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Hepatic hypoxia

Yuhei Hamaguchi, Akira Mori, Yasuhiro Fujimoto, Takashi Ito, Taku Iida, Shintaro Yagi, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
BACKGROUND: The present study aimed to investigate the impact of the duration of hepatic pedicle clamping (HPC) on tumor growth after major hepatectomy in a rat model. METHODS: Rats were divided into 4 groups according to the length of HPC during 70% partial hepatectomy followed by N1S1 tumor cell implantation: group 1, without HPC; group 2, with 5-min HPC; group 3, 10-min HPC; and group 4, 15-min HPC. At three weeks after tumor cell implantation, liver tumor growth and its possible mechanisms were investigated...
October 13, 2016: Journal of Hepato-biliary-pancreatic Sciences
Xiqiang Liu, Gaojian Luo, Jingbo Jiang, Tonghui Ma, Xiaozhu Lin, Liping Jiang, Jilin Cheng, Ran Tao
: Terlipressin has been used extensively in the management of certain complications associated with end-stage liver diseases (ESLDs). In our pilot study, terlipressin treatment showed beneficial effects on liver function in patients with decompensated cirrhosis, however whether it plays a role in liver ischemia-reperfusion injury (IRI) remains unknown. Using a mouse nonlethal hepatic IR model, we found terlipressin administration significantly ameliorated IR-induced liver apoptosis, necrosis and inflammation...
October 4, 2016: Oncotarget
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
Wei-Hsiang Lin, Shiou-Hwei Yeh, Kun-Huei Yeh, Kai-Wei Chen, Ya-Wen Cheng, Tung-Hung Su, Ping Jao, Lin-Chun Ni, Pei-Jer Chen, Ding-Shinn Chen
Transarterial chemoembolization (TACE) is the main treatment for intermediate stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer classification because of its exclusive arterial blood supply. Although TACE achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon, and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ), a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which recapitulates transarterial embolization in mouse models, to enhance the efficacy of TACE...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Evanthia Pangou, Christina Befani, Ilias Mylonis, Martina Samiotaki, George Panayotou, George Simos, Panagiotis Liakos
Hypoxia Inducible Factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2α, involves post-translational modifications. Here, we demonstrate that casein kinase 1δ (CK1δ) phosphorylates HIF-2α at Ser383 and Thr528 in vitro Disruption of these phosphorylation sites and silencing or chemical inhibition of CK1δ reduced the expression of HIF-2 target genes and the secretion of erythropoietin (EPO) in two hepatic cancer cell lines, Huh7 and HepG2, without affecting levels of HIF-2α protein expression...
September 29, 2016: Journal of Cell Science
Wenxiao Ding, Qiang Zhang, Yanbin Dong, Ning Ding, Hanpeng Huang, Xianji Zhu, Sean Hutchinson, Xingya Gao, Xilong Zhang
This study was performed to assess the effect of chronic intermittent hypoxia (CIH) on the liver, the associated mechanisms and the potential therapeutic roles of adiponectin (Ad). Sixty rats were randomly assigned to four groups: the normal control (NC), NC and Ad supplement (NC + Ad), CIH, and CIH and Ad supplement (CIH + Ad) groups. The rats in the CIH and CIH + Ad groups were exposed to a hypoxic environment for 4 months. Rats in the NC + Ad and CIH + Ad groups were also treated with an intravenous injection of Ad (10 ug), twice a week...
September 28, 2016: Scientific Reports
Dong Ho Lee, Jeong Min Lee, Jung Hwan Yoon, Yoon Jun Kim, Joon Koo Han
Purpose To retrospectively evaluate whether thermal injury-induced hepatic parenchymal hypoperfusion can be a significant risk factor for tumor recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). Materials and Methods The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The study population comprised 130 patients (87 men, 43 women; mean age, 61.4 years ± 8.95; age range, 39-84 years) with single nodular HCCs smaller than 5 cm who underwent RFA between January 2011 and December 2012...
September 19, 2016: Radiology
Shinji Furuya, Grace A Chappell, Yasuhiro Iwata, Takeki Uehara, Yuki Kato, Hiroshi Kono, Ramon Bataller, Ivan Rusyn
Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl4)-induced fibrosis with chronic intra-gastric alcohol feeding...
November 1, 2016: Toxicology and Applied Pharmacology
Jia-Yan Ni, Lin-Feng Xu, Wei-Dong Wang, Qiao-Sheng Huang, Hong-Liang Sun, Yao-Ting Chen
PURPOSE: To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery...
September 16, 2016: Journal of Cancer Research and Clinical Oncology
Xiang Li, Dong Han, Zuhong Tian, Beilei Gao, Miaomiao Fan, Congye Li, Xiujuan Li, Yabin Wang, Sai Ma, Feng Cao
AIMS: Myocardial interstitial fibrosis is a major histologic landmark resulting in cardiac dysfunction after myocardial infarction (MI). Activation of cannabinoid receptor type II (CB2 receptor) have been demonstrated to reduce fibrosis in hepatic cirrhotic rat. However, the anti-fibrotic effect of CB2 receptor activation in infarcted hearts was still unclear. In this study, we aimed to investigate the effects of a CB2 receptor selective agonist AM1241 on myocardial fibrosis post MI in mice...
2016: Cellular Physiology and Biochemistry
Bin Liu, Xiaoli Su, Yan Zhang, Li Huang, Pinhua Pan, Chengping Hu
OBJECTIVE: To explore the effect of chronic intermittent hypoxia (CIH) on liver injury and to examine the expression of liver CXC chemokine ligand-10 (CXCL10) in the rats, and to explore the effect of N-acetylcysteine (NAC).
 METHODS: A total of 21 male SD rats were randomly divided into a control group, a CIH group and a CIH+NAC group (n=7 in each group). The control group exposed to normal gaseous environment, the other 2 groups were exposed to CIH for 5 weeks (8 h/d); the control group and the CIH group were given daily saline lavage, the CIH+NAC group daily received NAC solution...
August 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Haojun Yang, Haoming Zhou, Lin Zhuang, Xuehao Wang, Ling Lv
BACKGROUND: The G protein-coupled receptor TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA) receptor. TGR5-induced liver protection has been demonstrated during several liver diseases, except during ischemia/reperfusion injury (IRI). METHOD: Male adult wild-type and TGR5 knockout mice were subjected to liver partial warm ischemia/reperfusion. Hepatic injury was evaluated based on serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST)...
September 6, 2016: Liver Transplantation
Caroline R Alquist, Zbigniew M Szczepiorkowski, Nancy Dunbar
Babesiosis is an increasingly recognized disease which may benefit from therapeutic apheresis (Category II/Grade 2C). Vulnerable populations include the splenectomized, those aged >50, those with malignancies, and the immunocompromised. In the setting of parasite levels > 10%, significant anemia, renal impairment, pulmonary compromise, or hepatic dysfunction, RBC exchange can rapidly reduce parasite burdens and decrease the bioavailability of proinflammatory cytokines. No previous report has shown such a rapid rebound in parasitemia despite adequate organism removal...
September 1, 2016: Journal of Clinical Apheresis
Masayoshi Yada, Masayuki Miyazaki, Kenta Motomura, Akihide Masumoto, Makoto Nakamuta, Motoyuki Kohjima, Rie Sugimoto, Yoshifusa Aratake, Nobuhiko Higashi, Shusuke Morizono, Shinichiro Takao, Naoki Yamashita, Takeaki Satoh, Shinsaku Yamashita, Masami Kuniyoshi, Kazuhiro Kotoh
BACKGROUND: Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis...
August 2016: Journal of Gastrointestinal Oncology
Min Ni, Hui Fu, Fang Huang, Ting Zhao, Ji-Kuai Chen, Dong-Jie Li, Fu-Ming Shen
BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a complication of liver surgery. As much as 50% of hepatocytes undergo apoptosis within the first 24 h of reperfusion. The neurotransmitters of the vagus nerve can activate α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages. The function of Kupffer cells (KCs) determines HIR injury. We hypothesize that the vagus nerve could attenuate HIR-induced hepatocyte apoptosis by activating α7nAChR on KCs. METHODS: Hepatic vagotomized C57BL/6J mice, KC-eliminated C57BL/6J mice, and α7nAChR mice were used for HIR...
November 2016: Anesthesiology
Stephanie H Greco, Alejandro Torres-Hernandez, Aleksandr Kalabin, Clint Whiteman, Rae Rokosh, Sushma Ravirala, Atsuo Ochi, Johana Gutierrez, Muhammad Atif Salyana, Vishnu R Mani, Savitha V Nagaraj, Michael Deutsch, Lena Seifert, Donnele Daley, Rocky Barilla, Mautin Hundeyin, Yuriy Nikifrov, Karla Tejada, Bruce E Gelb, Steven C Katz, George Miller
Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jie Wang, Hyoung-Won Koh, Lu Zhou, Ui-Jin Bae, Hwa-Suk Lee, In Hyuk Bang, Sun-O Ka, Seon-Hee Oh, Eun Ju Bae, Byung-Hyun Park
: Sirtuin 2 (Sirt2) is known to negatively regulate anoxia-reoxygenation injury in myoblasts. Because we observed increased protein levels of Sirt2 in ischemia-reperfusion (I/R)-injured liver tissues, we here examined whether Sirt2 is protective or detrimental against hepatic I/R injury. We overexpressed Sirt2 in the liver of C57BL/6 mice using a Sirt2 adenovirus. Wild-type and Sirt2 knockout mice were subjected to a partial (70%) hepatic ischemia for 45 minutes, followed by various periods of reperfusion...
August 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Michael I Koukourakis, Alexandra Giatromanolaki, Christos E Zois, Dimitra Kalamida, Stamatia Pouliliou, Ilias V Karagounis, Tzu-Lan Yeh, Martine I Abboud, Timothy D W Claridge, Christopher J Schofield, Efthimios Sivridis, Costantinos Simopoulos, Savvas P Tokmakidis, Adrian L Harris
The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase...
2016: Scientific Reports
Shikha S Sundaram, Ann Halbower, Zhaoxing Pan, Kristen Robbins, Kelley E Capocelli, Jelena Klawitter, Colin T Shearn, Ronald J Sokol
BACKGROUND & AIMS: Oxidative stress is proposed as a central mediator in NAFLD pathogenesis, but the specific trigger for reactive oxygen species generation has not been clearly delineated. In addition, emerging evidence shows that obesity related obstructive sleep apnea (OSA) and nocturnal hypoxia are associated with NAFLD progression in adults. The aim of this study was to determine if OSA/nocturnal hypoxia-induced oxidative stress promotes the progression of pediatric NAFLD. METHODS: Subjects with biopsy proven NAFLD and lean controls were studied...
September 2016: Journal of Hepatology
Micah A Skeens, Jennifer McArthur, Ira M Cheifetz, Christine Duncan, Adrienne G Randolph, Joseph Stanek, Leslie Lehman, Rajinder Bajwa
Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Patients with VOD are often critically ill and require close collaboration between transplant physicians and intensivists. We surveyed members of a consortium of pediatric intensive care unit (PICU) and transplant physicians to assess variability in the self-reported approach to the diagnosis and management of VOD. An internet-based self-administered survey was sent to pediatric HSCT and PICU providers from September 2014 to February 2015...
October 2016: Biology of Blood and Marrow Transplantation
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