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https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#1
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28749426/a-novel-perspective-on-the-apom-s1p-axis-highlighting-the-metabolism-of-apom-and-its-role-in-liver-fibrosis-and-neuroinflammation
#2
REVIEW
Stefan Hajny, Christina Christoffersen
Hepatocytes, renal proximal tubule cells as well as the highly specialized endothelium of the blood brain barrier (BBB) express and secrete apolipoprotein M (apoM). ApoM is a typical lipocalin containing a hydrophobic binding pocket predominantly carrying Sphingosine-1-Phosphate (S1P). The small signaling molecule S1P is associated with several physiological as well as pathological pathways whereas the role of apoM is less explored. Hepatic apoM acts as a chaperone to transport S1P through the circulation and kidney derived apoM seems to play a role in S1P recovery to prevent urinal loss...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749086/1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-plag-reduces-hepatic-injury-in-concanavalin-a-treated-mice
#3
Young-Eun Ko, Sun Young Yoon, Sun-Yung Ly, Joo-Heon Kim, Ki-Young Sohn, Jae Wha Kim
1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a chemically synthesized monoacetyldiaglyceride, is one of the constituents in Sika deer antlers and has been known traditionally as having immunomodulatory effects. However, the mechanism by which PLAG controls neutrophil migration, which evokes liver injury in the hepatitis animal model, remains largely unknown. This study was designed to evaluate the immunomodulatory effects of PLAG on cytokine secretion and neutrophil migration in vivo and in vitro. The injection of mice with Concanavalin A (Con A) induced leukocyte infiltration in the liver and increased plasma cytokine levels...
July 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28749066/donor-dependent-and-other-nondefined-factors-have-greater-influence-on-the-hepatic-phenotype-than-the-starting-cell-type-in-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells
#4
James A Heslop, Richard Kia, Christopher S Pridgeon, Rowena L Sison-Young, Triantafillos Liloglou, Mohamed Elmasry, Stephen W Fenwick, John S Mills, Neil R Kitteringham, Chris E Goldring, B Kevin Park
No abstract text is available yet for this article.
August 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28749008/propofol-post-conditioning-alleviates-hepatic-ischaemia-reperfusion-injury-via-brg1-mediated-nrf2-ho-1-transcriptional-activation-in-human-and-mice
#5
Mian Ge, Huixin Chen, Qianqian Zhu, Jun Cai, Chaojin Chen, Dongdong Yuan, Yi Jin, Weifeng Yao, Ziqing Hei
To explore the effects of propofol post-conditioning (PPC) on hepatic ischaemia/reperfusion injury (HIRI) and the potential mechanisms that might be involved in the interaction of Brahma-related gene1(BRG1) and Nuclear-related factor 2(Nrf2). Patients were randomized into PPC(n = 16) and non-PPC(NPC)( n = 21) groups. Propofol(2 mg/kg) was infused within 10 min. of the onset of liver reperfusion during liver transplantation in the PPC group. Liver function tests, as well as Brg1, Nrf2, Heme oxygenase-1(HO-1) and NADPH:quinone oxidoreductase1(NQO1) expression levels were evaluated...
July 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#6
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28747678/the-liver-enriched-lnc-lfar1-promotes-liver-fibrosis-by-activating-tgf%C3%AE-and-notch-pathways
#7
Kun Zhang, Xiaohui Han, Zhen Zhang, Lina Zheng, Zhimei Hu, Qingbin Yao, Hongmei Cui, Guiming Shu, Maojie Si, Chan Li, Zhemin Shi, Ting Chen, Yawei Han, Yanan Chang, Zhi Yao, Tao Han, Wei Hong
Long noncoding RNAs (lncRNAs) play important roles in various biological processes such as proliferation, cell death and differentiation. Here, we show that a liver-enriched lncRNA, named liver fibrosis-associated lncRNA1 (lnc-LFAR1), promotes liver fibrosis. We demonstrate that lnc-LFAR1 silencing impairs hepatic stellate cells (HSCs) activation, reduces TGFβ-induced hepatocytes apoptosis in vitro and attenuates both CCl4- and bile duct ligation-induced liver fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFβR1 and its phosphorylation in the cytoplasm...
July 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747084/mir-615-5p-depresses-natural-killer-cells-cytotoxicity-through-repressing-igf-1r-in-hepatocellular-carcinoma-patients
#8
Mai Atef Rahmoon, Rana Ahmed Youness, Asmaa Ibrahim Gomaa, Mohamed Tarif Hamza, Imam Waked, Hend Mohamed El Tayebi, Ahmed Ihab Abdelaziz
miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56(dim), increased CD56(bright) NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins...
July 27, 2017: Growth Factors
https://www.readbyqxmd.com/read/28746468/ischemic-preconditioning-vs-adenosine-vs-prostaglandin-e1-for-protection-against-liver-ischemia-reperfusion-injury
#9
M Radojkovic, M Stojanovic, G Stanojevic, D Radojkovic, J Gligorijevic, I Ilic, N Stojanovic
Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning...
July 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28745862/galnac-conjugated-atorvastatin-with-enhanced-water-solubility-and-cellular-internalization
#10
Xinfu Zhang, Xiaofang Chen, Weiyu Zhao, Chunxi Zeng, Xiao Luo, Wenqing Li, Bin Li, Justin Jiang, Yizhou Dong
Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GalNAc (N-Acetylgalactosamine, a hepatocyte-targeting ligand) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently achieved significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase...
July 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28744811/evidence-of-vanillin-binding-to-camkiv-explains-the-anti-cancer-mechanism-in-human-hepatic-carcinoma-and-neuroblastoma-cells
#11
Huma Naz, Mohd Tarique, Parvez Khan, Suaib Luqman, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28744103/clinical-utility-of-evolocumab-in-the-management-of-hyperlipidemia-patient-selection-and-follow-up
#12
REVIEW
Dave L Dixon, Leo F Buckley, Cory R Trankle, Dinesh Kadariya, Antonio Abbate
Inhibition of PCSK9 is a novel therapeutic strategy aimed at reducing low-density-lipoprotein cholesterol (LDL-C) and cardiovascular risk. Evolocumab is a fully humanized monoclonal antibody that inhibits PCSK9, an enzyme that binds to LDL receptors and prevents them from recycling to the hepatocyte surface. Clinical trials have demonstrated 50%-70% reductions in LDL-C with evolocumab when used in combination with statin therapy. The recent FOURIER trial demonstrated that evolocumab further reduces cardiovascular events, but not mortality, in high-risk patients already receiving statin therapy...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28744018/cxcl10-is-produced-in-hepatitis-a-virus-infected-cells-in-an-irf3-dependent-but-ifn-independent-manner
#13
Pil Soo Sung, Seon-Hui Hong, Jeewon Lee, Su-Hyung Park, Seung Kew Yoon, Woo Jin Chung, Eui-Cheol Shin
Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743992/endotoxemia-mediated-activation-of-acetyltransferase-p300-impairs-insulin-signaling-in-obesity
#14
Jia Cao, Jinghua Peng, Hongying An, Qiyi He, Tatiana Boronina, Shaodong Guo, Morris F White, Philip A Cole, Ling He
Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28743983/liver-cholangiocytes-regenerate-hepatocytes-during-severe-liver-injury
#15
Iain Dickson
No abstract text is available yet for this article.
July 26, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28743914/cyclic-gmp-amp-ameliorates-diet-induced-metabolic-dysregulation-and-regulates-proinflammatory-responses-distinctly-from-sting-activation
#16
Xin Guo, Chang Shu, Honggui Li, Ya Pei, Shih-Lung Woo, Juan Zheng, Mengyang Liu, Hang Xu, Rachel Botchlett, Ting Guo, Yuli Cai, Xinsheng Gao, Jing Zhou, Lu Chen, Qifu Li, Xiaoqiu Xiao, Linglin Xie, Ke K Zhang, Jun-Yuan Ji, Yuqing Huo, Fanyin Meng, Gianfranco Alpini, Pingwei Li, Chaodong Wu
Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses. In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammatory responses in liver and adipose tissues and ameliorates metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effects on macrophages, hepatocytes, and adipocytes, which is distinct from the effect of STING activation by DMXAA on enhancing proinflammatory responses...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743900/long-term-hepatitis-b-infection-in-a-scalable-hepatic-co-culture-system
#17
Benjamin Y Winer, Tiffany S Huang, Eitan Pludwinski, Brigitte Heller, Felix Wojcik, Gabriel E Lipkowitz, Amit Parekh, Cheul Cho, Anil Shrirao, Tom W Muir, Eric Novik, Alexander Ploss
Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28743512/inferring-transcription-factor-activity-from-microarray-data-reveals-novel-targets-for-toxicological-investigations
#18
T M Souza, T van den Beucken, J C S Kleinjans, D G J Jennen
Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28743107/a-prozone-like-effect-influences-the-efficacy-of-the-monoclonal-antibody-abt-700-against-the-hepatocyte-growth-factor-receptor
#19
Kedar S Vaidya, Anatol Oleksijew, Lora A Tucker, William N Pappano, Mark G Anderson, Christine M Grinnell, Qian Zhang, Sarah J Heighton, Michael J Mitten, Sasmita Mishra, Joann P Palma, Jieyi Wang, Edward B Reilly, Erwin R Boghaert
ABT-700 is a therapeutic antibody against the hepatocyte growth factor receptor (MET). At doses or regimens that lead to exposures exceeding optimum in vivo, the efficacy of ABT-700 is unexpectedly reduced. We hypothesized that this reduction in efficacy was due to a "prozone-like" effect in vivo. A prozone-like effect, which is a reduction in efficacy beyond optimum exposure, is caused due a mechanism similar to the generation of false negative flocculation tests by excessive antibody titres. In vitro, we demonstrate that at higher ABT-700 concentrations, this "prozone-like" effect is mediated by a progressive conversion from bivalent to ineffective monovalent binding of the antibody...
July 26, 2017: Pharmacology
https://www.readbyqxmd.com/read/28742374/high-throughput-analysis-identifying-drugs-that-regulate-apolipoprotein-a-i-synthesis
#20
Michael J Haas, Luisa Onstead-Haas, William Kurban, Harshit Shah, Monica Plazarte, Ayham Chamseddin, Arshag D Mooradian
Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high-density lipoprotein (HDL). Despite the controversy as to the clinical effectiveness of raising HDL, the search is ongoing for safe and effective drugs that increase HDL and apo A-I levels. To identify novel compounds that can increase hepatic apo A-I production, two drug libraries were screened. The NIH clinical collection (NCC) and the NIH clinical collection 2 (NCC2) were purchased from Evotec (San Francisco, CA). The NCC library contains 446 compounds and the NCC2 library contains 281 compounds, all dissolved in dimethylsulfoxide at a concentration of 10 mM...
July 25, 2017: Assay and Drug Development Technologies
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