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https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#1
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#2
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351921/inhibitory-effects-of-endogenous-linoleic-acid-and-glutaric-acid-on-the-renal-glucuronidation-of-berberrubine-in-mice-and-on-recombinant-human-ugt1a7-1ab-and-1a9
#3
Na Yang, Sijia Li, Caixia Yan, Runbin Sun, Jun He, Yuan Xie, Ying Peng, Guangji Wang, Jiye Aa
Berberrubine (BRB) has a strong lipid-lowering effect and can be extensively metabolized into berberrubine-9-O-β-D-glucuronide (BRBG) in vivo. Recently, pharmacokinetics studies showed that the production of BRBG was significantly decreased in the urine of mice fed with a high fat diet (HFD), indicating a decreased glucuronidation capacity. Based on the UGT isoform identification, hepatic and renal microsomal incubation, glucuronidation was examined to suggest the metabolism of BRB in liver and kidneys. The results showed that the renal UGT activity for metabolizing BRB markedly decreased, which may be highly related to the decreased expression and activity of renal Ugt1a7c...
January 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29350757/hepatoprotective-effects-of-sophoricoside-against-fructose-induced-liver-injury-via-regulating-lipid-metabolism-oxidation-and-inflammation-in-mice
#4
Wenfeng Li, Yalong Lu
The dried fruit of Sophora japonica L. is a traditional Chinese herb tea rich in sophoricoside that is an isoflavone glycoside. The aim of current study was to investigate the hepatic protective effect of sophoricoside in high fructose (HF) diet fed mice. Healthy male mice were fed 30% fructose water and treated 80 and 160 mg/kg·bw sophoricoside continuously for 8 wk. Our data showed that administration of sophoricoside at 80 and 160 mg/kg·bw observably decreased the body weight and liver weight in HF-fed mice...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350162/new-parvovirus-associated-with-serum-hepatitis-in-horses-after-inoculation-of-common-biological-product
#5
Thomas J Divers, Bud C Tennant, Arvind Kumar, Sean McDonough, John Cullen, Nishit Bhuva, Komal Jain, Lokendra Singh Chauhan, Troels Kasper Høyer Scheel, W Ian Lipkin, Melissa Laverack, Sheetal Trivedi, Satyapramod Srinivasa, Laurie Beard, Charles M Rice, Peter D Burbelo, Randall W Renshaw, Edward Dubovi, Amit Kapoor
Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H...
February 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29349902/association-between-pre-sarcopenia-sarcopenia-and-bone-mineral-density-in-patients-with-chronic-hepatitis-c
#6
Tatiana Bering, Kiara G D Diniz, Marta Paula P Coelho, Diego A Vieira, Maria Marta S Soares, Adriana M Kakehasi, Maria Isabel T D Correia, Rosângela Teixeira, Dulciene M M Queiroz, Gifone A Rocha, Luciana D Silva
BACKGROUND: Preserved skeletal muscle is essential for the maintenance of healthy bone. Loss of bone mineral density (BMD) and muscle strength, considered a predictor of BMD, have been demonstrated in patients with cirrhosis, but they are poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to evaluate the prevalence of low BMD and its association with body composition, muscle strength, and nutritional status in CHC. METHODS: One hundred and four subjects [mean age, 50...
January 19, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29349793/the-effectiveness-and-safety-of-ledipasvir-plus-sofosbuvir-in-adolescents-with-chronic-hepatitis-c-virus-genotype-4-infection-a-real-world-experience
#7
H R El-Khayat, E M Kamal, M H El-Sayed, M El-Shabrawi, H Ayoub, A RizK, M Maher, R Y El Sheemy, Y M Fouad, D Attia
BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients. AIM: To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world. METHODS: This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males)...
January 19, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29348606/amp-activated-protein-kinase-agonist-n6-3-hydroxyphenyl-adenosine-protects-against-fulminant-hepatitis-by-suppressing-inflammation-and-apoptosis
#8
Jin Li, Bo Chen, Liping Zhong, Feng Gao, Haibo Zhu, Fengzhong Wang
Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348125/metabolism-and-disposition-of-a-novel-selective-%C3%AE-7-neuronal-acetylcholine-receptor-agonist-abt-126-in-humans-characterization-of-the-major-roles-for-flavin-containing-monooxygenases-and-udp-glucuronosyl-transferase-1a4-and-2b10-in-catalysis
#9
Hong Liu, David M Stresser, Melissa J Michmerhuizen, XIaofeng Li, Ahmed A Othman, Aimee D Reed, Michael R Schrimpf, Jens Sydor, Anthony J Lee
Mass balance, metabolism and excretion of ABT-126, an α7 nAChRs agonist, were characterized in healthy male subjects (n=4) following a single 100 mg (100 μCi) oral dose. The total recovery of the administered radioactivity was 94.0% (±2.09%) with 81.5% (± 10.2%) in urine and 12.4% (± 9.3%) in feces. Metabolite profiling indicated that ABT-126 had been extensively metabolized with 6.6% of the dose remaining as unchanged parent drug in urine. Parent drug accounted for 12.2% of the administered radioactivity in feces...
January 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29346443/exposure-to-previous-cart-is-associated-with-significant-liver-fibrosis-and-cirrhosis-in-human-immunodeficiency-virus-infected-patients
#10
Evrim Anadol, Kristina Lust, Christoph Boesecke, Carolynne Schwarze-Zander, Raphael Mohr, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Jonel Trebicka
INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. METHODS: This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE)...
2018: PloS One
https://www.readbyqxmd.com/read/29346260/race-risk-and-willingness-of-end-stage-renal-disease-patients-without-hepatitis-c-hcv-to-accept-an-hcv-infected-kidney-transplant
#11
Maureen McCauley, Adam Mussell, David Goldberg, Deirdre Sawinski, Rodolfo N Molina, Ricarda Tomlin, Sahil D Doshi, Peter Abt, Roy Bloom, Emily Blumberg, Sanjay Kulkarni, Gabriela Esnaola, Justine Shults, Carrie Thiessen, Peter P Reese
BACKGROUND: Despite effective antiviral treatment, hundreds of kidneys from deceased donors with hepatitis C virus (HCV) are discarded annually. Little is known about the determinants of willingness to accept HCV-infected kidneys among HCV-negative patients. METHODS: At 2 centers, 189 patients undergoing initial or reevaluation for transplant made 12 hypothetical decisions about accepting HCV-infected kidneys in which we systematically varied expected HCV cure rate, allograft quality and wait-time for an uninfected kidney...
January 18, 2018: Transplantation
https://www.readbyqxmd.com/read/29345050/metabolic-alterations-in-a-rat-model-of-hepatic-ischemia-reperfusion-injury-in-vivo-hyperpolarized-13-c-mrs-and-metabolic-imaging
#12
Chung-Man Moon, Sang-Soo Shin, Nam-Yeol Lim, Seul-Kee Kim, Yang-Joon Kang, Hyoung-Ook Kim, Seung-Jin Lee, Byung-Hyun Beak, Gwang-Woo Jeong
BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI remains elusive. This study investigated the metabolic alterations in a rat model of hepatic IRI using the in vivo hyperpolarized ¹³C MRS and metabolic imaging. METHODS: Hyperpolarized 13 C MRS with IVIM-DWI were performed on the liver of seven sham-operated control rats, and seven rats before and after hepatic IRI...
January 18, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29344353/effects-of-tnf-receptor-blockade-on-in-vitro-cell-survival-and-response-to-negative-energy-balance-in-dairy-cattle
#13
C A Martel, L K Mamedova, J E Minton, M Garcia, C Legallet, B J Bradford
Background: Associative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor (TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed restriction...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29343706/caloric-restriction-lowers-endocannabinoid-tonus-and-improves-cardiac-function-in-type-2-diabetes
#14
Huub J van Eyk, Linda D van Schinkel, Vasudev Kantae, Charlotte E A Dronkers, Jos J M Westenberg, Albert de Roos, Hildo J Lamb, J Wouter Jukema, Amy C Harms, Thomas Hankemeier, Mario van der Stelt, Ingrid M Jazet, Patrick C N Rensen, Johannes W A Smit
BACKGROUND/OBJECTIVES: Endocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD). SUBJECTS/METHODS: In a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450-1000 kcal/day)...
January 17, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29343038/-diagnostic-value-of-albumin-bilirubin-grade-combined-with-serum-ammonia-in-cirrhosis-with-hepatic-encephalopathy
#15
Y L Hou, M D Gao, H Y Guo, R Wang, Z Wang, Y H Yu, J L Lou, Y Zhao
Objective: To explore the value of albumin-bilirubin (ALBI) grade combined with serum ammonia in the diagnosis of cirrhosis with hepatic encephalopathy (HE). Methods: The serum level of total bilirubin(TBIL), albumin( ALB )and blood ammonia were detected in 139 patients including 73 cirrhosis patients without HE and 66 cirrhosis patients with HE from January 2015 to January 2017 in Beijing You'an Hospital, and the relationship between ALBI and blood ammonia value and Child grade and hepatic encephalopathy was analyzed...
January 9, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29342358/synthesis-and-biological-characterization-of-aryl-uracil-inhibitors-of-hepatitis-c-virus-ns5b-polymerase-discovery-of-abt-072-a-trans-stilbene-analog-with-good-oral-bioavailability
#16
John Randolph, A Chris Krueger, Pamela Donner, John K Pratt, Dachun Liu, Christopher E Motter, Todd W Rockway, Mike D Tufano, Rolf Wagner, Hock B Lim, Jill M Beyer, Rubina Mondal, Neeta S Panchal, Lynn Colletti, Yaya Liu, Gennadiy Koev, Warren M Kati, Lisa E Hernandez, David W A Beno, Kenton L Longenecker, Kent D Stewart, Emily O Dumas, Akhteruzzaman Molla, Clarence Maring
ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection. This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication. Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility, and provided much better pharmacokinetic properties in preclinical species...
January 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29341965/osmotic-shifts-cerebral-edema-and-neurologic-deterioration-in-severe-hepatic-encephalopathy
#17
Eric Michael Liotta, Anna L Romanova, Bryan D Lizza, Laura J Rasmussen-Torvik, Minjee Kim, Brandon Francis, Rajbeer Singh Sangha, Timothy J Carroll, Daniel Ganger, Daniela P Ladner, Andrew M Naidech, James J Paparello, Shyam Prabhakaran, Farzaneh A Sorond, Matthew B Maas
OBJECTIVES: We sought to determine the effect of acute electrolyte and osmolar shifts on brain volume and neurologic function in patients with liver failure and severe hepatic encephalopathy. DESIGN: Retrospective analysis of brain CT scans and clinical data. SETTING: Tertiary care hospital ICUs. PATIENTS: Patients with acute or acute-on-chronic liver failure and severe hepatic encephalopathy. INTERVENTIONS: Clinically indicated CT scans and serum laboratory studies...
February 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29341936/rheumatic-manifestations-among-cancer-patients-treated-with-immune-checkpoint-inhibitors
#18
REVIEW
Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, Ronnie Shapira-Frommer, Gal Markel
BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts...
January 13, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29340893/a-prospective-study-of-humoral-and-cellular-immune-responses-to-hepatitis-b-vaccination-in-habitual-marijuana-smokers
#19
Sylvia M Kiertscher, Pallavi R Gangalum, Grace Ibrahim, Donald P Tashkin, Michael D Roth
Exposure to Δ9-tetrahydrocannabinol (THC) in vitro and in animal models can significantly impair the differentiation, activation and function of dendritic cells, T cells and B cells. However, studies directly assessing the impact of marijuana smoking on human immunity are lacking. A prospective study of immune responses to a standard hepatitis B vaccination was therefore carried out in a matched cohort of 9 marijuana smokers (MS) and 9 nonsmokers (NS). In addition to their regular marijuana use, MS smoked four marijuana cigarettes in a monitored setting on the day of each vaccination...
January 16, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29340742/-wilson-disease
#20
D Huster
Wilson disease is a rare hereditary disorder of copper metabolism. The genetic defect is caused by various mutations in the copper-transporting enzyme ATP7B, located mainly in the liver and brain. Clinical symptoms are highly variable, with any combination of hepatic and/or neurological or psychiatric manifestations. The age of onset varies from early childhood to young adults and can even be manifested in later ages. The clinical diagnosis is based on a combination of clinical, biochemical and molecular markers...
January 16, 2018: Der Internist
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