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Articles by W. Liu
Total Records ( 4 ) for W. Liu
  D Song , X Liu , R Liu , L Yang , J Zuo and W. Liu

Connexin 43 (Cx43), known to be the main protein building blocks of gap junctions and hemichannels in mammalian heart, plays an important role in cardiocytes proliferation. Gap junctional intercellular communication has been suggested to be necessary for cellular proliferation and differentiation. However, the effect of Cx43 hemichannel on cardiocytes proliferation and the mechanism remain unclear. In this study, rat heart cell line H9c2 was used. The Cx43 location, the proliferation rate and hemichannel activity of H9c2 cells and Wnt-3a+-H9c2 cells were investigated and the changes of intracellular ATP and [Ca2+] were determined. Results showed that the inhibited hemichannel induced by 18β-glycyrrhetinic acid (GA) evoked intracellular ATP and [Ca2+] increase and enhanced H9c2 cell proliferation. Wnt-3a+-H9c2 cells displayed enhanced hemichannel activity and proliferation rate. Inhibited hemichannel of Wnt-3a+-H9c2 cells induced by 18β-GA decreased intracellular ATP, increased [Ca2+], and enhanced the proliferation of H9c2 cells. This study validated the role of hemichannel in H9c2 cell proliferation regulation, and showed a mechanism involved in the regulation of H9c2 cell proliferation. The proliferation could be enhanced by Cx43 hemichannel-mediated ATP release accompanying intracellular [Ca2+] change. However, different changes of ATP were observed in Wnt-3a+-H9c2 cells. These findings provided new insights into the molecular mechanisms of proliferation regulation in H9c2 cells and the effect of Wnt-3a on intracellular ATP.

  A. Louie , H. S. Heine , K. Kim , D. L. Brown , B. VanScoy , W. Liu , M. Kinzig-Schippers , F. Sorgel and G. L. Drusano
  Simulating the average non-protein-bound (free) human serum drug concentration-time profiles for linezolid in an in vitro pharmacodynamic model, we characterized the pharmacodynamic parameter(s) of linezolid predictive of kill and for prevention of resistance in Bacillus anthracis. In 10-day dose-ranging studies, the average exposure for ≥700 mg of linezolid given once daily (QD) resulted in >3-log CFU/ml declines in B. anthracis without resistance selection. Linezolid at ≤600 mg QD amplified for resistance. With twice-daily (q12h) dosing, linezolid at ≥500 mg q12 h was required for resistance prevention. In dose fractionation studies, killing of B. anthracis was predicted by the area under the time-concentration curve (AUC)/MIC ratio. However, resistance prevention was linked to the maximum serum drug concentration (Cmax)/MIC ratio. Monte Carlo simulations predicted that linezolid at 1,100 mg QD would produce in 96.7% of human subjects a free 24-h AUC that would match or exceed the average 24-h AUC of 78.5 mg·h/liter generated by linezolid at 700 mg QD while reproducing the shape of the concentration-time profile for this pharmacodynamically optimized regimen. However, linezolid at 700 mg q12h (cumulative daily dose of 1,400 mg) would produce an exposure that would equal or exceed the average free 24-h AUC of 90 mg·h/liter generated by linezolid at 500 mg q12h in 93.8% of human subjects. In conclusion, in our in vitro studies, the QD-administered, pharmacodynamically optimized regimen for linezolid killed drug-susceptible B. anthracis and prevented resistance emergence at lower dosages than q12h regimens. The lower dosage for the pharmacodynamically optimized regimen may decrease drug toxicity. Also, the QD administration schedule may improve patient compliance.
  C. Ju , B. Xu , Y. Lu , X.J. Mo , T. Zhang , S.B Chen , F. Liu , S.J. Cui , W. Liu , J.H. Chen , Z. Feng , J.X. Peng and W. Hu
  Schistosomiasis ranks as the second most serious parasitic disease worldwide after malaria. More than 250 million people are infected with schistosomes in the tropics or subtropics. The treatment and control of schistosomiasis which is a major neglected tropical parasitic disease, depends almost exclusively on chemotherapy with Praziquantel (PZQ). Current serologic diagnostic assays have shown that schistosome specific antibodies in human serum may remain for at least 1 year after cure. Repeated administration of PZQ for a long time might induce drug resistance to the parasite which is a big challenge for strategizing for the prevention and control of schistosomiasis. As schistosome eggs represent the most pathogenic form causing the disease, it is essential to determine if and how the level of antibodies against schistosome Soluble Egg Antigens (SEA) is affected by PZQ treatment. In this study, researchers carried out an immunomic analysis to profile Schistosoma japonicum SEA reacting with pooled human serum samples of pre and post treatment with PZQ by two dimensional electrophoresis combined with Western blotting. A total of 67 protein spots that were serologically recognized by serum samples were successfully subjected to mass spectrometric analysis. Of them, 37 different characterized proteins were successfully identified. Furthermore, of 67 protein spots, the reactivity of 49 protein spots to sera was reduced 20 weeks after PZQ treatment whereas only 5 spots showed increases in the intensity of recognition by post treatment sera. The present study suggested that chemotherapy with PZQ mainly affects the intensity of serological recognition of S. japonicum SEA. The immunomic proteins that were identified may facilitate a better understanding of the egg induced pathogenesis of schistosomiasis and host-parasite interplay and may provide potential targets for the diagnosis and evaluation of treatment for the disease as well.
  Y.L. Dong , W. Liu , Y.M. Gao , R.D. Wu , Y.H. Zhang , H.F. Wang and B. Wei

Background: Neural stem cell (NSC) transplantation is a promising tool for restoring the nervous system in a variety of neurodegenerative disorders. The aim of this study was to determine the potential of NSC transplantation as a therapeutic strategy for neuronal replacement of the enteric nervous system of the rectum in an aganglionic rat.

Materials and Methods: Rat central nervous system–derived NSCs (CNS-NSCs) obtained from the cortex of the fetal brain (E16) were transplanted into the benzalkonium chloride (BAC)-induced rat aganglionic rectum. Survival and differentiation of the implanted cells were assessed at 8 weeks posttransplantation using immunostaining and Western blotting. The rectoanal inhibitory reflex (RAIR) was also be measured.

Results: Eight weeks following transplantation, grafted CNS-NSCs differentiated into neurons and glial cells in the aganglionic rectum. The protein expression of neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) were significantly increased and the RAIR restored after cell implantation.

Conclusions: CNS-NSC transplantation may provide a viable therapeutic option for disorders of the enteric nervous system.
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