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S Oliveira, A K Samba, A J Towbin, A Gupta, J I Geller, J D Nathan, R Kohli
: Hepatocellular adenomas (HCA) are benign tumours with potential for malignant transformation with no recommendations regarding management in the paediatric population. We report a case of an inflammatory adenoma with β-catenin activated pathway in an obese, paediatric patient with nonalcoholic steatohepatitis (NASH). CASE REPORT: An 11-year-old female presented with a microlobulated liver lesion measuring >5 cm in magnetic resonance imaging (MRI) with inflammatory adenoma with β-catenin activated pathology arising in a background of NASH, nonalcoholic fatty liver disease (NAFLD) activity score 5/8...
October 25, 2016: Pediatric Obesity
Masaya Kozono, Hirofumi Uto, Rie Ibusuki, Shiho Arima, Kohei Oda, Hiroki Taguchi, Fumisato Sasaki, Yuichiro Nasu, Shinichi Hashimoto, Hitoshi Setoyama, Shuji Kanmura, Masatsugu Numata, Hirohito Tsubouchi, Akio Ido
Metabolic syndrome based on insulin resistance (IR) and hypertension is a risk factor for advanced liver disease and cardiovascular disease in patients with nonalcoholic steatohepatitis (NASH). The present study investigated the effects of severe hypertension induced by a high‑salt (HS) diet and antihypertensive therapy on the pathophysiological condition of spontaneously hypertensive rats (SHRs) with steatohepatitis. Steatohepatitis was induced using a choline-deficient, L-amino acid-defined diet (CDAA)...
October 21, 2016: Molecular Medicine Reports
Michael Pavlides, Rajarshi Banerjee, Elizabeth M Tunnicliffe, Catherine Kelly, Jane Collier, Lai Mun Wang, Kenneth A Fleming, Jeremy F Cobbold, Matthew D Robson, Stefan Neubauer, Eleanor Barnes
BACKGROUND AND AIMS: The diagnosis of non-alcoholic steatohepatitis (NASH) and fibrosis staging are central to non-alcoholic fatty liver disease (NAFLD) assessment. We evaluated multi-parametric magnetic resonance (MR) in the assessment of NASH and fibrosis using histology as standard in NAFLD. METHODS: Seventy one patients with suspected NAFLD were recruited within one month of liver biopsy. MR data were used to define the liver inflammation and fibrosis score (LIF 0-4)...
October 25, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
S A Harrison, S R Marri, N Chalasani, R Kohli, W Aronstein, G A Thompson, W Irish, M V Miles, S A Xanthakos, E Lawitz, M Noureddin, T D Schiano, M Siddiqui, A Sanyal, B A Neuschwander-Tetri, P G Traber
BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis...
October 24, 2016: Alimentary Pharmacology & Therapeutics
Y Ilan
BACKGROUND: The systemic immune system plays a role in inflammation and fibrogenesis associated with non-alcoholic steatohepatitis (NASH) and has become a potential target for drug development. In particular, the gut immune system has been suggested as a means for generating signals that can target the systemic immune system. AIM: To describe seven novel methods being developed for the treatment of NASH that target the gut immune system for alleviation of the systemic inflammatory response, including oral administration of fatty-liver-derived proteins, anti-CD3 antibodies, tumour necrosis factor fusion protein, anti-lipopolysaccharide antibodies, glucosylceramide, delayed-release mercaptopurine, and soy-derived extracts...
October 24, 2016: Alimentary Pharmacology & Therapeutics
Habeeb Salameh, Muhannad Al Hanayneh, Maen Masadeh, Mohammed Naseemuddin, Tasnia Matin, Angelika Erwin, Ashwani K Singal
Background and Aims:Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals...
September 28, 2016: Journal of Clinical and Translational Hepatology
Sylvia S Villarreal, Woods Nash, Thomas R Cole
No abstract text is available yet for this article.
October 2016: Journal of Graduate Medical Education
Nina Galanter, Dennis Silva, Jonathan T Rowell, Jan Rychtář
Many organisms maintain collective territories and compete on behalf of the fitness of the overall group. Inspired by this concept, the territorial raider model is a graph-based resource competition in which populations have fixed home locations and a limited range of sites accessible for raiding. In our present extension of the model, groups control "colonies" or "armies" which can be divided across multiple locations. We present Nash equilibria for games played on both regular graphs and regular bipartite graphs, and we also examine differences that emerge when populations are composed of discrete units (pack scale) or when they are continuously divisible (colony scale)...
October 21, 2016: Journal of Theoretical Biology
Jessica A Nash, Albert L Kwansa, James Samuel Peerless, Ho Shin Kim, Yaroslava G Yingling
Nanoparticles (NPs) play increasingly important roles in nanotechnology and nanomedicine where nanoparticle surface chemistry allows for control over interactions with other nanoparticles and biomolecules. In particular, for applications in drug and gene delivery, a fundamental understanding of the NP-nucleic acid interface allows for development of more efficient and effective nanoparticle carriers. Computational modeling can provide insights of processes occurring at the inorganic NP-nucleic interface, in detail which is difficult to access by experimental methods...
October 24, 2016: Bioconjugate Chemistry
A Gentilini, A Caligiuri, A Provenzano, F Marra
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, characterized by inflammation, hepatocyte injury and fibrogenesis. Overall mortality, and liver-related mortality, are both increased in NASH patients. Considering that nonalcoholic fatty liver disease is the most prevalent hepatic abnormality in the Western world, understanding the mechanisms leading to NASH and its progression to cirrhosis is critical for a better management of these patients. Moreover, a more detailed knowledge of this condition may be helpful to identify those subjects which are more susceptible to develop progressive liver disease...
October 21, 2016: Current Molecular Medicine
Qiang Meng, Xing-Ping Duan, Chang-Yuan Wang, Zhi-Hao Liu, Peng-Yuan Sun, Xiao-Kui Huo, Hui-Jun Sun, Jin-Yong Peng, Ke-Xin Liu
AIM: Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks...
October 24, 2016: Acta Pharmacologica Sinica
Helen L Barr, Nigel Halliday, David A Barrett, Paul Williams, Douglas L Forrester, Daniel Peckham, Kate Williams, Alan R Smyth, David Honeybourne, Joanna L Whitehouse, Edward F Nash, Jane Dewar, Andrew Clayton, Alan J Knox, Miguel Cámara, Andrew W Fogarty
BACKGROUND: Pulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are detectable in the sputum, plasma and urine of adults with CF, suggesting that they have potential as biomarkers for P. aeruginosa infection. AIM: To investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P...
October 20, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Yusuf Ransome, Ichiro Kawachi, Sarah Braunstein, Denis Nash
In the United States, research is limited on the mechanisms that link socioeconomic and structural factors to HIV diagnosis outcomes. We tested whether neighborhood income inequality, socioeconomic deprivation, and black racial concentration were associated with gender-specific rates of HIV in the advanced stages of AIDS (i.e., late HIV diagnosis). We then examined whether HIV testing prevalence and accessibility mediated any of the associations above. Neighborhoods with highest (relative to lowest) black racial concentration had higher relative risk of late HIV diagnosis among men (RR=1...
October 19, 2016: Health & Place
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
: Bile acids (BAs) play critical physiological functions in cholesterol homeostasis and deregulation of BA metabolism causes cholestatic liver injury. Maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor, however its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Pat Whitworth, Peter Beitsch, Angela Mislowsky, James V Pellicane, Charles Nash, Mary Murray, Laura A Lee, Carrie L Dul, Michael Rotkis, Paul Baron, Lisette Stork-Sloots, Femke A de Snoo, Jennifer Beatty
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity...
October 21, 2016: Annals of Surgical Oncology
Marlies Bekaert, D Margriet Ouwens, Tina Hörbelt, Frederique Van de Velde, Pia Fahlbusch, Daniella Herzfeld de Wiza, Yves Van Nieuwenhove, Patrick Calders, Marleen Praet, Anne Hoorens, Anja Geerts, Xavier Verhelst, Jean-Marc Kaufman, Bruno Lapauw
OBJECTIVE: This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance. METHODS: Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects...
October 21, 2016: Obesity
Bradley P Weegman, Ahmad Essawy, Peter Nash, Alexandra L Carlson, Kristin J Voltzke, Zhaohui Geng, Marjan Jahani, Benjamin B Becker, Klearchos K Papas, Meri T Firpo
In this demonstration, spheroids formed from the β-TC6 insulinoma cell line were cultured as a model of manufacturing a mammalian islet cell product to demonstrate how regulating nutrient levels can improve cell yields. In previous studies, bioreactors facilitated increased culture volumes over static cultures, but no increase in cell yields were observed. Limitations in key nutrients such as glucose, which were consumed between batch feedings, can lead to limitations in cell expansion. Large fluctuations in glucose levels were observed, despite the increase in glucose concentrations in the media...
September 25, 2016: Journal of Visualized Experiments: JoVE
Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown...
October 2016: Diabetes & Metabolism Journal
Ryan D Sheldon, Kayla M Kanosky, Kevin D Wells, Lili Miles, James W Perfield, Stavra Xanthakos, Thomas H Inge, R Scott Rector
BACKGROUND: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. METHODS: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology...
October 7, 2016: Physiological Genomics
Thomas Gilliland, Sylvie Dufour, Gerald I Shulman, Kitt Falk Petersen, Sukru H Emre
NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency...
October 20, 2016: Pediatric Transplantation
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