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https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#1
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28338838/cohort-profile-the-hepatitis-c-virus-hcv-research-uk-clinical-database-and-biobank
#2
J McLauchlan, H Innes, J F Dillon, G Foster, E Holtham, S McDonald, B Wilkes, S J Hutchinson, W L Irving
No abstract text is available yet for this article.
February 27, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28336111/hepatoprotective-effects-of-curcumin-in-rats-after-bile-duct-ligation-via-downregulation-of-rac1-and-nox1
#3
Zohreh-Al-Sadat Ghoreshi, Razieh Kabirifar, Fatemeh Safari, Alireza Karimollah, Ali Moradi, Ebrahim Eskandari-Nasab
OBJECTIVES: New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Rac1-Guanosine triphosphate (Rac1-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model. METHODS: Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#4
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333769/the-incidence-of-low-seroimmunity-to-hepatitis-b-virus-in-children-with-inflammatory-bowel-disease
#5
Abhishek Watts, William E Bennett, Jean P Molleston, Sandeep K Gupta, Joseph M Croffie, Shamaila Waseem, Brian A McFerron, Steven J Steiner, Sanjay Kumar, Charles P Vanderpool, Emily C Hon, Molly A Bozic, Girish C Subbarao, Marian D Pfefferkorn
OBJECTIVES: Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus (HBV) titers are low in the vaccinated pediatric IBD population. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers. METHODS: Patients with diagnosis of IBD, ages 5-18 years, were prospectively enrolled...
March 22, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28332476/new-onset-hepatitis-c-virus-associated-glomerulonephritis-following-sustained-virologic-response-with-direct-acting-antiviral-therapy%C3%A2
#6
Muriel Ghosn, Matthew B Palmer, Catherine E Najem, Danny Haddad, Peter A Merkel, Jonathan J Hogan
Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies...
March 23, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28331563/%C3%A2-evaluation-of-serum-hbv-viral-load-transaminases-and-histological-features-in-chronic-hbeag-negative-hepatitis-b-patients
#7
Abbas Esmaeelzadeh, Hassan Saadatnia, Bahram Memar, Elham Mokhtari Amirmajdi, Azita Ganji, Ladan Goshayeshi, Zahra Meshkat, Alireza Pasdar, Hassan Vosoughinia, Mohammadreza Farzanehfar, Shahrzad Tehranian, Kamran Ghaffarzadehgan, Farnood Rajabzadeh, Mitra Ahadi
AIM: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). BACKGROUND: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. METHODS: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28330813/atp-binding-cassette-transporter-a1-deficiency-in-human-induced-pluripotent-stem-cell-derived-hepatocytes-abrogates-hdl-biogenesis-and-enhances-triglyceride-secretion
#8
Xin Bi, Evanthia E Pashos, Marina Cuchel, Nicholas N Lyssenko, Mayda Hernandez, Antonino Picataggi, James McParland, Wenli Yang, Ying Liu, Ruilan Yan, Christopher Yu, Stephanie L DerOhannessian, Michael C Phillips, Edward E Morrisey, Stephen A Duncan, Daniel J Rader
Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28330662/pericardial-but-not-hepatic-fat-by-ct-is-associated-with-cv-outcomes-and%C3%A2-structure-the-multi-ethnic-study-of-atherosclerosis
#9
Ravi V Shah, Amanda Anderson, Jingzhong Ding, Matthew Budoff, Oliver Rider, Steffen E Petersen, Majken Karoline Jensen, Manja Koch, Matthew Allison, Nadine Kawel-Boehm, Jessica Wisocky, Michael Jerosch-Herold, Kenneth Mukamal, Joao A C Lima, Venkatesh L Murthy
OBJECTIVES: The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity. BACKGROUND: The impact of pericardial fat-a local fat depot encasing the heart-on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate. METHODS: We studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat)...
March 10, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28329347/off-treatment-hepatitis-b-virus-hbv-dna-levels-and-the-prediction-of-relapse-after-discontinuation-of-nucleos-t-ide-analogue-therapy-in-patients-with-chronic-hepatitis-b-a-prospective-stop-study
#10
Jiawei Cao, Heng Chi, Tao Yu, Zhandong Li, Bettina E Hansen, Xiaoyong Zhang, Chunxiu Zhong, Jian Sun, Jinlin Hou, Harry L A Janssen, Jie Peng
Background.: The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy. Methods.: A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated...
January 19, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329245/hepatitis-e-virus-associated-neurological-injury-in-china
#11
Lin Wang, Jiexi Wen, Feng Gao, Hongjun Hao, Ling Wang
No abstract text is available yet for this article.
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329061/pegylated-interferon-alfa-2b-add-on-treatment-in-hepatitis-b-virus-envelope-antigen-positive-chronic-hepatitis-b-patients-treated-with-nucleos-t-ide-analogue-a-randomized-controlled-trial-pegon
#12
Heng Chi, Bettina E Hansen, Simin Guo, Ning Ping Zhang, Xun Qi, Liang Chen, Qing Guo, Pauline Arends, Ji-Yao Wang, Elke Verhey, Robert J de Knegt, Qing Xie, Harry L A Janssen
Background.: We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t)ide analogue (NA) therapy, compared with continued NA monotherapy. Methods.: This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for >12 months and had an HBV DNA load of <2000 IU/mL...
March 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328962/the-blood-dna-virome-in-8-000-humans
#13
Ahmed Moustafa, Chao Xie, Ewen Kirkness, William Biggs, Emily Wong, Yaron Turpaz, Kenneth Bloom, Eric Delwart, Karen E Nelson, J Craig Venter, Amalio Telenti
The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches...
March 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28328941/cynomolgus-monkeys-are-successfully-and-persistently-infected-with-hepatitis-e-virus-genotype-3-hev-3-after-long-term-immunosuppressive-therapy
#14
Noemi Rovaris Gardinali, Juliana Rodrigues Guimarães, Juliana Gil Melgaço, Yohan Britto Kevorkian, Fernanda de Oliveira Bottino, Yasmine Rangel Vieira, Aline Campos de Azevedo da Silva, Douglas Pereira Pinto, Laís Bastos da Fonseca, Leandro Schiavo Vilhena, Edilson Uiechi, Maria Cristina Carlan da Silva, Julio Moran, Renato Sérgio Marchevsky, Oswaldo Gonçalves Cruz, Rodrigo Alejandro Arellano Otonel, Amauri Alcindo Alfieri, Jaqueline Mendes de Oliveira, Ana Maria Coimbra Gaspar, Marcelo Alves Pinto
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28328813/evaluation-of-apri-and-fib-4-for-noninvasive-assessment-of-significant-fibrosis-and-cirrhosis-in-hbeag-negative-chb-patients-with-alt%C3%A2-%C3%A2-%C3%A2-2-uln-a-retrospective-cohort-study
#15
Qiang Li, Xiaojing Ren, Chuan Lu, Weixia Li, Yuxian Huang, Liang Chen
To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328162/predictive-model-for-inflammation-grades-of-chronic-hepatitis-b-large-scale-analysis-of-clinical-parameters-and-gene-expressions
#16
Weichen Zhou, Yanyun Ma, Jun Zhang, Jingyi Hu, Menghan Zhang, Yi Wang, Yi Li, Lijun Wu, Yida Pan, Yitong Zhang, Xiaonan Zhang, Xinxin Zhang, Zhanqing Zhang, Jiming Zhang, Hai Li, Lungen Lu, Li Jin, Jiucun Wang, Zhenghong Yuan, Jie Liu
BACKGROUND: Liver biopsy is the gold standard to assess pathological features (e.g. inflammation grades) for hepatitis B virus infected patients, although it's invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small HBV-infected samples. We aimed to analyze correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase, and HBV-DNA) in large-scale CHB samples, and to predict inflammation grades by using clinical parameters and/or gene expressions...
March 22, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28326402/total-joint-arthroplasty-in-patients-with-chronic-infectious-liver%C3%A2-disease
#17
Jeremy N Truntzer, Kalpit N Shah, Derek R Jenkins, Lee E Rubin
The opportunity for total joint arthroplasty (TJA) in patients with chronic infectious liver disease is rapidly expanding. This is the product of both superior survival of chronic hepatitis patients, evolving implant technologies, and improvement of techniques in TJA. Unfortunately, treating this group of patients is not without significant challenges that can stem from both intrahepatic and extrahepatic clinical manifestations. Moreover, many subclinical changes occur in this cohort that can alter hemostasis, wound healing, and infection risk even in the asymptomatic patient...
June 2016: Arthroplasty Today
https://www.readbyqxmd.com/read/28325923/clinical-features-and-viral-quasispecies-characteristics-associated-with-infection-by-the-hepatitis-b-virus-g145r-immune-escape-mutant
#18
Yuan Xue, Ming-Jie Wang, Zhi-Tao Yang, De-Min Yu, Yue Han, Dao Huang, Dong-Hua Zhang, Xin-Xin Zhang
Coexistence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon phenomenon, and the underlying mechanisms remain largely unknown. Amino-acid (aa) substitution from glycine to arginine at aa 145 (G145R), in the major hydrophilic region, has been reported in patients with HBsAg and anti-HBs coexistence. However, there is limited knowledge about the clinical features and viral quasispecies characteristics associated with G145R mutant hepatitis B virus (HBV) infection...
March 22, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28325286/inclusion-of-the-woodchuck-hepatitis-virus-posttranscriptional-regulatory-element-enhances-aav2-driven-transduction-of-mouse-and-human-retina
#19
Maria I Patrício, Alun R Barnard, Harry O Orlans, Michelle E McClements, Robert E MacLaren
The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) has been included in the transgene cassette of adeno-associated virus (AAV) in several gene therapy clinical trials, including those for inherited retinal diseases. However, the extent to which WPRE increases transgene expression in the retina is still unclear. To address this question, AAV2 vectors containing a reporter gene with and without WPRE were initially compared in vitro and subsequently in vivo by subretinal delivery in mice...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323991/whole-body-vibration-mimics-the-metabolic-effects-of-exercise-in-male-leptin-receptor-deficient-mice
#20
Meghan E McGee-Lawrence, Karl H Wenger, Sudipta Misra, Catherine L Davis, Norman K Pollock, Mohammed Elsalanty, Kehong Ding, Carlos M Isales, Mark W Hamrick, Joanna R Erion, Marlena Wosiski-Kuhn, Phonepasong Arounleut, Mark P Mattson, Roy G Cutler, Jack C Yu, Alexis M Stranahan
Whole-body vibration has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether whole-body vibration recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wildtype (Wt) and leptin receptor deficient (db/db) mice to daily treadmill exercise or whole-body vibration for three months. Body weights were analyzed and compared with Wt and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following treadmill exercise or whole-body vibration...
March 15, 2017: Endocrinology
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