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国家自然科学基金(81101248)

作品数:3 被引量:11H指数:2
相关作者:冯雪梅王俊忠黄顺梅王宝菊朱彬更多>>
相关机构:华中科技大学华中科技大学同济医学院附属同济医院更多>>
发文基金:国家自然科学基金国家科技重大专项更多>>
相关领域:医药卫生更多>>

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Molecular Cloning,Characterization and Expression Analysis of Woodchuck Retinoic Acid-Inducible GeneⅠ
2016年
Cytosolic retinoic acid-inducible gene I(RIG-I) is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-β(IFN-β). Innate immune response to hepatitis B virus(HBV) plays a pivotal role in viral clearance and persistence. However, knowledge of the role that RIG-I plays in HBV infection is limited. The woodchuck is a valuable model for studying HBV infection. To characterize the molecular basis of woodchuck RIG-I(w RIG-I), we analyzed the complete coding sequences(CDSs) of w RIG-I, containing 2778 base pairs that encode 925 amino acids. The deduced w RIG-I protein was 106.847 k D with a theoretical isoelectric point(p I) of 6.07, and contained three important functional structures [caspase activation and recruitment domains(CARDs), DEx D/H-box helicases, and a repressor domain(RD)]. In woodchuck fibroblastoma cell line(WH12/6), w RIG-I-targeted small interfering RNA(si RNA) down-regulated RIG-I and its downstrean effector–IFN-β transcripts under RIG-I' ligand, 5'-ppp double stranded RNA(ds RNA) stimulation. We also measured m RNA levels of w RIG-I in different tissues from healthy woodchucks and in the livers from woodchuck hepatitis virus(WHV)-infected woodchucks. The basal expression levels of w RIG-I were abundant in the kidney and liver. Importantly, w RIG-I was significantly up-regulated in acutely infected woodchuck livers, suggesting that RIG-I might be involved in WHV infection. These results may characterize RIG-I in the woodchuck model, providing a strong basis for further study on RIG-I-mediated innate immunity in HBV infection.
严琦刘钦李蒙蒙李芳慧朱彬Jun-zhong WANG王俊忠卢银平刘嘉吴珺郑昕陆蒙吉王宝菊杨东亮
用大鼠模型评价齐多夫定及阿德福韦酯对线粒体的毒性损伤被引量:2
2012年
目的用大鼠模型评估齐多夫定(AZT)及阿德福韦酯(ADV)对线粒体的毒性损伤。方法SD大鼠随机分为AZT、ADV和空白对照三组,连续灌胃给药28d,检测大鼠肝、肾、骨骼肌、心肌线粒体的细胞色素c氧化酶活性、细胞色素b基因含量,及用电子显微镜观察各组织线粒体超微病理结构的改变隋况。对数据进行方差分析或非参数检验的Kruskal-wallis检验。结果AZT组大鼠细胞色素c氧化酶活性(单位为U/mg)在肝、肾、心肌和骨骼肌分别为9.44±3.09、4.42±1.53、32.74±5.52、33.75±8.74,低于空白对照组的17.8±12.38、14.45±13.75、24.74±20.59、40.04±2.49,也较ADV组低,但三组间的差异均无统计学意义(肝脏:H=3.08,P=0.21,肾脏:H=3.44,P=0.18;骨骼肌:H=1.61,P=0.45;心肌:H=2.52,P=0.28)。AZT组大鼠线粒体细胞色素b基因含量在肝脏、心肌分别为0.61±0.95、0.15±0.13,ADV组分别为0.52±0.68、0.17±0.08,相比空白对照组明显减少,但差异无统计学意义(肝脏:H=3.398,P=0.18,心肌:H=0.33,P=0.85)。AZT组的肝、肾、骨骼肌和心肌都出现明显的线粒体损伤改变。结论连续给药28d后,AZT可造成明显的线粒体损伤,而ADV仅导致线粒体细胞色素b基因含量偏低。
朱彬朱珍妮王俊忠黄顺梅冯雪梅李安意杨东亮王宝菊
关键词:线粒体细胞色素C氧化酶齐多夫定阿德福韦酯
New therapeutic vaccination strategies for the treatment of chronic hepatitis B被引量:9
2014年
Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.
Jia LiuAnna KosinskaMengji LuMichael Roggendorf
关键词:IMMUNOMODULATION
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