Zou M.,Henan Academy of Medical and Pharmaceutical science |
Lu J.-R.,Tianjin University of Technology |
Chen H.-P.,Henan Academy of Medical and Pharmaceutical science
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities | Year: 2012
A series of novel N-[1-(substituted-phenyl)ethyl]-2-hydroxybenzohydrazide derivatives was designed and synthesized by combining o-hydroxyl phenyl and substituted phenyl ethyl with the bridge of hydrazide bond, based on antibacterial characteristics of o-hydroxydiphenyl ethers and aromatic hydrazine compounds. Salicylic hydrazide was prepared by hydrazinolysis of methylsalicylate, and then condensated with the substituted acetophenones, finally reacted with NaBH 4 to obtain the title compounds. The structures of the seven compounds were confirmed by 1H NMR, IR and elemental analysis. The results of preliminary bioassay showed that the title compounds had obvious specificity and selective antibacterial activities to different classificatory bacterium, and the inhibitory rates against Escherichia coli and Monilia albican of compounds 3b and 3e were as high as 100% at a mass concentration of 1×10 -4 g/mL, which displayed excellent antibacterial activities, and the inhibitory rates against Staphlococcus aureus were over 70%, which exhibited a certain extent antibacterial activities. The analysis of structure-activity relationship showed that the antibacterial activities of the title compounds were enhanced by the halogen groups of the phenyl ring, but reduced by -NO 2 and -CH 3 of the phenyl ring.
Wang Y.,Zhengzhou University |
Wu J.,Zhengzhou University |
Guo W.,Henan Academy of Medical and Pharmaceutical science |
Sun Q.,Zhengzhou University |
And 4 more authors.
Cellular Physiology and Biochemistry | Year: 2016
Background: Esophageal cancer (EC) is one of the most common malignant tumors in the world. Due to difficulties with performing the operation, most patients choose to have palliative treatment instead. Radiotherapy is one of the main palliative treatments of EC. However, the clinical efficacy of radiotherapy is not satisfactory α-Solanine is a bioactive component of steroidal glycoalkaloids which has been demonstrated to exhibit anti-metastasis activity in different cancers. In the present study, we determined the effect of α-solanine on the radiosensitivity of EC cells and priliminarily explored the underlying molecular mechanisms. Methods: Cell Counting Kit-8 (CCK-8) assay was conducted to found the cytotoxic effect of α-solanine on EC cells. CCK-8 assay and colony-forming survival assays were performed to explore the effect of α-solanine on cell viability and proliferation of EC cells after irradiation. Immunofluorescence and comet assays were used to detect the effect of α-solanine on DNA repair capacity of EC cells after irradiation. The flow cytometry (FCM) and Hoechst/PI staining were conductd to study the effect of α-solanine on apoptosis of EC cells after irradiation. Results: The cytotoxic effect of α-solanine to EC cells was dose-dependent. The results of CCK-8, colony-forming survival assay, immunofluorescence, comet assay, FCM and Hoechst/PI staining showed that α-solanine could enhance the radiosensitivity of EC cells. α-Solanine could downregulate Survivin expression level by upregulating miR-138 expression in EC cells. Upregulation of miR-138 and knock down Survivin both enhanced the radiosensitivity of EC cells. Moreover, Survivin could restore the effect of α-solanine and miR-138 on radiosensitivity of EC cells. Conclusions: α-solanine could enhance the radiosensitivity of esophageal cancer cells by inducing microRNA-138 expression, and probably be an effective radiosensitizer in treating EC. © 2016 The Author(s) Published by S. Karger AG, Basel.
Zhai Q.-Q.,Jinan University |
Zhai Q.-Q.,Peking Union Medical College |
Gong G.-Q.,Jinan University |
Luo Y.,Jinan University |
And 8 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2010
A sensitive and specific reversed-phase high-performance liquid chromatography method with ultraviolet detection has been developed and validated for the identification and quantification of SNX-2112 in rat plasma. Following sample preparation using liquid-liquid extraction, the analytes were separated by the mobile phase acetonitrile-water (40:60, v/v) with an Agilent RP-HPLC column (ZORBAX SB-C18, 5μm, 4.6mm×250mm) at a flow rate of 1ml/min, column temperature of 30°C and detection wavelength of 251nm. The retention time of SNX-2112 was 11.2min. A good linear relationship was obtained in the concentration range studied (0.07-21μg/ml, R2>0.9982), and the LLOD and LLOQ for SNX-2112 were 0.02 and 0.07μg/ml, respectively. The mean absolute recovery of SNX-2112 in plasma ranged from 88.58 to 99.61% at the studied concentrations. The intra- and inter-batch relative standard deviations were 1.7-3.5 and 1.9-4.4%, respectively. This method was successfully applied to pharmacokinetic studies in rats after intravenous administration of SNX-2112. © 2010.
Zou M.,Tianjin University of Technology |
Lu J.,Tianjin University of Technology |
Xin C.,Tianjin University of Technology |
Bao X.,Tianjin University of Technology |
And 5 more authors.
Chinese Journal of Organic Chemistry | Year: 2010
A series of 1-(2-hydroxybenzoyl)-3-methyl-4-substituted phenylhydrazono-pyrazolones (4a∼4f) and their intermediates 3a∼3f were designed and synthesized by combining o-hydroxyl pheny, pyrazoleone and phenylhydrazone groups, according to the superposition principle of biological activities. Eight compounds and antibacterial-activity of all compounds have not been reported so far. Substituted anilines were diazotized and subsequently reacted with ethylacetoacetate, then condensed with salicylic hydrazide to obtain 3a∼3f. The title compounds were acquired by intramolecular cyclization reaction of 3a∼3f. The structures of all compounds were confirmed by IR, 1H NMR spectra and elemental analysis. The results of preliminary bioassay showed that the inhibitory rates against Escherichia coli of compounds 3b, 3c were high to 100% at 0.01% mass concentration, which displayed excellent antibacterial activities; and the inhibitory rates against Monilia albican and Staphlococcus aureus were over 70%, which exhibited a certain extent antibacterial activities. The inhibitory rates against Moniliaalbican and Escherichia coli of the compounds 4a∼4f reached to 100% at 0.01% mass concentration, which displayed excellent antibacterial activities. The inhibitory rates against Staphlococcus aureus were over 78%, which exhibited a certain extent antibacterial activities. Comparing with those of 3a∼3f, the inhibitory rates of the compounds 4a∼4f were enhanced.
Wang Q.,Zhengzhou University |
Liu X.,Arizona Cancer Center |
Wang Q.,Henan Academy of Medical and Pharmaceutical science |
Zhang Y.,Henan Academy of Medical and Pharmaceutical science |
And 10 more authors.
Biochemical Pharmacology | Year: 2011
Inhibition of cellular DNA synthesis is a strategy to block cancer cell division. Nucleoside analogues can incorporate into DNA and terminate DNA strand elongation. So far, several nucleoside analogues have been successfully used as anticancer drugs. FNC, 2′-deoxy-2′-β-fluoro-4′- azidocytidine is a novel cytidine analogue which demonstrated potent activity against hepatitis C virus (HCV). To investigate the therapeutic potential of FNC in human cancers we studied its activity in a number of cancer cells in vitro and in vivo. FNC potently inhibited cell proliferation with an IC50 of 0.95-4.55 μM in a variety of aggressive human cancer cell lines including B-cell non-Hodgkin's lymphomas, lung adenocarcinoma and acute myeloid leukemia. Cells treated with FNC exhibited G1 and S cell cycle arrest at high and low dose, respectively, which confirms the mechanism of action of nucleoside analogues. Treatment of B-NHL cell lines with FNC induced apoptosis in a dose and time dependent manner. Finally, mouse xenograft models of hepatocarcinoma (H22), sarcoma (S180) and gastric carcinoma (SGC7901) demonstrated that FNC had significant tumor growth inhibition activity in a dose-dependent manner with low toxicity. Together, our results suggest that FNC may be a valuable therapy in cancer patients and warrant early phase clinical trial evaluation. © 2011 Elsevier Inc. All rights reserved.
Qing-Duan W.,Henan Academy of Medical and Pharmaceutical science |
Li H.,Zhengzhou University |
Li H.,Henan Academy of Medical and Pharmaceutical science |
Yan Z.,Henan Academy of Medical and Pharmaceutical science |
And 5 more authors.
Journal of Biomedicine and Biotechnology | Year: 2011
The purpose of this study was the use of rhodamine 123 (Rho123) accumulation in peripheral blood CD8 + cells as a surrogate indicator to evaluate the modulating effect of P-glycoprotein (P-gp) inhibitors in the multidrug resistance (MDR) tumor-bearing mouse model. Rho123 was administered to mice, and the fluorescence level in CD8 + cells was measured. Cepharanthine hydrochloride (CH) and verapamil (VER), two P-gp inhibitors, were administered to mice 1 hour prior to Rho123 administration in vivo or added to peripheral blood 1 hour prior to Rho123 addition ex vivo. The tumor inhibition effect of 5-fluorouracil/adriamycin/cisplatin (FAP) protocol plus CH was also investigated. A concentration- or dose-response relationship was shown between the concentration and dose of CH and Rho123 accumulation or the antitumor activity. In conclusion, the measurement of Rho123 accumulation in CD8 + cells provides a surrogate assay for the screening of candidate P-gp inhibitors in preclinical trials, and CH is effective in modulating P-gp-mediated MDR in vivo. Copyright © 2011 Han Li et al.
Zhang L.-L.,Zhengzhou University |
Chen X.,McMaster University |
Zheng P.-Y.,Zhengzhou University |
Luo Y.,Henan Academy of Medical and Pharmaceutical science |
And 4 more authors.
Journal of Gastroenterology and Hepatology (Australia) | Year: 2010
Background and Aims: It is proposed that probiotics have a therapeutic effect on the treatment of immune disorders. However, the underlying mechanisms require clarification. The present study aimed to evaluate the effect of gavage-feeding Bifidobacteria on suppression of T helper 2 (Th2) pattern inflammation in the intestines of mice with food allergy. Methods: Mice were sensitized to ovalbumin to induce the intestinal Th2 pattern inflammation. Allergic mice were treated with or without Bifidobacteria via gavage-feeding. Th2 response, number of regulatory T cells (Treg) in the spleen and intestine, intestinal epithelial barrier function and bifidobacterial translocation were examined. Results: The results showed that serum-specific immunoglobulin E antibody and interleukin 4 (IL-4) were increased in allergic mice. Intestinal epithelial barrier function was impaired in allergic mice as shown by the increase in epithelial ion secretion and permeability to macromolecular protein horseradish peroxidase in Ussing chambers. Number of Treg was decreased in both spleen and intestines of allergic mice. Gavage-feeding Bifidobacteria significantly suppressed the skewed Th2 response and increased the number of Treg. Transient bifidobacterial translocation was observed in allergic mice. Conclusions: Oral administration of Bifidobacteria has the capacity to suppress the skewed Th2 response in allergic mice, increasing the number of Treg and IL-10-positive cells and improve the impaired intestinal epithelial barrier function. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Liu X.,Zhengzhou University |
Fu G.,Zhengzhou University |
Fu G.,Chongqing Medical University |
Ji Z.,Henan Academy of Medical and Pharmaceutical science |
And 7 more authors.
Inflammation | Year: 2016
Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R. © 2016, Springer Science+Business Media New York.
Yan Z.,Zhengzhou University |
Fan D.,Henan Academy of Medical and Pharmaceutical Science |
Meng Q.,Zhengzhou University |
Yang J.,Zhengzhou University |
And 6 more authors.
Reproduction | Year: 2016
The production of haploid gametes by meiosis is a cornerstone of sexual reproduction and maintenance of genome integrity. Zfp38 mRNA is expressed in spermatocytes, indicating that transcription factor ZFP38 has the potential to regulate transcription during meiosis. In this study, we generated Zfp38 conditional knockout mice (Zfp38flox/flox, Stra8-Cre, hereafter called Zfp38 cKO) and found that spermatogenesis did not progress beyond meiosis prophase I in Zfp38 cKO mice. Using a chromosomal spread technique, we observed that Zfp38 cKO spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3 double staining. Progression of DNA double-strand breaks (DSB) repair is disrupted in Zfp38 cKO spermatocytes, as revealed by γ-H2AX, RAD51 and MLH1 staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51, TEX15 and PALB2, were significantly reduced in Zfp38 cKO spermatocytes. Taken together, our data suggest that ZFP38 is critical for the chromosomal synapsis and DSB repairs partially via its regulation of DSB repairassociated protein expression during meiotic progression in mouse. © 2016 Society for Reproduction and Fertility.
PubMed | Zhengzhou University and Henan Academy of Medical and Pharmaceutical science
Type: Journal Article | Journal: Inflammation | Year: 2016
Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.