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Dong C.,Laiwu City Peoples Hospital | Xu C.,Rizhao City Peoples Hospital | Liu H.,Laiwu City Peoples Hospital | Liu H.,Taishan Medical University | And 3 more authors.
Fitoterapia | Year: 2015

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of pristimerin in rat plasma, cell incubation media and metabolism incubation mixtures. The absolute oral bioavailability of pristimerin is 28.4% at a dose of 1 mg · kg- 1, and the bioavailability was poor. The bidirectional transport of pristimerin across Caco-2 cells was studied in vitro. A markedly higher transport of pristimerin across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the transport of pristimerin in intestine. The phase I and phase II metabolic stability was also investigated using human liver microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9 fractions but metabolized in HLM with a half-life of 20.4 min, which indicated that pristimerin could be mainly metabolized by phase I enzymes. In conclusion, the absolute oral bioavailability of pristimerin in plasma, transport across Caco-2 cell monolayers, and metabolic stability in HLM and S9 fractions were systematically investigated by using a sensitive and reliable LC-MS/MS method. © 2015 Elsevier B.V. All rights reserved. Source


Ma X.,Zhengzhou Peoples Hospital | Li H.,Rizhao City Peoples Hospital | Xiao Z.,Chongqing Medical University | Li M.,Luohe City Peoples Hospital | And 3 more authors.
Turkish Neurosurgery | Year: 2016

Aim: This study aims to apply computed tomography perfusion imaging (CTPI) technology under in vivo conditions in order to explore its reliability and accuracy in evaluating the rat acute cerebral ischemia-reperfusion model (RACIRM). Material and Methods: The thread embolism method was used in 48 rats to create the RACIRM. Rats were divided into 2 groups as ischemia group and ischemia-reperfusion group. We then compared and evaluated the results of CTPI, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and hematoxylin and eosin (HE) staining of both groups. Results: There were no significant differences in the volumes of hypoperfusion regions in the cerebral blood flow (CBF) and cerebral blood volume (CBV) of each group at each CTPI time point and these volumes were not significantly different from the corresponding findings on the TTC-stained infarct regions. The mean transit time (MTT) did show a significant difference, as did the volumes observed in both the MTT ischemic region and TTC-stained infarct region. The CTPI parameters exhibited correlation with the infarct volumes calculated in TTC staining, among which CBV exhibited the highest correlation. Conclusion: CTPI could rapidly, accurately, and non-invasively evaluate the site, size, and hemodynamic changes in the cerebral ischemia-reperfusion animal model. Source


Xu W.,Rizhao City Peoples Hospital
International Journal of Genomics | Year: 2014

Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. It is usually caused by a combination of complex and incompletely understood environmental and genetic interactions. We obtained gene expression data with high-throughput screening and identified biomarkers of children's asthma using bioinformatics tools. Next, we explained the pathogenesis of children's asthma from the perspective of gene regulatory networks: DAVID was applied to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriching analysis for the top 3000 pairs of relationships in differentially regulatory network. Finally, we found that HAND1, PTK1, NFKB1, ZIC3, STAT6, E2F1, PELP1, USF2, and CBFB may play important roles in children's asthma initiation. On account of regulatory impact factor (RIF) score, HAND1, PTK7, and ZIC3 were the potential asthma-related factors. Our study provided some foundations of a strategy for biomarker discovery despite a poor understanding of the mechanisms underlying children's asthma. © 2014 Wen Xu. Source


Liu J.,Beijing Normal University | Zhang K.,Rizhao City Peoples Hospital | Zhen Y.-Z.,University of Science and Technology of China | Wei J.,Beijing Hospital and Beijing Institute of Geriatrics | And 4 more authors.
Oncology Reports | Year: 2016

In previous studies, we demonstrated that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells derived from breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma. Based on these observations, human glioma U87 cells and a xenograft model in BALB/c nude mice were used to examine the antitumor activity of RHL against human glioma. Notably, RHL statistically significantly suppressed the growth of human glioma U87 xenografts in BALB/c nude mice. In vitro, there was a significant reduction in cell proliferation after treatment with RHL in a dose- and time-dependent manner. The overall growth inhibition was correlated with the increase in reactive oxygen species (ROS) production and cell apoptosis. The apoptosis- and cell cycle-related proteins including BAX and Bim were increased, whereas Bcl-2 and cyclin D were decreased in the RHL-treated cells. The results demonstrated that RHL is highly effective against the growth of human glioma U87 xenografts in BALB/c nude mice. The potent antitumor activity of RHL may be mediated through downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression. Source


Zhang G.,Capital Medical University | Jin G.,Capital Medical University | Nie X.,Rizhao City Peoples Hospital | Mi R.,Capital Medical University | And 3 more authors.
PLoS ONE | Year: 2014

Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, the use of a herpes simplex virus carrying endostatin-angiostatin (VAE) as a novel therapeutic targeting strategy for glioblastoma-derived cancer stem cells was investigated. We isolated six stable GSC-enriched cultures from 36 human glioblastoma specimens and selected one of the stable GSCs lines for establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in GSCs and expressed endo-angio in vitro and in vivo 48 h and 10 d after infection, respectively; (b) compared with the control gliomas treated with rHSV or Endostar, the subcutaneous gliomas derived from the GSCs showed a significant reduction in microvessel density after VAE treatment; (c) compared with the control, a significant improvement was observed in the length of the survival of mice with intracranial and subcutaneous gliomas treated with VAE; (d) MRI analysis showed that the tumor volumes of the intracranial gliomas generated by GSCs remarkably decreased after 10 d of VAE treatment compared with the controls. In conclusion, VAE demonstrated oncolytic therapeutic efficacy in animal models of human GSCs and expressed an endostatin-angiostatin fusion gene, which enhanced antitumor efficacy most likely by restricting tumor microvasculature development. © 2014 Zhang et al. Source

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