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https://www.readbyqxmd.com/read/29769640/hypoxia-induced-microrna-191-contributes-to-hepatic-ischemia-reperfusion-injury-through-the-zonab-cyclin-d1-axis
#1
Wenming Pan, Lin Wang, Xiao-Fei Zhang, Hongji Zhang, Jinxiang Zhang, Guoliang Wang, Peng Xu, Yunwei Zhang, Ping Hu, Xiao-Dong Zhang, Run-Lei Du, Hui Wang
Hepatic ischemia/reperfusion injury (IRI) is a common cause of morbidity and mortality in liver transplantation settings and involves severe cell death and inflammatory responses. MicroRNA-191 has recently been reported to be abnormally expressed in hepatocellular carcinoma and other liver diseases in the regulation of important cellular processes. However, little is known about its function and molecular mechanism in IRI. Here, we demonstrate that miR-191 is significantly upregulated in a cultured cell line during hypoxia/reperfusion (H/R) and in liver tissue during IRI in mice...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29750997/the-role-of-spatial-variations-of-abiotic-factors-in-mediating-intratumour-phenotypic-heterogeneity
#2
Tommaso Lorenzi, Chandrasekhar Venkataraman, Alexander Lorz, Mark A J Chaplain
We present here a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silico multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography...
May 8, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29686697/ppar-%C3%AE-antagonizes-hypoxia-induced-activation-of-hepatic-stellate-cell-through-cross-mediating-pi3k-akt-and-cgmp-pkg-signaling
#3
Qinghui Zhang, Shihao Xiang, Qingqian Liu, Tao Gu, Yongliang Yao, Xiaojie Lu
Background and Aims: Accumulating evidence reveals that PPAR γ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPAR γ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods: Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPAR γ agonist rosiglitazone...
2018: PPAR Research
https://www.readbyqxmd.com/read/29682743/the-selective-mineralcorticoid-receptor-mr-antagonist-eplerenon-prevents-decompensation-of-liver-cirrhosis
#4
Barbara Schreier, Anja Wolf, Stefanie Hammer, Sabine Pohl, Sigrid Mildenberger, Sindy Rabe, Michael Gekle, Alexander Zipprich
BACKGROUND & AIMS: The MR contributes to fibrosis in various tissues and MR antagonists, like eplerenone, are used to prevent fibrosis. The role of MR antagonists for hepatic fibrosis and cirrhosis is unknown. Here, we investigated the role of MR and eplerenone in cirrhosis development. METHODS: Liver fibrosis (5 weeks), cirrhosis without (8w) and with ascites (12w) were induced by CCl4 in rats and comprehensively analyzed. In addition the effect of eplerenone (MR antagonist) on the development of cirrhosis with ascites was assessed...
April 22, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29599488/author-correction-prevalence-and-characteristics-of-hypoxic-hepatitis-in-the-largest-single-centre-cohort-of-avian-influenza-a-h7n9-virus-infected-patients-with-severe-liver-impairment-in-the-intensive-care-unit
#5
Yi Min Zhang, Ji Min Liu, Liang Yu, Ning Zhou, Wei Ding, Shu Fa Zheng, Ding Shi, Lan Juan Li
Correction to: Emerging Microbes & Infections (2016) 5:e1; https://doi.org/10.1038/emi.2016.1 ; Article published online 6 January 2016.
March 29, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29558045/liver-dysfunction-in-sepsis
#6
REVIEW
Ewa A Woźnica, Małgorzata Inglot, Ryszard K Woźnica, Lidia Łysenko
Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29544682/intermittent-hypoxia-suppression-of-growth-hormone-and-insulin-like-growth-factor-i-in-the-neonatal-rat-liver
#7
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/29508705/clinical-phenotypes-of-delirium-during-critical-illness-and-severity-of-subsequent-long-term-cognitive-impairment-a-prospective-cohort-study
#8
Timothy D Girard, Jennifer L Thompson, Pratik P Pandharipande, Nathan E Brummel, James C Jackson, Mayur B Patel, Christopher G Hughes, Rameela Chandrasekhar, Brenda T Pun, Leanne M Boehm, Mark R Elstad, Richard B Goodman, Gordon R Bernard, Robert S Dittus, E W Ely
BACKGROUND: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment. METHODS: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study...
March 2018: Lancet Respiratory Medicine
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
#9
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/29428024/effect-of-systemic-triphenylphosphonium-on-organ-function-and-oxidative-stress
#10
Rebecca D Powell, Donna A Goodenow, A Britton Christmas, Iain H Mckillop, Susan L Evans
Conditions of systemic stress can lead to increased reactive oxygen species production, mitochondrial dysfunction, systemic inflammation, and multiorgan dysfunction. Triphenylphosphonium (TPP+) is a lipophilic cation used to target therapeutics to mitochondria. We sought to determine the effects of TPP+ on mitochondrial integrity. Male rats were anesthetized and TPP+ (5 mg/kg) or vehicle (saline) was administered intravenously 30-minutes after anesthesia initiation and intraperitoneally (20 mg/kg) 60-minutes later...
January 1, 2018: American Surgeon
https://www.readbyqxmd.com/read/29399736/oxygen-drives-hepatocyte-differentiation-and-phenotype-stability-in-liver-cell-lines
#11
Martien van Wenum, Aziza A A Adam, Vincent A van der Mark, Jung-Chin Chang, Manon E Wildenberg, Erik J Hendriks, Aldo Jongejan, Perry D Moerland, Thomas M van Gulik, Ronald P Oude Elferink, Robert A F M Chamuleau, Ruurdtje Hoekstra
The in vitro generation of terminally differentiated hepatocytes is an unmet need. We investigated the contribution of oxygen concentration to differentiation in human liver cell lines HepaRG and C3A. HepaRG cells were cultured under hypoxia (5%O2 ), normoxia (21%O2 ) or hyperoxia (40%O2 ). Cultures were analysed for hepatic functions, gene transcript levels, and protein expression of albumin, hepatic transcription factor CEBPα, hepatic progenitor marker SOX9, and hypoxia inducible factor (HIF)1α. C3A cells were analysed after exposure to normoxia or hyperoxia...
February 4, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29396500/hepatocellular-carcinoma-targeting-oncolytic-adenovirus-overcomes-hypoxic-tumor-microenvironment-and-effectively-disperses-through-both-central-and-peripheral-tumor-regions
#12
A-Rum Yoon, JinWoo Hong, Minjung Kim, Chae-Ok Yun
Cancer-specific promoter driven replication of oncolytic adenovirus (Ad) is cancer-specific, but shows low transcriptional activity. Thus, we generated several chimeric α-fetoprotein (AFP) promoter variants, containing reconstituted enhancer and silencer regions, to preferentially drive Ad replication in hepatocellular carcinoma (HCC). Modified AFP promoter, containing 2 enhancer A regions and a single enhancer B region (a2bm), showed strong and HCC-specific transcription. In AFP-positive HCCs, gene expression was 43- to 456-fold higher than those of control AFP promoter lacking enhancers...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29383510/epidemiology-causes-evolution-and-outcome-in-a-single-center-cohort-of-1116-critically-ill-patients-with-hypoxic-hepatitis
#13
Astrid Van den Broecke, Laura Van Coile, Alexander Decruyenaere, Kirsten Colpaert, Dominique Benoit, Hans Van Vlierberghe, Johan Decruyenaere
BACKGROUND: Hypoxic hepatitis (HH) is a type of acute hepatic injury that is histologically characterized by centrilobular liver cell necrosis and that is caused by insufficient oxygen delivery to the hepatocytes. Typical for HH is the sudden and significant increase of aspartate aminotransferase (AST) in response to cardiac, circulatory or respiratory failure. The aim of this study is to investigate its epidemiology, causes, evolution and outcome. METHODS: The screened population consisted of all adults admitted to the intensive care unit (ICU) at the Ghent University Hospital between January 1, 2007 and September 21, 2015...
January 30, 2018: Annals of Intensive Care
https://www.readbyqxmd.com/read/29360756/selective-blockade-of-the-metabotropic-glutamate-receptor-mglur5-protects-mouse-livers-in-in-vitro-and-ex-vivo-models-of-ischemia-reperfusion-injury
#14
Andrea Ferrigno, Clarissa Berardo, Laura Giuseppina Di Pasqua, Veronica Siciliano, Plinio Richelmi, Ferdinando Nicoletti, Mariapia Vairetti
2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be self-contradictory, since ATP depletion is a fundamental stressor in ischemia. This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion and the consequences of ATP depletion on protection against ischemic injury. We compared the effects of MPEP and other mGluR5 negative modulators on ATP concentration when measured in rat hepatocytes and acellular solutions...
January 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29359998/prolongation-of-liver-specific-function-for-primary-hepatocytes-maintenance-in-3d-printed-architectures
#15
Yohan Kim, Kyojin Kang, Sangtae Yoon, Ji Sook Kim, Su A Park, Wan Doo Kim, Seung Bum Lee, Ki-Young Ryu, Jaemin Jeong, Dongho Choi
Isolated primary hepatocytes from the liver are very similar to in vivo native liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells (MSCs) as an attractive assistant cell source to extend lifespan can be used, it cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture leads to cell death because of hypoxic stress. Therefore, to overcome the drawback of 2D and 3D organoids, we try to use a 3D printing technique using alginate hydrogels with primary hepatocytes and MSCs...
January 23, 2018: Organogenesis
https://www.readbyqxmd.com/read/29357720/severity-of-asphyxia-is-a-covariate-of-phenobarbital-clearance-in-newborns-undergoing-hypothermia
#16
Pavla Pokorná, Lenka Posch, Martin Šíma, Petr Klement, Ondrej Slanar, John van den Anker, Dick Tibboel, Karel Allegaert
AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution volume (Vd) and elimination half-life (t1/2 ) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (Tnorm aEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7...
February 5, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29316220/interactive-effects-of-hypoxia-and-pcb-co-exposure-on-expression-of-cyp1a-and-its-potential-regulators-in-atlantic-croaker-liver
#17
Md Saydur Rahman, Peter Thomas
Although marine and coastal environments which are contaminated with xenobiotic organic compounds often become hypoxic during the summer, the interactive effects of hypoxia and xenobiotic exposure on marine species such as teleost fishes remain poorly understood. The expression and activity of monooxygenase enzyme cytochrome P450-1A (CYP1A) in fishes are upregulated by exposure to polychlorinated biphenyls (PCBs), whereas they are down-regulated during hypoxia exposure. We investigated the interactive effects of hypoxia and PCB co-exposure on hepatic CYP1A expression in Atlantic croaker and on potential regulators of CYP1A...
April 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29311395/risk-and-prognosis-of-acute-liver-injury-among-hospitalized-patients-with-hemodynamic-instability-a-nationwide-analysis
#18
Najeff Waseem, Berkeley N Limketkai, Brian Kim, Tinsay Woreta, Ahmet Gurakar, Po-Hung Chen
Risk and Prognosis of Acute Liver Injury Among Hospitalized Patients with Hemodynamic Instability: A Nationwide Analysis Introduction and aim. Critically ill patients in states of circulatory failure are at risk of acute liver injury, from mild elevations in aminotransferases to substantial rises consistent with hypoxic hepatitis or "shock liver". The present study aims to quantify the national prevalence of acute liver injury in patients with hemodynamic instability, identify risk factors for its development, and determine predictors of mortality...
January 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29299120/hif-1%C3%AE-contributes-to-hypoxia-adaptation-of-the-naked-mole-rat
#19
Bang Xiao, Shiyong Wang, Guoshi Yang, Xiaoxi Sun, Shanmin Zhao, Lifang Lin, Jishuai Cheng, Wenjing Yang, Wei Cong, Wei Sun, Guanghan Kan, Shufang Cui
Background/Aims: Naked mole rats (NMRs) spend their lives in burrow systems containing very low levels of oxygen, indicating long-term hypoxic exposure, and suggesting that pathological changes caused by hypoxia are attenuated or absent in this hypoxia-tolerant species. The mechanisms underlying NMRs hypoxia tolerance remain poorly understood. In this study, we explored whether hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) play a role in NMRs adaption to hypoxia...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29262398/characteristic-microrna-expression-induced-by-%C3%AE-opioid-receptor-activation-in-the-rat-liver-under-prolonged-hypoxia
#20
Feng Zhi, Naiyuan Shao, Lian Xue, Yuan Xu, Xuezhi Kang, Yilin Yang, Ying Xia
BACKGROUND/AIMS: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia...
2017: Cellular Physiology and Biochemistry
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