However, nuclear translocation of IRF-7 was impaired following HCV infection.
In HCV-infected IHH, IFN-alpha expression initially increased (up to 24 h) and then decreased at later time points, and IFN-alpha-inducible protein 27 was not induced. Interestingly, HCV infection blocked IRF-7 nuclear translocation upon poly(I-C) or IFN-alpha Bindarit treatment of IHH. Together, our data suggest that HCV infection enhances STAT1 expression but impairs nuclear translocation of IRF-7 and its downstream molecules. These impairments in the IFN-alpha signaling pathway may, in part, be responsible for establishment of chronic HCV infection.”
“Ginkgo biloba extract, EGb 761, a popular and standardized natural extract, contains 24% ginkgo-flavonol glycosides and 6% terpene lactones. EGb 761 is used worldwide to treat many ailments, and although a number of studies have shown its neuroprotective properties, the mechanisms of action have not been elucidated fully. We hypothesize that EGb 761 and some of its bioactive components [Bilobalide (BB), Ginkgolide A (GA), Ginkgolide B (GB), and Terpene Free Material QNZ research buy (TFM)] could provide neuroprotection in ischemic conditions through heme oxygenase 1 (HO1). Mice were subjected to permanent distal middle cerebral artery occlusion (pMCAO) and survived for 7 days. HO1 knockout (HO1(-/-)) mice showed significantly
higher (P < 0.05) infarct volume and
Neurologic Deficit Scores (NDS) as compared to their wildtype (WT) counterparts. In another cohort, WT mice subjected to pMCAO and treated at 4 h of pMCAO with 100 mg/kg EGb 761, 6 mg/kg BB, GA, GB, or 10 mg/kg TFM showed significantly lower (P<0.05) infarct volumes (BB; 29.0 +/- 3.9%, GA; 31.3 +/- 4.0%, GB; 32.0 +/- 3.8%, TFM; 32.5 +/- 3.5%, and EGb 761; 27.4 +/- 4.5%) than those in the vehicle-treated those mice (46.0 +/- 3.7%). Similarly, NDS were lower in BB; 7.1 +/- 1.8, GA; 7.4 +/- 2.1, GB; 7.9 +/- 1.8, TFM; 7.7 +/- 1.7, and EGb 761; 6.8 +/- 2.0 groups as compared with the vehicle-treated group (13.8 +/- 1.5). Interestingly, the protective effect of EGb 761 was essentially lost when HO1 knockout mice were treated with EGb 761. In another cohort, HO1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) protein levels in the brain cortices appeared to be higher in EGb 761 and BB but not in GA, GB and TFM treated groups. Together, these results suggest that HO1 plays, at least in part, an important role in the neuroprotective mechanism of EGb 761 and in delayed ischemia. Targeting this pathway could lead to neuroprotective agents against ischemic stroke. (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We analyzed the biochemical and ultrastructural properties of hepatitis C virus (HCV) particles produced in cell culture.