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Hypoxia and liver disease

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https://www.readbyqxmd.com/read/28775066/the-interplay-between-iron-and-oxygen-homeostasis-with-a-particular-focus-on-the-heart
#1
Samira Lakhal-Littleton, Peter A Robbins
Iron is subject to tight homeostatic control in mammals. At the systemic level, iron homeostasis is controlled by the liver-derived hormone hepcidin acting on its target ferroportin in the gut, spleen and liver, which form the sites of iron uptake, recycling and storage, respectively. At the cellular level, iron homeostasis is dependent on the iron regulatory proteins IRP1/IRP2. Unique chemical properties of iron underpin its importance in biochemical reactions involving oxygen. As such, it is not surprising that there are reciprocal regulatory links between iron and oxygen homeostasis, operating both at the systemic and cellular levels...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28768719/the-specialized-pro-resolving-lipid-mediator-maresin-1-protects-hepatocytes-from-lipotoxic-and-hypoxia-induced-endoplasmic-reticulum-stress
#2
Bibiana Rius, Marta Duran-Güell, Roger Flores-Costa, Cristina López-Vicario, Aritz Lopategi, José Alcaraz-Quiles, Mireia Casulleras, Juan José Lozano, Esther Titos, Joan Clària
Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are hallmarks of nonalcoholic fatty liver disease (NAFLD), which is the hepatic manifestation of the metabolic syndrome associated with obesity. The specialized pro-resolving lipid mediator maresin 1 (MaR1) preserves tissue homeostasis by exerting cytoprotective actions, dampening inflammation, and expediting its timely resolution. Here, we explored whether MaR1 protects liver cells from lipotoxic and hypoxia-induced ER stress...
August 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28759737/differential-diagnosis-of-hepatopulmonary-syndrome-hps-portopulmonary-hypertension-pph-and-hereditary-hemorrhagic-telangiectasia-hht
#3
REVIEW
Inna Krynytska, Mariya Marushchak, Anna Mikolenko, Anzhela Bob, Iryna Smachylo, Ludmyla Radetska, Olga Sopel
Hepatopulmonary syndrome (HPS) is a severe complication of advanced liver disease associated with an extremely poor prognosis. HPS is diagnosed in 4-47% of patients with cirrhosis and in 15-20% of candidates for liver transplantation. In addition, severe hypoxia is associated with a high risk of complications of liver transplantation (a 30% chance during the first 90 days) and increases the gap between transplantation and improving arterial oxygenation. The pathogenesis of HPS is not fully understood, and no effective pharmacological treatment has been developed yet...
July 31, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28754107/interaction-between-obesity-and-the-hypoxia-inducible-factor-3-alpha-subunit-rs3826795-polymorphism-in-relation-with-plasma-alanine-aminotransferase
#4
Shuo Wang, Jieyun Song, Yide Yang, Yining Zhang, Nitesh V Chawla, Jun Ma, Haijun Wang
BACKGROUND: Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation...
July 28, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28745372/systems-level-organization-of-non-alcoholic-fatty-liver-disease-progression-network
#5
K Shubham, L Vinay, P K Vinod
Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex spectrum of diseases ranging from simple steatosis to Non-Alcoholic Steatohepatitis (NASH) with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of the adipose tissue plays a central role in NAFLD progression. Here, we analysed transcriptomics data obtained from the Visceral Adipose Tissue (VAT) of NAFLD patients to understand how the VAT metabolism is altered at the genome scale and co-regulated with other cellular processes during the progression from obesity to NASH with fibrosis...
July 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28704229/treatment-of-hyponatremic-encephalopathy-in-the-critically-ill
#6
Steven G Achinger, Juan Carlos Ayus
OBJECTIVES: Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness...
July 11, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28676332/circulating-exosomes-in-obstructive-sleep-apnea-as-phenotypic-biomarkers-and-mechanistic-messengers-of-end-organ-morbidity
#7
REVIEW
Abdelnaby Khalyfa, Leila Kheirandish-Gozal, David Gozal
Obstructive sleep apnea (OSA), the most severe form of sleep disordered breathing, is characterized by intermittent hypoxia during sleep (IH), sleep fragmentation, and episodic hypercapnia. OSA is associated with increased risk for morbidity and mortality affecting cardiovascular, metabolic, and neurocognitive systems, and more recently with non-alcoholic fatty liver disease (NAFLD) and cancer-related deaths. Substantial variability in OSA outcomes suggests that genetically-determined and environmental and lifestyle factors affect the phenotypic susceptibility to OSA...
July 1, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28632747/selective-cyclooxygenase-inhibition-by-sc-560-improves-hepatopulmonary-syndrome-in-cirrhotic-rats
#8
Ching-Chih Chang, Wen-Shin Lee, Hsian-Guey Hsieh, Chiao-Lin Chuang, Hui-Chun Huang, Fa-Yauh Lee, Shou-Dong Lee
OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS...
2017: PloS One
https://www.readbyqxmd.com/read/28623125/chronic-intermittent-hypoxia-induces-liver-fibrosis-in-mice-with-diet-induced-obesity-via-tlr4-myd88-mapk-nf-kb-signaling-pathways
#9
Hyeon Hui Kang, In Kyoung Kim, Hye In Lee, Hyonsoo Joo, Jeong Uk Lim, Jongmin Lee, Sang Haak Lee, Hwa Sik Moon
Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28611447/serpinb3-promotes-pro-fibrogenic-responses-in-activated-hepatic-stellate-cells
#10
Erica Novo, Gianmarco Villano, Cristian Turato, Stefania Cannito, Claudia Paternostro, Chiara Busletta, Alessandra Biasiolo, Santina Quarta, Elisabetta Morello, Claudia Bocca, Antonella Miglietta, Ezio David, Salvatore Sutti, Mario Plebani, Emanuele Albano, Maurizio Parola, Patrizia Pontisso
SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606929/targeting-oxygen-sensing-prolyl-hydroxylase-for-metformin-associated-lactic-acidosis-treatment
#11
Tomoko Oyaizu-Toramaru, Tomohiro Suhara, Noriyo Hayakawa, Takashi Nakamura, Akiko Kubo, Shizuka Minamishima, Kyoji Yamaguchi, Takako Hishiki, Hiroshi Morisaki, Makoto Suematsu, Yoji Andrew Minamishima
Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anticancer and antiaging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate the transcription factor hypoxia-inducible factor (HIF) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels...
August 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#12
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28583670/hepatic-hypoxia-inducible-factors-inhibit-ppar%C3%AE-expression-to-exacerbate-acetaminophen-induced-oxidative-stress-and-hepatotoxicity
#13
Dawei Li, Yingdong Du, Xiaodong Yuan, Xiaoxiao Han, Zhen Dong, Xiaosong Chen, Haoyu Wu, Jianjun Zhang, Longmei Xu, Conghui Han, Ming Zhang, Qiang Xia
Oxidative stress has a critical role in the pathogenesis of acetaminophen (APAP) induced hepatocellular necrosis, and the identification of novel approaches to attenuate oxidative stress is essential to prevent/revert the disease. This study investigated the role of both HIF-1 and HIF-2 in the pathogenesis of APAP-induced oxidative stress, as well as the underlying mechanisms. In the present study, we initially found that knockout of HIF-1α or HIF-2α reduced APAP toxicity, and double knockout afforded the best protection...
June 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28560400/altered-gene-expression-of-hepatic-cytochrome-p450-in-a-rat-model-of-intermittent-hypoxia-with-emphysema
#14
Hongzhi Yu, Hongxia Shao, Qi Wu, Xin Sun, Li Li, Kuan Li, Xue Li, Yu Li, Qiuyang Zhang, Junping Wu, Huaiyong Chen
Patients with respiratory overlap syndrome (OS), defined as concomitant chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, may exhibit an increased blood concentration of ingested drugs. This poor elimination of drugs is primarily attributed to downregulated gene expression of the drug‑metabolizing cytochrome P450 enzymes (CYPs) in the liver. However, the underlying mechanisms of the decreased expression of CYPs in OS are poorly understood. In order to address this, a rat model of intermittent hypoxia with emphysema was evaluated in the present study, by analyzing liver gene expression using the reverse transcription‑quantitative polymerase chain reaction...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28529559/fbp1-expression-is-associated-with-basal-like-breast-carcinoma
#15
Lei Shi, Chunbo Zhao, Haihong Pu, Qingyuan Zhang
The present study aimed to investigate the value of liver fructose 1,6-bisphophatase (FBP1) and hypoxia-inducible factor-1α (HIF-1α) in the molecular subtyping of breast carcinoma. Tissue obtained from 60 surgical specimens from patients with breast carcinoma underwent immunohistochemical staining for cytokeratin 5/6, HIF-1α and FBP1. The variation in the expression levels of these markers and clinicopathological factors were compared between molecular subtypes. In addition, disease-free survival was compared between basal-like and luminal breast carcinoma, according to differing expression levels of HIF-1α and FBP1...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28452956/protective-effect-of-caffeic-acid-derivatives-on-tert-butyl-hydroperoxide-induced-oxidative-hepato-toxicity-and-mitochondrial-dysfunction-in-hepg2-cells
#16
Tzung-Hsun Tsai, Chun-Hsien Yu, Yu-Ping Chang, Yu-Ting Lin, Ching-Jang Huang, Yueh-Hsiung Kuo, Po-Jung Tsai
Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME)...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28440316/modest-and-severe-maternal-iron-deficiency-in-pregnancy-are-associated-with-fetal-anaemia-and-organ-specific-hypoxia-in-rats
#17
Andrew G Woodman, Alison S Care, Yael Mansour, Stephana J Cherak, Sareh Panahi, Ferrante S Gragasin, Stephane L Bourque
Prenatal iron-deficiency (ID) is known to alter fetal developmental trajectories, which predisposes the offspring to chronic disease in later life, although the underlying mechanisms remain unclear. Here, we sought to determine whether varying degrees of maternal anaemia could induce organ-specific patterns of hypoxia in the fetuses. Pregnant female Sprague Dawley rats were fed iron-restricted or iron-replete diets to induce a state of moderate (M-ID) or severe ID (S-ID) alongside respective controls. Ultrasound biomicroscopy was performed on gestational day (GD)20 to assess uterine and umbilical artery blood flow patterns...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378526/placental-growth-factor-silencing-ameliorates-liver-fibrosis-and-angiogenesis-and-inhibits-activation-of-hepatic-stellate-cells-in-a-murine-model-of-chronic-liver-disease
#18
Xi Li, Qun-Yan Yao, Hong-Chun Liu, Qian-Wen Jin, Bei-Li Xu, Shun-Cai Zhang, Chuan-Tao Tu
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and is involved in pathological angiogenesis associated with chronic liver diseases. However, the precise mechanisms underlying PlGF signalling contributing to liver fibrosis and angiogenesis remain largely unexplored. This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms...
April 5, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28360450/renal-medullary-carcinoma-a-rare-entity
#19
Selahattin Çalışkan, Ali Murat Gökçe, Gülistan Gümrükçü, Mine Önenerk
Renal medullary carcinoma (RMC) is an uncommon aggressive neoplasm of the kidney. RMC is biologically aggressive with a very poor prognosis, and metastasis is seen in up to 95% of the patients at diagnosis or shortly thereafter. The common sites of metastasis are respectively lymph nodes, lungs, livers, and adrenal glands in order of frequency. The presence of poorly differentiated eosinophilic cells in a characteristic fibro-inflammatory stroma is seen in histological examination. The origin and pathogenesis of RMC are unclear...
March 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28289017/activated-tafi-promotes-the-development-of-chronic-thromboembolic-pulmonary-hypertension-a-possible-novel-therapeutic-target
#20
Taijyu Satoh, Kimio Satoh, Nobuhiro Yaoita, Nobuhiro Kikuchi, Junichi Omura, Ryo Kurosawa, Kazuhiko Numano, Elias Al-Mamun, Mohammad Abdul Hai Siddique, Shinichiro Sunamura, Masamichi Nogi, Kota Suzuki, Satoshi Miyata, John Morser, Hiroaki Shimokawa
RATIONALE: Pulmonary hypertension is a fatal disease; however, its pathogenesis still remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) is synthesized by the liver and inhibits fibrinolysis. Plasma TAFI levels are significantly increased in chronic thromboembolic pulmonary hypertension (CTEPH) patients. OBJECTIVE: To determine the role of activated TAFI (TAFIa) in the development of CTEPH. METHODS AND RESULTS: Immunostaining showed that TAFI and its binding partner thrombomodulin (TM) were highly expressed in the pulmonary arteries (PAs) and thrombus in patients with CTEPH...
April 14, 2017: Circulation Research
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