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Yao X.-Q.,Tianjin University | Yao X.-Q.,Tianjin Chase Sun Pharmaceutical Co. | Zhang Y.-H.,Tianjin University | Long W.,Peking Union Medical College | Liu P.-X.,Peking Union Medical College
Chinese Journal of Integrative Medicine | Year: 2012

Objective: To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms. Methods: C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously, then divided into 5 groups (14 per group), and treated with oxysophoridine (50, 100, or 150 mg/kg) or cisplatin (4 mg/kg) for 10 days. Inhibitory rate of tumor, body weight gain, and influence indices on internal organs (liver, spleen and thymus) were evaluated. The differentially expressed genes between the oxysophoridine-treated group, and the control group were analyzed using cDNA microarray and quantitative real-time PCR (qRT-PCR) experiments. Results: Compared with the tumor weight of the control group (2.75±0.66 g), oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice (P<0.01), with 0.82±0.36 g, 0.57±0.22 g, and 1.22±0.67 g for the tumor weight in the low, moderate, and high dose treatment group, respectively. The moderate dose led to the highest inhibitory rate, 79.3%. Observation of body weight gain and influence on three organs showed that compared with cisplatin, oxysophoridine produced fewer side effects in vivo. cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis, with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected. Conclusion: Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect was probably related to osteoprotegerin activation. © The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2012. Source

Ding J.,Institute of Neurology | Ding J.,Fudan University | Li Q.-Y.,Institute of Neurology | Yu J.-Z.,Shanxi Datong University | And 4 more authors.
Molecular and Cellular Neuroscience | Year: 2010

Rho kinase (ROCK) is important in fundamental processes of cell proliferation and survival. Blockade of ROCK promotes stem cell survival in vitro and axonal regeneration in vivo, exhibiting therapeutic potential such as spinal cord injuries and stroke. Here, we used the model of hypoxia/reoxygenation (H/R) injury to explore the possibility whether Fasudil, a ROCK inhibitor in clinical application for subarachnoid hemorrhage and stroke, mobilizes adult neural stem cells in vivo. Most interestingly, Fasudil triggers neurogenesis especially in the subventricular zone after H/R. The increase of Brdu+ cholinergic neurons was observed in striatum and forebrain cortex of Fasudil-treated mice after 30 days. Further observation demonstrates that both levels of granulocyte colony-stimulating factor (G-CSF) and astrocytes expressing G-CSF were elevated in mice treated with Fasudil, as compared to mice injected with saline. In vitro H/R model of cultured astrocytes, Fasudil promoted astrocytes to produce G-CSF in a dose-dependent manner. In addition, antibody neutralization and receptor blocking of the G-CSF pathway clearly demonstrate that Fasudil-induced neurogenesis was mediated partially through astrocyte-derived G-CSF. Our results indicate that Fasudil might represent a promising therapeutic perspective by mobilizating endogenous adult neural stem cells in the CNS. © 2009 Elsevier Inc. All rights reserved. Source

Ding J.,Fudan University | Li Q.-Y.,Fudan University | Wang X.,Fudan University | Sun C.-H.,Tianjin Chase Sun Pharmaceutical Co. | And 2 more authors.
Journal of Neurochemistry | Year: 2010

Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. Our previous studies have demonstrated that Fasudil, a selective ROCK inhibitor, induced neuroprotection in vitro. Here we used an in vivo model of hypoxia/reoxygenation (H/R) injury to examine the neuroprotective effect of Fasudil, and explore its possible mechanism(s) in vivo. H/R resulted in the loss of hippocampal neurons, accompanied by increased apoptosis of neurons in hippocampus. The expression of ROCK II and activity of ROCK in the brain were increased after H/R, and located only in microglia, but not in astrocytes and neurons. The administration of Fasudil inhibited the activity of ROCK in brain tissue and cultured microglia, and protected hippocampal neurons against H/R injury. Further immunohistochemical analysis and cytokine determination revealed that Fasudil inhibited inducible nitric oxide synthase immunoreactivity in microglia and pro-inflammatory factors in brain tissue after H/R, which is consistent with the observation wherein Fasudil reduced the pro-inflammatory factors nitric oxide, IL-1β, IL-6 and TNF-α, and increased anti-inflammatory factor IL-10 in cultured microglia under normoxic or hypoxic conditions. Our results indicate that inhibition of ROCK by Fasudil may represent a useful therapeutic perspective by inhibiting microglial inflammatory responses in the CNS. © 2010 International Society for Neurochemistry. Source

Sun C.,Tianjin Chase Sun Pharmaceutical Co. | Cao J.,Tianjin University of Science and Technology
Lecture Notes in Electrical Engineering | Year: 2014

Pyrrolizinone derivatives were discovered showing remarkable anti-inflammatory and analgesic activities. Based on the SAR summarized before, a series of pyrrolizinone derivatives were designed and synthesized in this paper. All the eight target compounds were characterized by 1HNMR spectra, and the test of anti-inflammatory and analgesic activities is in progress. © Springer-Verlag Berlin Heidelberg 2014. Source

Ye H.,Nankai University | Liu R.,Nankai University | Li D.,Nankai University | Liu Y.,Nankai University | And 7 more authors.
Organic Letters | Year: 2013

A facile approach to the diazotransfer reagent of imidazole-1-sulfonyl azide was reported. The procedure was well optimized to clarify potential explosion risks. A high production yield as well as small batch variation was achieved even without careful pretreatment of reagents and solvents. HPLC and NMR methods to monitor the process were provided. These features made this protocol suitable for large scale preparation in academia and industry as well. © 2012 American Chemical Society. Source

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