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Hepatitis B genetics

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https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#1
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28643196/genetic-variants-in-cell-death-pathway-genes-and-hbv-related-hepatocellular-carcinoma-among-a-chinese-han-population
#2
Fei Liu, Fuqiang Li, Limei Luo, Hanteng Yang, Yonggang Wei, Wentao Wang, Lvnan Yan, Tianfu Wen, Jiayin Yang, Bo Li
Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population...
June 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28640108/correlation-of-hla-dp-dq-polymorphisms-with-transplant-etiologies-and-prognosis-in-liver-transplant-recipients
#3
Yi Li, Qian Huang, Jiang-Tao Tang, Tian-Tian Wei, Lin Yan, Zhi-Qiang Yang, Yang-Juan Bai, Lan-Lan Wang, Yun-Ying Shi
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28627394/novel-non-canonical-genetic-rearrangements-termed-complex-structural-variations-in-hbv-genome
#4
Kei Fujiwara, Kayoko Matsunami, Etsuko Iio, Shunsuke Nojiri, Takashi Joh
BACKGROUNDS AND AIMS: Chronic hepatitis B virus (HBV) infection is an important worldwide public health issue. Further knowledge on the characteristics of HBV will facilitate its eradication. Genome structural variations (SVs) are defined by its canonical form such as duplication, deletion, and insertion. However, recent studies have reported complex SVs that cannot be explained by those canonical SVs. A HBV strain (UK2) with an unusual genome structure rearrangement that was completely different from known mutations or rearrangements was previously reported...
June 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28627389/association-of-genetic-variation-in-b-cell-activating-factor-with-chronic-hepatitis-b-virus-infection
#5
Qunying Han, Cuiling Yang, Na Li, Fang Li, Jiao Sang, Yi Lv, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
The outcome of hepatitis B virus (HBV) infection is considered to be related to the host immunogenetic susceptibility. B cell activating factor (BAFF) is involved in both B cell and T cell mediated immunity and its circulating levels were shown to be significantly elevated in HBV-related liver diseases. This study examined BAFF rs9514828 and rs12583006 polymorphisms in 386 patients with various liver diseases related to chronic HBV infection, 69 HBV infection resolvers, and 191 healthy controls. Both rs9514828 and rs12583006 polymorphisms and serum BAFF levels were determined in 232 patients with chronic HBV infection, and 61 healthy controls...
June 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28621226/pten-a-potential-prognostic-marker-in-virus-induced-hepatocellular-carcinoma
#6
REVIEW
Ayesha Khalid, Tabinda Hussain, Sobia Manzoor, Muhammad Saalim, Saba Khaliq
PTEN is the second most frequently mutated tumor suppresser gene in cancers after p53. Genetic and epigenetic alterations in the PTEN gene and its regulatory regions have been reported in various studies. PTEN is a crucial downregulator of the pro-survival phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway and also suppresses insulin signaling. Failure to regulate these pathways leads to increase in cell proliferation and migration which in turn promotes tumorigenesis. PTEN underexpression is mediated by a variety of cytokines and stress kinases which seem to collectively induce the RAS/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617615/association-between-pnpla3-gene-polymorphisms-and-risk-of-hepatitis-b-virus-related-hepatocellular-carcinoma-in-han-population-in-china-a-case-control-study
#7
Xia Gao, Wenxuan Liu, Lei Yang, Xiaolin Zhang, Ning Ma, Liqin Wang, Lina Yan, Longmei Tang, Haitao Yang, Dianwu Liu
BACKGROUND AND AIM: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese. METHODS: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry...
June 15, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28615356/sulforaphane-reduces-hepatic-glucose-production-and-improves-glucose-control-in-patients-with-type-2-diabetes
#8
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M J Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, Anders H Rosengren
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28611341/prevalence-and-molecular-characterization-of-hepatitis-d-virus-in-saudi-arabia-a-single-center-study
#9
Ghazi A Jamjoom, Mai M El-Daly, Esam I Azhar, Hind I Fallatah, Hisham O Akbar, Mohammed Babatin, Abdullah S Alghamdi, Mohammed I Dgdgi, Mohamed A Hamid, Yousef A Qari, Sherif A El-Kafrawy
BACKGROUND/AIMS: Hepatitis D virus (HDV) is a defective RNA virus that is dependent on hepatitis B surface antigen (HBsAg) for transmission and replication. HDV significance arises from the possibility of poor prognosis of hepatitis B virus (HBV) infection. In Saudi Arabia, HDV prevalence varied from 8 to 32% before the HBV vaccination program and ranged from 0 to 14.7% after the vaccination program was started. The last study, performed in 2004, showed a prevalence of 8.6% in hospital-based HBV cases and 3...
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28607531/endogenous-il-33-deficiency-exacerbates-liver-injury-and-increases-hepatic-influx-of-neutrophils-in-acute-murine-viral-hepatitis
#10
Virginie Carrière, Muhammad Imran Arshad, Jacques Le Seyec, Benjamin Lefevre, Muhammad Farooq, Aurélien Jan, Christelle Manuel, Laurence Touami-Bernard, Catherine Lucas-Clerc, Valentine Genet, Hugues Gascan, Jean-Philippe Girard, Frédéric Chalmel, Lucie Lamontagne, Claire Piquet-Pellorce, Michel Samson
The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28604703/cold-induced-conversion-of-cholesterol-to-bile-acids-in-mice-shapes-the-gut-microbiome-and-promotes-adaptive-thermogenesis
#11
Anna Worthmann, Clara John, Malte C Rühlemann, Miriam Baguhl, Femke-Anouska Heinsen, Nicola Schaltenberg, Markus Heine, Christian Schlein, Ioannis Evangelakos, Chieko Mineo, Markus Fischer, Maura Dandri, Claus Kremoser, Ludger Scheja, Andre Franke, Philip W Shaul, Joerg Heeren
Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28592560/ectopic-calcification-in-pseudoxanthoma-elasticum-responds-to-inhibition-of-tissue-nonspecific-alkaline-phosphatase
#12
Shira G Ziegler, Carlos R Ferreira, Elena Gallo MacFarlane, Ryan C Riddle, Ryan E Tomlinson, Emily Y Chew, Ludovic Martin, Chen-Ting Ma, Eduard Sergienko, Anthony B Pinkerton, José Luis Millán, William A Gahl, Harry C Dietz
Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction and shared biochemical and cellular mechanisms underlying ectopic calcification in PXE and related disorders caused by defined perturbations in extracellular adenosine 5'-triphosphate catabolism...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28584302/crispr-cas9-mediated-p53-and-pten-dual-mutation-accelerates-hepatocarcinogenesis-in-adult-hepatitis-b-virus-transgenic-mice
#13
Yongzhen Liu, Xuewei Qi, Zhenzhen Zeng, Lu Wang, Jie Wang, Ting Zhang, Qiang Xu, Congle Shen, Guangde Zhou, Shaomin Yang, Xiangmei Chen, Fengmin Lu
The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene disruption via hydrodynamic tail vein injection, allowing for in vivo targeting p53 and Pten simultaneously in adult HBV transgenic mice. Here we demonstrated that the utility of this approach resulted in macroscopic liver tumors as early as 4 months' post injection and most tumors harbored both p53 and Pten loss-of-function alterations...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28567562/identification-and-comparative-analysis-of-hepatitis-b-virus-genotype-d-e-recombinants-in-africa
#14
Ceejay L Boyce, Lilia Ganova-Raeva, Timothy N A Archampong, Margaret Lartey, Kwamena W Sagoe, Adjoa Obo-Akwa, Ernest Kenu, Awewura Kwara, Jason T Blackard
Globally, there are approximately 240 million people chronically infected with hepatitis B virus (HBV)-a major cause of hepatocellular carcinoma. Ten different HBV genotypes (A-J) have been identified with distinct geographic distributions. Novel variants generated by recombination between different HBV genotypes have been documented worldwide and represent an important element of genetic variability with possible clinical implications. Here, the complete genome sequence of an HBV genotype D/E recombinant from Ghana is reported...
May 31, 2017: Virus Genes
https://www.readbyqxmd.com/read/28566880/immune-response-to-vaccines-in-children-with-celiac-disease
#15
EDITORIAL
Caterina Anania, Francesca Olivero, Alessandra Spagnolo, Claudio Chiesa, Lucia Pacifico
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28566379/discovery-and-mechanistic-study-of-benzamide-derivatives-that-modulate-hepatitis-b-virus-capsid-assembly
#16
Shuo Wu, Qiong Zhao, Pinghu Zhang, John Kulp, Lydia Hu, Nicky Hwang, Jiming Zhang, Timothy M Block, Xiaodong Xu, Yanming Du, Jinhong Chang, Ju-Tao Guo
Chronic hepatitis B virus (HBV) infection is a global public health problem. Although the currently approved medications can reliably reduce the viral load and prevent the progression of liver diseases, they fail to cure the viral infection. In an effort toward discovery of novel antiviral agents against HBV, a group of benzamide (BA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA were discovered. The initial lead optimization efforts identified two BA derivatives with improved antiviral activity for further mechanistic studies...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28559891/systematic-optimization-of-protein-secretory-pathways-in-saccharomyces-cerevisiae-to-increase-expression-of-hepatitis-b-small-antigen
#17
Jiayuan Sheng, Hunter Flick, Xueyang Feng
Hepatitis B is a major disease that chronically infects millions of people in the world, especially in developing countries. Currently, one of the effective vaccines to prevent Hepatitis B is the Hepatitis B Small Antigen (HBsAg), which is mainly produced by the recombinant yeast Saccharomyces cerevisiae. In order to bring down the price, which is still too high for people in developing countries to afford, it is important to understand key cellular processes that limit protein expression. In this study, we took advantage of yeast knockout collection (YKO) and screened 194 S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#18
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546913/genetic-assembly-of-double-layered-fluorescent-protein-nanoparticles-for-cancer-targeting-and-imaging
#19
Seong-Eun Kim, Sung Duk Jo, Koo Chul Kwon, You-Yeon Won, Jeewon Lee
Hepatitis B virus capsid (HBVC), a self-assembled protein nanoparticle comprised of 180 or 240 subunit proteins, is used as a cage for genetic encapsulation of fluorescent proteins (FPs). The self-quenching of FPs is controlled by varying the spacing between FPs within the capsid structure. Double-layered FP nanoparticle possessing cancer cell-targeting capabilities is also produced by additionally attaching FPs and cancer cell receptor-binding peptides (affibodies) to the outer surface of the capsid. The generically modified HBVC with double layers of mCardinal FPs and affibodies (mC-DL-HBVC) exhibit a high fluorescence intensity and a strong photostability, and is efficiently internalized by cancer cells and significantly stable against intracellular degradation...
May 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28544258/incidence-and-risk-factors-for-non-alcoholic-fatty-liver-disease-a-7-year-follow-up-study-among-urban-adult-sri-lankans
#20
Madunil A Niriella, Arunasalam Pathmeswaran, Shamila T De Silva, Anuradhani Kasturiratna, Ruwan Perera, Chamila E Subasinghe, Kuleesha Kodisinghe, Chathura Piyaratna, Vithiya Rishikesawan, Anuradha S Dassanayaka, Arjuna P De Silva, Rajitha Wickramasinghe, Fumihiko Takeuchi, Norihiro Kato, Hithanadura J de Silva
BACKGROUND: This study investigated incidence and risk factors for NAFLD among an adult cohort with 7-year follow-up. METHODS: The study population (age-stratified random sampling, Ragama MOH area) was screened initially in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers...
May 19, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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