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Non-alcoholic steatohepatitis

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https://www.readbyqxmd.com/read/29792946/investigation-of-nonalcoholic-fatty-liver-disease-induced-drug-metabolism-by-comparative-global-toxicoproteomics
#1
Ann-Yae Na, Jung Jae Jo, Ok Kwang Kwon, Riya Shrestha, Piljoung Cho, Kyu Min Kim, Sung Hwan Ki, Tae Hee Lee, Tae Won Jeon, Tae Cheon Jeong, Sangkyu Lee
Non-alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non-alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well-established, NAFLD-induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD-induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine-choline deficient (MCD) diet to induce development of NAFLD, tandem mass tags-based liquid chromatography-tandem mass spectrometry analysis was conducted to investigate the dynamics of hepatic proteins...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29790591/synthesis-of-13-c-6-labeled-dual-target-inhibitor-of-cannabinoid-1-receptor-cb-1-r-and-inducible-nitric-oxide-synthase-inos
#2
Malliga R Iyer, Resat Cinar, Nathan J Coffey, George Kunos
Cannabinoid-1 receptor (CB1 R) antagonists/inverse agonists have great potential in the treatment of metabolic disorders like dyslipidemia, type 2 diabetes and non-alcoholic steatohepatitis (NASH). CB1 R inverse agonists have also been reported to be effective in mitigating fibrotic disorders in murine models. Inducible nitric oxide synthase is another promising target implicated in fibrotic and inflammatory disorders. We have disclosed MRI-1867 as a potent and selective, peripherally acting dual-target inhibitor of the cannabinoid receptor (CB1 R) and inducible nitric oxide synthase (iNOS)...
May 23, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29789866/role-of-peroxisome-proliferator-activated-receptors-in-non-alcoholic-fatty-liver-disease-inflammation
#3
REVIEW
Amanda Karolina Soares Silva, Christina Alves Peixoto
Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide...
May 22, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29787859/design-and-rationale-of-the-insyte-study-a-randomised-placebo-controlled-study-to-test-the-efficacy-of-a-synbiotic-on-liver-fat-disease-biomarkers-and-intestinal-microbiota-in-non-alcoholic-fatty-liver-disease
#4
Eleonora Scorletti, Paul R Afolabi, Elizabeth A Miles, Debbie E Smith, Amal Almehmadi, Albandri Alshathry, Helen E Moyses, Geraldine F Clough, Mark Wright, Janisha Patel, Laure Bindels, Nathalie M Delzenne, Philip C Calder, Christopher D Byrne
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp...
May 19, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29785151/non-alcoholic-fatty-liver-disease-an-update-on-diagnosis
#5
REVIEW
Dan L Dumitrascu, Manuela G Neuman
Background and aim: The non-alcoholic fatty liver disease (NAFLD) and its sub-entity, the non-alcoholic steatohepatitis (NASH) represent a field of a tremendous progress in recent years. Clinicians need to remain updated with new data on pathogenesis and therapy. The present mini review aims to present some new scientific reports on the diagnosis of NAFLD and NASH for clinical practitioners. Methods: A systematic literature search of the main international databases was performed...
2018: Clujul Medical (1957)
https://www.readbyqxmd.com/read/29783208/the-role-of-hydrogen-sulfide-in-the-progression-mechanisms-of-non-alcoholic-steatohepatitis-and-chronic-kidney-disease
#6
Oksana S Khukhlina, Igor V Gerush, Alona A Antoniv, Olha Ye Mandryk, Tamara G Kopchuk, Svitlana P Melnychuk, Zoriana Ia Kotsiubiichuk
OBJECTIVE: Introduction: The steady increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine. The aim: To establish the role of hydrogen sulfide in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 114 patients with NASH were examined on the background of obesity of І-ІІ degree, including: 52 patients with NASH (group 1) (without accompanying CKD), 62 patients with NASH with a comorbid CKD І-ІІ degree (group 2)...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29781162/predictors-of-ultrasound-failure-to-detect-hepatocellular-carcinoma
#7
Mariya L Samoylova, Neil Mehta, John P Roberts, Francis Y Yao
Current guidelines recommend ultrasound (US) for hepatocellular carcinoma (HCC) surveillance in cirrhosis. We assess predictors of decreased US sensitivity for detecting HCC. At a single U.S. center, all HCC patients evaluated for liver transplant (LT) receive an abdominal US. In consecutive patients presenting 2007-2015, untreated lesions found on CT/MRI within 3 months of US were compared with US findings. Multivariable logistic regression models compared US sensitivities by patient characteristics. Of 1008 patients completing LT evaluation, 47...
May 21, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29780857/multi-omic-network-based-interrogation-of-rat-liver-metabolism-following-gastric-bypass-surgery-featuring-swath-proteomics
#8
Gautham Vivek Sridharan, Matthew D'Alessandro, Shyam Sundhar Bale, Vicky Bhagat, Hugo Gagnon, John M Asara, Korkut Uygun, Martin L Yarmush, Nima Saeidi
Morbidly obese patients often elect for Roux-en-Y gastric bypass (RYGB), a form of bariatric surgery that triggers a remarkable 30% reduction in excess body weight and reversal of insulin resistance for those who are type II diabetic. A more complete understanding of the underlying molecular mechanisms that drive the complex metabolic reprogramming post-RYGB could lead to innovative non-invasive therapeutics that mimic the beneficial effects of the surgery, namely weight loss, achievement of glycemic control, or reversal of non-alcoholic steatohepatitis (NASH)...
September 2017: Technology
https://www.readbyqxmd.com/read/29779170/histological-improvement-of-non-alcoholic-steatohepatitis-with-a-prebiotic-a-pilot-clinical-trial
#9
Marc R Bomhof, Jill A Parnell, Hena R Ramay, Pam Crotty, Kevin P Rioux, Chris S Probert, Saumya Jayakumar, Maitreyi Raman, Raylene A Reimer
PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted...
May 19, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29774570/high-mobility-group-box-1-drives-fibrosis-progression-signaling-via-the-receptor-for-advanced-glycation-end-products-in-mice
#10
Xiaodong Ge, Elena Arriazu, Fernando Magdaleno, Daniel J Antoine, Rouchelle Dela Cruz, Neil Theise, Natalia Nieto
BACKGROUND & RATIONALE: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific signaling mechanisms. RESULTS: liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic Hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC) and alcoholic steatohepatitis (ASH)...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774155/is-de-novo-hepatocellular-carcinoma-after-transjugular-intrahepatic-portosystemic-shunt-increased
#11
A Hüsing-Kabar, T Meister, M Köhler, W Domschke, I Kabar, C Wilms, B Hild, H H Schmidt, H S Heinzow
Background: Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. Aim: This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer...
April 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29766802/endoplasmic-reticulum-stress-related-molecular-mechanisms-in-nonalcoholic-fatty-liver-disease-nafld
#12
Lifeng Wang, Jun Ren
Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem and a common cause of chronic liver diseases. However, the underlying mechanisms leading to the development and progression of NAFLD remain elusive. Accumulating evidence has depicted an essential role for endoplasmic reticulum (ER) stress in the development of steatosis and later progression into nonalcoholic steatohepatitis and hepatocarcinoma. With the accumulation of unfolded and misfolded proteins in the ER lumen, ER stress is provoked to turn on the unfolded protein response (UPR)...
May 16, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29766791/immunometabolic-changes-in-hepatocytes-arising-from-obesity-and-the-practice-of-physical-exercise
#13
Paula Alves Monteiro, Wagner Prado, Thiago Ricardo Dos Santos Tenório, Luciane Magri Tomaz, David H St-Pierre, Fabio Santos Lira
Over the recent years, a particular interest was shown towards understanding the roles of excessive hepatic fat accumulation and the development of obesity-related diseases. While hepatic triacylglycerol accumulation seems to be a response to the systemic increase of insulin release, fatty acid metabolites contribute to the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). It is widely accepted that NAFLD is a polygenic and multifactorial disease under the influence of critical behavioral factors such as overeating and sedentary lifestyles...
May 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29765319/progression-and-regression-of-hepatic-lesions-in-a-mouse-model-of-nash-induced-by-dietary-intervention-and-its-implications-in-pharmacotherapy
#14
Zhi-Ming Ding, Yue Xiao, Xikun Wu, Haixia Zou, Shurong Yang, Yiyun Shen, Juehua Xu, Heather C Workman, Amy L Usborne, Haiqing Hua
Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29764908/management-of-endocrine-disease-which-metabolic-procedure-comparing-outcomes-in-sleeve-gastrectomy-and-roux-en-y-gastric-bypass
#15
Adrian T Billeter, Javier de la Garza Herrera, Katharina M Scheurlen, Felix Nickel, Franck Billmann, Beat Müller-Stich
Obesity and its associated comorbidities have become one of the largest challenges for health care in the near future. Conservative therapy for obesity and related comorbidities have a very high failure rate and poor long-term results. Similarly, the conservative and medical management of the majority of metabolic diseases such as type 2 diabetes mellitus are only able to slow down disease progression but have no causal effect on the disease process. Obesity surgery has evolved as a highly effect therapy for severe obesity achieving long-lasting weight loss...
May 15, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29760499/hepatic-stellate-cells-secrete-ccl5-to-induce-hepatocyte-steatosis
#16
Byeong-Moo Kim, Ahmed Maher Abdelfattah, Robin Vasan, Bryan C Fuchs, Michael Y Choi
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are known to contribute to fibrosis, but less is known about their function during NAFLD's early stages prior to fibrosis. We developed an ex vivo assay that cocultures primary HSCs from mouse models of liver disease with healthy hepatocytes to study their interaction...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29758334/genetic-inactivation-of-nrf2-prevents-clonal-expansion-of-initiated-cells-in-a-nutritional-model-of-rat-hepatocarcinogenesis
#17
Claudia Orrù, Marta Szydlowska, Keiko Taguchi, Patrizia Zavattari, Andrea Perra, Masayuki Yamamoto, Amedeo Columbano
BACKGROUND & AIMS: Dysregulation of the Keap1-Nrf2 pathway has been observed in experimental and human tumors, suggesting possible roles of the pathway in cancer development. Here we examined whether Nrf2 activation occurs at early steps of rat hepatocarcinogenesis, to assess critical contributions of Nrf2 to the onset of hepatocellular carcinoma (HCC). METHODS: We used wild type (WT) and Nrf2 knockout (Nrf2KO) rats treated with a single injection of diethylnitrosamine (DENA) followed by choline-devoid methionine-deficient (CMD) diet...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29757947/membrane-remodeling-as-a-key-player-of-the-hepatotoxicity-induced-by-co-exposure-to-benzo-a-pyrene-and-ethanol-of-obese-zebrafish-larvae
#18
Muhammad Imran, Odile Sergent, Arnaud Tête, Isabelle Gallais, Martine Chevanne, Dominique Lagadic-Gossmann, Normand Podechard
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling-changes in membrane fluidity and lipid-raft characteristics. In this study, the possible involvement of membrane remodeling in the in vivo progression of steatosis to a steatohepatitis-like state upon co-exposure to B[a]P and ethanol was tested in obese zebrafish larvae...
May 14, 2018: Biomolecules
https://www.readbyqxmd.com/read/29753678/deficiency-of-fibroblast-growth-factor-21-fgf21-promotes-hepatocellular-carcinoma-hcc-in-mice-on-a-long-term-obesogenic-diet
#19
Garima Singhal, Gaurav Kumar, Suzanne Chan, Ffolliott M Fisher, Yong Ma, Hilde G Vardeh, Imad A Nasser, Jeffrey S Flier, Eleftheria Maratos-Flier
OBJECTIVE: Non-alcoholic fatty liver (NAFL) associated with obesity is a major cause of liver diseases which can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) plays an important role in liver metabolism and is also a potential marker for NAFL. Here we aimed to test the effect of FGF21 deficiency on liver pathology in mice consuming a conventional high fat, high sucrose (HFHS) obesogenic diet for up to 52 weeks...
March 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29750881/pathophysiological-characteristics-of-non-alcoholic-steatohepatitis-like-changes-in-cholesterol-loaded-type-2-diabetic-rats
#20
Y Toriniwa, M Muramatsu, Y Ishii, E Riya, K Miyajima, S Ohshida, K Kitatani, S Takekoshi, T Matsui, S Kume, T Yamada, T Ohta
Spontaneously Diabetic Torii (SDT) fatty rats, a new obese diabetic model, reportedly presented with features of non-alcoholic steatohepatitis (NASH) after 32 weeks of age. We tried to accelerate the onset of NASH in SDT fatty rats using dietary cholesterol loading and noticed changes in the blood choline level which is expected to be a NASH biomarker. Body weight and biochemical parameters were measured from 8 to 24 weeks of age. At 16 or 24 weeks, pathophysiological analysis of the livers were performed, hepatic lipids, lipid peroxides, and the expression of mRNA related to triglyceride (TG) synthesis, inflammation, and fibrosis were evaluated...
May 10, 2018: Physiological Research
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