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https://www.readbyqxmd.com/read/29656250/exposure-to-environmental-level-phenanthrene-induces-a-nash-like-phenotype-in-new-born-rat
#1
Jiaojiao Guo, Chonggang Wang, Zhizhun Guo, Zhenghong Zuo
More and more evidence indicates that persistent organic pollutants (POPs) are a risk factor for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Phenanthrene (Phe) is a kind of POP which existed extensively in the environment, but whose toxicity on mammals has so far received less focus. Subcutaneously injection of Phe (0.5, 5, 50 μg/kg) for 21 days induced significant NAFLD/NASH symptoms in new born rats. Exposure to environmental levels of Phe decreased body weight and liver-somatic index; impaired histology of liver; influenced the peroxisome proliferator-activated receptor gamma (PPARγ) signaling and lipid metabolism in liver; stimulated oxidative stress in the rats' liver; induced the variation of NFκB pathway and liver inflammatory response; and caused liver fibrosis via transforming growth factor β1 (tgfβ1)...
April 12, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29649907/farnesoid-x-receptor-modulators-2014-present-a-patent-review
#2
Valentina Sepe, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
The nuclear receptor FXR regulates the expression of genes involved in bile acids, glucose and lipid homeostasis. For its role as guardian of metabolism, FXR has been identified a promising pharmacological target in liver bile acid and lipid accumulation, such as cholestasis and non-alcoholic fatty liver disease (NAFLD). The field of FXR research is extremely competitive with a large number of patents and articles published in the last decades identifying promising hit compounds. Areas covered. The present review summarizes recent patent activity (2014-to date) filing for synthetic and natural FXR ligands, including bile acid derivatives and non-steroidal compounds, alongside their in vitro and in vivo efficacy as well as their therapeutic applications...
April 13, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29627620/efficacy-safety-and-tolerability-of-lubiprostone-for-the-treatment-of-non-alcoholic-fatty-liver-disease-in-adult-patients-with-constipation-the-lubiprone-double-blind-randomised-placebo-controlled-study-design
#3
Takaomi Kessoku, Kento Imajo, Takashi Kobayashi, Yasushi Honda, Takayuki Kato, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Takuma Higurashi, Masato Yoneda, Hiroyuki Kirikoshi, Kazuki Kubota, Masataka Taguri, Takeharu Yamanaka, Haruki Usuda, Koichiro Wada, Satoru Saito, Atsushi Nakajima
BACKGROUND: This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism...
April 5, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29609501/the-relationship-between-obesity-and-the-severity-of-non-alcoholic-fatty-liver-disease-systematic-review-and-meta-analysis
#4
Feng-Bin Lu, En-De Hu, Lan-Man Xu, Lu Chen, Jin-Lu Wu, Hui Li, Da-Zhi Chen, Yong-Ping Chen
A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive. Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies...
April 2, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29600430/targeting-incretin-hormones-and-the-ask-1-pathway-as-therapeutic-options-in-the-treatment-of-non-alcoholic-steatohepatitis
#5
REVIEW
Alexander J Kovalic, Sanjaya K Satapathy, Naga Chalasani
Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms of chronic liver disease, and its rising frequency worldwide has reached epidemic proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex, and as such myriad therapies are under investigation targeting different pathophysiological mechanisms...
March 29, 2018: Hepatology International
https://www.readbyqxmd.com/read/29599925/a-porcine-placental-extract-prevents-steatohepatitis-by-suppressing-activation-of-macrophages-and-stellate-cells-in-mice
#6
Liang Xu, Naoto Nagata, Mayumi Nagashimada, Fen Zhuge, Yinhua Ni, Guanliang Chen, Junzo Kamei, Hiroki Ishikawa, Yasuhiko Komatsu, Shuichi Kaneko, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29599631/the-effect-of-amygdalin-on-endoplasmic-reticulum-er-stress-induced-hepatic-steatosis-in-mice
#7
Azam Moslehi, Mohsen Farahabadi, Sayyed Abdollah Chavoshzadeh, Akram Barati, Shima Ababzadeh, Abolfazl Mohammadbeigi
Background: Endoplasmic reticulum (ER) stress creates abnormalities in the insulin action, inflammatory responses, lipoprotein B100 degradation, and hepatic lipogenesis. Hepatic steatosis leads to a broad spectrum of hepatic disorders such as nonalcoholic fatty liver disease (NAFLD) and NASH. Amygdalin has beneficial effects on asthma, bronchitis, diabetes, and atherosclerosis. We designed this study to evaluate the effect of amygdalin on the ER stress induced hepatic steatosis. Methods: Inbred mice received saline, DMSO and amygdalin, as control groups...
February 2018: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/29590379/increased-plasma-proneurotensin-levels-identify-nafld-in-adults-with-and-without-type-2-diabetes
#8
Ilaria Barchetta, Flavia Agata Cimini, Frida Leonetti, Danila Capoccia, Claudio Di Cristofano, Gianfranco Silecchia, Marju Orho-Melander, Olle Melander, Maria Gisella Cavallo
Context: Neurotensin (NT) is an intestinal peptide released by fat ingestion and promoting lipids absorption; higher circulating NT levels associate with type 2 diabetes (T2D), obesity and cardiovascular disease. Whether NT is related to non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) has not been fully investigated. Objective: To study the relationship between plasma proneurotensin1-117 (pro-NT), a stable fragment of the NT precursor hormone, and the presence/severity of NAFLD/NASH and to unravel correlates of increased pro-NT levels...
March 23, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29580767/fatty-liver-index-is-associated-to-pulse-wave-velocity-in-healthy-subjects-data-from-the-brisighella-heart-study
#9
Arrigo F G Cicero, Stefano Gitto, Federica Fogacci, Martina Rosticci, Marina Giovannini, Sergio D'Addato, Pietro Andreone, Claudio Borghi
BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is associated to increased risk of cardiovascular disease. Our aim was to evaluate association of indexes of fatty liver with arterial stiffness (AS). METHODS: We analyzed data of adult volunteers visited during the last Brisighella survey. We evaluated the Pulse Wave Velocity (PWV) and the following non-invasive indexes of liver steatosis: Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), Hepatic Steatosis Index (HSI)...
March 23, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29577364/screening-for-therapeutic-trials-and-treatment-indication-in-clinical-practice-mack-3-a-new-blood-test-for-the-diagnosis-of-fibrotic-nash
#10
J Boursier, R Anty, L Vonghia, V Moal, T Vanwolleghem, C M Canivet, S Michalak, S Bonnafous, P Michielsen, F Oberti, A Iannelli, L Van Gaal, S Patouraux, O Blanchet, A Verrijken, P Gual, M-C Rousselet, A Driessen, G Hunault, S Bertrais, A Tran, P Calès, S Francque
BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest...
March 25, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29574534/to-die-or-not-to-die-death-signaling-in-nonalcoholic-fatty-liver-disease
#11
REVIEW
Yuko Akazawa, Kazuhiko Nakao
Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease worldwide. In subset of patients, NAFLD progresses to its advanced form, nonalcoholic steatohepatitis (NASH), which is accompanied with inflammation and fibrosis. Saturated free fatty acid-induced hepatocyte apoptosis is a feature of NASH. Death signaling in NASH does not always result in apoptosis, but can alternatively lead to the survival of cells presenting signs of pro-inflammatory and pro-fibrotic signals. With the current lack of established treatments for NASH, it is important to understand the molecular mechanisms responsible for disease development and progression...
March 24, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29572825/new-onset-non-alcoholic-fatty-liver-disease-after-resection-of-pancreatic-neuroendocrine-tumors
#12
Tara Michella Mackay, Cansu Güney Genç, Robert Bart Takkenberg, Marc Gerard Besselink, Inne Somers, Elisabeth Jacqueline Maria Nieveen van Dijkum
BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatis (NASH) may occur after pancreatic resection due to exocrine pancreatic insufficiency (EPI). Patients with long-term survival, such as after pancreatic neuroendocrine tumor (pNET) resection, are at risk of NAFLD/NASH. We aimed to determine the incidence and risk factors for new onset NAFLD/NASH and EPI after pNET resection. METHODS: Retrospective monocenter cohort study...
March 24, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29572095/a-simple-diet-and-chemical-induced-murine-nash-model-with-rapid-progression-of-steatohepatitis-fibrosis-and-liver-cancer
#13
Takuma Tsuchida, Youngmin A Lee, Naoto Fujiwara, Maria Ybanez, Brittany Allen, Sebastiao Martins, M Isabel Fiel, Nicolas Goossens, Hsin-I Chou, Yujin Hoshida, Scott L Friedman
BACKGROUND AND AIMS: Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. METHODS: We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl4 ), which served as an accelerator...
March 20, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29568887/genome-wide-analysis-of-dna-methylation-in-human-peripheral-leukocytes-identifies-potential-biomarkers-of-nonalcoholic-fatty-liver-disease
#14
Rui-Nan Zhang, Qin Pan, Rui-Dan Zheng, Yu-Qiang Mi, Feng Shen, Da Zhou, Guang-Yu Chen, Chan-Yan Zhu, Jian-Gao Fan
The aim of the present study was to uncover the role of leukocytic DNA methylation in the evaluation of nonalcoholic fatty liver disease (NAFLD). Patients with biopsy-proven NAFLD (n=35) and normal controls (n=30) were recruited from Chinese Han population. Their DNA methylation in peripheral leukocytes was subjected to genome-wide profiling. The association between differential methylation of CpG sites and NAFLD was further investigated on the basis of histopathological classification, bioinformatics, and pyrosequencing...
March 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29560693/apoptosis-and-disease-severity-is-associated-with-insulin-resistance-in-non-alcoholic-fatty-liver-disease
#15
Kadri Atay, Billur Canbakan, Emine Koroglu, Ibrahim Hatemi, Mustafa Canbakan, Nuray Kepil, Murat Tuncer, Hakan Senturk
BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods...
April 2017: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/29557675/the-hedgehog-pathway-in-nonalcoholic-fatty-liver-disease
#16
Mariana Verdelho Machado, Anna Mae Diehl
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer...
March 20, 2018: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29555473/long-noncoding-rna-lncarsr-promotes-hepatic-lipogenesis-via-akt-srebp-1c-pathway-and-contributes-to-the-pathogenesis-of-nonalcoholic-steatohepatitis
#17
Ming Zhang, Xiaoming Chi, Na Qu, CongYing Wang
Non-alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH) account for the majority of liver disease in industrialized countries. However, the pathogenesis still unclear. Long non-coding RNAs (lncRNAs) has been reported to be involved in various pathophysiological processes. Here, we reported a novel role of lncARSR in hepatic lipogenesis in NAFLD. The expression of lncARSR was induced both in NAFLD patients and mouse model, as well as in hepatocytes treated with fatty acid. Moreover, overexpression of lncARSR enhanced while knockdown of lncARSR ameliorated hepatic lipid accumulation in vivo and in vitro...
March 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29540533/serum-liver-and-bile-sitosterol-and-sitostanol-in-obese-patients-with-and-without-nafld
#18
Milla-Maria Tauriainen, Ville Männistö, Dorota Kaminska, Maija Vaittinen, Vesa Kärjä, Pirjo Käkelä, Sari Venesmaa, Helena Gylling, Jussi Pihlajamäki
Background & aims : Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. However, parenterally given plant sterols may lead to liver injury. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD. Methods : Out of the 138 individuals (age: 46.3±8.9, BMI: 43.3±6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD...
March 14, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29527789/use-of-a-metabolomic-approach-to-non-invasively-diagnose-nonalcoholic-fatty-liver-disease-in-patients-with-type-2-diabetes-mellitus
#19
Fernando Bril, Laura Millán, Srilaxmi Kalavalpalli, Michael J McPhaul, Michael P Caulfield, Ibon Martinez-Arranz, Cristina Alonso, Pablo Ortiz Betes, José M Mato, Kenneth Cusi
AIMS: While several non-invasive clinical/metabolic scores have been designed to predict the presence of nonalcoholic steatohepatitis (NASH), none was specifically validated in patients with T2DM. We aimed to assess the utility of existing metabolomics scores to classify liver disease in patients with T2DM. MATERIALS AND METHODS: A total of 220 patients with T2DM were recruited. Patients underwent routine lab tests, a liver proton magnetic resonance spectroscopy (1 H-MRS), a 75-gram OGTT, and a liver biopsy if they had NAFLD by1 H-MRS...
March 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29527140/proteomic-characterization-of-high-density-lipoprotein-particles-in-patients-with-non-alcoholic-fatty-liver-disease
#20
Prahlad K Rao, Kate Merath, Eugene Drigalenko, Avinash Y L Jadhav, Richard A Komorowski, Matthew I Goldblatt, Anand Rohatgi, Mark A Sarzynski, Samer Gawrieh, Michael Olivier
Background: Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications...
2018: Clinical Proteomics
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