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https://www.readbyqxmd.com/read/29162431/adenine-accelerated-the-diabetic-wound-healing-by-ppar-delta-and-angiogenic-regulation
#1
Jyh-Gang Leu, Ming-Hsing Chiang, Chao-Yi Chen, Jiun-Tsai Lin, Han-Min Chen, Yen-Lin Chen, Yao-Jen Liang
Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP-activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin-induced diabetic mice...
November 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29152762/optimizing-lonafarnib-treatment-for-the-management-of-chronic-delta-hepatitis-the-lowr-hdv-1-study
#2
Cihan Yurdaydin, Onur Keskin, Çağdaş Kalkan, Fatih Karakaya, Aysun Çalişkan, Ersin Karatayli, Senem Karatayli, A Mithat Bozdayi, Christopher Koh, Theo Heller, Ramazan Idilman, Jeffrey S Glenn
BACKGROUND AND RATIONALE: In a proof-of-concept (POC) study, the oral prenylation inhibitor lonafarnib (LNF) decreased HDV RNA during 4 weeks of treatment. Here we explored optimal LNF regimens. METHODS: 15 patients (5 groups; 3 per group) completed dosing as follows: 1) LNF 200 mg BID (12 weeks); 2) LNF 300 mg BID (12 weeks); 3) LNF 100 mg TID (5 weeks); 4) LNF 100 mg BID + pegylated interferon alfa (PEG-IFNα) 180 mcg QW (8 weeks); and 5) LNF 100 mg BID + ritonavir (RTV) 100 mg QD (8 weeks)...
November 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29134331/optimization-and-application-of-a-dna-launched-infectious-clone-of-equine-arteritis-virus
#3
Ting Qi, Xiaojun Wang
Reverse genetics is one of the most powerful tools in modern virology. Equine arteritis virus (EAV) is the prototype member of the Equartevirus. In this study, a new reverse genetics system for the recovery of equine arteritis virus from a cDNA plasmid, which contains viral cDNA sequence flanked by hammerhead ribozyme (HamRz) and hepatitis delta virus ribozyme (HdvRz) sequences in both terminals of the viral genome, was developed by optimization of the promoter and terminator regions. Cellular RNA polymerase II drove the transcription of the viral genome...
November 13, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29127322/reduced-hepatitis-b-and-d-viral-entry-using-clinically-applied-drugs-as-novel-inhibitors-of-the-bile-acid-transporter-ntcp
#4
Joanne M Donkers, Benno Zehnder, Gerard J P van Westen, Mark J Kwakkenbos, Adriaan P IJzerman, Ronald P J Oude Elferink, Ulrich Beuers, Stephan Urban, Stan F J van de Graaf
The sodium taurocholate co-transporting polypeptide (NTCP, SLC10A1) is the main hepatic transporter of conjugated bile acids, and the entry receptor for hepatitis B virus (HBV) and hepatitis delta virus (HDV). Myrcludex B, a synthetic peptide mimicking the NTCP-binding domain of HBV, effectively blocks HBV and HDV infection. In addition, Myrcludex B inhibits NTCP-mediated bile acid uptake, suggesting that also other NTCP inhibitors could potentially be a novel treatment of HBV/HDV infection. This study aims to identify clinically-applied compounds intervening with NTCP-mediated bile acid transport and HBV/HDV infection...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107885/structure-based-mechanistic-insights-into-catalysis-by-small-self-cleaving-ribozymes
#5
REVIEW
Aiming Ren, Ronald Micura, Dinshaw J Patel
Small self-cleaving ribozymes are widely distributed in nature and are essential for rolling-circle-based replication of satellite and pathogenic RNAs. Earlier structure-function studies on the hammerhead, hairpin, glmS, hepatitis delta virus and Varkud satellite ribozymes have provided insights into their overall architecture, their catalytic active site organization, and the role of nearby nucleobases and hydrated divalent cations in facilitating general acid-base and electrostatic-mediated catalysis. This review focuses on recent structure-function research on active site alignments and catalytic mechanisms of the Rzb hammerhead ribozyme, as well as newly-identified pistol, twister and twister-sister ribozymes...
November 3, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29088999/antioxidant-antihyperglycemic-and-antidyslipidemic-effects-of-brazilian-native-fruit-extracts-in-an-animal-model-of-insulin-resistance
#6
Juliane de Souza Cardoso, Pathise Souto Oliveira, Natália Pontes Bona, Flávia Aleixo Vasconcellos, Jucimara Baldissarelli, Marcia Vizzotto, Mayara Sandrielly Pereira Soares, Vanessa Plasse Ramos, Roselia Maria Spanevello, Claiton Leoneti Lencina, Rejane Giacomelli Tavares, Francieli Moro Stefanello
OBJECTIVE: Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX). METHODS: Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days...
October 31, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29056891/polygala-tenuifolia-extract-inhibits-lipid-accumulation-in-3t3-l1-adipocytes-and-high-fat-diet-induced-obese-mouse-model-and-affects-hepatic-transcriptome-and-gut-microbiota-profiles
#7
Chun-Chung Wang, Jui-Hung Yen, Yi-Cheng Cheng, Chia-Yu Lin, Cheng-Ta Hsieh, Rung-Jiun Gau, Shu-Jiau Chiou, Hwan-You Chang
Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/29056006/-mechanism-of-astragaloside-prevents-cholestatic-liver-fibrosis-through-inhibition-of-notch-signaling-activation
#8
Y P Mu, X Zhang, W W Fan, X W Li, G F Chen, J M Chen, H Zhang, P Liu
Objective: The Notch signaling pathway is closely related to biliary fibrosis. Previous studies have shown that Astragaloside (AS) can prevent the progression of cholestatic liver fibrosis. The purpose of this study is to observe the effect of AS on the regulation of Notch signaling pathway in biliary fibrosis. Methods: Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. Two weeks after BDL, the rats were randomly divided into a model group (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive control group and treated for 3 weeks...
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29023927/hepatitis-b-virus-dual-infection-disrupts-platelet-count-recovery-in-chronic-hepatitis-c-patients-with-curative-antiviral-therapy
#9
Chung-Feng Huang, Ming-Lun Yeh, Ching-I Huang, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is associated with thrombocytopenia. Thrombocytopenia recovers after viral eradication. The current study explored the rate and factors associated with platelet (PLT) recovery, which may represent the degree of liver fibrosis regression. METHODS: A total of 466 patients who achieved a sustained virological response (SVR) were enrolled to compare the PLT change after a mean follow-up period of 85.5months (range 12-163 months)...
October 11, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29023121/discovery-of-3-5-diphenyl-4-methyl-1-3-oxazolidin-2-ones-as-novel-potent-and-orally-available-%C3%AE-5-desaturase-d5d-inhibitors
#10
Jun Fujimoto, Rei Okamoto, Naoyoshi Noguchi, Ryoma Hara, Shinichi Masada, Tetsuji Kawamoto, Hiroki Nagase, Yumiko Okano Tamura, Mitsuaki Imanishi, Shuichi Takagahara, Kazuki Kubo, Kimio Tohyama, Koichi Iida, Tomohiro Andou, Ikuo Miyahisa, Junji Matsui, Ryouta Hayashi, Tsuyoshi Maekawa, Nobuyuki Matsunaga
The discovery and optimization of Δ-5 desaturase (D5D) inhibitors are described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a pharmacophore model constructed from the common features of several hit compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one 5h as a novel lead showing potent in vitro activity. Subsequent optimization focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a derivative with improved metabolic stability. Moreover, adding a substituent into the upper phenyl moiety further enhanced the intrinsic activity, which led to the discovery of 5-[(4S,5S)-5-(4fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-dicarbonitrile (4S,5S)-5n, endowed with excellent D5D binding affinity, cellular activity, and high oral bioavailability in a mouse...
October 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28992360/genetic-diversity-and-worldwide-distribution-of-the-deltavirus-genus-a-study-of-2-152-clinical-strains
#11
Frédéric Le Gal, Ségolène Brichler, Tudor Drugan, Chakib Alloui, Dominique Roulot, Jean-Michel Pawlotsky, Paul Dény, Emmanuel Gordien
Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of eight major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotides 889 to 1289 encompassing the 3' end of the delta protein-coding gene...
December 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28988126/quantitative-characterization-of-hepatitis-delta-virus-genome-edition-by-next-generation-sequencing
#12
Sara Sopena, Cristina Godoy, David Tabernero, Maria Homs, Josep Gregori, Mar Riveiro-Barciela, Alicia Ruiz, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías
AIM: To determine the capacity of next-generation sequencing (NGS) for quantifying edited and unedited HDV populations, and to confirm if edition is a general phenomenon taking place along the entire HDV region analyzed, as we previously reported (Homs M et al. PLoS One 2016, 11, e0158557). METHODS: Four serum samples from 4 patients with chronic HDV/HBV infection were included in the study. The region selected for analysis covered 360 nucleotides (nt), positions 910-1270 of the HDV genome, which included the HDAg ORF editing site (nt 1014 within codon 196)...
October 4, 2017: Virus Research
https://www.readbyqxmd.com/read/28980394/hepatitis-delta-virus-infection-in-a-large-cohort-of-chronic-hepatitis-b-patients-in-ethiopia
#13
Hanna Aberra, Emmanuel Gordien, Hailemichael Desalegn, Nega Berhe, Girmay Medhin, Bitsatab Mekasha, Svein Gunnar Gundersen, Athenaïs Gerber, Kathrine Stene-Johansen, Joakim Øverbø, Asgeir Johannessen
BACKGROUND: Hepatitis D Virus (HDV)-infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV-infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. METHODS: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays...
October 4, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28977829/analyses-of-a-whole-genome-inter-clade-recombination-map-of-hepatitis-delta-virus-suggest-a-host-polymerase-driven-and-viral-rna-structure-promoted-template-switching-mechanism-for-viral-rna-recombination
#14
Mei Chao, Tzu-Chi Wang, Chia-Chi Lin, Robert Yung-Liang Wang, Wen-Bin Lin, Shang-En Lee, Ying-Yu Cheng, Chau-Ting Yeh, Shan-Bei Iang
The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977233/chronic-hepatitis-b-and-d-prognosis-according-to-child-pugh-score
#15
Marcelo Siqueira de Oliveira, Romeu Paulo Martins Silva, Suiane da Costa Negreiros do Valle, Elisabeth Níglio de Figueiredo, Dayana Fram
Objective: compare chronic hepatitis B patients to those superinfected with hepatitis D virus, according to Child-Pugh score regarding disease severity. Method: retrospective descriptive study, performed with 59 patients followed in the ambulatory, of which 22 (37.3%) were chronically infected with hepatitis B virus (Group HBV) and 37 (62.7%) superinfected with Delta virus (Group HBV+HDV); variables of sex, age and items of Child-Pugh score were collected by consulting medical records...
September 2017: Revista Brasileira de Enfermagem
https://www.readbyqxmd.com/read/28968053/improving-the-identification-and-monitoring-of-cirrhosis
#16
Margaret G Keane, Charles Hensher, Stephen P Pereira
Morbidity and mortality associated with cirrhosis are on the increase. In a recent UK cohort study the incidence of cirrhosis increased by 50.6% between 1998 and 2009. Although all causes of liver disease increased during this period, this trend was primarily attributed to rising levels of alcohol misuse and obesity. Cirrhosis generally results from chronic liver damage over many years. It is characterised by fibrosis and nodularity of the parenchyma, which interferes with the synthetic, metabolic and excretory functions of the liver...
November 2016: Practitioner
https://www.readbyqxmd.com/read/28964935/new-chemotype-of-selective-and-potent-inhibitors-of-human-delta-24-dehydrocholesterol-reductase
#17
Christoph Müller, Sandra Hemmers, Nicholas Bartl, Alois Plodek, Andreas Körner, Valbona Mirakaj, Martin Giera, Franz Bracher
The enzyme Δ(24)-dehydrocholesterol reductase (DHCR24) catalyzes the reduction of the Δ(24)-double bond in the side chain of cholesterol precursors. Recent biochemical investigations fuel the hope that inhibition of DHCR24, resulting in an accumulation of desmosterol, can open new therapeutic options for treating hepatitis C virus infections, certain forms of cancer and atherosclerosis. In turn, there is a high need for selective, potent and non-toxic inhibitors of DHCR24. Previous reports as well as our re-evaluation showed that established DHCR24 inhibitors are not suitable for this purpose...
September 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28963781/clinical-and-virological-heterogeneity-of-hepatitis-delta-in-different-regions-world-wide-the-hepatitis-delta-international-network-hdin
#18
Anika Wranke, Lourdes M Pinheiro Borzacov, Raymundo Parana, Cirley Lobato, Saeed Hamid, Emanoil Ceausu, George N Dalekos, Mario Rizzetto, Adela Turcanu, Grazia A Niro, Farheen Lubna, Minaam Abbas, Patrick Ingiliz, Maria Buti, Peter Ferenci, Thomas Vanwolleghem, Tonya Hayden, Naranjargal Dashdorj, Adriana Motoc, Markus Cornberg, Zaigham Abbas, Cihan Yurdaydin, Michael P Manns, Heiner Wedemeyer, Svenja Hardtke
Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. METHODS: The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis...
September 29, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28961326/delta-hepatitis-toward-improved-diagnostics
#19
Saleem Kamili, Jan Drobeniuc, Tonya Mixson-Hayden, Maja Kodani
No abstract text is available yet for this article.
December 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28957872/utility-of-post-liver-transplantation-meld-and-delta-meld-in-predicting-early-and-late-mortality
#20
Talaat Zakareya, Mohammed Abbasy, Wael Abdel-Razek, Hussein Elsiesy, Faisal Abal Khail, Mohammed Al Sebayel, Imam Waked
INTRODUCTION: The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. AIM: The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. PATIENTS AND METHODS: Data of 209 consecutive patients who underwent LT in two centers were reviewed...
September 27, 2017: European Journal of Gastroenterology & Hepatology
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