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Hepatic hypoxia

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https://www.readbyqxmd.com/read/28104753/the-effect-of-adrenal-medullectomy-on-metabolic-responses-to-chronic-intermittent-hypoxia-in-the-frequently-sampled-intravenous-glucose-tolerance-test
#1
Mi-Kyung Shin, Woobum Han, Hoon Joo, Shannon Bevans-Fonti, Masakazu Shiota, Darko Stefanovski, Vsevolod Y Polotsky
Obstructive sleep apnea is associated with type 2 diabetes. We have previously developed a mouse model of intermittent hypoxia (IH) mimicking oxyhemoglobin desaturations in patients with sleep apnea and have shown that IH increases fasting glucose, hepatic glucose output, and plasma catecholamines. We hypothesize that adrenal medulla modulates glucose responses to IH, and that such responses can be prevented by adrenal medullectomy. We performed adrenal medullectomy or sham surgery in lean C57BL/6J mice, which were exposed to IH or intermittent air (control) for 4 weeks followed by the frequently sampled intravenous glucose tolerance test (FSIVGTT) in unanesthetized unrestrained animals...
January 19, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#2
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28075452/a-novel-pathway-in-nsclc-cells-mir%C3%A2-191-targeting-nfia-is-induced-by-chronic-hypoxia-and-promotes-cell-proliferation-and-migration
#3
Jia Zhao, Cheng-Rui Qiao, Zheng Ding, Yin-Liang Sheng, Xiang-Nan Li, Yang Yang, Deng-Yan Zhu, Chun-Yang Zhang, Dong-Lei Liu, Kai Wu, Song Zhao
MicroRNAs (miRs) have emerged as being important in cancer biology. miR‑191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)‑1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR‑191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non‑small cell lung cancer (NSCLC) cells in patients in vivo...
January 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28066916/ammonia-mediates-cortical-hemichannel-dysfunction-in-rodent-models-of-chronic-liver-disease
#4
Anna Hadjihambi, Francesco De Chiara, Patrick S Hosford, Abeba Habtetion, Anastassios Karagiannis, Nathan Davies, Alexander V Gourine, Rajiv Jalan
: The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte-neuron lactate shuttle hypothesis suggests that neuronal activity is fuelled (at least in part) by lactate provided by neighbouring astrocytes...
January 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signaling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#5
Feng Zhang, Meng Hao, Huanhuan Jin, Zhen Yao, Naqi Lian, Li Wu, Jiangjuan Shao, Anping Chen, Shizhong Zheng
BACKGROUND AND PURPOSE: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signaling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were intoxicated with carbon tetrachloride for in vivo evaluation of hepatic angiogenesis and fibrotic injury. Diversified molecular approaches including real-time PCR, Western blot, luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay, and co-immunoprecipitation were used to investigate the underlying mechanisms in vitro...
January 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28051796/%C3%A2-differences-in-hepatic-expression-of-iron-inflammation-and-stress-related-genes-in-patients-with-nonalcoholic-steatohepatitis
#6
Priya Handa, Akhila L Vemulakonda, Bryan D Maliken, Vicki Morgan-Stevenson, James E Nelson, Barjinder K Dhillon, Kelly A Hennessey, Rohit Gupta, Matthew M Yeh, Kris V Kowdley
 Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28030556/hepatocyte-hypoxia-inducible-factor-1-mediates-the-development-of-liver-fibrosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#7
Omar A Mesarwi, Mi-Kyung Shin, Shannon Bevans-Fonti, Christina Schlesinger, Janet Shaw, Vsevolod Y Polotsky
BACKGROUND: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis...
2016: PloS One
https://www.readbyqxmd.com/read/27999186/lhbs-can-elevate-the-expression-of-mdr1-through-hif-1%C3%AE-in-patients-with-chb-infection-a-comparative-proteomic-study
#8
Shiying Li, Yixuan Yang, Xiangchun Ding, Min Yang, Sha She, Hong Peng, Xiaoming Xu, Xiaoping Ran, Sanglin Li, Peng Hu, Huaidong Hu, Dazhi Zhang, Hong Ren
BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). To gain a better understanding of the pathogenesis of HBV infection, this study aimed to investigate the differentially expressed proteins (DEPs) in liver tissues from patients with chronic hepatitis B (CHB) infection. RESULTS: Seventy-one DEPs were identified. Overexpression of multi-drug resistance protein 1 (MDR1) was validated by RT-qPCR and western blot analyses...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27941931/in-vivo-functional-dissection-of-a-context-dependent-role-for-hif1%C3%AE-in-pancreatic-tumorigenesis
#9
T Cheng, Z Jian, K Li, S Raulefs, I Regel, S Shen, X Zou, J Ruland, G O Ceyhan, H Friess, C W Michalski, J Kleeff, B Kong
Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27938560/-effect-of-targeted-inhibition-of-hypoxia-inducible-factor-1%C3%AE-by-3-5-hydroxymethyl-2-furyl-1-benzylindazole-on-the-progression-of-non-alcoholic-fatty-liver-disease-in-rats
#10
W D Shen, W Zhang, Q H Xu, P F Liu
Objective: To investigate the effect of targeted inhibition of hypoxia-inducible factor-1α (HIF-1α) by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on the progression of non-alcoholic fat liver diseases (NAFLD) in rats. Methods: A total of 72 male Sprague-Dawley rats were randomly divided into normal group, model group, and intervention group, and the rats were given high-fat feed to establish the rat model of fatty liver disease. After the establishment of the model, the rats in the intervention group were given intraperitoneally injected YC-1 (at a dose of 2 mg/kg) every two weeks and were observed at 4, 8, 12, and 16 weeks...
October 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27932515/genotoxic-effect-of-iron-overload-and-disease-complications-in-transfused-%C3%AE-thalassaemic-patients
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
Elisabetta Ceni, Tommaso Mello, Simone Polvani, Mireille Vasseur-Cognet, Mirko Tarocchi, Sara Tempesti, Duccio Cavalieri, Luca Beltrame, Giada Marroncini, 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
#18
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
#19
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
#20
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard E Van Beers, Sandrine Faivre, Pierre Bedossa, Valérie Paradis
Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices...
January 1, 2017: Clinical Science (1979-)
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