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Hepatic hypoxia

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https://www.readbyqxmd.com/read/28632747/selective-cyclooxygenase-inhibition-by-sc-560-improves-hepatopulmonary-syndrome-in-cirrhotic-rats
#1
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/28627649/hypoxia-serves-a-key-function-in-the-upregulated-expression-of-vascular-adhesion-protein%C3%A2-1-in%C3%A2-vitro-and-in-a-rat-model-of-hemorrhagic-shock
#2
Yuxing Zhang, Wei Yi, Jun Yao, Xiaojun Yu, Cheng Qian, Zhiqian Hu
Hemorrhagic shock following major trauma results in mortality, but the function of vascular adhesion protein‑1 (VAP‑1), implicated in intracranial hemorrhage, remains unknown. This study aimed to determine whether expression of the AOC3 gene and its encoded protein, VAP‑1, is altered by hypoxia. Rat hepatic sinusoidal endothelial cells (RHSECs) and rat intestinal microvascular endothelial cells (RIMECs) were transduced with a viral vector carrying AOC3, and AOC3 mRNA expression levels were measured by reverse transcription‑quantitative polymerase chain reaction...
June 8, 2017: Molecular Medicine Reports
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
#3
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...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622333/acute-40-exchange-transfusion-with-hemoglobin-vesicles-in-a-mouse-pneumonectomy-model
#4
Mitsutomo Kohno, Tatsuhiko Ikeda, Ryo Hashimoto, Yotaro Izumi, Masazumi Watanabe, Hirohisa Horinouchi, Hiromi Sakai, Koichi Kobayashi, Masayuki Iwazaki
OBJECTIVES: Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. METHODS: Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA)...
2017: PloS One
https://www.readbyqxmd.com/read/28611447/serpinb3-promotes-pro-fibrogenic-responses-in-activated-hepatic-stellate-cells
#5
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/28611199/u-s-food-and-drug-administration-approval-summary-atezolizumab-for-metastatic-non-small-cell-lung-cancer
#6
Chana Weinstock, Sean Khozin, Daniel Suzman, Lijun Zhang, Shenghui Tang, Sakar Wahby, Kirsten B Goldberg, Geoffrey Kim, Richard Pazdur
On October 18 2016, the U.S. Food and Drug Administration approved atezolizumab (TECENTRIQ®, Genentech Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months (95% confidence interval [CI] 11...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#7
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/28595534/a-review-of-levetiracetam-in-neonates
#8
Amit Agrawal, Anita Banergee
BACKGROUND: Neonatal seizures are the most common clinical manifestation of central nervous system (CNS) dysfunction and are associated with various neurological sequelae. There are currently no evidence-based guidelines for the management of neonatal seizures and currently used drugs such as phenobarbital, and phenytoin have limited efficacy and potential toxicities. Newer second line anticonvulsant, levetiracetam, has been used in refractory neonatal seizures despite limited data and off-label use...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28594103/dietary-%C3%AE-ketoglutarate-supplementation-improves-hepatic-and-intestinal-energy-status-and-anti-oxidative-capacity-of-cherry-valley-ducks
#9
Shuangshuang Guo, Rui Duan, Lei Wang, Yongqing Hou, Linglin Tan, Qiang Cheng, Man Liao, Binying Ding
α-Ketoglutarate (AKG) is an extensively used dietary supplement in human and animal nutrition. The aim of the present study was to investigate effects of dietary AKG supplementation on the energy status and anti-oxidative capacity in liver and intestinal mucosa of Cherry Valley ducks. A total of 80 1-day-old ducks were randomly assigned into four groups, in which ducks were fed basal diets supplemented with 0% (control), 0.5%, 1.0% and 1.5% AKG, respectively. Graded doses of AKG supplementation linearly decreased the ratio of adenosine monophosphate (AMP) to adenosine triphosphate (ATP) in the liver, but increased ATP content and adenylate energy charge (AEC) in a quadratic and linear manner, respectively (P < 0...
June 8, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28583670/hepatic-hypoxia-inducible-factors-inhibit-ppar%C3%AE-expression-to-exacerbate-acetaminophen-induced-oxidative-stress-and-hepatotoxicity
#10
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/28569786/brg1-mediated-nrf2-ho-1-pathway-activation-alleviates-hepatic-ischemia-reperfusion-injury
#11
Mian Ge, Weifeng Yao, Dongdong Yuan, Shaoli Zhou, Xi Chen, Yihan Zhang, Haobo Li, Zhengyuan Xia, Ziqing Hei
Cytoprotective gene heme oxygenase 1 (HO-1) could be induced by nuclear factor E2-related factor 2 (Nrf2) nuclear translocation. The purpose of this study was to determine the role of Brahma-related gene 1 (Brg1), a catalytic subunit of SWI2/SNF2-like chromatin remodeling complexes, in Nrf2/HO-1 pathway activation during hepatic ischemia-reperfusion (HIR). Our results showed that hepatic Brg1 was inhibited during early HIR while Brg1 overexpression reduced oxidative injury in CMV-Brg1 mice subjected to HIR...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28560400/altered-gene-expression-of-hepatic-cytochrome-p450-in-a-rat-model-of-intermittent-hypoxia-with-emphysema
#12
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/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#13
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28539891/double-knockdown-of-phd1-and-keap1-attenuated-hypoxia-induced-injuries-in-hepatocytes
#14
Jing Liu, Yiping Li, Lei Liu, Zhi Wang, Chuanbing Shi, Zhengyuan Cheng, Xiaoyi Zhang, Fengan Ding, Ping Sheng Chen
Background and Aims: Hypoxia and oxidative stress contribute toward liver fibrosis. In this experiment, we used small hairpin RNA (shRNA) to interfere with the intracellular oxygen sensor-prolyl hydroxylase 1 (PHD1) and the intracellular oxidative stress sensor-kelch-like ECH associated protein 1 (Keap1) in the hypoxic hepatocytes in order to investigate the function of PHD1and Keap1. Methods: We first established the CCl4-induced liver fibrosis model, subsequently, the levels of the PHD1, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), Keap1, and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) were detected in liver tissues...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28495962/dietary-supplementation-of-heat-treated-gracilaria-and-ulva-seaweeds-enhanced-acute-hypoxia-tolerance-in-gilthead-sea-bream-sparus-aurata
#15
Leonardo J Magnoni, Juan Antonio Martos-Sitcha, Augusto Queiroz, Josep Alvar Calduch-Giner, José Fernando Magalhães Gonçalves, Cristina M R Rocha, Helena T Abreu, Johan W Schrama, Rodrigo O A Ozorio, Jaume Pérez-Sánchez
Intensive aquaculture practices involve rearing fish at high densities. In these conditions, fish may be exposed to suboptimal dissolved O2 levels with an increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW) contain biologically active substances with efficient antioxidant capacities. This study evaluated the effects of dietary supplementation of heat-treated SW (5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in sea bream subjected to a hypoxic challenge. 168 fish (104...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28485808/influences-of-rfa-combined-with-tace-on-the-hif-1%C3%AE-and-egr-level-of-patients-with-primary-hepatic-carcinoma
#16
G Yuan, C-L Zeng, D-D Zhu, X-J Shi
OBJECTIVE: To discuss the influences of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization on the expression level of immunity and hypoxia-inducible factor (HIF-1a) and early growth response protein2 (EGR2) of patients with hepatocarcinoma. PATIENTS AND METHODS: Patients with primary hepatic carcinoma treated in our hospital from 2011 to 2014 were divided into research group (RFA+TACE) and control group (TACE) according to different therapy methods, with 72 patients in each group...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28416613/hypoxia-inducible-factor-1%C3%AE-activates-insulin-induced-gene-2-insig-2-transcription-for-degradation-of-3-hydroxy-3-methylglutaryl-hmg-coa-reductase-in-the-liver
#17
Seonghwan Hwang, Andrew D Nguyen, Youngah Jo, Luke J Engelking, James Brugarolas, Russell A DeBose-Boyd
Cholesterol synthesis is a highly oxygen-consuming process. As such, oxygen deprivation (hypoxia) limits cholesterol synthesis through incompletely understood mechanisms mediated by the oxygen-sensitive transcription factor hypoxia-inducible factor 1α (HIF-1α). We show here that HIF-1α links pathways for oxygen sensing and feedback control of cholesterol synthesis in human fibroblasts by directly activating transcription of the INSIG-2 gene. Insig-2 is one of two endoplasmic reticulum membrane proteins that inhibit cholesterol synthesis by mediating sterol-induced ubiquitination and subsequent endoplasmic reticulum-associated degradation of the rate-limiting enzyme in the pathway, HMG-CoA reductase (HMGCR)...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28401647/mg53-anchored-by-dysferlin-to-cell-membrane-reduces-hepatocyte-apoptosis-which-induced-by-ischaemia-reperfusion-injury-in%C3%A2-vivo-and-in%C3%A2-vitro
#18
Weifeng Yao, Haobo Li, Xue Han, Chaojin Chen, Yihan Zhang, Wai Lydia Tai, Zhengyuan Xia, Ziqing Hei
Hepatic ischaemia/reperfusion (HIR) induces severe damage on hepatocyte cell membrane, which leads to hepatocyte death and the subsequent HIR injury. In this study, we investigated the role and the mechanism of mitsugumin-53 (MG53), a novel cell membrane repair protein, in protecting the liver against HIR injury. Rats were subjected to sham operation or 70% warm HIR with or without recombined MG53 (rhMG53), caudal vein-injected 2 hrs before inducing HIR. In vitro, cultured hepatocyte AML12 cells were subjected to hypoxia/reoxygenation (H/R) in the presence of rhMG53 and/or dysferlin gene shRNAs or adenovirus transfection...
April 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28383617/plasma-amino-acids-of-the-transsulfuration-pathway-and-plasma-lactate-in-septic-patients
#19
C Chiarla, I Giovannini, G Miggiano
OBJECTIVES: In sepsis increasing plasma lactate, even if unrelated to hypoperfusion and hypoxia, is a cause of concern. Among the patterns associated with increasing lactate, several plasma amino acid (AA) abnormalities, more in particular those of sulfur AAs, have remained unexplored, and their assessment has been the purpose of our study. MATERIALS AND METHODS: A systematic and detailed analysis of 183 simultaneous determinations of plasma AA-grams and lactate, from 12 trauma surgery patients who had developed sepsis, was performed...
March 2017: La Clinica Terapeutica
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
#20
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
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