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Hepatic hypoxia

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https://www.readbyqxmd.com/read/28280902/ginsenoside-rg5-attenuates-hepatic-glucagon-response-via-suppression-of-succinate-associated-hif-1%C3%AE-induction-in-hfd-fed-mice
#1
Na Xiao, Meng-Die Lou, Yi-Tong Lu, Le-Le Yang, Qun Liu, Baolin Liu, Lian-Wen Qi, Ping Li
AIMS/HYPOTHESIS: Ginsenosides regulate glucose homeostasis. This study investigated the effect of ginsenoside Rg5 (Rg5) on the hepatic glucagon response, focusing on the regulation of metabolism. METHODS: Mice fed a high-fat diet (HFD) showed increased hepatic glucose production (HGP). We observed the effects of Rg5 on hepatic fatty acid oxidation and glucagon response. The regulation of phosphodiesterase (PDE) 4B by succinate was also investigated in hepatocytes...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28198596/propofol-protects-against-hepatic-ischemia-reperfusion-injury-via-mir-133a-5p-regulating-the-expression-of-mapk6
#2
Wei Hao, Zhi-Hui Zhao, Qing-Tao Meng, Mu-Er Tie, Shao-Qing Lei, Zhong-Yuan Xia
Propofol has been found to play an important role in hepatic ischemia/reperfusion (I/R) injury with the antioxidant effects. However, the molecular mechanism of propofol in hepatic I/R injury has not been fully understood. Male Sprague-Dawley rats were randomly assigned into Sham group, hepatic I/R group, and propofol treatment group. I/R injury was attained by ischemia for 1 h and reperfusion for 2 h. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were detected. QSG-7701 cells were cultured in hypoxia condition for 15 h and then in reoxygenation condition for 6 h to imitate hypoxia/reoxygenation (H/R) injury in vitro...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28193580/astaxanthin-inhibits-inflammation-and-fibrosis-in-the-liver-and-adipose-tissue-of-mouse-models-of-diet-induced-obesity-and-nonalcoholic-steatohepatitis
#3
Bohkyung Kim, Callie Farruggia, Chai Siah Ku, Tho X Pham, Yue Yang, Minkyung Bae, Casey J Wegner, Nicholas J Farrell, Ellen Harness, Young-Ki Park, Sung I Koo, Ji-Young Lee
The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0...
March 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28178202/increased-dicarbonyl-stress-as-a-novel-mechanism-of-multi-organ-failure-in-critical-illness
#4
Bas C T van Bussel, Marcel C G van de Poll, Casper G Schalkwijk, Dennis C J J Bergmans
Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone) that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28170202/autologous-neohep-derived-from-chronic-hepatitis-b-virus-patients-blood-monocytes-by-upregulation-of-c-met-signaling
#5
Jashdeep Bhattacharjee, Barun Das, Disha Sharma, Preeti Sahay, Kshama Jain, Alaknanda Mishra, Srikanth Iyer, Puja Nagpal, Vinod Scaria, Perumal Nagarajan, Prakash Khanduri, Asok Mukhopadhyay, Pramod Upadhyay
In view of the escalating need for autologous cell-based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)-positive (HNP) blood were differentiated to hepatocyte-like cells (NeoHep) in vitro by a two-step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c-MET signaling pathway in the second step...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28133883/carbon-monoxide-ameliorates-hepatic-ischemia-reperfusion-injury-via-sirtuin-1-mediated-deacetylation-of-high-mobility-group-box-1-in-rats
#6
Jian Sun, Enshuang Guo, Jiankun Yang, Yan Yang, Shenpei Liu, Jifa Hu, Xiaojing Jiang, Olaf Dirsch, Uta Dahmen, Wei Dong, Anding Liu
Carbon monoxide (CO) exerts protective effects on hepatic ischemia/reperfusion injury (IRI), but the underlying molecular mechanisms are not fully understood. High-mobility group box 1 (HMGB1) is an important mediator of injury and inflammation in hepatic IRI. Here, we investigated whether CO could attenuate hepatic IRI via inhibition of HMGB1 release, particularly through sirtuin 1 (SIRT1). CO was released by treatment with carbon monoxide-releasing molecule (CORM)-2. CORM-2-delivered CO ameliorated hepatic IRI, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory responses, and less severe ischemia/reperfusion-associated histopathologic changes...
April 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28131540/fabrication-of-a-fiber-type-hepatic-tissue-by-bottom-up-method-using-multilayer-spheroids
#7
Tatsuya Okudaira, Ryohei Yabuta, Hiroshi Mizumoto, Toshihisa Kajiwara
Liver regenerative medicine, a therapy using cultured hepatocytes or hepatic tissues, has the potential to replace liver transplantation. However, this therapeutic strategy has challenges to overcome, including in construction of the hepatic tissues. As an approach to fabricating functional 3D hepatic tissues, we focused on hepatocyte spheroids, which have high cell density and maintain high liver-specific functions. We employed a bottom-up method using spheroids, arranging hepatocytes and endothelial cells regularly at the time of tissue construction...
January 25, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#8
Michelle J Farquhar, Isla S Humphreys, Simon A Rudge, Garrick K Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M Reynolds, Margaret Aschcroft, Peter Balfe, Thomas F Baumert, Stephanie Roessler, Michael J O Wakelam, Jane A McKeating
BACKGROUND AND AIMS: Chronic hepatitis C is a global health problem with an estimated 170 million HCV infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX) is a phospholipase with diverse roles in physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood...
January 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28123525/correlation-between-liver-cancer-pain-and-the-hif-1-and-vegf-expression-levels
#9
Geng Zhang, Gui-Yin Feng, Yan-Ru Guo, Dong-Qi Liang, Yuan Yuan, Hai-Lun Wang
A possible correlation between liver cancer pain and the hypoxia-inducible factor (HIF)-1 and vascular endothelial growth factor (VEGF) expression levels was examined. From January, 2015 to January, 2016, 30 patients suffering from liver cancer with pain, 30 patients with liver cancer without pain and 30 hepatitis patients with pain were enrolled in the study. Pain level was evaluated by visual analogue scale (VAS), the expression levels of HIF-1 and VEGF mRNA were determined by RT-PCR and the expression levels of HIF-1 and VEGF proteins were examined by ELISA...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28112704/evaluation-and-treatment-of-hyperglycemia-in-critically-ill-patients
#10
Andrea Balloni, Federico Lari, Fabrizio Giostra
The hyperglycemic reaction to stress is part of adaptive metabolic response to critical illness, especially hypoxia, hemorrhage and sepsis. It involves neuro-endocrine and immune pathways leading to the development of insulin resistance and hepatic glucose production by gluconeogenesis and glycogenolysis. Over the last years the concept of stress related hyperglycemia has been replaced by the concept of dysglycemia and its three domains: hyperglycemia, hypoglycemia and glycemic variability. Each of the three domains is independently associated with increased risk of mortality in patients admitted in intensive care unit and non critically ill patients, both medical and surgical...
January 16, 2017: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/28112475/tetramethylpyrazine-attenuates-sinusoidal-angiogenesis-via-inhibition-of-hedgehog-signaling-in-liver-fibrosis
#11
Shifeng Zhao, Zili Zhang, Zhen Yao, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Accumulating evidence indicates that hedgehog signaling plays a pivotal role in pathological angiogenesis and is involved in wound-healing responses in a number of adult tissues, including the liver. We previously demonstrated that hedgehog signaling promoted proliferation and inhibited apoptosis in hepatic stellate cells. This study was aimed to evaluate the effect of tetramethylpyrazine (TMP) on hedgehog signaling and to further examine the molecular mechanisms of TMP-induced antiangiogenesic effects in liver fibrosis...
February 2017: IUBMB Life
https://www.readbyqxmd.com/read/28112200/reduction-of-hepatic-fibrosis-by-overexpression-of-von-hippel-lindau-protein-in-experimental-models-of-chronic-liver-disease
#12
Jizhou Wang, Zhaoyang Lu, Zhilin Xu, Pei Tian, Hui Miao, Shangha Pan, Ruipeng Song, Xueying Sun, Baolei Zhao, Dawei Wang, Yong Ma, Xuan Song, Shugeng Zhang, Lianxin Liu, Hongchi Jiang
Hypoxia-inducible factor (HIF)-1α and HIF-2α play an important role in liver fibrosis. von Hippel-Lindau protein (VHL), a key mediator of HIF-α, regulates fibrosis in an organ- and cell-specific way. In this study, human liver samples were collected from hepatitis C-, alcoholic-, and cholestatic-associated fibrotic and healthy individuals. Two mouse models of liver fibrosis were established: bile duct ligation and carbon tetrachloride injection. We constructed adenovirus vectors to overexpress VHL, normoxia-active HIF-α, and lentiviral vectors to silence HIF-α...
January 23, 2017: Scientific Reports
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
#13
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
#14
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
#15
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
#16
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 fueled (at least in part) by lactate provided by neighboring astrocytes...
April 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signalling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#17
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 signalling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were treated 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...
March 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
#18
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
#19
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
#20
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
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