Jiang E.-P.,Beihua University |
Jiang E.-P.,Guangdong Medical College |
Wang S.-Q.,Beihua University |
Wang Z.,Jilin Central General Hospital |
And 3 more authors.
Zhongguo Zhongyao Zazhi | Year: 2014
Objective: To observe the effect of Schisandra chinensis lignans(SCL) on neuronal apoptosis and PI3K/AKT signaling pathway of rats in the cerebral ischemia injury model, and study its possible mechanism. Method: Rats were orally administered SCL high, middle and low dose groups (100, 50, 25 mg·kg-1) for 14 days. The cerebral ischemia injury model was established by using the suture-occluded method to rate the neurological functions. The cerebral infarction area was observed by TTC staining. The pathological changes in brain tissues were determined by HE staining. Bcl-2 and Bax expressions were detected by immunohistochemical assay. The protein expressions of p-AKT and AKT were assayed by Western blotting. Result: Compared with the model group, SCL high, middle and low dose groups showed reduction in the cerebral infarction area to varying degrees, improve the pathological changes in brain tissues, promote the expression of apoptin Bcl-2 and p-AKT, and inhibit the expression of apoptin Bax. Conclusion: SCL shows a protective effect on rats with cerebral ischemia injury. Its mechanism may be related to the increase in p-AKT ability and anti-ischemic brain injury capacity and the inhibition of nerve cells. Source
Li J.,Peking University |
Li J.,Beijing Tiantan Biological Products |
Zhang D.,Beijing Tiantan Biological Products |
Ma R.,Beijing Tiantan Biological Products |
And 7 more authors.
Human Vaccines and Immunotherapeutics | Year: 2013
Aims: The current 3-dose regimen of hepatitis B vaccination for infants requiring over 6 mo period may pose the poor rate of compliance and later protection from hepatitis B virus (HBV) infection. This preclinical study is to investigate the feasibility of reducing the number of doses of hepatitis B (HB) vaccine. Results: Eight groups of guinea pigs immunized with two doses of HP-HB vaccines at either 0 and 4 weeks or 0 and 8 weeks elicited geometric titers (GMT) of anti-HBs similar to that of four groups immunized with three doses of controls. The overall GMT of anti-HBs were not significantly different between the E- and C-groups (p > 0.05) of monkeys. Specifically, the anti-HBs titers in the C-group reached the peak of 24857 (938.3-104585) mIU/mL one week after the 3rd dose, which were statistically higher than those of the E-group. However, they were reduced to comparable levels of anti-HBs in the E-group during weeks 9-12, suggesting comparable immune response of both vaccination regimens. Methods: Twelve groups of guinea pigs (four animals in each group) were immunized with 2 experimental recombinant yeast Hansenula polymorpha derived HB vaccines (HP-HB vaccine) and 2 commercial recombinant yeast Saccharomyces cerevisiae vaccines (Temrevac-HB) as controls at 0, 4 and 8 weeks, 0 and 4 weeks, and 0 and 8 weeks respectively. Each guinea pig received 2 μg vaccine. Twelve Cynomolgus monkeys were randomly divided into two groups (six animals in each group). Animals in the experimental group (E-group) were injected with two doses of pilot produced 20 μg HP-HB vaccine. Animals in the control group (C-Group) were immunized with three doses of 10 μg Temrevac-HB. Both vaccines were administered at an interval of 3 weeks for monkeys. Conclusions: The 2-dose regimen of the HP-HB vaccine has comparable HBV immune responses as the 3-dose regimen of Temrevac-HB vaccine in Cynomolgus monkeys. © 2013 Landes Bioscience. Source
Jiang E.-P.,Guangdong Medical College |
Li H.,Beihua University |
Yu C.-R.,JOINN Laboratories |
Yu C.-Y.,Beihua University |
And 6 more authors.
NeuroReport | Year: 2015
Increasing evidence places Schisandrin B (Sch B) at an important position in nerve protection, indicating that Sch B might play a positive role in the therapy of neurodegenerative diseases. However, there is little information on it. Our studies showed that pretreatment with Sch B could reduce lactate dehydrogenase, malondialdehyde, and reactive oxygen species release and significantly increase the cell viability and the superoxide dismutase level. Sch B (10 μM) markedly inhibited cell apoptosis, whereas LY294002 (20 μM), a phosphatidylinositol-3 kinase inhibitor, blocked the antiapoptotic effect. More importantly, Sch B (10 μM) increased the phosphoprotein kinase B/protein kinase B (Akt) and B-cell lymphoma-2/Bcl-2 associated X protein ratios on preincubation with cells for 2 h, which was then inhibited by LY294002 (20 μM). Results indicate that Sch B can protect PC12 cells from apoptosis by activating the phosphatidylinositol-3 kinase/Akt signaling pathway and may emerge as a potential drug for neurodegenerative diseases. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source
Li Y.-P.,Peking Union Medical College |
Gao L.-Y.,Peking Union Medical College |
Li K.-T.,JOINN Laboratories |
Meng S.,Peking Union Medical College |
And 5 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2013
A LC-MS/MS method for determining the concentration of the small molecule Hsp90 inhibitor, GM-AMPL, has been developed and validated in rat plasma to support preclinical development. 17-[2-(morpholine-4-yl)ethyl]amino-17-demethoxygeldanamycin (GM-AMPL) and the internal standard 17-allylamino-17-demethoxygeldanamycin (17-AAG) were sufficiently separated on a Venusil MP C18 column that was eluted with 80% methanol in water at 40 °C. Quantification studies were performed with a multiple reaction monitoring (MRM) transition of m/z 657.3→614.3 and 584.3→541.3 for GM-AMPL and IS, respectively, in the negative ion mode. The present method exhibited good linearity (R> 0.999) over the concentration range of 2-600. ng/mL for GM-AMPL in rat plasma with a lower limit of quantification (LLOQ) of 2. ng/mL. The intra-batch and inter-batch assay coefficients of variation (CV) were in range of 1.56-6.84% and 1.62-6.98%, respectively. The plasma samples were extracted with methanol to precipitate protein with extraction recovery in range of 84.09-95.25%. The matrix effect was determined as internal substance (IS) normalized matrix factor of 1.09, 1.18 and 1.05 for samples with three concentration levels of 4, 40 and 400. ng/mL, respectively. This validated method was further applied to successfully determine the pharmacokinetic parameters and oral availability of GM-AMPL in Sprague-Dawley rats following intravenous injection and oral administration. © 2012. Source
Duong-Ly K.C.,Johns Hopkins University |
Duong-Ly K.C.,Fox Chase Cancer Center |
Woo H.N.,Johns Hopkins University |
Woo H.N.,Case Western Reserve University |
And 8 more authors.
PLoS ONE | Year: 2013
The gene for a Nudix enzyme (SP_1669) was found to code for a UDP-X diphosphatase. The SP_1669 gene is localized among genes encoding proteins that participate in cell division in Streptococcus pneumoniae. One of these genes, MurF, encodes an enzyme that catalyzes the last step of the Mur pathway of peptidoglycan biosynthesis. Mur pathway substrates are all derived from UDP-glucosamine and all are potential Nudix substrates. We showed that UDP-X diphosphatase can hydrolyze the Mur pathway substrates UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. The 1.39 Å resolution crystal structure of this enzyme shows that it folds as an asymmetric homodimer with two distinct active sites, each containing elements of the conserved Nudix box sequence. In addition to its Nudix catalytic activity, the enzyme has a 3′5′ RNA exonuclease activity. We propose that the structural asymmetry in UDP-X diphosphatase facilitates the recognition of these two distinct classes of substrates, Nudix substrates and RNA. UDP-X diphosphatase is a prototype of a new family of Nudix enzymes with unique structural characteristics: two monomers, each consisting of an N-terminal helix bundle domain and a C-terminal Nudix domain, form an asymmetric dimer with two distinct active sites. These enzymes function to hydrolyze bacterial cell wall precursors and degrade RNA. © 2013 Duong-Ly et al. Source