Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tre...Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.展开更多
Ebola virus(EBOV) and Marburg virus(MARV),belonging to the Filoviridae family,emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.As high as 50-90% mortality,filoviruses can ...Ebola virus(EBOV) and Marburg virus(MARV),belonging to the Filoviridae family,emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.As high as 50-90% mortality,filoviruses can cause significant threats to public health.However,so far no specific and efficient vaccine has been available,nor have other treatment methods proved to be effective.It is of great importance to detect these pathogens specific,rapidly and sensitively in order to control future filovirus outbreaks.Here,recent progresses in the development of detection and diagnosis methods for EBOV and MARV are summarized.展开更多
Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. T...Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. To date, there is no specific laboratory diagnostic test in China, while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. In this study, the TaqMan RT-PCR assays targeting the nucleoprotein genes of the Zaire Ebolavirus （ZEBOV） and MARV were developed and their sensitivities and specificities were investigated. Our results indicated that the assays were able to make reliable diagnosis over a wide range of virus copies from 103 to 109, corresponding to the threshold of a standard RNA transcript. The results showed that there were about 101 RNA copies per milliliter of virus culture supernatant, equivalent to 10,000 RNA molecules per infectious virion, suggesting the presence of many non-infectious particles. These data indicated that the TaqMan RT-PCR assays developed in this study will be suitable展开更多
The present work is the first report of the biochemical characterization of the venom from nematocysts of the jellyfish Rhopilema esculentum Kishinouye. The nematocysts were isolated by autolysis and centrifugation an...The present work is the first report of the biochemical characterization of the venom from nematocysts of the jellyfish Rhopilema esculentum Kishinouye. The nematocysts were isolated by autolysis and centrifugation and separated by flow cytometry. Four types of nematocysts were identified： mastigophores, euryteles, and atrichous and holotrichous isorhiza. SDS-PAGE and amino acid analyses demonstrated that most of the proteins in the nematocyst extract were between 10 kDa and 40 kDa, and that glutamic acid was the main amino acid. A hemolytic activity assay showed that the activity of the nematocyst venom （RNV） was strongest in Tris-HCl buffer （50 mmol/L, pH 7.8, 5% glycerol, 0.5 mmol/L EDTA, 0.1 mol/L NaC1）. The hemolytic activity was related to protein concentration and the HU50 against chicken erythrocytes was 0.91 μg/mL.展开更多
In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the...In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the transforming growth factor β signal transduction pathway,the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction pathway.All of them are activated by many different cytokines and growth factors.They regulate specific cell mechanisms such as hepatocytes proliferation,growth,differentiation,adhesion,apoptosis,and synthesis and degradation of the extracellular matrix.The replication cycle of hepatitis C virus(HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes.Moreover,HCV itself,by its structural and non-structural proteins,could influence the activity of the second signal messengers.Thus,the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment.展开更多
基金Supported by Foundation for Liver and Gastrointestinal Research (SLO)The Netherlands Organisation for Scientific Research (NWO), No. VENI-grant 916-13-032 (to Pan Q)
文摘Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.
文摘Ebola virus(EBOV) and Marburg virus(MARV),belonging to the Filoviridae family,emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.As high as 50-90% mortality,filoviruses can cause significant threats to public health.However,so far no specific and efficient vaccine has been available,nor have other treatment methods proved to be effective.It is of great importance to detect these pathogens specific,rapidly and sensitively in order to control future filovirus outbreaks.Here,recent progresses in the development of detection and diagnosis methods for EBOV and MARV are summarized.
基金Supported by Important National Science&Technology Specific Projects(2009ZX10004-504,2009ZX09301-014)National Natural Science Foundation of China(81072675)
文摘Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. To date, there is no specific laboratory diagnostic test in China, while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. In this study, the TaqMan RT-PCR assays targeting the nucleoprotein genes of the Zaire Ebolavirus （ZEBOV） and MARV were developed and their sensitivities and specificities were investigated. Our results indicated that the assays were able to make reliable diagnosis over a wide range of virus copies from 103 to 109, corresponding to the threshold of a standard RNA transcript. The results showed that there were about 101 RNA copies per milliliter of virus culture supernatant, equivalent to 10,000 RNA molecules per infectious virion, suggesting the presence of many non-infectious particles. These data indicated that the TaqMan RT-PCR assays developed in this study will be suitable
基金Supported by Qingdao Science and Technology Project (No. 08-1-3-51- JCH)the Award Foundation of Scientific Research for Excellent Young and Middle-Age Scientist of Shandong Province (No.2006BS 07003)
文摘The present work is the first report of the biochemical characterization of the venom from nematocysts of the jellyfish Rhopilema esculentum Kishinouye. The nematocysts were isolated by autolysis and centrifugation and separated by flow cytometry. Four types of nematocysts were identified： mastigophores, euryteles, and atrichous and holotrichous isorhiza. SDS-PAGE and amino acid analyses demonstrated that most of the proteins in the nematocyst extract were between 10 kDa and 40 kDa, and that glutamic acid was the main amino acid. A hemolytic activity assay showed that the activity of the nematocyst venom （RNV） was strongest in Tris-HCl buffer （50 mmol/L, pH 7.8, 5% glycerol, 0.5 mmol/L EDTA, 0.1 mol/L NaC1）. The hemolytic activity was related to protein concentration and the HU50 against chicken erythrocytes was 0.91 μg/mL.
文摘In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the transforming growth factor β signal transduction pathway,the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction pathway.All of them are activated by many different cytokines and growth factors.They regulate specific cell mechanisms such as hepatocytes proliferation,growth,differentiation,adhesion,apoptosis,and synthesis and degradation of the extracellular matrix.The replication cycle of hepatitis C virus(HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes.Moreover,HCV itself,by its structural and non-structural proteins,could influence the activity of the second signal messengers.Thus,the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment.
