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Immunostimulating hbv

Zehua Lin, Wenzhen Liao, Jiaoyan Ren
A polysaccharide fraction, here called POP1, was purified from the leaves of Platycladus orientalis (L.) Franco by water extraction and alcohol precipitation. Physicochemical characterization indicated that POP1 had a relative molecular weight of 8.10 × 10(3) Da and consisted of rhamnose (5.74%), arabinose (12.58%), mannose (10.97%), glucose (64.96%), and galactose (6.55%). The main linkage types of POP1 consisted of (1→5)-linked α-l-Ara, (1→3)-linked α-l-Man, (1→6)-linked β-l-Rha, (1→4)-linked α-d-Glc, (1→6)-linked α-d-Glc, (1→6)-linked β-d-Gal, (1→3,6)-linked β-d-Gal, and termination with α-l-Man and α-d-Glc residues based on periodate oxidation, Smith degradation, methylation, and NMR analysis...
July 27, 2016: Journal of Agricultural and Food Chemistry
Sirio Fiorino, Elisabetta Loggi, Gabriella Verucchi, Donatella Comparcola, Ranka Vukotic, Michele Pavoni, Elena Grandini, Carmela Cursaro, Silvia Maselli, Maria Letizia Bacchi Reggiani, Cristina Puggioli, Lorenzo Badia, Silvia Galli, Pierluigi Viale, Mauro Bernardi, Pietro Andreone
BACKGROUND & AIMS: The treatment of chronic hepatitis B infection (CHB) in children is still an area of great uncertainty. Vitamin E is an immunostimulating/antioxidant compound proven to be safe and effective for the treatment of adult CHB. The aim of this phase 2 controlled study was to evaluate the safety and efficacy of vitamin E for the treatment of pediatric HBeAg-positive CHB. METHODS: Forty-six children were randomized in a 1:1 ratio to receive vitamin E at a dose of 15 mg/kg/day (in galenic preparation) or no treatment for 12 months and were monitored for the subsequent 12 months...
June 22, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Faseeha Noordeen, Catherine A Scougall, Arend Grosse, Qiao Qiao, Behzad B Ajilian, Georget Reaiche-Miller, John Finnie, Melanie Werner, Ruth Broering, Joerg F Schlaak, Andrew Vaillant, Allison R Jilbert
Previous studies have demonstrated that nucleic acid polymers (NAPs) have both entry and post-entry inhibitory activity against duck hepatitis B virus (DHBV) infection. The inhibitory activity exhibited by NAPs prevented DHBV infection of primary duck hepatocytes in vitro and protected ducks from DHBV infection in vivo and did not result from direct activation of the immune response. In the current study treatment of primary human hepatocytes with NAP REP 2055 did not induce expression of the TNF, IL6, IL10, IFNA4 or IFNB1 genes, confirming the lack of direct immunostimulation by REP 2055...
2015: PloS One
Wei Hu, Hai Huang, Ting-Yu Zhang, Ying-Ying Mao, Xue-Jun Wang, Sheng-Qi Wang
BACKGROUND: Chronic HBV infection is a significant public health problem and one major cause of liver cirrhosis and hepatocellular carcinoma (HCC). HBV impairs the host immune system and results in immunotolerance, which is a major obstacle to HBV therapy. CpG oligodeoxynucleotide (ODN) is a strong immunostimulant which activates the innate immune response rapidly and has been shown to be an efficient therapy agent in viral infection treatment. Here, we report the anti-HBV activity of CpG-1826 in a hydrodynamic injection murine model...
2015: Antiviral Therapy
Alicja E Grzegorzewska
The protective immunization rates in response to hepatitis B vaccination in chronic kidney disease (CKD) patients are lower than response rates in the general population because of genetic and CKD-related factors as well as logistic problems with a proper providing of the recommended vaccination schedules. This review focuses on third-generation vaccines and adjuvanted vaccines commercially introduced in some countries, investigated in clinical trials, especially involving CKD patients or used only in the experimental studies...
November 2014: Expert Review of Vaccines
Mohube B Mowa, Carol Crowther, Abdullah Ely, Patrick Arbuthnot
Hepatitis B virus (HBV) infection is endemic to southern Africa and parts of Asia where approximately 350 million individuals are chronically infected. Persistent infection increases risk for the serious complications of cirrhosis and hepatocellular carcinoma. Licensed HBV treatments rarely eradicate the virus, which makes developing new strategies for the treatment of chronic HBV a priority. Pol II-transcribed mono- and trimeric primary micro RNAs (primiRNAs) have previously been used to activate RNA interference (RNAi) and inhibit HBV gene expression, indicating that this approach holds promise for HBV therapy...
2012: MicroRNA
Carol Crowther, Mohube B Mowa, Abdullah Ely, Patrick B Arbuthnot
BACKGROUND: HBV is hyperendemic to southern Africa and parts of Asia, but licensed antivirals have little effect on limiting life-threatening complications of the infection. Although RNA interference (RNAi)-based gene silencing has shown therapeutic potential, difficulties with delivery of anti-HBV RNAi effectors remain an obstacle to their clinical use. To address concerns about the transient nature of transgene expression and toxicity resulting from immunostimulation by recombinant adenovirus vectors (Ads), utility of RNAi-activating anti-HBV helper-dependent (HD) Ads were assessed in this study...
2014: Antiviral Therapy
Peixiang Lan, Cai Zhang, Qiuju Han, Jian Zhang, Zhigang Tian
UNLABELLED: Hepatitis B virus (HBV) persistence aggravates hepatic immunotolerance, leading to the failure of cell-intrinsic type I interferon and antiviral response, but whether and how HBV-induced hepatocyte-intrinsic tolerance influences systemic adaptive immunity has never been reported, which is becoming the major obstacle for chronic HBV therapy. In this study, an HBV-persistent mouse, established by hydrodynamic injection of an HBV-genome-containing plasmid, exhibited not only hepatocyte-intrinsic but also systemic immunotolerance to HBV rechallenge...
July 2013: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Alicja E Grzegorzewska
CONTEXT: Hepatitis B vaccination of hemodialysis patients is performed all over the world. There are also recommendations from world health organizations to vaccinate patients with chronic kidney disease (CKD) prior dialysis commencement, but the implementation of a hepatitis B vaccination program is less common and not well organized. EVIDENCE ACQUISITION: This review article summarizes data indicating why, when and how to vaccinate CKD patients before they start renal replacement therapy...
November 2012: Hepatitis Monthly
Sung Mi Shim, Jae Seong Lee, Tae Soo Lee, U Youn Lee
Elfvingia applanata, a medicinal mushroom belonging to Basidiomycota, has been used in the effort to cure cancers of the esophagus and stomach, and is also known to have inhibitory effects on hepatitis B virus infection. The hot water soluble fraction (as Fr. HW) was extracted from fruiting bodies of the mushroom. In vitro cytotoxicity tests showed that hot water extract was not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, HepG2, and TR at concentrations of 10~2,000 µg/mL. Intraperitoneal injection with Fr...
March 2012: Mycobiology
Itziar Otano, Lester Suarez, Javier Dotor, Manuela Gonzalez-Aparicio, Julien Crettaz, Cristina Olagüe, Africal Vales, Jose Ignacio Riezu, Esther Larrea, Francisco Borras, Alberto Benito, Ruben Hernandez-Alcoceba, Stephan Menne, Jesús Prieto, Gloria González-Aseguinolaza
UNLABELLED: Regulatory T cells (Treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. Woodchucks (Marmota monax) infected with the woodchuck hepatitis virus (WHV) represent the best animal model for chronic hepatitis B virus (HBV) infection. Examination of intrahepatic and peripheral Treg in uninfected and WHV chronically infected woodchucks showed a significant increase of intrahepatic Treg numbers in chronically infected animals, whereas no differences were found in peripheral blood...
August 2012: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jolanta Brzezinska, Jennifer D'Onofrio, Maximilian C R Buff, Justin Hean, Abdullah Ely, Musa Marimani, Patrick Arbuthnot, Joachim W Engels
Synthetic RNAi activators have shown considerable potential for therapeutic application to silencing of pathology-causing genes. Typically these exogenous RNAi activators comprise duplex RNA of approximately 21 bp with 2 nt overhangs at the 3' ends. To improve efficacy of siRNAs, chemical modification at the 2'-OH group of ribose has been employed. Enhanced stability, gene silencing and attenuated immunostimulation have been demonstrated using this approach. Although promising, efficient and controlled delivery of highly negatively charged nucleic acid gene silencers remains problematic...
February 15, 2012: Bioorganic & Medicinal Chemistry
Behnam Hashemi, Mitra Mahdavi-Mazdeh, Mohammadreza Abbasi, Seyed Mohammadmehdi Hosseini-Moghaddam, Nadia Hatmi Zinat, Farrokhlagh Ahmadi
BACKGROUND: Despite improvement in hepatitis B infection prevention through national vaccination programs, implementation of compulsory and thorough blood donor screening, and reduction of transfusion numbers due to erythropoietin administration,hepatitis B remains a major concern in hemodialysis (HD) centers [1]. Compared to aresponse rate of over 90% in the normal population, only 50 to 60% of those with endstage renal disease (ESRD) achieve protective antibody levels following immunization against hepatitis B [2][3]...
October 2011: Hepatitis Monthly
Justin Hean, Carol Crowther, Abdullah Ely, Rafique Ul Islam, Samantha Barichievy, Kristie Bloom, Marc S Weinberg, Willem Al van Otterlo, Charles B de Koning, Felix Salazar, Patricia Marion, Eric B Roesch, Marc Lemaitre, Piet Herdewijn, Patrick Arbuthnot
Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma. Current treatment options have limited efficacy and chronic HBV infection is likely to remain a significant global medical problem for many years to come. Silencing HBV gene expression by harnessing RNA interference (RNAi) presents an attractive option for development of novel and effective anti HBV agents. However, despite significant and rapid progress, further refinement of existing technologies is necessary before clinical application of RNAi-based HBV therapies is realized...
July 2010: Artificial DNA, PNA & XNA
Saket Chattopadhyay, Abdullah Ely, Kristie Bloom, Marc S Weinberg, Patrick Arbuthnot
RNA interference (RNAi) may be harnessed to inhibit viral gene expression and this approach is being developed to counter chronic infection with hepatitis B virus (HBV). Compared to synthetic RNAi activators, DNA expression cassettes that generate silencing sequences have advantages of sustained efficacy and ease of propagation in plasmid DNA (pDNA). However, the large size of pDNAs and inclusion of sequences conferring antibiotic resistance and immunostimulation limit delivery efficiency and safety. To develop use of alternative DNA templates that may be applied for therapeutic gene silencing, we assessed the usefulness of PCR-generated linear expression cassettes that produce anti-HBV micro-RNA (miR) shuttles...
November 20, 2009: Biochemical and Biophysical Research Communications
Ta-Chiang Liu, Taeho Hwang, Byeong-Ho Park, John Bell, David H Kirn
JX-594 is a targeted oncolytic poxvirus that is designed to eradicate cancer cells having cell-cycle defects, through replication, cell lysis, and spread within tumors; oncolysis-induced tumor vascular shutdown and immunostimulation are augmented by granulocyte monocyte-colony-stimulating factor (GM-CSF) transgene expression. We have previously shown, in animal models of hepatocellular carcinoma (HCC), that JX-594 is a promising anticancer agent. We tested JX-594 in three patients with advanced refractory hepatitis B virus (HBV)-associated HCC through intratumoral administration...
September 2008: Molecular Therapy: the Journal of the American Society of Gene Therapy
Yong Chen, Guofeng Cheng, Ram I Mahato
Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-alpha and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection...
January 2008: Pharmaceutical Research
Fikret Demirci, Ziya Bayraktaroğlu, Murat Karaoğlan, Yavuz Coşkun, Ilkay Karaoğlan, Vahap Okan
BACKGROUND/AIMS: Pathogenesis of chronic hepatitis B and hepatitis B carrier status is related to deficiencies in the immune system. Thus, treatments regulating the immune system are under discussion. The aim of this study was to investigate the effects of HBsAg vaccine and levamisole on lymphocyte subgroups and immunoglobulins in children with chronic hepatitis B and hepatitis B carriers. METHODS: A total of 93 naive children (43 chronic hepatitis B carriers, 50 chronic hepatitis B patients) were treated in three groups with HBsAg vaccine, levamisole or levamisole plus HBsAg vaccine...
December 2005: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
Peter Stärkel, Michel Stoffel, Jan Lerut, Yves Horsmans
Strategies using lamivudine and hepatitis B immunoglobulins (HBIg) for prevention of hepatitis B virus (HBV) reinfection after liver transplantation (LT) are expensive since life-long treatment is needed. We evaluated the possibility to obtain protective hepatitis B surface antigen (HBsAg) antibody (anti-HBs) titers after LT and to discontinue HBIg prophylaxis after a reinforced course of vaccination against HBV using an experimental adjuvant HBsAg / AS04 vaccine (GlaxoSmithKline Biologicals [GSK], Rixensart, Belgium) in patients transplanted for hepatitis B...
October 2005: Liver Transplantation
Hong-Zhen Yang, Song Xu, Xue-Yan Liao, Suo-De Zhang, Zheng-Lun Liang, Bai-He Liu, Jin-Ye Bai, Chao Jiang, Jian Ding, Gui-Fang Cheng, Gang Liu
N(2)-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N(6)-trans-(m-nitrocinnamoyl)-L-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs...
August 11, 2005: Journal of Medicinal Chemistry
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