15 research outputs found

    Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

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    Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients

    Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry

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    Abl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantly decreased HCV RNA and protein levels in HCV-infected cells. We showed that both imatinib and dasatinib selectively inhibited HCV infection at the entry step of HCV life cycle, suggesting that Abl kinase activity may be necessary for HCV entry. Using HCV pseudoparticle infection assays, we verified that Abl is required for viral entry. By employing transferrin uptake and immunofluorescence assays, we further demonstrated that Abl was involved in HCV entry at a clathrin-mediated endocytosis step. These data suggest that Abl may represent a novel host factor for HCV entry

    Beyond Battery State of Charge Estimation: Observer for Electrode-Level State and Cyclable Lithium with Electrolyte Dynamics

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    This paper presents a provably convergent battery estimation scheme based on a single particle model with electrolyte dynamics (SPMe), by proposing a systematic methodology to estimate critical information such as electrode-level states, electrolyte dynamics, and cyclable lithium. Electrode-level state estimation suffers from weak observability originating from two standalone electrode dynamics, which is then aggravated by the addition of electrolyte dynamics. This lack of observability can be alleviated by exploiting lithium inventory conservation enabled by Kalman decomposition, allowing one to separate out the unobservable subspace. Assuming the knowledge of cyclable lithium, a nonlinear state observer with provable convergence can be constructed for the SPMe model, using voltage and current measurements. To relax this strong assumption, a sensitivity-based parameter estimation scheme is also deployed to track cyclable lithium &x2013; a crucial physical variable for capacity fade. Ultimately, the estimation framework can perform finer monitoring and diagnosis of battery charge and health down to the level of individual electrode and the electrolyte. Experimental validation demonstrates &x003C;1% estimation error for cyclable lithium inventory. Solid phase lithium concentration estimates, especially in the negative electrode, can be sensitive to disturbances in cyclable lithium.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

    Saponin inhibits HCV replication in Huh7 cells harboring subgenomic HCV replicon.

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    <p>(A) HCV protein expressions were decreased by saponin. Both IFN-cured and subgenomic replicon cells were either left untreated or treated with 25 and 50 µg/ml of saponin, respectively. At 24 h after saponin treatment, total cell lysates were immunoblotted with the indicated antibodies. β-actin was used as a loading control for the same amount of cell lysates. (B) Total cellular RNAs were extracted from HCV replicon cells treated with saponin and intracellular HCV RNAs were quantified by qRT-PCR. (C) Subgenomic replicon cells were left untreated or treated with 25 and 50 µg/ml of saponin, respectively. At 24 h after saponin treatment, cell viability was determined by cytotoxicity assay.</p
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