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https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#1
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28522403/multiplex-autoantibody-detection-for-autoimmune-liver-diseases-and-autoimmune-gastritis
#2
Joris Vanderlocht, Mart van der Cruys, Frans Stals, Liesbeth Bakker-Jonges, Jan Damoiseaux
Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs...
May 15, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#3
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515388/nitric-oxide-is-critical-for-avoiding-hepatic-lipid-overloading-via-il6-induction-during-liver-regeneration-after-partial-hepatectomy-in-mice
#4
Yue Yu, Miho Tamai, Yoh-Ichi Tagawa
Nitric oxide (NO), generated from L-arginine by three different isoforms of nitric oxide synthase (NOS), is a pleiotropic factor to regulate physiological functions in almost every organ and tissue. Each knockout mouse of iNOS or eNOS has been used to suggest that NO has a crucial role in liver regeneration after partial hepatectomy (PH), for NO may inhibit caspase 3 activity and is required for EGFR signaling. In previous reports, defective mitochondrial β-oxidation was observed in eNOS KO mice, and hepatic steatosis was often correlated to deficient liver regeneration, so we focused on metabolic perspective and hypothesized that NO depletion in PH mice would affect hepatocytic lipolysis and impair hepatocytes proliferation...
May 18, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28515350/fam3a-enhances-adipogenesis-of-3t3-l1-preadipocytes-via-activation-of-atp-p2-receptor-akt-signaling-pathway
#5
Yujing Chi, Jing Li, Na Li, Zhenzhen Chen, Liping Ma, Weikang Peng, Xiuying Pan, Mei Li, Weidong Yu, Xiangjun He, Bin Geng, Qinghua Cui, Yulan Liu, Jichun Yang
FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and the proliferation of VSMCs. This study determined the role and mechanism of FAM3A in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1 preadipocytes, FAM3A expression was significantly increased. FAM3A overexpression enhanced 3T3-L1 preadipocyte adipogenesis with increased phosphorylated Akt (pAkt) level, whereas FAM3A silencing inhibited 3T3-L1 preadipocyte adipogenesis with reduced pAkt level. Moreover, FAM3A silencing reduced the expression and secretion of adipokines in 3T3-L1 cells...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508193/neutrophil-depletion-improves-diet-induced-non-alcoholic-fatty-liver-disease-in-mice
#6
Rongying Ou, Jia Liu, Mingfen Lv, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao, Yunsheng Xu
PURPOSE: Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. METHODS: To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks...
April 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28504722/thyroid-hormone-protects-hepatocytes-from-hbx-induced-carcinogenesis-by-enhancing-mitochondrial-turnover
#7
H-C Chi, S-L Chen, S-L Lin, C-Y Tsai, W-Y Chuang, Y-H Lin, Y-H Huang, M-M Tsai, C-T Yeh, K-H Lin
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28504310/aerobic-capacity-mediates-susceptibility-for-the-transition-from-steatosis-to-steatohepatitis
#8
E Matthew Morris, Colin S McCoin, Julie A Allen, Michelle L Gastecki, Lauren G Koch, Steven L Britton, Justin A Fletcher, Xiarong Fu, Wen-Xing Ding, Shawn C Burgess, R Scott Rector, John P Thyfault
BACKGROUND & AIMS: Low aerobic capacity increases risk for NAFLD and liver-related disease mortality, but mechanisms mediating these effects remain unknown. We recently reported that rats bred for low aerobic capacity (low capacity runner (LCR)) displayed susceptibility to high-fat diet-induced steatosis in association with reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity compared to high aerobic capacity (high capacity runners (HCR)) rats. Here we tested the impact of aerobic capacity on susceptibility for progressive liver disease following a 16 week 'western diet' high in fat (45% kcal), cholesterol (1% w w(-1) ), and sucrose (15% kcal)...
May 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28503408/trifluoperazine-inhibits-acetaminophen-induced-hepatotoxicity-and-hepatic-reactive-nitrogen-formation-in-mice-and-in-freshly-isolated-hepatocytes
#9
Sudip Banerjee, Stepan B Melnyk, Kimberly J Krager, Nukhet Aykin-Burns, Sandra S McCullough, Laura P James, Jack A Hinson
The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28502921/umbilical-cord-mscs-reverse-d-galactose-induced-hepatic-mitochondrial-dysfunction-via-activation-of-nrf2-ho-1-pathway
#10
Weihong Yan, Dong Li, Tong Chen, Guiying Tian, Panpan Zhou, Xiuli Ju
Mitochondria are the central hubs for cellular bioenergetics and are crucial to cell survival. It is well accepted that compromised mitochondrial function is linked with hepatocytes injury and contribute to progression of liver diseases. Despite the therapeutic potential of mesenchymal stem cells (MSCs) transplantation on hepatic disorders have been extensively investigated, the effects of MSCs on mitochondrial function in liver injury models remain unknown. Here we investigated the effects of treatment with umbilical cord (UC) MSC in a rat model of D-Gal induced liver injury, characterized by organ damage, oxidative stress and mitochondrial dysfunction...
May 13, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28500970/histopathological-changes-and-lipid-metabolism-in-the-liver-of-bufo-gargarizans-tadpoles-exposed-to-triclosan
#11
Lihong Chai, Aixia Chen, Pingping Luo, Hongfeng Zhao, Hongyuan Wang
In the current study, the adverse effects of TCS on liver health of B. gargarizans tadpoles were assessed. B. gargarizans larvae were exposed to TCS at 0, 10, 30, 60, and 150 μg L(-1) from Gosner stage 3 until metamorphic climax. The hepatosomatic index (HSI), hepatic histological and ultrastructural features, and transcript levels of genes associated with detoxification and oxidative stress as well as lipid metabolism in the livers were determined. Exposure to 150 μg L(-1) TCS resulted in increased HSI of tadpoles at metamorphic climax...
May 7, 2017: Chemosphere
https://www.readbyqxmd.com/read/28499395/time-course-of-blood-lactate-levels-inflammation-and-mitochondrial-function-in-experimental-sepsis
#12
Thiago Domingos Corrêa, Adriano José Pereira, Sebastian Brandt, Madhusudanarao Vuda, Siamak Djafarzadeh, Jukka Takala, Stephan Mathias Jakob
BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each)...
May 12, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28494547/-dynamic-expression-of-carnitine-palmitoyltransferase-ii-in-the-mitochondrial-inner-membrane-during-hepatocyte-malignant-transformation-induced-by-lipid-accumulation
#13
J J Gu, M Yao, Y Cai, M Fang, L Wang, W J Zheng, D B Yao, Z Z Dong, D F Yao
Objective: To investigate the dynamic expression of hepatic carnitine palmitoyltransferase-II (CPT-II) in the mitochondrial inner membrane during hepatocyte malignant transformation induced by lipid accumulation. Methods: Male Sprague-Dawley rats were divided randomly into control, fatty liver, and induced cancer groups, which were fed with normal, high-fat (HF), and HF containing 2-fluorenylacetamide (0.05%, 2-FAA) diets, respectively, for 14 weeks. One rat from each group was sacrificed every two weeks and the blood and liver samples were collected...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28493820/deoxyguanosine-kinase-deficiency-a-report-of-four-patients
#14
Özlem Ünal, Burcu Hişmi, Mustafa Kılıç, Hayriye Hızarcıoğlu Gülşen, Turgay Coşkun, Serap Hatice Sivri, Ali Dursun, Aysel Yüce, Ayşegül Tokatlı
BACKGROUND: Hepatic involvement is a common feature in childhood mitochondrial disorders. Deoxyguanosine kinase (DGUOK) deficiency is one of the mitochondrial DNA depletion syndromes associated with hepatocerebral syndrome. Hepatic disease and neurologic dysfunction occurs within weeks after birth. Low birth weight is one of the common features. This study aims to describe the clinical and laboratory features of four infants carrying four different pathogenic variants in the DGUOK gene...
May 11, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28490733/pharmacometabolomics-for-predicting-variable-busulfan-exposure-in-paediatric-haematopoietic-stem-cell-transplantation-patients
#15
Bora Kim, Ji Won Lee, Kyung Taek Hong, Kyung-Sang Yu, In-Jin Jang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn, Joo-Youn Cho, Hyoung Jin Kang
Owing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490610/mechanisms-of-insulin-resistance-in-primary-and-secondary-non-alcoholic-fatty-liver
#16
Tomas Jelenik, Kirti Kaul, Gilles Séquaris, Ulrich Flögel, Esther Phielix, Jörg Kotzka, Birgit Knebel, Pia Fahlbusch, Tina Hörbelt, Stefan Lehr, Anna Lena Reinbeck, Dirk Müller-Wieland, Irene Esposito, Gerald I Shulman, Julia Szendroedi, Michael Roden
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose-tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific sterol regulatory-element binding protein-1c (SREBP-1c) overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol (DAG) content and protein kinase C (PKC)ε translocation...
May 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28487163/a-multi-year-study-of-hepatic-biomarkers-in-coastal-fishes-from-the-gulf-of-mexico-after-the-deepwater-horizon-oil-spill
#17
Marci Smeltz, Laura Rowland-Faux, Céline Ghiran, William F Patterson, Steven B Garner, Alan Beers, Quentin Mièvre, Andrew S Kane, Margaret O James
Following the 2010 Gulf of Mexico oil spill, concerns were raised regarding exposure of fish to crude oil components, particularly polycyclic aromatic hydrocarbons (PAHs). This three year study examined hepatic enzymes in post-mitochondrial supernatant fractions from red snapper (Lutjanus campechanus) and gray triggerfish (Balistes capriscus) collected in the north central Gulf of Mexico between 2011 and 2014. Biomarker activities evaluated included benzo(a)pyrene hydroxylase (AHH), ethoxyresorufin O-deethylase (EROD), glutathione transferase (GST), and glutathione peroxidase (GPx)...
April 27, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/28483922/quantitative-micro-spectroscopic-imaging-reveals-viral-and-cellular-rna-helicase-interactions-in-live-cells
#18
M J Corby, Michael R Stoneman, Gabriel Biener, Joel D Paprocki, Rajesh Kolli, Valerica Raicu, David N Frick
Human cells detect RNA viruses through a set of helicases called RIG-I like receptors (RLRs) that initiate the interferon response via a mitochondrial signaling complex. Many RNA viruses also encode helicases, which sometimes are covalently linked to proteases that cleave signaling proteins. One unresolved question is how RLRs interact with each other and with viral proteins in cells. This study examined the interactions among the hepatitis C virus (HCV) helicase and RLR helicases in live cells with quantitative micro-spectroscopic imaging (Q-MSI), a technique that determines Forster Resonance Energy Transfer (FRET) efficiency and sub-cellular donor and acceptor concentrations...
May 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28482236/ablation-of-%C3%AE-%C3%AE-carotene-9-10-oxygenase-2-remodels-the-hypothalamic-metabolome-leading-to-metabolic-disorders-in-mice
#19
Xin Guo, Lei Wu, Yi Lyu, Winyoo Chowanadisai, Stephen L Clarke, Edralin A Lucas, Brenda J Smith, Hui He, Weiqun Wang, Denis M Medeiros, Dingbo Lin
β,β-Carotene-9',10'-oxygenase 2 (BCO2) is a protein localized to the inner membrane of mitochondria. It was initially discovered as an enzyme that catalyzes the asymmetric cleavage of carotenoids. Systemic depletion of BCO2 causes increased food intake and impaired hepatic lipid metabolism in mice. The aim of this current study was to determine the extent to which BCO2 exerts its role in hypothalamic nutrient metabolism and feeding behavior through remodeling the hypothalamic metabolome in mice. Male BCO2 knockout (KO) and the isogenic wild-type 129S6 (WT) mice at 6 weeks of age were used for metabolic and cytokine and hypothalamic metabolomics and biochemical analysis...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28480979/down-regulation-of-trif-tlr3-and-mavs-in-hcv-infected-liver-correlates-with-the-outcome-of-infection
#20
Premashis Kar, Deepak Kumar, Phani Kumar Gumma, Soumya Jyoti Chowdhury, Vijay Kumar Karra
AIMS: In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF) and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF and TRAF6 outcome of HCV infection...
May 8, 2017: Journal of Medical Virology
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