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Hypoxia and liver disease

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https://www.readbyqxmd.com/read/29404462/intermittent-hypoxia-is-a-proinflammatory-stimulus-resulting-in-il-6-expression-and-m1-macrophage-polarization
#1
Esperance Schaefer, Winona Wu, Christina Mark, Andrew Yang, Erik DiGiacomo, Charles Carlton-Smith, Shadi Salloum, Cynthia Brisac, Wenyu Lin, Kathleen E Corey, Raymond T Chung
The biological factors that promote inflammation or nonalcoholic steatohepatitis (NASH) in the setting of nonalcoholic fatty liver disease remain incompletely understood. Clinical studies have demonstrated an association between obstructive sleep apnea (OSA) and both inflammation and fibrosis in NASH, but the mechanism has not been identified. In this study, we use in vitro modeling to examine the impact of intermittent hypoxia on the liver. Hepatocyte, stellate cell, and macrophage cell lines were exposed to intermittent or sustained hypoxia...
June 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29369172/long-noncoding-rna-hypoxia-inducible-factor-1-alpha-antisense-rna-1-promotes-tumor-necrosis-factor-%C3%AE-induced-apoptosis-through-caspase-3-in-kupffer-cells
#2
Yanghe Wu, Jiguang Ding, Qingfeng Sun, Ke Zhou, Weiwei Zhang, Qingwei Du, Tingyan Xu, Wangwang Xu
Kupffer cells (KCs) play a crucial role in the pathogenesis of acute-on-chronic liver failure (ACLF) which is characterized by acute and severe disease in patients with preexisting liver disease and shows high mortality. Long noncoding RNAs (lncRNAs) are recently found to be involved in gene regulation. However, the mechanisms of how KCs are regulated by inflammatory factors, tumor necrosis factor-α (TNF-α), and whether lncRNAs are involved in the process remain largely unknown. Hence, we investigated the role of lncRNAs in the cytotoxicity of TNF-α on KCs...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29363499/metabolic-profiling-of-the-novel-hif2%C3%AE-inhibitor-pt2385-in-vivo-and-in-vitro
#3
Cen Xie, Xiaoxia Gao, Dongxu Sun, Youbo Zhang, Kristopher W Krausz, Xuemei Qin, Frank Gonzalez
PT2385 is a first-in-class, selective small molecule inhibitor of hypoxia inducible factor-2α (HIF-2α) developed for the treatment of advanced clear cell renal cell carcinoma. Preclinical results demonstrated that PT2385 has potent anti-tumor efficacy in mouse xenograft models of kidney cancer. It also has activity toward metabolic disease in a mouse model. However, no metabolism data is currently publicly available. It is of great importance to characterize the metabolism of PT2385 and identify its effect on systemic homeostasis in mice...
January 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29343429/translational-control-of-human-acetyl-coa-carboxylase-1-mrna-is-mediated-by-an-internal-ribosome-entry-site-in-response-to-er-stress-serum-deprivation-or-hypoxia-mimetic-cocl2
#4
Fabrizio Damiano, Mariangela Testini, Romina Tocci, Gabriele V Gnoni, Luisa Siculella
Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA...
January 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29326427/severe-steatosis-induces-portal-hypertension-by-systemic-arterial-hyporeactivity-and-hepatic-vasoconstrictor-hyperreactivity-in-rats
#5
Denise Van der Graaff, Wilhelmus J Kwanten, Filip J Couturier, Jesse S Govaerts, Wim Verlinden, Isabel Brosius, Michiel D'Hondt, Ann Driessen, Benedicte Y De Winter, Joris G De Man, Peter P Michielsen, Sven M Francque
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown...
January 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29316681/non-transfusion-dependent-thalassemia-an-update-on-complications-and-management
#6
REVIEW
Joseph Sleiman, Ali Tarhini, Rayan Bou-Fakhredin, Antoine N Saliba, Maria Domenica Cappellini, Ali T Taher
Patients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension...
January 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29276790/a-central-role-for-hypoxia-inducible-factor-hif-2%C3%AE-in-hepatic-glucose-homeostasis
#7
REVIEW
Sadeesh K Ramakrishnan, Yatrik M Shah
Hepatic glucose production is regulated by hormonal and dietary factors. At fasting, 80% of glucose released into the circulation is derived from the liver, among which gluconeogenesis accounts for 55% and the rest by glycogenolysis. Studies suggest a complex mechanism involved in the regulation of hepatic glucose metabolism during fasting and post-absorptive phase. Oxygen plays a key role in numerous metabolic pathways such as TCA cycle, gluconeogenesis, glycolysis and fatty acid oxidation. Oxygenation of the gastrointestinal tract including liver and intestine is dynamically regulated by changes in the blood flow and metabolic activity...
December 7, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/29217649/an-unusual-cause-of-hypoxia-getting-to-the-heart-of-the-matter
#8
Daniel Hammersley, Aamire Shamsi, Mohammad Murtaza Zaman, Phillip Berry, Lydia Sturridge
A 63 year old female presented to hospital with progressive exertional dyspnoea over a 6 month period. In the year preceding her admission, she reported an intercurrent history of abdominal pain, diarrhoea and weight loss. She was found to be hypoxic, the cause for which was initially unclear. A ventilation-perfusion scan identified a right-to-left shunt. Transoesophageal echocardiography (TOE) demonstrated a significant right-to-left intracardiac shunt through a patent foramen ovale (PFO); additionally severe tricuspid regurgitation was noted through a highly abnormal tricuspid valve...
December 7, 2017: Echo Research and Practice
https://www.readbyqxmd.com/read/29156788/modulation-of-hif-1%C3%AE-and-stat3-signaling-contributes-to-anti-angiogenic-effect-of-yc-1-in-mice-with-liver-fibrosis
#9
Tzung-Yan Lee, Yann-Lii Leu, Chorng-Kai Wen
Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The aim of the study was to evaluate the mechanisms of HIF-1α inhibitor, YC-1, during bile duct ligation (BDL)-induced liver fibrosis in mice. Liver fibrosis was induced in mice, and YC-1 was then given intraperitoneally (50 mg/kg) once daily following 5 days. Liver injuries mice that were treated with YC-1 showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. YC-1 treatment inhibited liver neutrophil infiltration, while a decreased in TNF-α signaling as well as macrophage aggregation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29116999/treatment-outcome-of-combined-continuous-venovenous-hemofiltration-and-hemoperfusion-in-acute-paraquat-poisoning-a-prospective-controlled-trial
#10
COMPARATIVE STUDY
Changbin Li, Dayong Hu, Wen Xue, Xinhua Li, Zhen Wang, Zisheng Ai, Yaxiang Song, Xinying Liu, Jiafeng Cheng, Shuling Fan, Limin Zhao, Liya Wang, Chandra Mohan, Ai Peng
OBJECTIVES: To investigate whether combined continuous venovenous hemofiltration and hemoperfusion among paraquat-poisoned patients would improve survival. DESIGN: Prospective, controlled interventional study over 4 years. SETTING: Single, tertiary, academic medical center. PATIENTS: We recruited patients admitted to Shanghai Tenth People's Hospital within 48 hours after paraquat ingestion. Exclusions were under 14 years old, ingestion of paraquat with other toxicants, pregnant, a history of chronic pulmonary disease, psychosis, hyperthyroidism, or diabetes with impaired liver or renal function...
January 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29113675/surgery-induced-tumor-growth-in-metastatic-colorectal-cancer
#11
REVIEW
Klaas M Govaert, Jennifer M J Jongen, Onno Kranenburg, Inne H M Borel Rinkes
Metastatic colorectal cancer (mCRC) is a devastating disease causing 700.000 deaths annually worldwide. Metastases most frequently develop in the liver. Partial hepatectomy has dramatically improved clinical outcome and is the only curative treatment option for eligible patients with mCRC. Pre-clinical studies have shown that surgical procedures can have tumor-promoting local 'side-effects' such as hypoxia and inflammation, thereby altering the behaviour of residual tumor cells. In addition, systemically released factors following (colon or liver) surgery can act as a wakeup-call for dormant tumor cells in distant organs and/or help establish a pre-metastatic niche...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29068390/does-hypoxia-cause-carcinogenic-iron-accumulation-in-alcoholic-liver-disease-ald
#12
REVIEW
Inês Silva, Vanessa Rausch, Helmut-Karl Seitz, Sebastian Mueller
Alcoholic liver disease (ALD) is a leading health risk worldwide. Hepatic iron overload is frequently observed in ALD patients and it is an important and independent factor for disease progression, survival, and the development of primary liver cancer (HCC). At a systemic level, iron homeostasis is controlled by the liver-secreted hormone hepcidin. Hepcidin regulation is complex and still not completely understood. It is modulated by many pathophysiological conditions associated with ALD, such as inflammation, anemia, oxidative stress/H₂O2, or hypoxia...
October 25, 2017: Cancers
https://www.readbyqxmd.com/read/29050006/recent-insights-into-the-biological-functions-of-sestrins-in-health-and-disease
#13
Menglong Wang, Yao Xu, Jianfang Liu, Jing Ye, Wenhui Yuan, Huimin Jiang, Zhen Wang, Hong Jiang, Jun Wan
Sestrins (Sesns) have been identified as a family of highly conserved stress-inducible proteins that are strongly up-regulated by various stresses, including DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in most physiological and pathological conditions mainly through the regulation of oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and metabolic homeostasis. In this review, we discussed the possible regulators of Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2 (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor-1α (Hif-1α), and the downstream pathways regulated by the Sesns including AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling, NADPH oxidase signaling and transforming growth factor β (TGF-β) signaling in heart diseases, lung diseases, gastrointestinal tract diseases, liver and metabolism diseases, neurological diseases, kidney diseases and immunological diseases...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29042934/intermittent-hypoxia-simulating-obstructive-sleep-apnea-causes-pulmonary-inflammation-and-activates-the-nrf2-ho-1-pathway
#14
Yeying Wang, Yanling Chai, Xiaojie He, Li Ai, Xia Sun, Yiling Huang, Yongxia Li
Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA damages multiple organs and tissues, including the cardiovascular and cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA-induced damage is earliest and greatest to the pulmonary tissue. The present study established a rat OSA model of differing severity by inducing intermittent hypoxia with different concentrations of O2 and it was determined that OSA caused a severe oxidative stress response and pulmonary inflammation in a dose-dependent manner...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29035368/activation-of-intestinal-hypoxia-inducible-factor-2%C3%AE-during-obesity-contributes-to-hepatic-steatosis
#15
Cen Xie, Tomoki Yagai, Yuhong Luo, Xianyi Liang, Tao Chen, Qiong Wang, Dongxue Sun, Jie Zhao, Sadeesh K Ramakrishnan, Lulu Sun, Chunmei Jiang, Xiang Xue, Yuan Tian, Kristopher W Krausz, Andrew D Patterson, Yatrik M Shah, Yue Wu, Changtao Jiang, Frank J Gonzalez
Nonalcoholic fatty liver disease is becoming the most common chronic liver disease in Western countries, and limited therapeutic options are available. Here we uncovered a role for intestinal hypoxia-inducible factor (HIF) in hepatic steatosis. Human-intestine biopsies from individuals with or without obesity revealed that intestinal HIF-2α signaling was positively correlated with body-mass index and hepatic toxicity. The causality of this correlation was verified in mice with an intestine-specific disruption of Hif2a, in which high-fat-diet-induced hepatic steatosis and obesity were substantially lower as compared to control mice...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#16
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29026849/increased-levels-of-vegf-a-and-hif-1%C3%AE-in-turkish-children-with-crimean-congo-hemorrhagic-fever
#17
Murat Sefikogullari, Ali Kaya, Huseyin Aydin, Enver Sancakdar, Veysel Kenan Celik, Gokhan Bagci
BACKGROUND: Crimean-Congo Hemorrhagic Fever (CCHF) is a disease characterized by serious course, including acute viral fever, ecchymosis, thrombocytopenia, liver dysfunction and high rate of mortality. Hypoxia Inducible Factor-1α (HIF-1α) and Vascular Endothelial Growth Factor-A (VEGF-A) play an important role both in the inflammatory process and plasma leakage. The aim of this study was to define HIF-1α and VEGF-A serum levels obtained from CCHF patients and control group and to investigate whether these factors were correlated with the pathogenesis of this disease...
March 2017: Journal of Arthropod-borne Diseases
https://www.readbyqxmd.com/read/28987423/microrna-122-regulated-by-grlh2-protects-livers-of-mice-and%C3%A2-patients-from-ethanol-induced-liver-disease
#18
Abhishek Satishchandran, Aditya Ambade, Sitara Rao, Ying-Chao Hsueh, Arvin Iracheta-Vellve, David Tornai, Patrick Lowe, Benedek Gyongyosi, Jia Li, Donna Catalano, Li Zhong, Karen Kodys, Jun Xie, Shashi Bala, Guangping Gao, Gyongyi Szabo
BACKGROUND & AIMS: Chronic, excessive alcohol consumption leads to alcoholic liver disease (ALD) characterized by steatosis, inflammation, and eventually cirrhosis. The hepatocyte specific microRNA 122 (MIR122) regulates hepatocyte differentiation and metabolism. We investigated whether an alcohol-induced decrease in level of MIR122 contributes to development of ALD. METHODS: We obtained liver samples from 12 patients with ALD and cirrhosis and 9 healthy individuals (controls) and analyzed them by histology and immunohistochemistry...
January 2018: Gastroenterology
https://www.readbyqxmd.com/read/28983709/late-complications-of-biliary-atresia-hepatopulmonary-syndrome-and-portopulmonary-hypertension
#19
Frederick M Karrer, Bradley J Wallace, Arturo E Estrada
Children with biliary atresia (BA) following Kasai portoenterostomy have a high risk for portal hypertension, however, while variceal and hemorrhagic complications have been more commonly studied, less frequent but no less possibly devastating complications of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) remain less well understood. HPS and PPH both occur in a setting of portal hypertension, however, paradoxically patients with HPS develop pulmonic vasculature dilation leading to shunting and hypoxia, while those with PPH develop an opposite progression of pulmonary vasoconstriction eventually leading to cor pulmonale and decompensation...
December 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28962181/tauroursodeoxycholic-acid-attenuates-endoplasmic-reticulum-stress-and-protects-the-liver-from-chronic-intermittent-hypoxia-induced-injury
#20
Yanpeng Hou, Huai'an Yang, Zeshi Cui, Xuhui Tai, Yanling Chu, Xing Guo
Obstructive sleep apnea that characterized by chronic intermittent hypoxia (CIH) has been reported to associate with chronic liver injury. Tauroursodeoxycholic acid (TUDCA) exerts liver-protective effects in various liver diseases. The purpose of this study was to test the hypothesis that TUDCA could protect liver against CIH injury. C57BL/6 mice were subjected to intermittent hypoxia for eight weeks and applied with TUDCA by intraperitoneal injection. The effect of TUDCA on liver histological changes, liver function, oxidative stress, inflammatory response, hepatocyte apoptosis and endoplasmic reticulum (ER) stress were investigated...
September 2017: Experimental and Therapeutic Medicine
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