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Hepatic hypoxia

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https://www.readbyqxmd.com/read/27932515/genotoxic-effect-of-iron-overload-and-disease-complications-in-transfused-%C3%AE-thalassaemic-patients
#1
Elisa Ferro, Giuseppa Visalli, Maria Angela La Rosa, Basilia Piraino, Rosa Civa, Gaetano Randazzo Papa, Angela Di Pietro
In previously reported studies, we observed significantly high genotoxicity biomarkers in regularly transfused thalassaemic patients, thus, in this study, we better investigated the genotoxic effect of iron overload and of thalassaemia complications, including their drug treatments. The assessment was performed in 64 regularly transfused thalassaemic patients using cytokinesis-block micronucleus and comet assays. All patients were splenectomised and undergoing iron chelation therapy. To reduce hypoxia-induced oxidative damage, the patients with haemoglobin levels <9...
December 8, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27924246/adenovirus-and-culture-negative-sepsis-in-a-preterm-neonate
#2
Mohannad Moallem, Eunkyung Song, Preeti Jaggi, Miriam R Conces, Adriana E Kajon, Pablo J Sánchez
Background Respiratory viral infections remain an underrecognized cause of morbidity and mortality among preterm infants in the neonatal intensive care unit (NICU). Case Report An eight day old, 650 gram birth weight, 23 weeks' gestational age female developed "culture-negative" sepsis manifested by respiratory deterioration, hypoxia, leukocytosis, and thrombocytopenia. She was diagnosed with pneumonia and hepatitis due to adenovirus HAdV-D (H29F9) by polymerase chain reaction (PCR) testing, but died at the age of 18 days despite treatment with cidofovir and immune globulin intravenous...
October 2016: American Journal of Perinatology Reports
https://www.readbyqxmd.com/read/27916083/-effects-of-chronic-intermittent-hypoxia-on-hepatic-function-and-protective-mechanism-of-adiponectin-in-rats
#3
R Xue, J Cao, X L Zhang, W X Ding, W J Wang, H P Huang
Objective: To explore the effect of chronic intermittent hypoxia (CIH) on rats hepatic function, and the protective mechanism of adiponectin (Ad). Methods: Sixty healthy male wistar rats were randomly divided into 4 groups: normal control (NC), NC+ Ad, CIH, and CIH+ Ad groups with 15 rats in each. The rats in CIH and CIH+ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC + Ad groups were housed with normal pressure air. The rats in the NC+ Ad and CIH+ Ad groups were additionally treated with an intravenous injection of Ad (10 μg), twice a week for 4 months...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27900258/adipocyte-specific-hypoxia-inducible-gene-2-promotes-fat-deposition-and-diet-induced-insulin-resistance
#4
Marina T DiStefano, Rachel J Roth Flach, Ozlem Senol-Cosar, Laura V Danai, Joseph V Virbasius, Sarah M Nicoloro, Juerg Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T Gupta, Jason K Kim, Michael P Czech
OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27880930/lactate-dehydrogenase-is-a-prognostic-indicator-in-patients-with-hepatocellular-carcinoma-treated-by-sorafenib-results-from-the-real-life-practice-in-hbv-endemic-area
#5
Mu-Xing Li, Hong Zhao, Xin-Yu Bi, Zhi-Yu Li, Xue-Song Yao, Huai Li, Zhen Huang, Yue Han, Jian-Guo Zhou, Jian-Jun Zhao, Ye-Fan Zhang, Dong-Bin Zhao, Jian-Qiang Cai
PURPOSE: Lactate dehydrogenase (LDH), which was an indirect marker of hypoxia, was a potentially prognostic factor in several malignancies. There is a lack of evidence about the prognostic value of serum LDH level in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment from hepatitis B virus endemic areas. MATERIALS AND METHODS: A total of 119 HBV-related HCC patients treated by sorafenib from a Chinese center were included into the study. They were categorized into 2 groups according to the cut-off value of pre-treatment LDH, which was determined by the time dependent receiver operating characteristics (ROC) curve for the overall survival...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27872855/partial-portal-vein-arterialization-attenuates-acute-bile-duct-injury-induced-by-hepatic-dearterialization-in-a-rat-model
#6
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/27866920/the-orphan-nuclear-receptor-coup-tfii-coordinates-hypoxia-independent-proangiogenic-responses-in-hepatic-stellate-cells
#7
Elisabetta Ceni, Tommaso Mello, Simone Polvani, Mireille Vasseur-Cognet, Mirko Tarocchi, Sara Tempesti, Duccio Cavalieri, Luca Beltrame, Marroncini Giada, Massimo Pinzani, Stefano Milani, Andrea Galli
BACKGROUND & AIMS: Hepatic stellate cells (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) is involved in HSC activation and in the multifunctional role of these cells during the response to liver injury...
November 17, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27837167/nrf2-activation-is-required-for-ligustrazine-to-inhibit-hepatic-steatosis-in-alcohol-preferring-mice-and-hepatocytes
#8
Chunfeng Lu, Wenxuan Xu, Jiangjuan Shao, Feng Zhang, Anping Chen, Shizhong Zheng
Hepatic steatosis is the most distinctive feature of alcoholic liver disease (ALD). Our previous in vivo study showed that ligustrazine, a major active alkaloid isolated from Ligusticum chuanxiong Hort, attenuated alcohol-induced hepatic steatosis and in vitro study revealed that nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation might be a prerequisite. This study was aimed to explore the in vivo function of Nrf2 in the protective effect of ligustrazine and illustrate downstream mechanisms. Nrf2 shRNA lentivirus was introduced to establish Nrf2-knockdown mice...
November 11, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27803767/lycopene-modulates-cellular-proliferation-glycolysis-and-hepatic-ultrastructure-during-hepatocellular-carcinoma
#9
Prachi Gupta, Nisha Bhatia, Mohinder Pal Bansal, Ashwani Koul
AIM: To investigate the effect of lycopene extracted from tomatoes (LycT) on ultrastructure, glycolytic enzymes, cell proliferation markers and hypoxia during N-Nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. METHODS: Female BALB/c mice were randomly divided into four groups: The Control, NDEA (200 mg NDEA/kg b.w. given i.p.), LycT (5 mg/kg b.w. given orally on alternate days) and LycT + NDEA group. The mRNA and protein expression of various cell proliferation markers (PCNA, Cyclin D1, and p21) were assessed by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively...
October 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27803295/strong-antineoplastic-effects-of-metformin-in-preclinical-models-of-liver-carcinogenesis
#10
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard van Beers, Sandrine Faivre, Pierre Bedossa, Valerie Paradis
Studies suggest that metformin, widely used for treating type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma, metformin may provide antitumoral effects  We evaluated the impact of metformin on tumor growth and visceral fat composition using relevant preclinical models of metabolic syndrome.  EXPERIMENTAL DESIGN: Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow-diet (SC), 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured hepatocellular carcinoma slices...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27780972/developmental-origins-of-nafld-a-womb-with-a-clue
#11
REVIEW
Stephanie R Wesolowski, Karim C El Kasmi, Karen R Jonscher, Jacob E Friedman
Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally...
October 26, 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27734596/longer-warm-ischemia-can-accelerate-tumor-growth-through-the-induction-of-hif-1%C3%AE-and-the-il-6-jak-stat3-signaling-pathway-in-a-rat-hepatocellular-carcinoma-model
#12
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 four 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...
December 2016: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/27713143/signaling-through-hepatocyte-vasopressin-receptor-1-protects-mouse-liver-from-ischemia-reperfusion-injury
#13
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
https://www.readbyqxmd.com/read/27711215/heparanase-overexpression-reduces-hepcidin-expression-affects-iron-homeostasis-and-alters-the-response-to-inflammation
#14
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
https://www.readbyqxmd.com/read/27702890/hypoxia-activated-cytotoxic-agent-tirapazamine-enhances-hepatic-artery-ligation-induced-killing-of-liver-tumor-in-hbx-transgenic-mice
#15
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 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27686097/hif-2%C3%AE-phosphorylation-by-ck1%C3%AE-promotes-erythropoietin-secretion-in-liver-cancer-cells-under-hypoxia
#16
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 (also known as EPAS1), involves post-translational modifications. Here, we demonstrate that casein kinase 1δ (CK1δ; also known as CSNK1D) phosphorylates HIF-2α at Ser383 and Thr528 in vitro We found that 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 the levels of HIF-2α protein expression...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27678302/adiponectin-protects-the-rats-liver-against-chronic-intermittent-hypoxia-induced-injury-through-amp-activated-protein-kinase-pathway
#17
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
https://www.readbyqxmd.com/read/27643670/thermal-injury-induced-hepatic-parenchymal-hypoperfusion-risk-of-hepatocellular-carcinoma-recurrence-after-radiofrequency-ablation
#18
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
https://www.readbyqxmd.com/read/27641628/a-mouse-model-of-alcoholic-liver-fibrosis-associated-acute-kidney-injury-identifies-key-molecular-pathways
#19
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
https://www.readbyqxmd.com/read/27638772/transarterial-embolization-combined-with-rna-interference-targeting-hypoxia-inducible-factor-1%C3%AE-for-hepatocellular-carcinoma-a-preliminary-study-of-rat-model
#20
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
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