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https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#1
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28633871/high-fat-diet-induced-plasma-protein-and-liver-changes-in-obese-rats-can-be-attenuated-by-melatonin-supplementation
#2
Prapimpun Wongchitrat, Paul Klosen, Supitcha Pannengpetch, Kuntida Kitidee, Piyarat Govitrapong, Chartchalerm Isarankura-Na-Ayudhya
Obesity triggers changes in protein expression in various organs that might participate in the pathogenesis of obesity. Melatonin has been reported to prevent or attenuate such pathological protein changes in several chronic diseases. However, such melatonin effects on plasma proteins have not yet been studied in an obesity model. Using a proteomic approach, we investigated the effect of melatonin on plasma protein profiles after rats were fed a high-fat diet (HFD) to induce obesity. We hypothesized that melatonin would attenuate abnormal protein expression in obese rats...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28632778/over-expressing-the-soluble-gp130-fc-does-not-ameliorate-methionine-and-choline-deficient-diet-induced-non-alcoholic-steatohepatitis-in-mice
#3
Helene L Kammoun, Tamara Louise Allen, Darren Colin Henstridge, Michael James Kraakman, Lone Peijs, Stefan Rose-John, Mark Anthony Febbraio
Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice...
2017: PloS One
https://www.readbyqxmd.com/read/28632732/fructo-oligosaccharides-and-intestinal-barrier-function-in-a-methionine-choline-deficient-mouse-model-of-nonalcoholic-steatohepatitis
#4
Kotaro Matsumoto, Mayuko Ichimura, Koichi Tsuneyama, Yuki Moritoki, Hiromichi Tsunashima, Katsuhisa Omagari, Masumi Hara, Ichiro Yasuda, Hiroshi Miyakawa, Kentaro Kikuchi
Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet...
2017: PloS One
https://www.readbyqxmd.com/read/28630652/verification-of-b-lymphocyte-activating-factor-s-involvement-in-the-exacerbation-of-insulin-resistance-as-well-as-an-autoimmune-response-in-patients-with-nonalcoholic-steatohepatitis-and-patients-with-hcv-related-chronic-liver-disease
#5
Takashi Himoto, Koji Fujita, Takako Nomura, Joji Tani, Asahiro Morishita, Hirohito Yoneyama, Reiji Haba, Tsutomu Masaki
BACKGROUND: Ten to forty percent of nonalcoholic steatohepatitis (NASH) and HCV-related chronic liver disease (CLD-C) patients have antinuclear antibodies (ANAs). However, the relationship between autoimmune response and insulin resistance remains uncertain among those patients. The primary purpose of this study was to investigate whether or not ANA status was associated with the development of insulin resistance and obesity in NASH and CLD-C patients. METHODS: Degrees of hepatic fibrosis and steatosis were evaluated by the classification proposed by Brunt et al...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28629281/noninvasive-quantitative-assessment-of-hepatic-steatosis-by-proton-magnetic-resonance-spectroscopy-among-adult-patients-receiving-home-parenteral-nutrition
#6
Angelique Huijbers, Geert Wanten, Helena Maria Dekker, Marinette van der Graaf
BACKGROUND: Intestinal failure-associated liver disease is a frequent complication in patients with chronic intestinal failure (CIF), with steatosis as a dominant feature in adults. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive method to quantify liver fat content (LFC). In this study, LFC was assessed with 1H-MRS, taking into account the possible accumulation of paramagnetic components of home parenteral nutrition (HPN) that may disturb these measurements. METHODS: LFC was measured in 15 adult CIF patients who had been receiving HPN for >6 months...
June 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28628674/hepatic-microvascular-dysfunction-and-increased-advanced-glycation-end-products-are-components-of-non-alcoholic-fatty-liver-disease
#7
Evelyn Nunes Goulart da Silva Pereira, Raquel Rangel Silvares, Edgar Eduardo Ilaquita Flores, Karine Lino Rodrigues, Isalira Peroba Ramos, Igor José da Silva, Marcelo Pelajo Machado, Rosiane Aparecida Miranda, Carmen Cabanelas Pazos-Moura, Cassiano F Gonçalves-de-Albuquerque, Hugo Caire de Castro Faria-Neto, Eduardo Tibiriça, Anissa Daliry
BACKGROUND: This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). METHODS: In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28627473/glycyrrhetic-acid-but-not-glycyrrhizic-acid-strengthened-entecavir-activity-by-promoting-its-subcellular-distribution-in-the-liver-via-efflux-inhibition
#8
Qianying Chen, Hongzhu Chen, Wenjie Wang, Jiali Liu, Wenyue Liu, Ping Ni, Guowei Sang, Guangji Wang, Fang Zhou, Jingwei Zhang
Entecavir (ETV) is a superior nucleoside analogue used to treat hepatitis B virus (HBV) infection. Although its advantages over other agents include low viral resistance and the elicitation of a sharp decrease in HBV DNA, adverse effects such as hepatic steatosis, hepatic damage and lactic acidosis have also been reported. Glycyrrhizin has long been used as hepato-protective medicine. The clinical combination of ETV plus glycyrrhizin in China displays better therapeutic effects and lower rates of liver damage...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28626963/exercise-training-modulates-the-hepatic-renin-angiotensin-system-in-fructose-fed-rats
#9
Eliete Dalla Corte Frantz, Renata Frauches Medeiros, Isabele Gomes Giori, Juliana Bittencourt Silveira Lima, Thais Bento-Bernardes, Thaiane Gadioli Gaique, Caroline Fernandes-Santos, Tiago Fernandes, Edilamar Menezes Oliveira, Carla Paulo Vieira, Carlos Adam Conte-Junior, Karen Jesus Oliveira, Antonio Claudio Lucas da Nóbrega
The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and if this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high fructose (HFr) and exercise high fructose (HFr-Ex) groups. Fructose-drinking rats received D-fructose (100 g L(-1) ). After two weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate-intensity for eight weeks (60 min day(-1) , four days/week)...
June 19, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#10
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28626141/dietary-starfish-oil-prevents-hepatic-steatosis-and-hyperlipidemia-in-c57bl-6n-mice-fed-high-fat-diet
#11
Fumiaki Beppu, Haoqi Li, Kazuaki Yoshinaga, Toshiharu Nagai, Akihiko Yoshinda, Atsushi Kubo, Jota Kanda, Naohiro Gotoh
Starfish oil (SO) is characterized by functional lipids, including n-3 polyunsaturated fatty acid (both in the form of triacylglycerol and in the form of phospholipid), and carotenoids, which may exert beneficial effects on metabolic disorders in obesity-associated diseases. In the present study, the effect of SO on dysregulation of lipid metabolism was examined using C57BL/6N mice treated with high-fat (HF) diet. Mice were fed HF, HF with 2% SO, or HF with 5% SO diet for 8 weeks. Weight gain, blood glucose, serum and hepatic lipid contents, and hepatic fatty acid composition were measured...
June 13, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28625086/hepatitis-c-virus-apolipoprotein-interactions-molecular-mechanisms-and-clinical-impact
#12
Emilie Crouchet, Thomas F Baumert, Catherine Schuster
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma and liver failure. Moreover, chronic HCV infection is associated with liver steatosis and metabolic disorders. With 130-150 million people chronically infected in the world, HCV infection represents a major public health problem. One hallmark on the virus is its close link with hepatic lipid and lipoprotein metabolism. Areas covered: HCV is associated with lipoprotein components such as apolipoproteins. These interactions play a key role in the viral life cycle, viral persistence and pathogenesis of liver disease...
June 17, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28624579/epigenome-wide-association-study-identifies-methylation-sites-associated-with-liver-enzymes-and-hepatic-steatosis
#13
Jana Nano, Mohsen Ghanbari, Wenshi Wang, Paul S de Vries, Klodian Dhana, Taulant Muka, André G Uitterlinden, Joyce B J van Meurs, Albert Hofman, Oscar H Franco, Qiuwei Pan, Sarwa Darwish Murad, Abbas Dehghan
BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzymes levels including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624576/agreement-between-magnetic-resonance-imaging-proton-density-fat-fraction-measurements-and-pathologist-assigned-steatosis-grades-of-liver-biopsies-from-adults-with-nonalcoholic-steatohepatitis
#14
Michael S Middleton, Elhamy R Heba, Catherine A Hooker, Mustafa R Bashir, Kathryn J Fowler, Kumar Sandrasegaran, Elizabeth M Brunt, David E Kleiner, Edward Doo, Mark L Van Natta, James Tonascia, Joel E Lavine, Brent A Neuschwander-Tetri, Arun Sanyal, Rohit Loomba, Claude B Sirlin
BACKGROUND & AIMS: We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. METHODS: We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624109/the-use-of-old-donors-in-liver-transplantation
#15
REVIEW
Bobby V M Dasari, Andrea Schlegel, Hynek Mergental, M Thamara P R Perera
The process of ageing has an impact on the entire human body including the organ systems. In transplantation, professionals are daily faced with risk assessment of suitable donor offers , whether to accept a liver graft for a specific recipient. In this context, livers from elderly donors are more frequently accepted for transplantation, to increase the donor pool and compensate the high waiting list mortality. In the current practice it is not unusual to accept 60-year old donor livers for transplantation, as the donor demographics have significantly changed over the years...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28623272/exosomes-derived-from-palmitic-acid-treated-hepatocytes-induce-fibrotic-activation-of-hepatic-stellate-cells
#16
Young-Sun Lee, So Yeon Kim, Eunjung Ko, Jun-Hee Lee, Hyon-Seung Yi, Yang Jae Yoo, Jihye Je, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Won-Il Jeong, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621339/hepatokines-linking-nonalcoholic-fatty-liver-disease-and-insulin-resistance
#17
REVIEW
Ruth C R Meex, Matthew J Watt
Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle...
June 9, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28616781/impact-of-hyperglycemia-on-cystathionine-%C3%AE-lyase-expression-during-resuscitated-murine-septic-shock
#18
Tamara Merz, Josef A Vogt, Ulrich Wachter, Enrico Calzia, Csaba Szabo, Rui Wang, Peter Radermacher, Oscar McCook
BACKGROUND: Cystathionine-γ-lyase (CSE) was shown to have a regulatory role in glucose metabolism. Circulatory shock can induce metabolic stress, thereby leading to hyperglycemia and mitochondrial dysfunction. In vitro data suggest an effect of high glucose on CSE expression. Therefore, the aim of this study was to investigate the effects of hyperglycemia on CSE expression in resuscitated murine septic shock. METHODS: Normo- (80-150 mg/dl) and hyperglycemic (>200 mg/dl) male C57/BL6J mice (n = 5-6 per group) underwent cecal ligation and puncture (CLP)-induced polymicrobial sepsis or sham procedure (n = 6 per group) and, 15 h afterwards, were anesthetized again, surgically instrumented and received intensive care treatment, including antibiotics, lung protective mechanical ventilation, circulatory support, and intravenous (i...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28614536/implications-of-alcoholic-cirrhosis-in-atherosclerosis-of-autopsied-patients
#19
Luciano Alves Matias da Silveira, Bianca Gonçalves Silva Torquato, Mariana Silva Oliveira, Guilherme Ribeiro Juliano, Lívia Ferreira Oliveira, Camila Lourencini Cavellani, Luciana Santos Ramalho, Ana Paula Espindula, Vicente de Paula Antunes Teixeira, Mara Lúcia Fonseca Ferraz
Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver...
April 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28612750/genetic-and-epigenetic-profile-of-patients-with-alcoholic-liver-disease
#20
Luigi Boccuto, Ludovico Abenavoli
Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic reactions that affect the liver by inducing lipogenesis, increasing oxidative stress, and causing abnormal inflammatory responses. The metabolic pathways regulating lipids, reactive oxygen species (ROS), and immune system are closely related and in some cases cross-regulate each other. Therefore, it must be taken into account that major genetic and epigenetic abnormalities affecting enzymes involved in one of such pathways can play a pivotal role in ALD pathogenesis...
August 1, 2017: Annals of Hepatology
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