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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.

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.

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.

Wang X.-T.,Zhengzhou University | Liu Z.-Q.,Zhengzhou University | Zheng P.-Y.,Zhengzhou University | Yang P.-C.,McMaster University | And 3 more authors.
Life Science Journal | Year: 2011

Research in the area of food allergy has advanced rapidly in recent years, however, the mechanism of food allergy remains unclear. It has been shown that the T regulatory cells immunoglobulin and mucin domain protein TIM 1 interacted with its endogenous ligand of TIM4 may attenuate the oral immune tolerance and lead to hypersensitivity reactions in the intestine. Forty male BALB/c mice fed on the OVA-free diet were randomly divided into five groups, and eight mice were used for each group: A group of mice were sensitized by intraperitoneal injection (ip) with Staphylococcal enterotoxin B (SEB) + Ovalbumin (OVA) and the other four groups of mice were separately treated with normal saline (NS), anti-TIM1 (2 μg/mouse) +SEB + OVA, anti-TIM1 (10 μg/mouse) +SEB + OVA, anti-TIM4 (10 μg/mouse) + SEB + OVA, on the 0, 3rd and 9th day; and all of the mice were challenged by means of lavage with SEB+ OVA (except NS) on the 7th and 14th day. Mice were treated intraperitoneally with the same doses anti-TIM4 or anti-TIM1 30 minutes before gavage. Twenty-four hours after the last gavage, the mice were killed and subjected to immunologic analyses. The expressions of Foxp3 mRNA in the jejunum and spleen decreased significantly in SEB+OVA group compared with those treated with NS, but the expressions of TIM4 mRNA increased significantly (P<0.05). The levels of TGF-β1 in serum and jejunum decreased significantly compared with those treated with NS. The expressions of Foxp3 mRNA in the jejunum and spleen and the levels of TGF-β1 in the serum and jejunum were significantly higher in anti-TIM1+SEB+OVA and anti-TIM4+SEB+OVA groups compared with SEB+OVA group (all P<0.05). The function of Treg cells can be suppressed in the intestine by sensitization that can be prevented by pretreatment with antibodies against TIM1 or TIM4.

Fu L.,Zhengzhou University | Ji J.-W.,Zhengzhou University | Zheng P.-Y.,Zhengzhou University | Luo Y.,Henan Academy of Medical and Pharmaceutical science | Zhang J.,Zhengzhou University
World Chinese Journal of Digestology | Year: 2010

AIM: To determine the influence of chronic psychological stress on intestinal microflora and corticotropin-releasing factor (CRF) and to investigate the protective effects of Bifidobacterium on intestinal function in rats. METHODS: Fifty female Sprague-Dawley rats were randomly and equally divided into five groups: normal group, stress group, Bifidobacterium group, Smecta group, and Bifidobacterium plus Smecta group. All these groups were subjected to either water avoidance stress (WAS) or normal condition for 2 h per day for 7 consecutive days. The in vivo intestinal permeability was evaluated by measuring urinary sucralose and other sugar probes including lactulose and mannitol using capillary column gas chromatography (CCGC). Some representative genera of gut flora in rat feces were counted on selective culture medium plates. The mesenteric lymph nodes (MLN) were removed, homogenized and cultured to determine bacterial translocation. The contents of serum CRF and adrenocorticotrophic hormone (ACTH) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal group, the number of Escherichia coli (7.347 ± 0.277 vs 7.078 ± 0.229, P < 0.05), the 24-h urinary concentration of mannitol (5.097% ± 0.453% vs 4.718% ± 0.399%, P < 0.05), the rate of bacterial translocation to the MLN (40% vs 10%, P < 0.05), and the levels of CRF (300.8 ng/L ± 34.3 ng/L vs 267.0 ng/L ± 32.3 ng/L, P < 0.05) and ACTH (6.79 ng/L ± 0.651 ng/L vs 5.68 ng/L ± 0.799 ng/L, P < 0.05) increased significantly in the stress group. In comparison with the stress group, the number of Escherichia coli (7.044 ± 0.281 vs 7.347 ± 0.277, P < 0.05) and bacteroid (9.075 ± 0.393 vs 9.485 ± 0.306, P < 0.05); the rate of bacterial translocation to the MLN (10% vs 40%, P < 0.05) and ACTH level (5.92 ng/L ± 0.477 ng/L vs 6.79 ng/L ± 0.651 ng/L, P < 0.05) decreased significantly in the Bifidobacterium intervention group. CONCLUSION: The disturbance of intestinal microflora occurs and CRF increases significantly in rats suffered from chronic psychological stress. Bidifobacterium could alleviate the disturbance of gut microflora caused by chronic psychological stress and partly restore intestinal barrier function.

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