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Nonalcoholic steatohepatitis

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https://www.readbyqxmd.com/read/28218919/targeting-casp8-and-fadd-like-apoptosis-regulator-ameliorates-nonalcoholic-steatohepatitis-in-mice-and-nonhuman-primates
#1
Pi-Xiao Wang, Yan-Xiao Ji, Xiao-Jing Zhang, Ling-Ping Zhao, Zhen-Zhen Yan, Peng Zhang, Li-Jun Shen, Xia Yang, Jing Fang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin Zhang, Qiao-Fang Wei, Yong Wang, Jing Li, Lu Wan, Qingguo Xie, Zhi-Gang She, Zhihua Wang, Zan Huang, Hongliang Li
Nonalcoholic steatohepatitis (NASH) is a progressive disease that is often accompanied by metabolic syndrome and poses a high risk of severe liver damage. However, no effective pharmacological treatment is currently available for NASH. Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. We provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8 (also known as JNK1)...
February 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#2
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216979/association-between-endotoxemia-and-histological-features-of-nonalcoholic-fatty-liver-disease
#3
Hiroyuki Kitabatake, Naoki Tanaka, Naoyuki Fujimori, Michiharu Komatsu, Ayaka Okubo, Kyogo Kakegawa, Takefumi Kimura, Ayumi Sugiura, Tomoo Yamazaki, Soichiro Shibata, Yuki Ichikawa, Satoru Joshita, Takeji Umemura, Akihiro Matsumoto, Masayoshi Koinuma, Kenji Sano, Toshifumi Aoyama, Eiji Tanaka
AIM: To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD). METHODS: One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores...
January 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28215516/aisf-position-paper-on-nonalcoholic-fatty-liver-disease-nafld-updates-and-future-directions
#4
Amedeo Lonardo, Fabio Nascimbeni, Giovanni Targher, Mauro Bernardi, Ferruccio Bonino, Elisabetta Bugianesi, Alessandro Casini, Amalia Gastaldelli, Giulio Marchesini, Fabio Marra, Luca Miele, Filomena Morisco, Salvatore Petta, Fabio Piscaglia, Gianluca Svegliati-Baroni, Luca Valenti, Stefano Bellentani
This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic "hits". The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers)...
January 23, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28214827/potential-regulators-driving-the-transition-in-nonalcoholic-fatty-liver-disease-a-stage-based-view
#5
Yi Lou, Yi-Dan Chen, Fu-Rong Sun, Jun-Ping Shi, Yu Song, Jin Yang
BACKGROUND AND AIM: The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined. METHODS: A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214071/lipocalin-2-a-master-mediator-of-intestinal-and-metabolic-inflammation
#6
REVIEW
Alexander R Moschen, Timon E Adolph, Romana R Gerner, Verena Wieser, Herbert Tilg
Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is released by various cell types and is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Both intestinal and metabolic inflammation, as observed in obesity and related disorders, are associated with increased LCN2 synthesis. While LCN2 in the intestinal tract regulates the composition of the gut microbiota and shows anti-inflammatory activities, it also exhibits proinflammatory activities in other experimental settings...
February 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28212548/branched-chain-amino-acids-prevent-hepatic-fibrosis-and-development-of-hepatocellular-carcinoma-in-a-non-alcoholic-steatohepatitis-mouse-model
#7
Kai Takegoshi, Masao Honda, Hikari Okada, Riuta Takabatake, Naoto Matsuzawa-Nagata, Jean S Campbell, Masashi Nishikawa, Tetsuro Shimakami, Takayoshi Shirasaki, Yoshio Sakai, Taro Yamashita, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28206970/genetic-variation-in-long-noncoding-rnas-and-the-risk-of-nonalcoholic-fatty-liver-disease
#8
Silvia Sookoian, Cristian Rohr, Adrián Salatino, Hernán Dopazo, Tomas Fernandez Gianotti, Gustavo O Castaño, Carlos J Pirola
: The human transcriptome comprises a myriad of non protein-coding RNA species, including long noncoding RNAs (lncRNAs), which have a remarkable role in transcriptional and epigenetic regulation. We hypothesized that variants in lncRNAs influence the susceptibility to nonalcoholic fatty liver disease (NAFLD). Using next generation sequencing, we performed a survey of genetic variation associated with randomly selected lncRNA-genomic regions located within both experimentally validated and computationally predicted regulatory elements...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28201847/the-differentiation-of-intestinal-failure-associated-liver-disease-from-nonalcoholic-fatty-liver-and-nonalcoholic-steatohepatitis
#9
Alan L Buchman, Bita V Naini, Bert Spilker
Intestinal failure-associated liver disease (IFALD), formerly known as parenteral nutrition-associated liver disease has often been listed in textbooks as an example of nonalcoholic fatty liver disease (NAFLD). However, the etiology, pathophysiology, epidemiology, histology, and progression differ substantially between the conditions defined as NAFLD and the disease, IFALD. Therefore, IFALD should not be defined or considered as a type or a cause of nonalcoholic fatty liver or nonalcoholic steatohepatitis, but rather as a distinct disease...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28195199/pemafibrate-a-novel-selective-peroxisome-proliferator-activated-receptor-alpha-modulator-improves-the-pathogenesis-in-a-rodent-model-of-nonalcoholic-steatohepatitis
#10
Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Kento Imajo, Koji Fujita, Masato Yoneda, Toshiaki Takizawa, Satoru Saito, Yoji Nagashima, Atsushi Nakajima
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195177/prevalence-of-nonalcoholic-steatohepatitis-associated-cirrhosis-in-the-united-states-an-analysis-of-national-health-and-nutrition-examination-survey-data
#11
Mohammad Nasser Kabbany, Praveen Kumar Conjeevaram Selvakumar, Kymberly Watt, Rocio Lopez, Zade Akras, Nizar Zein, William Carey, Naim Alkhouri
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of manifestations ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and eventually cirrhosis. The prevalence of NAFLD has been shown to be increasing over time; however, the prevalence of NASH cirrhosis and advanced fibrosis over time has not been well studied. Estimate the changes in prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis among adults in the United States...
February 14, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28194671/activation-of-insulin-pi3k-akt-p70s6k-pathway-in-hepatic-stellate-cells-contributes-to-fibrosis-in-nonalcoholic-steatohepatitis
#12
Cindy X Cai, Hema Buddha, Shobha Castelino-Prabhu, Zhiwei Zhang, Robert S Britton, Bruce R Bacon, Brent A Neuschwander-Tetri
BACKGROUND AND AIMS: Hyperinsulinemia and insulin resistance are hallmark features of nonalcoholic fatty liver disease and steatohepatitis (NASH). It remains unclear whether and how insulin contributes to the development of fibrosis in NASH. In this study, we explored insulin signaling in the regulation of hepatic stellate cell (HSC) activation and the progression of NASH-fibrosis. METHODS: Phosphorylation of Akt and p70S6K were examined in primary HSC and in a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet for 24 weeks...
February 13, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28193580/astaxanthin-inhibits-inflammation-and-fibrosis-in-the-liver-and-adipose-tissue-of-mouse-models-of-diet-induced-obesity-and-nonalcoholic-steatohepatitis
#13
Bohkyung Kim, Callie Farruggia, Chai Siah Ku, Tho X Pham, Yue Yang, Minkyung Bae, Casey J Wegner, Nicholas J Farrell, Ellen Harness, Young-Ki Park, Sung I Koo, Ji-Young Lee
The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0...
March 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28185715/effects-of-oral-antidiabetic-drugs-on-changes-in-the-liver-to-spleen-ratio-on-computed-tomography-and-inflammatory-biomarkers-in-patients-with-type-2-diabetes-and-nonalcoholic-fatty-liver-disease
#14
Koichi Yabiku, Akiko Mutoh, Kazufumi Miyagi, Nobuyuki Takasu
PURPOSE: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD. METHODS: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months. All the patients received dietary and exercise guidance once a month during this study...
February 6, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28167852/salvia-nelumbinis-naturalis-formula-improved-inflammation-in-lps-stressed-macrophages-via-upregulating-microrna-152
#15
Zansong Ma, Xiangbing Shu, Jie Huang, Haiyan Zhang, Zhen Xiao, Li Zhang
Salvia-Nelumbinis naturalis (SNN) formula is an effective agent in treating nonalcoholic steatohepatitis (NASH); however, the precise mechanisms are still undefined. Activation of Kupffer cells by gut-derived lipopolysaccharide (LPS) plays a central role in the pathogenesis of NASH. In the present study, we aimed to explore the epigenetic regulation of microRNAs under the beneficial effects of SNN-containing serum in LPS stressed macrophages. Kupffer cells were isolated from C57BL/6 mice and treated with LPS or LPS and SNN-containing serum; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was assessed...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28166556/long-term-pioglitazone-treatment-for-patients-with-nonalcoholic-steatohepatitis
#16
Fernando Bril, Kenneth Cusi
No abstract text is available yet for this article.
February 7, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28166555/long-term-pioglitazone-treatment-for-patients-with-nonalcoholic-steatohepatitis
#17
James A Thomas, Rohit Gupta, Guruprasad P Aithal
No abstract text is available yet for this article.
February 7, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28166554/long-term-pioglitazone-treatment-for-patients-with-nonalcoholic-steatohepatitis
#18
Stuart K Sutton
No abstract text is available yet for this article.
February 7, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28164848/gut-microbiota-and-complications-of-liver-disease
#19
REVIEW
Chathur Acharya, Jasmohan S Bajaj
Chronic liver disease, cirrhosis, and its complications are epidemic worldwide. Most complications are mediated through a dysfunctional gut-liver axis. New techniques have made culture-independent analysis of the gut microbiome widespread. With insight into an unfavorable microbiome (dysbiosis) and how it affects liver disease, investigators have discovered new targets to potentially improve outcomes. Dysbiosis is associated with endotoxemia and propagates liver injury due to nonalcoholic steatohepatitis and alcohol...
March 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28148637/impact-of-nonalcoholic-fatty-liver-disease-on-toxicokinetics-of-tetrachloroethylene
#20
Joseph A Cichocki, Shinji Furuya, Kranti Konganti, Yu-Syuan Luo, Thomas J McDonald, Yasuhiro Iwata, Weihsueh A Chiu, David W Threadgill, Igor P Pogribny, Ivan Rusyn
Lifestyle factors and chronic pathological states are important contributors to inter-individual variability in susceptibility to xenobiotic-induced toxicity. Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that can dramatically affect chemical metabolism. We examined the effect of NAFLD on toxicokinetics of tetrachloroethylene (PERC), a ubiquitous environmental contaminant that requires metabolic activation to induce adverse health effects. Mice (C57Bl/6J, male) were fed a low-fat diet (LFD), high fat diet (HFD), or methionine/folate/choline-deficient diet (MCD) to model a healthy liver, steatosis, or nonalcoholic steatohepatitis (NASH), respectively...
February 1, 2017: Journal of Pharmacology and Experimental Therapeutics
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