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《植物分类与资源学报》2015,(6)
植物是发现先导药物的天然宝库,目前抗糖尿病药物的一个重要来源是植物。从植物中发现抗糖尿病药物的关键在于抗糖尿病药物筛选模型的建立。为获得一个更稳定、筛选结果更可靠的抗糖尿病药物筛选模型,本文对基于脂肪细胞摄取葡萄糖的药物筛选模型进行优化。文献报道的该类模型,只将胰岛素作为阳性对照,而本文同时将胰岛素和罗格列酮作为阳性对照,使模型更加稳定、筛选结果更加可靠。此外,本文还以胰岛素信号通路抑制剂Akt1/2抑制剂作为另一阳性对照,使之还可应用于胰岛素信号通路抑制剂的筛选,扩展了该模型的用途。最后,对16个植物来源的天然产物在该模型进行筛选,其结果稳定,并发现3个活性化合物。进一步对活性化合物X15、X16进行浓度梯度实验,结果表明,两者的活性都具有明显的浓度依赖性。X15和X16的细胞增敏活性的研究为后续进一步研究其分子作用机理奠定基础,并为后期可能的药物开发提供分子候选。 相似文献
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采用假病毒系统对5种具有抗HIV-1活性的天然化合物的作用机制进行研究, 建立了一种可在普通实验室进行抗HIV-1作用机理研究的实验平台。通过构建假病毒系统, 利用定量PCR实验分析感染细胞内病毒生命周期早期的特异性DNA产物, 发现5种化合物可通过不同的作用机制在早期抑制HIV-1复制。部分化合物表现出新的作用机制, 如LC-1、LC-2可抑制HIV-1的入核。通过分析药物对2种不同的逆转录病毒(HIV-1和MLV)的感染性, 发现LC-1可特异地阻断HIV-1的复制, 而对MLV无影响。同时为了检测药物是否也会在病毒的生命周期晚期有作用,利用直接转染前病毒质粒的方式进行了验证。利用以上方法, 初步确定了这几种药物的作用靶点, 构建了一个有效的抗HIV-1药物作用机理的研究平台。 相似文献
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病毒感染相关基因微阵列的制备及其在HBV感染应答基因筛选中的应用 总被引:1,自引:0,他引:1
为筛选乙型肝炎(乙肝)病毒(HBV)感染应答基因,探讨HBV感染分子机理,采用生物信息学分析、筛选宿主细胞中与乙肝病毒、丙型肝炎(丙肝)病毒、流行性感冒(流感)病毒等感染密切相关的基因,设计并合成寡核苷酸探针,制备了含231种病毒感染相关基因的寡核苷酸微阵列.利用此微阵列比较HepG2细胞、HepG2.2.15细胞之间的基因表达谱差异,筛选乙肝病毒感染候选应答基因,从分子水平对乙肝病毒感染作用机理进行初步研究.制备的病毒感染相关基因表达谱微阵列的监测结果显示,阳性对照和看家基因探针出现较强信号,空白点样液和阴性对照探针未出信号,大部分基因探针信号强度在可分析范围内,上矩阵和下矩阵反映的基因表达情况一致,证明微阵列的特异性、敏感性、重复性都较好.HepG2.2.15与HepG2细胞基因表达谱比较结果显示,28个宿主基因在HepG2.2.15细胞中高表达,包括ASGR1、AFP、Fibronectin、APOC等基因;4个基因低表达,包括RRM1、ICSBP等基因.初步筛选获得HBV感染候选应答基因.此结果表明,制备的微阵列敏感性、特异性、重复性好,可为研究病毒宿主相互作用关系提供技术平台,应用此微阵列筛选获得的HBV候选应答基因可为揭示HBV感染的分子致病机理提供新的信息,为抗HBV药物研究提供潜在的作用靶点. 相似文献
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《天然产物研究与开发》2017,(4)
临床真菌感染的发病率和死亡率逐年上升,其中以假丝酵母菌为代表的侵袭性真菌感染尤为严重,目前主要抗真菌药物的耐药性日趋严重,且多数具有毒副作用,寻找安全有效的新型抗真菌药物迫在眉睫。天然植物中抗真菌活性成分来源广泛,具有低毒、广谱、作用途径多样化等优点,成为新型抗真菌药物的一个重要研究方向。本文主要综述了近年来从天然植物中筛选抗假丝酵母菌活性成分的研究。 相似文献
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肠道病毒71型(Enterovirus 71,EV71)是引起重症手足口病(Hand,Foot and Mouth Disease,HFMD)的主要病原体。重症HFMD进展迅速,可表现为严重的神经系统并发症,甚至危及生命。目前临床上防治EV71感染缺乏特异、高效的药物,其残疾率和死亡率很高。随着研究的深入,已经发现了大量具有抗EV71能力的化合物,人们探索的药物机制和药物靶点各不相同。因此,本文从药物靶向病毒、宿主等角度出发,针对抗EV71感染的天然药物、合成药物及常见中药中活性成分作用机制的最新进展进行综述与讨论。此外,对抗病毒药物筛选技术进行简要概述,以期为抗EV71药物的筛选与研发设计等相关研究提供参考。 相似文献
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Andreas Rang Michael Bruns Tilman Heise Hans Will 《The Journal of biological chemistry》2002,277(10):7645-7647
It is well established that interferon-alpha can induce non-cytotoxic intracellular suppression of hepatitis B virus replication, but the mechanisms involved are unclear. Cell culture studies to characterize these mechanisms are restricted, in part because hepatitis B virus replicates almost exclusively in liver-derived cells. To overcome this limitation we used a cytomegalovirus promoter-controlled hepatitis B virus expression system, which leads to intracellular viral replication even in non-hepatic cell lines. In this experimental system interferon-alpha treatment specifically suppressed viral replication demonstrating that antiviral activities against hepatitis B virus are not restricted to hepatic cells. Furthermore, the interferon-inducible MxA protein was recently reported to play a key role in the antiviral action of interferon-alpha against hepatitis B virus. Our data demonstrate that interferon-alpha also suppresses hepatitis B virus replication in MxA-deficient HEp2 cells, indicating that MxA is not essential for these activities. Taken together, our data imply that the experimental approach presented can also be adapted to established cell lines which are deficient in parts of the signal transduction pathway or other elements located further downstream, providing important insights into mechanisms specifically suppressing hepatitis B virus. 相似文献
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绿茶的儿茶素、黑茶的茶黄素以及茶叶特有的L-茶氨酸是重要的药用化学成分。近年,国内外科学家在茶叶抗流感病毒、艾滋病毒、丙型和乙型肝炎病毒等研究方面取得重要突破。本文综述了茶叶抗病毒作用的基础研究及临床应用的新进展。 相似文献
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Antibodies to the RNase H domain of hepatitis B virus P protein are associated with ongoing viral replication. 总被引:2,自引:0,他引:2 下载免费PDF全文
T Weimer F Schdel M C Jung G R Pape A Alberti G Fattovich H Beljaars P M van Eerd H Will 《Journal of virology》1990,64(11):5665-5668
Antibodies against the RNase H domain of human hepatitis B virus P protein(s) are frequent markers of acute and chronic virus infection (T. Weimer, K. Weimer, Z.-X. Tu, M.-C. Jung, G. R. Pape, and H. Will, J. Immunol. 143:3750-3756, 1989). In the present study, these antibodies were determined in serial serum samples of experimentally infected chimpanzees and naturally infected human patients with acute and chronic hepatitis B virus infection. Anti-P antibodies were found in the sera of both chimpanzees and humans early in infection shortly after the immunoglobulin M anti-HBc response; they persisted in chronic carriers with ongoing viral replication but declined and disappeared at the time of virus clearance from the sera. These data demonstrate that antibodies to the RNase H domain of the hepatitis B virus P protein are early markers of infection and a signal of ongoing virus replication. Falling titers indicate the decline or end of active virus production and may therefore be a prognostic sign of virus elimination in natural infection and after antiviral therapy. 相似文献
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Jacob JR Mansfield K You JE Tennant BC Kim YH 《Journal of microbiology (Seoul, Korea)》2007,45(5):431-440
A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans. 相似文献
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Antisense therapy of hepatitis B virus infection 总被引:2,自引:0,他引:2
Wolf-Bernhard Offensperger Silke Offensperger Hubert E. Blum 《Molecular biotechnology》1998,9(2):161-170
Chronic infection with the hepatitis B virus (HBV) is a major health problem worldwide. The only established therapy is interferon-a
with an efficacy of only 30–40% in highly selected patients. The discovery of animal viruses closely related to the HBV has
contributed to active research on antiviral therapy of chronic hepatitis B. The animal model tested and described in this
article are Peking ducks infected with the duck hepatitis B virus (DHBV). Molecular therapeutic strategies aimed at blocking
gene expression include antisense DNA. An antisense oligodeoxynucleotide directed against the 5′-region of the preS gene of
DHBV inhibited viral replication and gene expression in vitro in primary duck hepatocytes and in vivo in Peking ducks. These
results demonstrate the potential clinical use of antisense DNA as antiviral therapeutics. 相似文献
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Interferon plays a critical role in the host's natural defense against viral infections and in their treatment. It is the only therapy for hepatitis C virus (HCV) infection; however, many virus isolates are resistant. Several HCV proteins have been shown to possess properties that enable the virus to evade the interferon-mediated cellular antiviral responses. 相似文献
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Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed. 相似文献
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Matthew R. Campagna Fei Liu Richeng Mao Courtney Mills Dawei Cai Fang Guo Xuesen Zhao Hong Ye Andrea Cuconati Haitao Guo Jinhong Chang Xiaodong Xu Timothy M. Block Ju-Tao Guo 《Journal of virology》2013,87(12):6931-6942
Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B. 相似文献
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Lu M Yao X Xu Y Lorenz H Dahmen U Chi H Dirsch O Kemper T He L Glebe D Gerlich WH Wen Y Roggendorf M 《Journal of virology》2008,82(5):2598-2603
The essential role of multispecific immune responses for the control of hepatitis B virus (HBV) infection implies the need of multimodal therapeutic strategies for chronic HBV infection, including antiviral chemotherapy and immunomodulation. This hypothesis was tested in the woodchuck model by a combination of lamivudine pretreatment and subsequent immunizations of woodchucks chronically infected with woodchuck hepatitis virus. The immunizations were performed with DNA vaccines or antigen-antibody immune complexes (IC)/DNA vaccines. Immunizations with IC/DNA vaccines led to an anti-woodchuck hepatitis virus surface antibody response and significant reductions of viral load and antigenemia, suggesting that such a strategy may be effective against chronic HBV infection. 相似文献