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https://www.readbyqxmd.com/read/29454797/alterations-in-intestinal-microbiota-lead-to-production-of-interleukin-17-by-intrahepatic-%C3%AE-%C3%AE-t-cell-receptor-positive-cells-and-pathogenesis-of-cholestatic-liver-disease
#1
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ATP binding cassette subfamily B member 4 gene (ABCB4 or MDR2) locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin 17 (IL17), yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29452147/combination-of-kras-activation-and-pten-deletion-contributes-to-murine-hepatopancreatic-ductal-malignancy
#2
Yun-Kai Lin, Zheng Fang, Tian-Yi Jiang, Zheng-Hua Wan, Yu-Fei Pan, Yun-Han Ma, Yuan-Yuan Shi, Ye-Xiong Tan, Li-Wei Dong, Yong-Jie Zhang, Hong-Yang Wang
Kras mutations are among the most common genetic abnormalities in human neoplasms, including cholangiocarcinomas, pancreatic cancer and colon cancer. PTEN has previously been associated with cholangiocarcinoma development in murine models. Here, we have established novel mouse models of neoplasms by liver-specific and biliary-pancreatic Kras activation and PTEN deletion. By liver-specific disruption of PTEN and activation of Kras in mice caused rapid development of intrahepatic biliary epithelial proliferative lesions (Intrahepatic cholangiocarcinoma, ICC), which progress through dysplasia to invasive carcinoma...
February 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29445068/lower-plasma-levels-of-il-35-in-patients-with-primary-biliary-cirrhosis
#3
Tengda Li, Yuanlan Huang, Peng Liu, Yun Liu, Jie Guo, Weiwei Zhang, Mingli Gu, Cheng Qian, Anmei Deng
Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29438852/transcriptome-analysis-to-assess-the-cholestatic-hepatotoxicity-induced-by-polygoni-multiflori-radix-up-regulation-of-key-enzymes-of-cholesterol-and-bile-acid-biosynthesis
#4
Li-Long Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Yi-Sheng Lai, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. Cholestasis often occurs in PMR-induced hepatotoxicity in clinical medicine, but the exact mechanism is not completely understood. An RNA-Seq method was employed, in the present study, to explore the molecular mechanism of cholestatic liver injury induced by PMR, characterized by the hepatic transcriptional response in rats exposed to 1 and 20 g/kg PMR for 90 days...
February 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29438839/sirtuin7-has-an-oncogenic-potential-via-promoting-the-growth-of-cholangiocarcinoma-cells
#5
Wenzhi Li, Zhe Sun, Chen Chen, Lin Wang, Zhimin Geng, Jie Tao
Accumulating evidence indicates that sirtuin7 (SIRT7) plays an oncogenic role in the main types of liver cancer, hepatocellular carcinoma (HCC). Nevertheless, the clinical significance of SIRT7 and its role in cholangiocarcinoma (CCA) is largely undiscovered. Here, we found that SIRT7 displayed higher expression in CCA tissues compared to intrahepatic normal bile duct and surrounding liver tissues based on The Cancer Genome Atlas (TCGA) data. Our data further confirmed that SIRT7 was overexpressed in CCA patient tissues and cell lines...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29437549/hepatic-and-renal-histology-and-mercury-concentrations-of-north-west-and-north-east-greenland-narwhals-monodon-monoceros
#6
Christian Sonne, Pall S Leifsson, Jens Søndergaard, Rune Dietz
Narwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males)...
February 13, 2018: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/29434696/tmem16a-regulates-portal-vein-smooth-muscle-cell-proliferation-in-portal-hypertension
#7
Xi Zeng, Ping Huang, Mingkai Chen, Shiqian Liu, Nannan Wu, Fang Wang, Jing Zhang
The aim of the present study was to elucidate the effect of transmembrane protein 16A (TMEM16A) on portal vein smooth muscle cell (PVSMC) proliferation associated with portal vein remodeling in portal hypertension (PHT). Sprague-Dawley rats were subjected to bile duct ligation to establish a rat model of liver cirrhosis and PHT. Sham-operated animals served as controls. At 8 weeks after bile duct ligation, the extent of liver fibrosis and the portal vein wall thickness were assessed using hematoxylin-eosin staining...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434290/induction-of-differentiation-of-intrahepatic-cholangiocarcinoma-cells-to-functional-hepatocytes-using-an-organoid-culture-system
#8
Yoshimasa Saito, Toshiaki Nakaoka, Toshihide Muramatsu, Hidenori Ojima, Aoi Sukeda, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Aya Kitahara, Toshiro Sato, Yae Kanai, Hidetsugu Saito
Intrahepatic cholangiocarcinoma (IHCC) is a highly aggressive malignancy with a poor prognosis. It is thought to originate from cholangiocytes, which are the component cells of intrahepatic bile ducts. However, as patients with viral hepatitis often develop IHCC, it has been suggested that transformed hepatocytes may play a role in IHCC development. To investigate whether IHCC cells can be converted to functional hepatocytes, we established organoids derived from human IHCC and cultured them under conditions suitable for hepatocyte differentiation...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433876/autogenous-hepatic-tissue-transplantation-into-the-omentum-in-a-novel-ectopic-liver-regeneration-murine-model
#9
Francisco Igor Macedo, Joseph J Eid, Milessa Decker, Barry Herschman, Edsa Negussie, Vijay K Mittal
BACKGROUND: Liver regeneration involves hyperplasia and hypertrophy of hepatic cells. The capacity of macroscopic liver tissue to regenerate in ectopic sites is unknown. We aim to develop a novel in vivo model of ectopic liver survivability and regeneration and assess its functionality. METHODS: Adult male Sprague-Dawley rats (n = 23) were divided into four groups: (1) single-stage (SS) group, wedge liver resection was performed, and the parenchyma was directly implanted into the omentum; (2) double-stage (DS) group, omentum pedicle was transposed over the left hepatic lobe followed by wedge liver resection along with omental flap; (3) Biogel + DS group, rats received intraperitoneal injection of inert polymer particles prior to DS; (4) Biogel + DS + portal vein ligation (PVL) group, Biogel + DS rats underwent subsequent PVL...
March 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29428971/emergence-of-anti-mitochondrial-m2-antibody-in-patient-with-angioimmunoblastic-t-cell-lymphoma
#10
Shun-Ichi Wakabayashi, Takefumi Kimura, Naoki Tanaka, Satoru Joshita, Kazuhito Kawata, Takeji Umemura, Yuki Hiroshima, Hiromitsu Mori, Hikaru Kobayashi, Shuichi Wada, Eiji Tanaka
A 68-year-old woman was referred to our hospital due to fever and rash on the neck and extremities. Laboratory findings revealed hepatic dysfunction and positivity for anti-mitochondrial M2 antibody (AMA-M2). Hepatosplenomegaly and systemic lymphadenopathy were detected by enhanced computed tomography. One week after her first visit, hypoxemia, ascites, and Coomb test-positive autoimmune hemolytic anemia had newly appeared in addition to worsened fever, hepatosplenomegaly, and lymphadenopathy. Results of axillary lymph node, skin, and bone-marrow biopsies led to the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), for which CEPP therapy (cyclophosphamide, etoposide, procarbazine, and prednisolone) was initiated...
February 10, 2018: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/29428575/s-adenosylmethionine-attenuates-bile-duct-early-warm-ischemia-reperfusion-injury-after-rat-liver-transplantation
#11
Yong Tang, Hongpeng Chu, Guojun Cao, Xiaolong Du, Xiaobo Min, Chidan Wan
Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation...
February 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29414666/dexamethasone-restores-transforming-growth-factor-%C3%AE-activated-kinase-1-expression-and-phagocytosis-activity-of-kupffer-cells-in-cholestatic-liver-injury
#12
Chih-Sung Hsieh, Jiin-Haur Chuang, Ming-Huei Chou, Ying-Hsien Kao
The role of transforming growth factor-β activated kinase 1 (TAK1) in modulating the function of Kupffer cells (KCs) within cholestatic livers remains unclear. This study examined the immunopharmacological action of dexamethasone (DEX) in modulating hepatic TAK1 expression and related signaling activity in a rat model of bile duct ligation-mimicked obstructive jaundice. The in vitro effects of DEX on porcine biliary extract (PBE)-modulated gene expression and phagocytosis of KCs were examined using a rat alveolar macrophage cell line (NR8383 cells)...
February 4, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29408314/fibroblast-growth-factor-receptor-inhibition-induces-loss-of-matrix-mcl1-and-necrosis-in-cholangiocarcinoma
#13
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia1 (MCL1), a prosurvival member of the BCL2 protein family, plays a pivotal role in human cholangiocarcinoma (CCA) cell survival. We have previously reported that fibroblast growth factor receptor (FGFR) signaling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
February 2, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29404441/the-role-of-human-cytochrome-p450-2e1-in-liver-inflammation-and-fibrosis
#14
Jun Xu, Hsiao-Yen Ma, Shuang Liang, Mengxi Sun, Gabriel Karin, Yukinori Koyama, Ronglin Hu, Oswald Quehenberger, Nicholas O Davidson, Edward A Dennis, Tatiana Kisseleva, David A Brenner
Cytochrome P450 2E1 ( CYP2E1 ) plays an important role in alcohol and toxin metabolism by catalyzing the conversion of substrates into more polar metabolites and producing reactive oxygen species. Reactive oxygen species-induced oxidative stress promotes hepatocyte injury and death, which in turn induces inflammation, activation of hepatic stellate cells, and liver fibrosis. Here, we analyzed mice expressing only the human CYP2E1 gene (hCYP2E1) to determine differences in hCYP2E1 versus endogenous mouse Cyp2e1 function with different liver injuries...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29403081/hepatotoxicity-of-immune-checkpoint-inhibitors-a-histology-study-of-seven-cases-in-comparison-with-autoimmune-hepatitis-and-idiosyncratic-drug-induced-liver-injury
#15
Yoh Zen, Matthew M Yeh
The adverse effects of immune checkpoint inhibitors in various organs may be attributed to immune-mediated processes triggered by disrupted self-tolerance; however, it remains unclear whether they are similar or dissimilar to classic organ-specific autoimmune diseases. The present study aimed to compare clinicopathologic features between checkpoint inhibitor-induced liver injury and acutely presenting autoimmune hepatitis or idiosyncratic drug-induced liver injury. Seven patients treated with nivolumab (n = 5) or ipilimumab (n = 2) presented with liver dysfunction a median of 41 days (range 21-120) after the initiation of immunotherapy...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29394807/-a-case-of-successful-adjuvant-surgery-for-the-pancreas-head-cancer-with-peritoneal-metastasis
#16
Yukie Kyakumoto, Tatsuyuki Takadate, Masamichi Mizuma, Tatsuo Hata, Masahiro Iseki, Hideo Ohtsuka, Naoaki Sakata, Kei Nakagawa, Takanori Morikawa, Hiroki Hayashi, Fuyuhiko Motoi, Takeshi Naitoh, Atsushi Kanno, Tooru Shimosegawa, Michiaki Unno
We report a case of the pancreas head cancer with peritoneal metastasis, which was resected curatively after chemotherapy. A6 6-year-old male was referred to our hospital for the treatment of biliary stenosis. The serum CA19-9 level was elevated and abdominal CT scan showed stenosis of distal bile duct. By laparotomy, we noticed mass in the head of the pancreas with 8mm of the seeding nodule in a diameter at jejunal mesentery which was diagnosed as adenocarcinoma by intraoperative frozen sections. Therefore, the patient was diagnosed as pancreas head cancer with peritoneal metastasis...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29392752/increased-expression-of-senescence-associated-cell-cycle-regulators-in-the-progression-of-biliary-atresia-an-immunohistochemical-study
#17
Motoko Sasaki, Fang-Ying Kuo, Chao-Cheng Huang, Paul E Swanson, Chao-Long Chen, Jiin-Haur Chuang, Matthew M Yeh
AIMS: Cellular senescence plays a role in tumor suppression and in the pathogenesis of various non-neoplastic diseases, including primary biliary cholangitis and other adult cholangiopathies. Less is known about the role of cellular senescence in cholangiopathies in children. With that in mind, we examined the expression of senescence-associated cell cycle regulators in biliary atresia, the most common form of pediatric obliterative cholangiopathy. METHODS AND RESULTS: The expression of s senescence-associated cell cycle regulators (p16Ink4a and p21WAF1/Cip1 ) and a ductular reaction related marker (neural cell adhesion molecule - NCAM), was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia (n=80; including 23 samples at the time of Kasai-procedure (KP) and 63 obtained from the explanted liver (LT) [6 cases with samples at both surgical stages of disease]) and from appropriate controls (n=17)...
February 2, 2018: Histopathology
https://www.readbyqxmd.com/read/29388792/transcription-factor-gata6-a-novel-marker-and-putative-inducer-of-ductal-metaplasia-in-biliary-atresia
#18
Tea Soini, Marjut Pihlajoki, Noora Andersson, Jouko Lohi, Kari A Huppert, David A Rudnick, Stacey S Huppert, David B Wilson, Mikko P Pakarinen, Markku Heikinheimo
Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive liver fibrosis. To gain insights into the pathophysiology of BA, we focused attention on GATA6, a transcription factor implicated in biliary development. Early in fetal development GATA6 expression is evident in cholangiocytes and hepatocytes, but by late gestation it is extinguished in hepatocytes. Utilizing a unique set of BA liver samples collected before and after successful portoenterostomy (PE), we found that GATA6 expression is markedly upregulated in hepatocytes of patients with BA compared to healthy and cholestatic disease controls...
February 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29383175/apancreatic-pigs-cloned-using-pdx1-disrupted-fibroblasts-created-via-talen-mediated-mutagenesis
#19
Jin-Dan Kang, Hyojin Kim, Long Jin, Qing Guo, Cheng-Du Cui, Wen-Xue Li, Seokjoong Kim, Jin-Soo Kim, Xi-Jun Yin
Pancreatic and duodenal homeobox 1 (PDX1) plays a crucial role in pancreas development, β-cell differentiation, and maintenance of mature β-cell function. In this study, we designed a strategy to produce PDX1-knockout (KO) pigs. A transcription activator-like effector nuclease (TALEN) pair targeting exon 1 of the swine PDX1 gene was constructed. Porcine fetal fibroblasts (PFFs) were transfected with the TALEN plasmids plus a surrogate reporter plasmid. PDX1-mutated PFFs were enriched by magnetic separation and used to produce homozygous PDX1-KO pigs via a two-step somatic cell nuclear transfer (SCNT) cloning process...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29380119/granular-cell-tumor-of-the-pancreas-diagnosed-by-endoscopic-ultrasound-guided-fine-needle-aspiration
#20
Koji Takahashi, Rintaro Mikata, Toshio Tsuyuguchi, Junichiro Kumagai, Masato Nakamura, Yotaro Iino, Ayako Shingyoji, Mutsumi Yamato, Hiroshi Ohyama, Yuko Kusakabe, Shin Yasui, Harutoshi Sugiyama, Takashi Kishimoto, Yukio Nakatani, Naoya Kato
A 68-year-old woman was referred to our hospital for the treatment of bile duct stone, pancreatic tumor, and pancreatic cysts. First, bile duct stone was removed using endoscopic retrograde cholangiopancreatography. By abdominal contrast-enhanced computed tomography, a 12-mm diameter tumor was found in the pancreatic body. The tumor was isodense compared with the surrounding pancreatic parenchyma in the non-contrast phase and poorly enhanced in the arterial phase; it exhibited gradual enhancement from the portal vein phase to the late phase...
January 27, 2018: Clinical Journal of Gastroenterology
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