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Xian, China

Wang H.,Life Detection Systems | Kim R.A.,GenePrism Inc. | Sun D.,Xuzhou Normal University | Gao Y.,Life Detection Systems | And 2 more authors.
Xenobiotica | Year: 2011

To comprehensively understand the effects of CYP2C19 genetic polymorphisms on inhibition-based drugdrug interactions (DDIs), 18 human CYP2C19 non-synonymous single-nucleotide polymorphic variants and the wild-type isoform (CYP2C19.1A) were expressed in yeast cells. Using a fluorescence-based high-throughput method, the kinetic constants of these variants, as well as the inhibition constants for 10 drugs, were determined. CYP2C19.5B and CYP2C19.6 showed no activity towards CEC (3-cyano-7-ethoxycoumarin) O-deethylation. CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.16, CYP2C19.19, E122A and A161P* (an allele containing both A161P and I331V) exhibited significantly reduced catalytic activities compared with CYP2C19.1A. The inhibition assay showed that the CYP2C19 genotype significantly affected the in vitro drug inhibition potential. Although the effect on drug inhibition potential is genotype- and inhibitor-dependent, there was an obvious trend: drugs tended to exhibit higher IC50 values (i.e. decreased inhibition potential) towards variants with reduced activity compared with variants with normal activity. This indicated that patients with reduced-function alleles may be less susceptible to CYP2C19-related DDIs. In this study, we provided the first in vitro evidence of CYP2C19 genotype-dependent effects on drug inhibition potential. This work greatly extends our understanding of the functional consequences of CYP2C19 genetic polymorphisms, and thus should prove valuable for CYP2C19 genotype-based therapy. © 2011 Informa UK, Ltd. Source


Zhang W.,Northwest University, China | Zhang W.,Jilin Medical College | Yan K.,Northwest University, China | Yan K.,Shaanxi Lifegen Co. | And 4 more authors.
Artificial Organs | Year: 2012

Hemoglobin-based oxygen carriers (HBOCs), with their capacity for delivering oxygen, could potentially function as red blood cell substitutes or primary resuscitation solutions. However, there has been some concern regarding redox-related safety issues of HBOCs. The present study describes a novel function of polymerized porcine hemoglobin (pPolyHb) in protecting a human umbilical vein endothelial cell line from H 2O 2-induced cytotoxicity. Through the examination of H 2O 2 consumption and ferrylhemoglobin formation, we found that pPolyHb exhibits antioxidant activity, suggesting that pPolyHb may protect cells from free radical-induced cell damage. Additionally, we investigated the effect of pPolyHb on H 2O 2-induced cell cytotoxicity, and found that pPolyHb significantly inhibits H 2O 2-mediated endothelial cell damage as well as apoptosis. Thus, pPolyHb may be developed as a new HBOC in the future. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Source


Zhu H.,Northwest University, China | Yan K.,Northwest University, China | Dang X.,Shaanxi Cancer Hospital | Huang H.,Northwest University, China | And 6 more authors.
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

Polymerized Porcine Hemoglobin (pPolyHb), a hemoglobin-based oxygen carrier (HBOC), was developed as a potential red blood substitute for clinical applications. Assessment of its effects on the immune system is an important component of the overall safety evaluation of HBOC. For this purpose, we assessed three inflammation indicators, including complement C3a, IL-6, and TNF-α in cultured cells and in a rat model when pPolyHb was incubated or administrated with the cells/animals. Our results suggested that the levels of these three indicators were not statistically changed upon pPolyHb stimulation, indicating that pPolyHb is not immunotoxic to cells and animals in this aspect. © 2011 Informa Healthcare USA, Inc. Source


Li G.,PLA Fourth Military Medical University | Jin T.,Life Detection Systems | Liang H.,PLA Fourth Military Medical University | Zhang Z.,PLA Fourth Military Medical University | And 7 more authors.
Diagnostic Pathology | Year: 2013

As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case-control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF) > 5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, P = 0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P = 0.001, OR: 1.33, 95% CI: 1.12-1.58) by χ2 test. It was identified the genotype "GG" of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; P = 0.0002), while the genotype "CC" of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0003). Furthermore, haplotype "GCT" in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher's P = 0.0005; Pearson's P = 0.0005), and haplotype "ATT" was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher's P = 0.0013; Pearson's P = 0.0013). Two single variants, the genotypes of "GG" of rs6010620 and "CC" of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998. © 2013 Li et al.; licensee BioMed Central Ltd. Source


Zhu H.,Northwest University, China | Dang X.,Shaanxi Cancer Hospital | Yan K.,Northwest University, China | Dai P.,Northwest University, China | And 5 more authors.
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

The objective of the present study is to evaluate the pharmacodynamic properties of polymerized porcine hemoglobin (pPolyHb) in an exchange transfusion model. Each of two groups of rats received a volume of pPolyHb or hetastarch that equalled 120-140% of estimated total blood volume (70 ml/kg) exchange transfusion. The results showed pPolyHb retained hemodynamic stability and exhibited superior volume expansion capability. Furthermore, pPolyHb effectively reverse anaerobic metabolism caused by a large amount of volume exchange. In comparison with hetastarch, pPolyHb increased blood oxygen content and tissue oxygenation. All these properties contribute to a higher effectiveness in sustaining the lives of rats in pPolyHb group. Copyright © 2011 Informa Healthcare USA, Inc. Source

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