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Wang H.,Life Detection Systems | An N.,Life Detection Systems | Gao Y.,Life Detection Systems | Liu D.,Shaanxi Lifegen Co. | And 4 more authors.
Drug Metabolism and Disposition | Year: 2011

CYP2C19 is a highly polymorphic enzyme that affects the metabolism of a wide range of therapeutic drugs. Almost all the identified alleles of CYP2C19 are derived from nonsynonymous single nucleotide polymorphisms (nsSNPs). The objective of this study was to functionally characterize 20 nsSNPs of CYP2C19, distributed throughout the entire coding region, most of which have not been thoroughly characterized. cDNAs of these variants were constructed and expressed in yeast cells. All variants had similar levels of apoprotein and holoprotein expression, except for CYP2C19.16 and D360N, which had significantly lower holoprotein levels than the wild-type (WT) CYP2C19 enzyme, and CYP2C19.5B, which showed only apoprotein. The activity of the CYP2C19 variants was investigated using two substrates, S-mephenytoin and omeprazole, and six different kinetic parameters were measured. CYP2C19.5B, CYP2C19.6, and CYP2C19.8 were found to be catalytically inactive. The entire dataset of the remaining 17 variants, together with the WT, was analyzed by multivariate analysis. This analysis indicated that CYP2C19.9, CYP2C19.10, CYP2C19.16, CYP2C19.18, CYP2C19.19, A161P, W212C, and D360N were substantially altered in catalytic properties in comparison with the WT, with each of these variants exhibiting either dramatically decreased catalytic activities or higher K m values. These results not only generally confirmed the function of previously reported variants but also identified additional reduced-function variants. These findings will greatly extend our understanding of CYP2C19 genetic polymorphisms in humans as well as facilitate the structure-function study of the CYP2C19 protein Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.

Huang T.,PLA Fourth Military Medical University | Zhang K.,Life Detection Systems | Sun L.,PLA Fourth Military Medical University | Xue X.,PLA Fourth Military Medical University | And 7 more authors.
Drug Design, Development and Therapy | Year: 2015

Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin–eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway. © 2015 Huang et al.

Wang S.,Chengdu Medical College | Chen Y.,PLA Fourth Military Medical University | Qu F.,PLA Fourth Military Medical University | He S.,PLA Fourth Military Medical University | And 5 more authors.
Neuro-Oncology | Year: 2014

Background. Compelling epidemiological evidence indicates that alterations of telomere length are associated with risks of many malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin's lymphoma. However, the association between leukocyte telomere length and glioma risk has not been investigated. Methods. Relative telomere length (RTL) of peripheral blood leukocytes from 467 glioma patients and 467 healthy controls, matched by age and sex, was measured using the real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between RTL and glioma risk. Results. Glioma patients showed notably longer RTL than controls (median, 0.555 vs 0.444; P >. 04). RTL was negatively correlated with age in both cases (ρ = -0.430; P <. 001) and controls (ρ = -0.388; P <. 001). After adjusting for age, sex, smoking status and family history of cancer, multivariate logistic regression analysis showed that there was a U-shaped association between RTL and glioma risk (P for nonlinearity <.001). Compared with individuals in the second tertile of RTL, the odds ratios (95% CI) for participants in the first and third tertiles were 2.16 (range, 1.52-3.09) and 3.51 (range, 2.45-5.00), respectively. Stratified analysis showed that the association between RTL and glioma risk was not modulated by major host characteristics. Conclusions. Our study demonstrates for the first time that either shorter or longer RTL in peripheral blood leukocytes is associated with increased glioma risk, which warrants further investigation in the future. © 2013 © The Author(s) 2013.

Zhou F.,Tangdu Hospital | He X.,Tangdu Hospital | Liu H.,PLA Fourth Military Medical University | Zhu Y.,Yale University | And 7 more authors.
Cancer | Year: 2012

Background: Previous studies have demonstrated that circadian genes play a role in the development and progression of many cancers. This study aims to assess the effects of single nucleotide polymorphisms (SNPs) in circadian genes on recurrence and survival of colorectal cancer (CRC) patients. Methods: Nine functional SNPs in 3 genes (CLOCK, NPAS2, and BMAL1) on the circadian positive feedback loop were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 411 resected Chinese CRC patients. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Results: The authors identified 2 SNPs in the CLOCK gene to be significantly associated with CRC overall survival. SNP rs3749474 exhibited a significant association with survival of CRC patients in the additive model (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.37-0.81; P =.003). In addition, patients carrying the heterozygous variant of rs1801260 had significantly increased overall survival compared with those carrying homozygous wild-type genotype (HR, 0.31; 95% CI, 0.11-0.88; P =.03). Findings from functional assay provided further biological support for these significant associations. Stratified analysis found no modifying effect of chemotherapy on the prognostic significance of both SNPs. Moreover, we observed cumulative effects of these 2 SNPs on CRC overall survival (P for trend =.01). Compared with patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 2.92-fold increased risk of death (P =.03). Conclusions: The results suggest for the first time that CLOCK gene polymorphisms may serve as an independent prognostic marker for CRC patients. © 2011 American Cancer Society.

Li S.,PLA Fourth Military Medical University | Jin T.,Life Detection Systems | Zhang J.,Life Detection Systems | Lou H.,Guangzhou First Municipal Peoples Hospital | And 4 more authors.
Cancer Epidemiology | Year: 2012

Introduction: Glioma is one of the most aggressive human tumors; however, little is known about its genetic risk factors. The role of heredity is likely to be explained by combinations of common low-risk variants. Previous studies have indicated that more than 100 single nucleotide polymorphisms (SNPs) are associated with the risk of glioma. Methods: To further investigate how and to what extent these SNPs contribute to glioma susceptibility in a Chinese population, we analyzed 43 SNPs of 226 glioma patients and 254 normal people in order to evaluate the associations between SNPs and the risk of glioma. Results: Overall, we found three protective alleles for glioma in patients: the allele " G" of rs1801275 in the IL4R gene by allele model (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.50-0.99; P= 0.04) and dominant model (OR, 0.67; 95% CI, 0.46-0.99; P= 0.04) analysis respectively, the allele " T" of rs17748 in the TREH gene by recessive model (OR, 0.48; 95% CI, 0.23-1.01; P= 0.05) analysis, and the allele " G" of rs6470745 in CCDC26 gene by recessive model (OR, 0.48; 95% CI, 0.26-0.89; P= 0.02) analysis. Conclusion: This study provides evidence for three glioma susceptibility genes - TREH, IL4R and CCDC26 - in a Chinese population; this may shed light on molecular markers of glioma susceptibility and could therefore be used as a diagnostic and prognostic marker for glioma patients in clinical study. © 2012 Elsevier Ltd.

Gao W.,Life Detection Systems
Chinese Journal of Organic Chemistry | Year: 2010

Naturally occurring terpenes constitute the largest group of natural products with complicated and variable structures and a great number of important biological activities. 2-Methyl-7D-erythreitol 4-phosphate (MEP) pathway is a newly found and established biosynthetic route for terpenoids and all the enzymes involved in this pathway can be used as targets for the screening of new antibiotics. Progress in chemical and enzymatic preparation of the key intermediates in MEP pathway, namely 1-deoxy-D-xylulose 5-phosphate and 2-methyk-D-erythreitol 4-phosphate is reviewed with the emphasis on the synthesis of these two compounds with isotope labels.

Methods and systems for monitoring the well-being of a target are disclosed. In a method embodiment, data representing a signal is received by a computer system. The signal may be generated at least in part by one or more sensors in response to the detection of a change in an electrical field, electric potential, capacitance, and/or dielectric constant of a target spaced apart from the one or more sensors. The method may further include identifying, using the computer system and based at least in part on the data electronically received by the computer system, a recurring pattern in the received data. The method may also include determining, using the computer system and based at least in part on the received data, whether a deviation from the recurring pattern transgresses a threshold. The deviation may comprise a subset of the data electronically received by the computer system.

Life Detection Systems | Date: 2014-06-29

Integrated circuits and software for use in monitoring, reporting and sending alerts regarding a person, animal or objects physical conditions, for use in detecting, recording, measuring, receiving, transmitting and displaying distances, location, activity and movement and biological function data about a person, animal or object and for use in monitoring and sending alerts regarding the activity of persons, animals and objects.

Li G.,PLA Fourth Military Medical University | Zhang Z.,PLA Fourth Military Medical University | Tu Y.,PLA Fourth Military Medical University | Jin T.,Life Detection Systems | And 4 more authors.
Diagnostic Pathology | Year: 2013

MicroRNA-372 (miR-372) acts as either an oncogenic miRNA or an anti-oncomiR in various human malignancies. However, its roles in gliomas have not been elucidated. To address this problem, we here detected miR-372 expression in human gliomas and non-neoplastic brain tissues by real-time quantitative RT-PCR assay. The association of miR-372 expression with clinicopathological factors or prognosis of glioma patients was also statistically analyzed. As the results, miR-372 expression levels were significantly upregulated in glioma tissues compared to the corresponding non-neoplastic brain tissues (P<0.001). In addition, the high miR-372 expression was significantly associated with the advanced pathological grade (P=0.008) and the low Karnofsky performance score (KPS) of glioma patients (P=0.01). Moreover, the overall survival of patients with high miR-372 expression was dramatically shorter than those with low miR-372 expression (P<0.001). Furthermore, multivariate Cox regression analysis indicated that miR-372 expression was an independent prognostic factor for glioma patients (P=0.008). More importantly, subgroup analyses according to tumor pathological grade revealed that the cumulative overall survival of glioma patients with advanced pathological grades was significantly worse for high miR-372 expression group than for low miR-372 expression group (P<0.001), but no significant difference was found for patients with low pathological grades (P=0.08). Taken together, these data offer the convincing evidence for the first time that miR-372 may act as an oncogenic miRNA in gliomas and represent a potential regulator of aggressive development and a candidate prognostic marker for this malignancy, especially for advanced tumors with high pathological grades.Virtual slides: The virtual slide(s) for this article can be found here: © 2013 Li et al.; licensee BioMed Central Ltd.

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