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Hypoxia and liver disease

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https://www.readbyqxmd.com/read/28170202/autologous-neohep-derived-from-chronic-hepatitis-b-virus-patients-blood-monocytes-by-upregulation-of-c-met-signaling
#1
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/28126520/metabolic-zonation-of-the-liver-the-oxygen-gradient-revisited
#2
Thomas Kietzmann
The liver has a multitude of functions which are necessary to maintain whole body homeostasis. This requires that various metabolic pathways can run in parallel in the most efficient manner and that futile cycles are kept to a minimum. To a large extent this is achieved due to a functional specialization of the liver parenchyma known as metabolic zonation which is often lost in liver diseases. Although this phenomenon is known for about 40 years, the underlying regulatory pathways are not yet fully elucidated...
January 17, 2017: Redox Biology
https://www.readbyqxmd.com/read/28126503/-pathophysiology-of-obstructive-sleep-apnea-syndrome-and-its-cardiometabolic-consequences
#3
Marie Destors, Renaud Tamisier, Louis-Marie Galerneau, Patrick Lévy, Jean-Louis Pepin
Obstructive sleep apnoea syndrome (OSAS) is characterized by recurrent partial or complete pharyngeal collapses during sleep. The pathophysiology of OSAS is complex and multifactorial. Factors influencing upper airway patency include a reduction in upper airway dimensions that can result from both anatomical and functional alterations (obesity, fluid shift or maxillo-facial structural changes), and increased pharyngeal collapsibility owing to reduced neuromuscular compensation and lack of the pharyngeal protective reflex during sleep...
January 23, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28126478/gene-signature-associated-with-upregulation-of-the-wnt-%C3%AE-catenin-signaling-pathway-predicts-tumor-response-to-transarterial-embolization
#4
Etay Ziv, Hooman Yarmohammadi, F Edward Boas, Elena Nadia Petre, Karen T Brown, Stephen B Solomon, David Solit, Diane Reidy, Joseph P Erinjeri
PURPOSE: To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization. MATERIALS AND METHODS: This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar-cell carcinoma...
January 23, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#5
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/28115235/anti-fibrotic-effects-of-chronic-treatment-with-the-selective-fxr-agonist-obeticholic-acid-in-the-bleomycin-induced-rat-model-of-pulmonary-fibrosis
#6
Paolo Comeglio, Sandra Filippi, Erica Sarchielli, Annamaria Morelli, Ilaria Cellai, Francesca Corcetto, Chiara Corno, Elena Maneschi, Alessandro Pini, Luciano Adorini, Gabriella Barbara Vannelli, Mario Maggi, Linda Vignozzi
Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated...
January 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28112200/reduction-of-hepatic-fibrosis-by-overexpression-of-von-hippel-lindau-protein-in-experimental-models-of-chronic-liver-disease
#7
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/28099905/prolyl-hydroxylase-domain-protein-3-and-asparaginyl-hydroxylase-factor-inhibiting-hif-1-levels-are-predictive-of-tumoral-behavior-and-prognosis-in-hepatocellular-carcinoma
#8
Mingyang Ma, Shuyao Hua, Gang Li, Sumei Wang, Xue Cheng, Songqing He, Ping Wu, Xiaoping Chen
Hypoxia-inducible factors (HIFs) are key regulators in oxygen homeostasis. Their stabilization and activity are regulated by prolyl hydroxylase domain (PHD)-1, -2, -3 and factor inhibiting HIF (FIH). This study investigated the relation between these oxygen sensors and the clinical behaviors and prognosis of hepatocellular carcinoma (HCC). Tissue microarray and RT-PCR analysis of tumor tissues and adjacent non-tumor liver tissues revealed that mRNA and protein levels of both PHD3 and FIH were lower within tumors...
January 16, 2017: Oncotarget
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
#9
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/28068331/modelling-systemic-iron-regulation-during-dietary-iron-overload-and-acute-inflammation-role-of-hepcidin-independent-mechanisms
#10
Mihaela Enculescu, Christoph Metzendorf, Richard Sparla, Maximilian Hahnel, Johannes Bode, Martina U Muckenthaler, Stefan Legewie
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28066916/ammonia-mediates-cortical-hemichannel-dysfunction-in-rodent-models-of-chronic-liver-disease
#11
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/28051796/%C3%A2-differences-in-hepatic-expression-of-iron-inflammation-and-stress-related-genes-in-patients-with-nonalcoholic-steatohepatitis
#12
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
#13
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/28004357/yttrium-90-radioembolization-for-colorectal-cancer-liver-metastases-a-prospective-cohort-study-on-circulating-angiogenic-factors-and-treatment-response
#14
C E N M Rosenbaum, A F van den Hoven, M N G J A Braat, M Koopman, M G E H Lam, B A Zonnenberg, H M Verkooijen, M A A J van den Bosch
BACKGROUND: Yttrium-90 radioembolization ((90)Y-RE) as a treatment for liver tumours induces radiation damage and hypoxia in liver tissue, which is also a trigger for systemic release of angiogenic factors, potentially stimulating tumour growth. We examined changes in circulating angiogenic factors following (90)Y-RE and investigated the association between response and angiogenic factors. In this prospective study, 42 patients with unresectable, chemorefractory metastatic colorectal cancer (CRCLM) were treated with (90)Y-RE...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/28000380/quercetin-inhibits-sodium-nitrite-induced-inflammation-and-apoptosis-in-different-rats-organs-by-suppressing-bax-hif1-%C3%AE-tgf-%C3%AE-smad-2-and-akt-pathways
#15
Nouf Mohamed Al-Rasheed, Laila Mohamed Fadda, Hala A Attia, Hanaa Mahmoud Ali, Nawal Mohamed Al-Rasheed
The objective of this work is to study the protective effects of Quercetin against sodium nitrite-induced hypoxia on liver, lung, kidney and cardiac tissues, also to explore novel mechanism of this compound. Male albino rats were injected with sodium nitrite (75 mg/kg). Quercetin (200 mg kg(-1) ,- i.p.) was administrated 24 and 1 h respectively prior to sodium nitrite intoxication, hypoxia significantly decreased hemoglobin concentration, while increased expressions of HIF, Bax, Smad-2, TGF-β, and AKT...
December 21, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27987431/acriflavine-inhibits-acquired-drug-resistance-by-blocking-the-epithelial-to-mesenchymal-transition-and-the-unfolded-protein-response
#16
Jeroen Dekervel, Ashenafi Bulle, Petra Windmolders, Diether Lambrechts, Eric Van Cutsem, Chris Verslype, Jos van Pelt
: Epithelial-to-mesenchymal transition (EMT) is linked to tumor invasion, drug resistance and aggressive disease and this is largely dependent on the cell's microenvironment. Acriflavine (ACF) is an old antibacterial drug recently also suggested as anticancer agent and HIF inhibitor. We wanted to study the effect of acriflavine on EMT in different human cancer models. Pancreatic cancer cells (Panc-1) were exposed to TGF-β1 or cobalt chloride (to mimick severe hypoxia) to induce EMT. For our third model we exposed HepG2 liver cancer cells to sorafenib which resulted in development of acquired drug resistance with strong features of EMT and aggressive behavior...
December 14, 2016: Translational Oncology
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
#17
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/27901270/adipose-tissue-inflammation-by-intermittent-hypoxia-mechanistic-link-between-obstructive-sleep-apnoea-and-metabolic-dysfunction
#18
Silke Ryan
Obstructive sleep apnoea (OSA) is a highly prevalent condition and recognized as a major public health burden conveying a significant risk of cardiometabolic diseases and mortality. Type 2 diabetes (T2D), insulin resistance (IR) and glucose tolerance are common in subjects with OSA and this association is at least in part independent of the effects of obesity. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on glycaemic health is uncertain...
November 29, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#19
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
January 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27899252/the-effects-of-metronidazole-on-cytochrome-p450-activity-and-expression-in-rats-after-acute-exposure-to-high-altitude-of-4300m
#20
COMPARATIVE STUDY
Rong Wang, Yuhuan Sun, Qiang Yin, Hua Xie, Wenbin Li, Chang Wang, Jiankui Guo, Ying Hao, Rui Tao, Zhengping Jia
BACKGROUND: The purpose is to observe the changes of CYP450 enzyme activity expression as well as the physiological and pathological states of Wistar rats given metronidazole drug intervention after acute exposure to high altitude of 4300m. METHODS AND RESULTS: Thirty healthy adult male Wistar rats of average weight 200 ± 20 g were randomly assigned into three groups of 10 rats per group as follows: Group A (55m), Group B (4300m) and Group C (metronidazole intervention, 4300m)...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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