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Hao J.,Shandong University | Hao J.,Taishan Medical University | Gao Y.,The Central Hospital of Taian | Zhao J.,Taishan Medical University | And 4 more authors.
AAPS PharmSciTech | Year: 2014

Resveratrol, a natural polyphenolic component, has inspired considerable interest for its extensive physiological activities. However, the poor solubility of resveratrol circumscribes its therapeutic applications. The purpose of this study was to optimize and prepare resveratrol nanosuspensions using the antisolvent precipitation method. The effects of crucial formulation and process variables (drug concentration, stabilizer, and surfactant contents) on particle size were investigated by utilizing a three-factor three-level Box-Behnken design (BBD) to perform this experiment. Different mathematical polynomial models were used to identify the impact of selected parameters and to evaluate their interrelationship for predictive formulation purposes. The optimal formulation consisted of drug 29.2 (mg/ml), polyvinylpyrrolidone (PVP) K17 0.38%, and F188 3.63%, respectively. The morphology of nanosuspensions was found to be near-spherical shaped by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis confirmed that the nanoparticles were in the amorphous state. Furthermore, in comparison to raw material, resveratrol nanosuspensions showed significantly enhanced saturation solubility and accelerated dissolution rate resulting from the decrease in particle size and the amorphous status of nanoparticles. Meanwhile, resveratrol nanosuspensions exhibited the similar antioxidant potency to that of raw resveratrol. The in vivo pharmacokinetic study revealed that the Cmax and AUC0→∞ values of nanosuspension were approximately 3.35- and 1.27-fold greater than those of reference preparation, respectively. Taken together, these results suggest that this study provides a beneficial approach to address the poor solubility issue of the resveratrol and affords a rational strategy to widen the application range of this interesting substance. © 2014, American Association of Pharmaceutical Scientists.

Zhang H.-X.,Taishan Medical University | Qiu Y.-Y.,Taishan Medical University | Zhao Y.-H.,Taishan Medical University | Liu X.-T.,Taishan Medical University | And 2 more authors.
Molecular and Cellular Probes | Year: 2014

Helicobacter pylori (H.pylori) infection remains a significant global public health problem. Vaccine, especially edible vaccine, is considered to be effective in the management of H.pylori infections. By using recombinant technology, Lactococcus lactis (L.lactis) could serve as an antigen-delivering vehicle for the development of edible vaccine. The aim of this study was to produce edible UreB (urease B) vaccine derived from L.lactis against H.pylori. The UreB subunit is the most effective and common immunogen of all strains of H.pylori. The UreB was produced as a chimeric protein fused with IL-2 (human interleukin 2) as the mucosal adjuvant. Mucosal immunization of mice with recombinant L.lactis NZ9000 containing the UreB-IL-2 protein elicited more anti-UreB antibody that specifically bounded to the purified bacterial UreB protein and more cytokines such as IFN-γ, IL-4, and IL-17, and had a lower H.pylori burden and urease activity than control mice. These results suggest that the recombinant L.lactis expressing UreB-IL-2 can be potentially used as an edible vaccine for controlling H.pylori infection. © 2013 Elsevier Ltd.

Zhang H.,Shandong Agricultural University | Zhang H.,Taishan Medical College | Liu M.,The Central Hospital of Taian | Li Y.,Shandong Agricultural University | And 4 more authors.
Protein Expression and Purification | Year: 2010

Helicobacter pylori (H. pylori) is established as the etiologic agent of chronic active gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. The development of a vaccine against H. pylori has become a priority to prevent and cure H. pylori infection. The UreB (urease B) subunit is the most effective and common immunogen of all strains of H. pylori and may stimulate the immunoresponse protecting the human body against the challenge of H. pylori. To date no report has documented an edible carrot vaccine against H. pylori. We transformed the gene of UreB into carrot by Agrobacterium-mediated transformation and the regenerated carrot plants demonstrated that the expressed UreB protein accounted for 25 μg/g roots and was effective to induce immune response in mice. These results suggest that the UreB transgenic carrot can be potentially used as an edible vaccine for controlling H. pylori. © 2009 Elsevier Inc. All rights reserved.

Liu Q.Q.,The Central Hospital of Taian
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2013

To explore the tumor growth inhibition of gamma secretase inhibitor MRK003 on human multiple myeloma xenograft mice by inhibition of AKT and Notch1 expression. NOD/SCID mice were injected with human multiple myeloma cell lines RPMI8226 to establish a xenograft mouse model. Mice were randomized into two groupsythe experimental group were injected with MRK003 at a dose of 5 mg× kg-1×d-1 for 14 days; the inhibitor was replaced by an equal saline in the control group. Mice were sacrificed by cervical dislocation on the next day after the last injection and tumor tissue was removed to detect the expression of Notch1 and AKT by immunohistochemistry. After subcutaneous injection with RPMI8226, mice had tumor formation in 5-7 days and the largest tumor block in 10-12 days. Before RPMI8226 injection, the mean sizes of tumor block in the experimental and the control groups were 509.2 mm3, 511.2 mm3(P>0.05). 9 days after injection, the mean sizes of tumor tissue in the experimental and the control groups were 636.6 mm3, 691.2 mm3(P<0.01). On the next day after the last injection, the tumor sizes of the experimental and the control groups were 683.5 mm3 and 1798.7 mm3(P<0.01). The size of tumor block in the experimental group was significantly smaller than that of the control group(P<0.01). Immunohistochemistry staining showed that the positive expression rates of Notch1(11.1%, P<0.01) and AKT(13.3%, P<0.01) in experimental group were significantly decreased compared with the control group(Notch1: 95.6%; AKT: 93.3%). Western blot results showed that Notch1 and AKT protein in experimental group were significantly lower than those in the control group. MRK003 could inhibit the tumor growth of human multiple myeloma xenograft mice by downregulated expression of Notch1 signaling pathway.

Wang J.,The Central Hospital of Taian | Li J.-Z.,The Central Hospital of Taian | Lu A.-X.,The Central Hospital of Taian | Li B.-J.,The Central Hospital of Taian
Oncology Letters | Year: 2014

Oxidative stress is important in carcinogenesis and metastasis. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant properties. The aim of the present study was to investigate the roles of salidroside in cell proliferation, the cell cycle, apoptosis, invasion and epithelial-mesenchymal transition (EMT) in A549 cells. The human alveolar adenocarcinoma cell line, A549, was incubated with various concentrations of salidroside (0, 1, 5, 10 and 20 μg/ml) and cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Propidium iodide (PI) staining was used to determine the cell cycle by flow cytometry. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and PI double-staining, and tumor invasion was detected by Boyden chamber invasion assay. Western blot analysis was performed to detect the expression of EMT markers, Snail and phospho-p38. The results showed that salidroside significantly reduced the proliferation of A549 cells, inhibited cell cycle arrest in the G0/G1 phase and induced apoptosis. Salidroside inhibited transforming growth factor-β-induced tumor invasion and suppressed the protein expression of Snail. As an antioxidant, salidroside inhibited the intracellular reactive oxygen species (ROS) formation in a dose-dependent manner in A549 cells, and depletion of intracellular ROS by vitamin C suppressed apoptosis by salidroside treatment. Salidroside was also found to inhibit the expression of phospho-p38 in A549 cells. In conclusion, salidroside inhibits cell proliferation, the cell cycle and metastasis and induces apoptosis, which may be due to its interference in the intracellular ROS generation, thereby, downregulating the ROS-phospho-p38 signaling pathway.

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