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Lipid and chronic hepatitis C

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https://www.readbyqxmd.com/read/28088354/uncovering-oxysterol-binding-protein-osbp-as-a-target-of-the-anti-enteroviral-compound-ttp-8307
#1
Lucian Albulescu, Joëlle Bigay, Bishyajit Biswas, Marion Weber-Boyvat, Cristina M Dorobantu, Leen Delang, Hilde M van der Schaar, Young-Sik Jung, Johan Neyts, Vesa M Olkkonen, Frank J M van Kuppeveld, Jeroen R P M Strating
The genus Enterovirus (e.g. poliovirus, coxsackievirus, rhinovirus) of the Picornaviridae family of positive-strand RNA viruses includes many important pathogens linked to a range of acute and chronic diseases for which no approved antiviral therapy is available. Targeting a step in the life cycle that is highly conserved provides an attractive strategy for developing broad-range inhibitors of enterovirus infection. A step that is currently explored as a target for the development of antivirals is the formation of replication organelles, which support replication of the viral genome...
January 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28056752/inhibiting-the-secretion-of-hepatitis-b-surface-antigen-hbsag-to-treat-hepatitis-b-infection-a-review
#2
Simon D Baugh
Chronic Hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease...
January 4, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28038469/polyunsaturated-fatty-acids-ameliorate-aging-via-redox-telomere-antioncogene-axis
#3
Jingnan Chen, Yan Wei, Xinyu Chen, Jingjing Jiao, Yu Zhang
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27989594/salvianolic-acid-b-protects-against-chronic-alcoholic-liver-injury-via-sirt1-mediated-inhibition-of-crp-and-chrebp-in-rats
#4
Ning Zhang, Yan Hu, Chunchun Ding, Wenjing Zeng, Wen Shan, Hui Fan, Yan Zhao, Xue Shi, Lili Gao, Ting Xu, Ruiwen Wang, Dongyan Gao, Jihong Yao
Salvianolic acid B (SalB), a water-soluble polyphenol extracted from Radix Salvia miltiorrhiza, has been reported to possess many pharmacological activities. This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels...
December 15, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27988942/young-healthy-south-asians-have-enhanced-lipogenic-sensitivity-to-dietary-sugar
#5
Lisa C Hudgins, Jonathan L Hugo, Samim Enayat, Thomas S Parker, Amanda S Artis, Daniel M Levine
OBJECTIVE: South Asians have higher rates of Type 2 diabetes and cardiovascular disease compared to most other racial/ethnic groups. Increased hepatic de novo lipogenesis (DNL) in response to dietary sugar may accelerate the development of these chronic diseases in this population. STUDY DESIGN: Hepatic DNL in response to a calorically sweetened beverage was measured in an outpatient setting in 15 South Asians and 15 Caucasians with similar and normal body mass indexes, waist circumferences, glucose tolerance and lipid profiles...
December 17, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/27941027/the-lipid-droplet-associated-protein-perilipin-3-facilitates-hepatitis-c-virus-driven-hepatic-steatosis
#6
Daniel Ferguson, Jun Zhang, Matthew A Davis, Robert N Helsley, Lise-Lotte Vedin, Richard G Lee, Rosanne M Crooke, Mark J Graham, Paolo Parini, J Mark Brown
Hepatitis C Virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LD) for steatosis development and viral particle assembly. Given the LD is an important component of hepatic lipid storage, and serves as a platform for HCV particle assembly; this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis...
December 10, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27940481/regulation-of-lipid-metabolism-by-obeticholic-acid-in-hyperlipidemic-hamsters
#7
Bin Dong, Mark Young, Xueqing Liu, Amar Bahadur Singh, Jingwen Liu
The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-C homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects yet have not been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR modulated gene and the major receptor for HDL-C...
December 9, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27929465/using-multi-fluorinated-bile-acids-and-in-vivo-magnetic-resonance-imaging-to-measure-bile-acid-transport
#8
Jessica Felton, Kunrong Cheng, Anan Said, Aaron C Shang, Su Xu, Diana Vivian, Melissa Metry, James E Polli, Jean-Pierre Raufman
Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19)...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27909723/inhibition-of-jnk-suppresses-autophagy-and-attenuates-insulin-resistance-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#9
Hua Yan, Yanqiong Gao, Ying Zhang
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the pathological process of which is complex. Activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway is associated with the mechanism underlying obesity-induced insulin resistance. Furthermore, the JNK signaling pathway and dysfunctional autophagy serve important roles in hepatic lipid metabolism. However, the exact role of JNK in autophagy and obesity‑induced insulin resistance is not fully understood. Therefore, the present study aimed to investigate the underlying mechanisms by which the JNK signaling pathway regulates autophagy and insulin resistance in fatty liver...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27903618/hypolipidemic-effect-of-oleanolic-acid-is-mediated-by-the-mir-98-5p-pgc-1%C3%AE-axis-in-high-fat-diet-induced-hyperlipidemic-mice
#10
Siyu Chen, Xiaoan Wen, Wenxiang Zhang, Chen Wang, Jun Liu, Chang Liu
Oleanolic acid (OA) is an active component of the traditional Chinese herb olea europaea l. and has been found to exhibit a significant lipid-lowering effect; however, its direct molecular target is still unknown, which limits its clinical application and the possible structure modification to improve its beneficial functions. In this regard, we carried out the present study to identify potential hepatic targets of OA to mediate its lipid-lowering effect. We found that both acute and chronic OA treatments reduced serum levels of triglycerides, total cholesterol, and LDL cholesterol, and decreased hepatic expression levels of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), which is an important regulator in maintaining hepatic lipid homeostasis, and its downstream target genes...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27888600/-darunavir-cobicistat-monotherapy-experience-in-a-tertiary-hospital
#11
L Yunquera-Romero, R Asensi-Díez, J C Del Rio-Valencia, I Muñoz-Castillo, M A Castaño-Carracedo
OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r...
December 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/27830380/recovery-of-pan-genotypic-and-genotype-specific-amino-acid-alterations-in-chronic-hepatitis-c-after-viral-clearance-transition-at-the-crossroad-of-metabolism-and-immunity
#12
Ming-Ling Chang, Mei-Ling Cheng, Su-Wei Chang, Hsiang-Yu Tang, Cheng-Tang Chiu, Chau-Ting Yeh, Ming-Shi Shiao
Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography-tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients...
November 10, 2016: Amino Acids
https://www.readbyqxmd.com/read/27788588/identification-of-circulating-protein-biomarkers-in-patients-with-hepatocellular-carcinoma-concomitantly-infected-with-chronic-hepatitis-c-virus
#13
Abdel-Hady Ali Abdel-Wahab, Medhat S El-Halawany, Ahmad A Emam, Ammar Elfiky, Zakaria Y Abd Elmageed
CONTEXT: The incidence rate of hepatocellular carcinoma (HCC) is higher in developing countries, and most cases are associated with chronic hepatitis C virus (HCV) infection. OBJECTIVE: To evaluate the circulating proteins as liver biomarkers for identification of HCC associated with HCV infection in Egyptian patients using LC-MS/MS analysis. METHODS: Blood sera were collected from 31 HCC patients and the fractionated proteins were subjected to LC-MS/MS analysis...
October 28, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27776194/rna-seq-based-analysis-of-differential-gene-expression-associated-with-hepatitis-c-virus-infection-in-a-cell-culture
#14
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27688688/incidence-of-insulin-resistance-and-diabetes-in-patients-with-portosystemic-shunts-without-liver-dysfunction
#15
Ying Li, Gao Yang, Jinwei Qiang, Songqi Cai, Hao Zhou
OBJECTIVE: To investigate the incidence of insulin resistance (IR) and diabetes in patients with chronic hepatic schistosomiasis japonica (HSJ) and portosystemic shunts (PSS). METHODS: Pre- and post-contrasted computed tomography images obtained from patients with HSJ and control subjects were reviewed by two radiologists who identified and graded any shunting vessels. Anthropometric measurements, hepatic enzymes, lipid profile, blood levels of albumin, glucose, insulin and homeostasis model assessment (HOMA-2) index of all participants were also assessed...
September 29, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27685337/effect-of-antiviral-therapy-for-hcv-on-lipid-levels
#16
Stefan Mauss, Florian Berger, Malte H Wehmeyer, Patrick Ingiliz, Dietrich Hueppe, Thomas Lutz, Karl G Simon, Knud Schewe, Juergen K Rockstroh, Axel Baumgarten, Stefan Christensen
HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon therapy has been shown to decrease cholesterol even further. With the availability of second generation direct acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation. 
Methods: Prospective German multicenter cohort on HCV- and HIV/HCV-infected patients treated with direct antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy...
September 29, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27680885/rapid-increase-in-serum-low-density-lipoprotein-cholesterol-concentration-during-hepatitis-c-interferon-free-treatment
#17
Satoru Hashimoto, Hiroshi Yatsuhashi, Seigo Abiru, Kazumi Yamasaki, Atsumasa Komori, Shinya Nagaoka, Akira Saeki, Shinjiro Uchida, Shigemune Bekki, Yuki Kugiyama, Kazuyoshi Nagata, Minoru Nakamura, Kiyoshi Migita, Kazuhiko Nakao
BACKGROUND & AIM: We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients' serum low-density lipoprotein cholesterol (LDL-C) concentration. METHODS: We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27677955/role-of-oxidative-stress-in-hepatitis-c-virus-induced-hepatocellular-carcinoma
#18
Na Fu, Hui Yao, Yuemin Nan, Liang Qiao
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is the predominant cause of chronic liver diseases and HCC, particularly in Western countries. Multiple molecular mechanisms are involved in the development and progression of HCV-related HCC, of which oxidative stress plays a pivotal role. HCV infection induces overproduction of reactive oxygen species (ROS) and impairs the function of endogenous antioxidants. Excessive amount of ROS directly damages DNA, lipids and proteins...
September 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27665576/lipoprotein-lipase-liberates-free-fatty-acids-to-inhibit-hcv-infection-and-prevent-hepatic-lipid-accumulation
#19
Hung-Yu Sun, Chun-Chieh Lin, Pei-Ju Tsai, Wei-Jen Tsai, Jin-Ching Lee, Chiung-Wen Tsao, Pin-Nan Cheng, I-Chin Wu, Yen-Cheng Chiu, Ting-Tsung Chang, Kung-Chia Young
Lipoprotein lipase (LPL) has been identified as an anti-HCV host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti-HCV. The functional activation of peroxisome proliferator-activated receptor (PPAR) α signal by LPL transducing into hepatocytes were investigated in HCV-infected cells, primary human heaptocytes (PHHs), and in HCV-core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARα in Huh7 cells and PHHs were elevated by physiologically ranged LPL treatment of either very-low-density lipoprotein or HCV particles...
September 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27664407/anti-adipogenic-and-antiviral-effects-of-l-carnitine-on-hepatitis-c-virus-infection
#20
Yoko Tsukuda, Goki Suda, Seiji Tsunematsu, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Takuya Sho, Osamu Maehara, Tomoe Shimazaki, Megumi Kimura, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Naoya Sakamoto
Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of l-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicon-transfected Huh7.5.1 cells were treated with or without l-carnitine to examine its anti-HCV effects. The effects of l-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined...
September 24, 2016: Journal of Medical Virology
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