liver-progenitor-cells-in-ddc-induced-cholestatic-liver-injury
#1
Annalisa Addante, Cesáreo Roncero, Laura Almalé, Nerea Lazcanoiturburu, María García-Álvaro, Margarita Fernández, Julián Sanz, Seddik Hammad, Zeribe Chike Nwosu, Se-Jin Lee, Isabel Fabregat, Steven Dooley, Peter Ten Dijke, Blanca Herrera, Aránzazu Sánchez
BACKGROUND & AIMS: Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. METHODS: WT and BMP9KO mice were submitted to DDC diet...
May 11, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29743440/hepatic-histopathological-changes-and-dysfunction-in-primates-following-exposure-to-organic-arsenic-diphenylarsinic-acid
#2
Tomoyuki Masuda, Kazuhiro Ishii, Yukio Morishita, Nobuaki Iwasaki, Yasuyuki Shibata, Akira Tamaoka
Organic arsenic diphenylarsinic acid (DPAA[V]) accumulates at high concentrations in the liver of primates after its subchronic administration. However, no studies on the hepatic effects of organic arsenic compounds, including DPAA(V), on primates have been reported to date. To clarify the toxicokinetics of DPAA(V) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of DPAA(V) for 28 days. Four histopathological changes in the specimens were observed and pathologically evaluated...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29736914/sinus-like-dilatations-of-the-mammary-milk-ducts-ki67-expression-and-cd3-positive-t-lymphocyte-infiltration-in-the-mammary-gland-of-wild-european-rabbits-during-pregnancy-and-lactation
#3
Katherine Hughes, Christine J Watson
Sinus-like dilatations of the mammary duct are recognisable in the mammary gland of pregnant and lactating wild European rabbits. These dilatations exhibit a bilaminar epithelial lining, with luminal epithelial cells expressing basal and lateral E-cadherin. Occasional binucleated mammary epithelial cells are present in the luminal layer. Underlying the luminal epithelial cells is a basal layer of cytokeratin 14-positive cells, supported by a thin layer of fibrous tissue. Multi-segmental epithelial proliferation, as indicated by Ki67 expression, is apparent in the luminal epithelial cells, suggesting a capacity for division during pregnancy and lactation...
May 7, 2018: Journal of Anatomy
https://www.readbyqxmd.com/read/29709678/lysyl-oxidase-like-protein-2-loxl2-modules-barrier-function-in-cholangiocytes-in-cholestasis
#4
Marion J Pollheimer, Silvia Racedo, Amanda Mikels-Vigdal, Derek Marshall, Christopher Bowlus, Carolin Lackner, Tobias Madl, Tom H Karlsen, Johannes R Hov, Susan K Lyman, Joanne Adamkewicz, Victoria Smith, Emmanuel Moreau, Gernot Zollner, Tor Jacob Eide, Tatjana Stojakovic, Hubert Scharnagl, Hans-Jürgen Gruber, Rudolf E Stauber, Michael Trauner, Peter Fickert
BACKGROUND: The lysyl oxidase-like protein 2 (LOXL2) promotes stabilization of the extracellular matrix, chemotaxis, cell growth and cell mobility. We aimed to (i) identify stimuli of LOXL2 in cholangiopathies, (ii) characterize the effects of LOXL2 on biliary epithelial cells' (BECs) barrier function, (iii) compare LOXL2 expression in PSC, PBC, and disease controls, and (iv) to determine LOXL2 expression and cellular sources in 4 mouse models for cholangiopathies. METHODS: Cultured murine BECs were challenged with well-known triggers of cellular senescence, hypoxia, phospholipid-deficient Abcb4-/- mouse bile and chenodeoxycholic acid (CDCA) and investigated for LOXL2, SNAIL1 and E-cadherin expression and transepithelial electrical resistance (TEER) with and without LOX-inhibition...
April 27, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29673755/understanding-liver-regeneration-from-mechanisms-to-regenerative-medicine
#5
REVIEW
Hélène Gilgenkrantz, Alexandra Collin de l'Hortet
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities...
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29594193/expression-of-intrahepatic-cd3-cd4-and-cd8-t-cells-in-biliary-atresia
#6
Behairy E Behairy, Nermine Ehsan, Magdy Anwer, Alif Allam, Ibramem El-Henawy, Nesreen Abdel Hameed, Haidy M Zakaria
Aim of the study: Assessment of the expression of cluster of differentiation (CD)3, CD4, and CD8 T cells in biliary atresia (BA) cases in comparison to neonatal cholestasis other than BA. Material and methods: This study included 79 patients: 34 patients with BA (BA group) and 35 patients with neonatal cholestasis due to causes other than BA (cholestasis group), and 10 normal liver donor as a control group. Immunohistochemical staining or CD3, CD4, and CD8 T cells in liver tissues for the 3 groups were evaluated...
March 2018: Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/29559246/intrahepatic-cholangiocarcinoma-after-fontan-procedure-in-an-adult-with-visceral-heterotaxy
#7
Dehua Wang, Darren Marshall, Gruschen Veldtman, Anita Gupta, Andrew T Trout, Juan Villafane, Kevin Bove
Hepatic dysfunction, including development of hepatocellular carcinoma and other liver lesions has been increasingly reported following Fontan procedure for congenital heart disease. We report a unique case of intrahepatic cholangiocarcinoma 28 years after a Fontan procedure in a 31year old female with heterotaxy syndrome. The subcapsular mass-forming tumor was composed of poorly differentiated tumor cells arranged in small vague glandular or slit-lumen nests, and focally fused or anastomosing large trabecular patterns within the prominent fibrotic stroma...
March 15, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29558368/hmgb1-promotes-ductular-reaction-and-tumorigenesis-in-autophagy-deficient-livers
#8
Bilon Khambu, Nazmul Huda, Xiaoyun Chen, Daniel J Antoine, Yong Li, Guoli Dai, Ulrike A Köhler, Wei-Xing Zong, Satoshi Waguri, Sabine Werner, Tim D Oury, Zheng Dong, Xiao-Ming Yin
Autophagy is important for liver homeostasis and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here we reveal the role of highmobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPC) implicated in liver repair and regeneration. DR caused by hepatic toxic diets (DDC or CDE) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios...
March 20, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29558367/hmgb1-links-chronic-liver-injury-to-progenitor-responses-and-hepatocarcinogenesis
#9
Celine Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29535774/transplantation-of-human-amniotic-membrane-over-the-liver-surface-reduces-hepatic-fibrosis-in-a-cholestatic-model-in-young-rats
#10
M Garrido, C Escobar, C Zamora, C Rejas, J Varas, C Córdova, C Papuzinski, M Párraga, S San Martín, S Montedonico
Purpose: Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods: Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29523685/the-transcription-factor-klf5-is-essential-for-intrahepatic-biliary-epithelial-tissue-remodeling-after-cholestatic-liver-injury
#11
Hajime Okada, Minami Yamada, Kenji Kamimoto, Cindy Yuet-Yin Kok, Kota Kaneko, Masatsugu Ema, Atsushi Miyajima, Tohru Itoh
Under various conditions of liver injury, the intrahepatic biliary epithelium undergoes dynamic tissue expansion and remodeling, a process known as ductular reaction. Mouse models defective in inducing such a tissue-remodeling process are more susceptible to liver injury, suggesting a crucial role of this process in liver regeneration. However, the molecular mechanisms regulating the biliary epithelial cell (BEC) dynamics in the ductular reaction remain largely unclear. Here, we demonstrate that the transcription factor Krüppel-like factor 5 (Klf5) is highly enriched in mouse liver BECs and plays a key role in regulating the ductular reaction, specifically under cholestatic injury conditions...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29517421/development-of-a-polarized-pancreatic-ductular-cell-epithelia-for-physiological-studies
#12
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29516857/prominent-hepatic-ductular-reaction-induced-by-oschmarinella-macrorchis-in-a-hubbs-beaked-whale-mesoplodon-carlhubbsi-with-biological-notes
#13
Shotaro Nakagun, Akira Shiozaki, Mari Ochiai, Ayaka Matsuda, Yuko Tajima, Takashi Matsuishi, Kenichi Watanabe, Noriyuki Horiuchi, Yoshiyasu Kobayashi
Beaked whales are among the least known group of cetaceans, and information regarding their pathology and parasitology is especially scarce. We describe a case of significant parasitism by a trematode found in the liver of an adult male Hubbs' beaked whale Mesoplodon carlhubbsi that stranded in Hokkaido, Japan. Post-mortem examinations revealed a localised area of discolouration restricted to the hilar region of the left hepatic lobe, where spindle-shaped trematodes occupied the dilated and hypertrophic bile ducts...
March 5, 2018: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/29507906/interleukins-17-and-27-promote-liver-regeneration-by-sequentially-inducing-progenitor-cell-expansion-and-differentiation
#14
Adrien Guillot, Imène Gasmi, Arthur Brouillet, Yeni Ait-Ahmed, Julien Calderaro, Isaac Ruiz, Bin Gao, Sophie Lotersztajn, Jean-Michel Pawlotsky, Fouad Lafdil
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other...
March 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29507901/a-novel-transforming-growth-factor-beta-induced-long-noncoding-rna-promotes-an-inflammatory-microenvironment-in-human-intrahepatic-cholangiocarcinoma
#15
Aude Merdrignac, Gaëlle Angenard, Coralie Allain, Kilian Petitjean, Damien Bergeat, Pascale Bellaud, Allain Fautrel, Bruno Turlin, Bruno Clément, Steven Dooley, Laurent Sulpice, Karim Boudjema, Cédric Coulouarn
Intrahepatic cholangiocarcinoma (iCCA) is a deadly liver primary cancer associated with poor prognosis and limited therapeutic opportunities. Active transforming growth factor beta (TGFβ) signaling is a hallmark of the iCCA microenvironment. However, the impact of TGFβ on the transcriptome of iCCA tumor cells has been poorly investigated. Here, we have identified a specific TGFβ signature of genes commonly deregulated in iCCA cell lines, namely HuCCT1 and Huh28. Novel coding and noncoding TGFβ targets were identified, including a TGFβ-induced long noncoding RNA (TLINC), formerly known as cancer susceptibility candidate 15 (CASC15)...
March 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29505766/a-case-of-syphilitic-hepatitis-in-an-hiv-infected-patient
#16
Margarita N German, Kristina A Matkowskyj, Robert J Hoffman, Parul D Agarwal
While the incidence of syphilis has been persistently on the rise in the United States, hepatitis as a complication of early syphilis is relatively uncommon. We present a case of a 51-year-old homosexual, HIV-positive male who presented with acute cholestatic hepatitis with a predominantly elevated alkaline phosphatase. After lab studies and imaging were unrevealing, a liver biopsy was performed that showed expanded portal tracts with a predominantly lymphoplasmacytic infiltrate and prominent bile ductular proliferation with periductal neutrophils...
March 2, 2018: Human Pathology
https://www.readbyqxmd.com/read/29491615/benign-lymphoepithelial-cyst-of-parotid-gland-review-and-case-report
#17
Jaya Joshi, Sonalee Shah, Deepak Agarwal, Ankit Khasgiwal
Benign lymphoepithelial cyst (BLC), also known as branchial cyst, is an infrequent lesion usually occurs in the parotid gland or the lateral cervical area including lymph nodes. It occurs due to the process of lymphocyte-induced cystic ductular dilatation and is always diagnosed postoperatively by histopathological examination (HPE). These dysontogenetic lesions are usually found in the lateral neck but can also be located in the salivary glands, mostly in the parotids. A 35-year-old male reported to Government Dental College, Indore, before 3 years, with a soft, nontender, gradually increasing, compressible diffuse swelling involving the left parotid gland for the last 9-10 months of size 3...
January 2018: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/29464551/immunohistochemical-assessment-of-the-expression-of-biliary-transportation-proteins-mrp2-and-mrp3-in-hepatocellular-carcinoma-and-in-cholangiocarcinoma
#18
Cinthya Santos Cirqueira, Aloisio Sousa Felipe-Silva, Alda Wakamatsu, Lidiane Vieira Marins, Eziel Cavalcanti Rocha, Evandro Sobroza de Mello, Venâncio Avancini Ferreira Alves
Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays...
February 20, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29424576/immunohistochemical-and-electron-microscopic-morphometric-image-analysis-of-hepatocellular-carcinoma-in-association-of-hcv-infection
#19
Sarah Hassan, Soheir S Mansy, Sahar A Tabak, Ahmed S AbdelFattah, Ahmed M Abdel-Aziz, Olfat Hamam, Mohammed I Seleem, Amr Abdelaal
Early detection of hepatocellular carcinoma (HCC) is crucial for successful therapy. The present work examined the value of ultrastructural morphometric image analysis of hepatocyte nuclei in patients with chronic hepatitis C virus (HCV) versus HCC cases with chronic HCV and the corresponding surgical tumor-free safe margins (TFMs), to highlight any early predictive signs of neoplastic cellular transformation. This work also performed an immunohistochemical assessment of cytokeratin 19 (CK19) and Ki-67-positive cells to visualize any associated proliferative activity in the examined groups...
March 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29415686/prenatal-and-accurate-perinatal-diagnosis-of-type-2-h-or-ductular-duplicate-gallbladder
#20
Umberto Maggi, Giorgio Farris, Alessandra Carnevali, Irene Borzani, Paola Clerici, Massimo Agosti, Giorgio Rossi, Ernesto Leva
BACKGROUND: Double gallbladder is a rare biliary anomaly. Perinatal diagnosis of the disorder has been reported in only 6 cases, and in 5 of them the diagnosis was based on ultrasound imaging only. However, the ultrasound technique alone does not provide a sufficiently precise description of cystic ducts and biliary anatomy, an information that is crucial for a correct classification and for a possible future surgery. CASE PRESENTATION: At 21 weeks of gestational age of an uneventful pregnancy in a 38 year old primipara mother, a routine ultrasound screening detected a biliary anomaly in the fetus suggestive of a double gallbladder...
February 7, 2018: BMC Pediatrics
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