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Hypoxia and liver disease

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https://www.readbyqxmd.com/read/29664738/pharmacological-induction-of-hypoxia-inducible-transcription-factor-arnt-attenuates-chronic-kidney-failure
#1
Björn Tampe, Désirée Tampe, Gunsmaa Nyamsuren, Friederike Klöpper, Gregor Rapp, Anne Kauffels, Thomas Lorf, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Samy Hakroush, Michael Zeisberg
Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge, because once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury...
April 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29609450/hepatopulmonary-syndrome-caused-by-hypothalamic-obesity-and-nonalcoholic-fatty-liver-disease-after-surgery-for-craniopharyngioma-a-case-report
#2
Dai Jung, Go Hun Seo, Yoon-Myung Kim, Jin-Ho Choi, Han-Wook Yoo
Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection...
March 2018: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29601782/hepatic-phd2-hif-1%C3%AE-axis-is-involved-in-postexercise-systemic-energy-homeostasis
#3
Beibei Luo, Dao Xiang, Die Wu, Changcheng Liu, Yiqun Fang, Peijie Chen, Yi-Ping Hu
Exercise plays an important role in the prevention and treatment of chronic liver disease and associated metabolic disorders. A single bout of exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal system and liver. The transcription factor, hypoxia inducible factor-1α (HIF-1α), and its regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to oxygen flux by regulating downstream gene expression levels in the liver...
March 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29544682/intermittent-hypoxia-suppression-of-growth-hormone-and-insulin-like-growth-factor-i-in-the-neonatal-rat-liver
#4
Charles Cai, Taimur Ahmad, Gloria B Valencia, Jacob V Aranda, Jiliu Xu, Kay D Beharry
OBJECTIVES: Extremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis...
March 8, 2018: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29508519/caffeic-acid-phenethyl-ester-improves-metabolic-syndrome-by-activating-ppar%C3%AE-and-inducing-adipose-tissue-remodeling-in-diet-induced-obese-mice
#5
Soon-Hee Kim, Hee-Sook Park, Moon Ju Hong, Haeng Jeon Hur, Dae Young Kwon, Myung-Sunny Kim
SCOPE: This study investigated the effects of caffeic acid phenethyl ester (CAPE), a bioactive component of honeybee hives, on the prevention and treatment of metabolic syndrome (MetS) by comparing the efficacy of CAPE intake at the beginning of obesity and after obesity. The functional mechanism of CAPE was also investigated. METHODS AND RESULTS: C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% CAPE (HFD+C) for 12 weeks (HFD+C(Pre) group) or received HFD+C for 6 weeks after consuming the HFD for 6 weeks (HFD+C(Post) group)...
March 5, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29502797/liver-damage-proliferation-and-progenitor-cell-markers-in-experimental-necrotizing-enterocolitis
#6
Hiromu Miyake, Bo Li, Carol Lee, Yuhki Koike, Yong Chen, Shogo Seo, Agostino Pierro
BACKGROUND: Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. METHODS: Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control...
February 7, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29476730/oroxylin-a-prevents-alcohol-induced-hepatic-steatosis-through-inhibition-of-hypoxia-inducible-factor-1alpha
#7
Huanhuan Jin, Naqi Lian, Mianli Bian, Chenxi Zhang, Xingran Chen, Jiangjuan Shao, Li Wu, Anping Chen, Qinglong Guo, Feng Zhang, Shizhong Zheng
Accumulating data reveal that oroxylin A has beneficial effects against chronic liver disease. The previously studies showed oroxylin A, a flavonoid extracted from Scutellariae radix, improved acute liver injury and accelerated liver regeneration in vivo. However, it's unclear that the effect of oroxylin A on alcoholic liver disease. The present study was aimed at elucidating the effect of oroxylin A on alcohol-induced hepatic steatosis and the underlying mechanisms. Human hepatocyte LO2 were cultured and stimulated with ethanol for inducing LO2 damage...
February 21, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29467552/metformin-attenuates-motility-contraction-and-fibrogenic-response-of-hepatic-stellate-cells-in-vivo-and-in-vitro-by-activating-amp-activated-protein-kinase
#8
Zhen Li, Qian Ding, Li-Ping Ling, Ying Wu, Dong-Xiao Meng, Xiao Li, Chun-Qing Zhang
AIM: To investigate the effect of metformin on activated hepatic stellate cells (HSCs) and the possible signaling pathways involved. METHODS: A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride (CCl4 ) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation (CCK8 assay), motility (scratch test and Transwell assay), contraction (collagen gel contraction assay), extracellular matrix (ECM) secretion (Western blot), and angiogenesis (ELISA and tube formation assay) was investigated...
February 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29465210/-correction-energy-deficient-states-as-possible-perioperative-adaptation-of-cancer-hepatopancreatoduodenal-zone-patients
#9
O I Kit, S V Tumanyan, O V Oros, L G Ivanova, N V Netyvchenko, E Y Sugak
The aim of this study was to determine the role remaxol in complex intensive therapy of various jorms gipoergosis dur- ing the perioperative period in patients with hepatopancreatoduodenal zone malignancies. The treatment of 48 patients was analyzed. Immediately prior to surgery, at random, patients were divided into primary (n = 26) and control group (n = 22). In the study group for compensation the energy deficient states and organ hypoxia in the pancreas and the liver during the intra- and postoperative periods remaxol was included in the infusion therapy, the introduction ofwhich had been began before the start of anesthesia...
September 2017: Anesteziologiia i Reanimatologiia
https://www.readbyqxmd.com/read/29404462/intermittent-hypoxia-is-a-proinflammatory-stimulus-resulting-in-il-6-expression-and-m1-macrophage-polarization
#10
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
#11
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-hypoxia-inducible-factor-2-%C3%AE-inhibitor-pt2385-in-vivo-and-in-vitro
#12
Cen Xie, Xiaoxia Gao, Dongxue Sun, Youbo Zhang, Kristopher W Krausz, Xuemei Qin, Frank J Gonzalez
PT2385 is a first-in-class, selective small-molecule inhibitor of hypoxia-inducible factor-2 α (HIF-2 α ) developed for the treatment of advanced clear cell renal cell carcinoma. Preclinical results demonstrated that PT2385 has potent antitumor efficacy in mouse xenograft models of kidney cancer. It also has activity toward metabolic disease in a mouse model. However, no metabolism data are currently publically available. It is of great importance to characterize the metabolism of PT2385 and identify its effect on systemic homeostasis in mice...
April 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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