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https://www.readbyqxmd.com/read/27922198/dnmt1-modulation-in-chronic-hepatitis-b-patients-and-hypothetic-influence-on-mitochondrial-dna-methylation-status-during-long-term-nucleo-t-side-analogues-therapy
#1
Giordano Madeddu, Silvia Ortu, Giovanni Garrucciu, Ivana Maida, Michela Melis, Alberto Augusto Muredda, Maria Stella Mura, Sergio Babudieri
Inhibition of viral replication is the most important goal in patients with Hepatitis B virus chronic infection (CHB). Currently, five oral nucleo(t)side analogues (NAs), including Lamivudine, Adefovir, Telbivudine, Entecavir and Tenofovir, have been approved for treatment. The widespread use of NAs has also been linked with a progressive growth of unlikely anomaly attributable to mitochondrial dysfunctions, not previously recognized. Here we explore the hypothesis that NAs may cause persistent epigenetic changes during prolonged NAs therapy in CHB patients...
December 6, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27917591/the-pde4-inhibitor-roflumilast-reduces-weight-gain-by-increasing-energy-expenditure-and-leads-to-improved-glucose-metabolism
#2
Julia Möllmann, Florian Kahles, Corinna Lebherz, Ben Kappel, Christer Baeck, Frank Tacke, Christian Werner, Massimo Federici, Nikolaus Marx, Michael Lehrke
AIMS: The PDE4 inhibitor roflumilast is a clinically approved anti-inflammatory drug used for the treatment of chronic obstructive pulmonary disease. In addition, roflumilast was found to reduce body weight and improve glucose metabolism by a yet unknown mechanism. MATERIALS AND METHODS: Metabolic effects of roflumilast were investigated in C57BL/6J mice on high fat western-type diet treated with or without roflumilast for a period of 12 weeks. RESULTS: Roflumilast led to a marked reduction of body weight gain, which became apparent in the second week following treatment initiation and was attributable to a pronounced increase of energy expenditure...
December 5, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27917263/changes-in-cellular-proliferation-and-plasma-products-are-associated-with-liver-failure
#3
Juliana Gil Melgaço, Frederico Marianetti Soriani, Pedro Henrique Ferreira Sucupira, Leonardo Assaf Pinheiro, Yasmine Rangel Vieira, Jaqueline Mendes de Oliveira, Lia Laura Lewis-Ximenez, Cristina Carvalho Vianna Araújo, Lúcio Filgueiras Pacheco-Moreira, Gustavo Batista Menezes, Oswaldo Gonçalves Cruz, Claudia Lamarca Vitral, Marcelo Alves Pinto
AIM: To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis. METHODS: Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27916511/liqustri-lucidi-fructus-inhibits-hepatic-injury-and-functions-as-an-antioxidant-by-activation-of-amp-activated-protein-kinase-in-vivo-and-in-vitro
#4
Hye Lim Seo, Su Youn Baek, Eun Hye Lee, Ju-Hee Lee, Seul-Gi Lee, Kwang-Youn Kim, Mi Hee Jang, Min-Hui Park, Joung-Hee Kim, Keun-Jun Kim, Hyeong Sik Lee, Soon-Cheol Ahn, Jong Rok Lee, Sook Jahr Park, Sang Chan Kim, Young Woo Kim
Medicinal herbs are used to treat or prevent various diseases, and function to regulate protective mechanisms as nutraceuticals. Fructus Ligustri lucidi is the fruit of Ligustrum lucidum and has been used for its tonic effects on the liver. This study was designed to examine the effects of Fructus Ligustri lucidi water extract (FLL) against severe oxidative stress and mitochondrial impairment in vivo and in vitro and to elucidate its cellular mechanisms of action. Treatment of HepG2 cells with arachidonic acid (AA) + iron successfully induced oxidative stress and apoptosis, as indicated by depletion of glutathione, formation of ROS, increases in mitochondrial membrane permeability (MMP), and altered expression of apoptosis-related proteins, such as procaspase-3 and Bcl-xL...
December 1, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27916083/-effects-of-chronic-intermittent-hypoxia-on-hepatic-function-and-protective-mechanism-of-adiponectin-in-rats
#5
R Xue, J Cao, X L Zhang, W X Ding, W J Wang, H P Huang
Objective: To explore the effect of chronic intermittent hypoxia (CIH) on rats hepatic function, and the protective mechanism of adiponectin (Ad). Methods: Sixty healthy male wistar rats were randomly divided into 4 groups: normal control (NC), NC+ Ad, CIH, and CIH+ Ad groups with 15 rats in each. The rats in CIH and CIH+ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC + Ad groups were housed with normal pressure air. The rats in the NC+ Ad and CIH+ Ad groups were additionally treated with an intravenous injection of Ad (10 μg), twice a week for 4 months...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27915142/atrazine-triggers-hepatic-oxidative-stress-and-apoptosis-in-quails-coturnix-c-coturnix-via-blocking-nrf2-mediated-defense-response
#6
Cong Zhang, Xue-Nan Li, Li-Run Xiang, Lei Qin, Jia Lin, Jin-Long Li
The bioaccumulation and environmental persistence of atrazine (ATZ) poses a severe hazard to animal ecosystem. Quail has strong sensitivity to environmental pollutant, thus it is one of the most important ecological pollution indicator. However, true proof for the effects of ATZ exposure on the liver of quails is lacking. To evaluate the liver injury and the role of Nrf2-mediated defense responses during ATZ exposure, male quails were treated with ATZ (0, 50, 250 and 500mg/kg) by oral gavage for 45 days. Histopathological and ultrastructural changes, oxidative stress indices, apoptosis-related factors and Nrf2 pathway were detected...
December 1, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27904677/an-engineered-fgf21-variant-ly2405319-can-prevent-non-alcoholic-steatohepatitis-by-enhancing-hepatic-mitochondrial-function
#7
Ju Hee Lee, Yea Eun Kang, Joon Young Chang, Ki Cheol Park, Hyeon-Woo Kim, Jung Tae Kim, Hyun Jin Kim, Hyon-Seung Yi, Minho Shong, Hyo Kyun Chung, Koon Soon Kim
Non-alcoholic fatty liver disease (NAFLD) is a prevalent obesity-related disease that affects large populations throughout the world due to excessive calorie intake and an increasingly sedentary lifestyle. Fibroblast growth factor 21 (FGF21) has recently emerged as a promising therapeutic candidate for the treatment of obesity and diabetes. FGF21 is a starvation-induced pleiotropic hormone with various beneficial metabolic effects, and pharmacological treatment in rodents has been shown to improve insulin sensitivity and decrease simple fatty liver disease...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903836/sericin-ameliorated-dysmorphic-mitochondria-in-high-cholesterol-diet-streptozotocin-rat-by-antioxidative-property
#8
Sumate Ampawong, Duangnate Isarangkul, Pornanong Aramwit
Sericin has been implicated in lower cholesterolemic effect due to its properties with several mechanisms. Mitochondria are one of the most important targets to be affected in high blood cholesterol and glucose conditions. The protective role of sericin on mitochondria remains doubtful. To examine this role, electron microscopic, histopathologic, immunohistochemical, and biochemical studies were performed in a high-cholesterol diet/streptozotocin rat model. The results demonstrated that sericin reduced blood cholesterol without hypoglycemic effect...
November 29, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27901267/binge-alcohol-intake-after-hypergravity-stress-sustainably-decreases-ampk-and-transcription-factors-necessary-for-hepatocyte-survival
#9
Sang Gil Lee, Hong Min Wu, Chan Gyu Lee, Choong Sik Oh, So Won Chung, Sang Geon Kim
BACKGROUND: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival...
November 30, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27899483/integrin-linked-kinase-is-necessary-for-the-development-of-diet-induced-hepatic-insulin-resistance
#10
Ashley S Williams, Elijah Trefts, Louise Lantier, Carrie Grueter, Deanna P Bracy, Freyja D James, Ambra Pozzi, Roy Zent, David H Wasserman
The liver extracellular matrix (ECM) expands with high fat (HF) feeding. This finding led us to address whether receptors for the ECM, integrins, are key to the development of diet-induced hepatic insulin resistance. Integrin-linked kinase (ILK) is a downstream integrin signaling molecule involved in multiple hepatic processes including those related to differentiation, wound healing and metabolism. We tested the hypothesis that deletion of ILK in mice on a HF diet would disrupt the ECM-Integrin signaling axis thereby preventing the transformation into the insulin resistant liver...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27890722/diabetes-induced-hepatic-oxidative-stress-a-new-pathogenic-role-for-glycated-albumin
#11
Jessica Patche, Dorothée Girard, Aurélie Catan, Florence Boyer, Anthony Dobi, Cynthia Planesse, Nicolas Diotel, Alexis Guerin-Dubourg, Pascal Baret, Susana B Bravo, Beatriz Paradela-Dobarro, Ezequiel Álvarez, M Faadiel Essop, Olivier Meilhac, Emmanuel Bourdon, Philippe Rondeau
Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#12
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27886623/liver-bcatm-transgenic-mouse-model-reveals-the-important-role-of-the-liver-in-maintaining-bcaa-homeostasis
#13
Elitsa A Ananieva, Cynthia G Van Horn, Meghan R Jones, Susan M Hutson
Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted...
November 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27886086/ligustrazine-oleanolic-acid-glycine-derivative-g-toa-selectively-inhibited-the-proliferation-and-induced-apoptosis-of-activated-hsc-t6-cells
#14
Siling Bi, Fuhao Chu, Mina Wang, Bi Li, Pei Mao, Huazheng Zhang, Penglong Wang, Wenbo Guo, Liang Xu, Liwei Ren, Haimin Lei, Yuzhong Zhang
Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA)...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27885055/17b-estradiol-improves-hepatic-mitochondrial-biogenesis-and-function-through-pgc1b
#15
Bel M Galmés-Pascual, Antonia Nadal-Casellas, Marco Bauza-Thorbrügge, Miquel Sbert-Roig, Francisco José García-Palmer, Am Proenza, Magdalena Gianotti, Isabel Llado
Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17b-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects...
November 24, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27880981/a-novel-glucagon-like-peptide-1-glucagon-receptor-dual-agonist-improves-steatohepatitis-and-liver-regeneration-in-mice
#16
M Pilar Valdecantos, Virginia Pardo, Laura Ruiz, Luis Castro-Sánchez, Borja Lanzón, Elisa Fernández-Millán, Carmelo García-Monzón, Ana I Arroba, Águeda González-Rodríguez, Fernando Escrivá, Álvarez Carmen, Francisco J Rupérez, Coral Barbas, Anish Konkar, Jacqui Naylor, David Hornigold, Ana Dos Santos, Maria Bednarek, Joseph Grimsby, Cristina M Rondinone, Ángela M Valverde
BACKGROUND AND AIMS: Since non-alcoholic steatohepatitis (NASH) is associated with impaired liver regeneration, we investigated the effects of G49, a dual glucagon-like peptide-1(GLP-1)/glucagon (GCG) receptor agonist, on NASH and hepatic regeneration. METHODS: C57Bl/6 mice fed chow or methionine and choline-deficient (MCD) diet for one week were divided into 4 groups: C (chow diet), MCD (MCD diet), C+G49 (chow diet plus G49) and M+G49 (MCD diet plus G49). Mice fed high fat diet (HFD) for 10 weeks were divided in groups: HFD and H+G49 (HFD plus G49)...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27873239/effects-of-acetaminophen-on-mitochondrial-complex-i-activity-in-the-rat-liver-and-kidney-a-pet-study-with-18-f-bcpp-bf
#17
Hiroyuki Ohba, Masakatsu Kanazawa, Takeharu Kakiuchi, Hideo Tsukada
BACKGROUND: In the present study, 2-tert-butyl-4-chloro-5-[6-(4-(18)F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one ((18)F-BCPP-BF), a PET probe for mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful biomarker for detecting acetaminophen-induced dysfunctions in the liver and kidney. The kinetic and distribution of (18)F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of (18)F-BCPP-BF to MC-I in the liver and kidney was confirmed by the pre-administration of rotenone, a specific MC-I inhibitor...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27868245/the-influence-of-sex-and-gonadectomy-on-hepatic-and-brain-fatty-acid-composition-lipogenesis-and-%C3%AE-oxidation
#18
K Starčević, N Filipović, M Šperanda, M Đidara, T Mašek
The aim of this study was to investigate the influence of sex and castration of rats on liver and brain fatty acid profile and liver mRNA expression of genes involved in lipogenesis and β-oxidation. Castration significantly increased body weight and liver index and decreased serum triglyceride content in the female rats. The fatty acid composition of the liver tissue was influenced by sex and castration. Male rats had higher content of C16:0, C18:1n7, C18:2n6 and C22:5n3, while female rats had higher content of C18:0, C20:4n6 and C22:6n3...
November 21, 2016: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/27866076/antioxidant-properties-of-tea-blunt-ros-dependent-lipogenesis-beneficial-effect-on-hepatic-steatosis-in-a-high-fat-high-sucrose-diet-nafld-obese-rat-model
#19
Laura Braud, Sylvain Battault, Grégory Meyer, Alessandro Nascimento, Sandrine Gaillard, Georges de Sousa, Roger Rahmani, Catherine Riva, Martine Armand, Jean-Michel Maixent, Cyril Reboul
Oxidative stress could trigger lipid accumulation in liver and thus hepatic steatosis. Tea is able to prevent liver disorders, but a direct link between antioxidant capacities and prevention of steatosis has not been reported yet. We aimed to investigate such relationship in a rat model of high fat-high sucrose diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated hepatocytes. Wistar rats were divided into a control group (standard diet), an HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum access to tea drink)...
October 29, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#20
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
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