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He M.,Shanghai University of Traditional Chinese Medicine | He M.,Shanghai nter for Standardization of Chinese Medicines | Wang H.,The Third Peoples Hospital of Jinan | Dou W.,Shanghai University of Traditional Chinese Medicine | And 7 more authors.
International Journal of Biological Macromolecules | Year: 2016

This study aimed to develop injectable norisoboldine (NOR) chitosan microspheres formulated through the emulsion cross-linking method. The formulation was optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The morphology, size, physicochemical characterization and in vitro release behavior of the optimized formulation were evaluated. Scanning electron micrographs (SEM) indicated that the microspheres were spherical with a smooth surface. The encapsulation efficiency and drug loading content of the microspheres were 38.89% ± 1.72% and 4.25% ± 0.15%, respectively, with an average size of 105 μm. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed the absence of a drug-polymer interaction and the amorphous nature of an entrapped drug. Analysis results of drug release in vitro show the burst release of the microsphere in 2 h and a slow progression afterward. In vivo studies using Sprague-Dawley rats revealed that the NOR-loaded chitosan microspheres were biocompatible. This study suggests that the BBD with desired formulation could provide a suitable drug delivery system of chitosan microspheres. © 2016 Elsevier B.V.


Wang W.,Shandong University | Li Z.,Taishan Medical University | Meng Q.,The Third Peoples Hospital of Jinan | Zhang P.,Shandong University | And 9 more authors.
Inflammation | Year: 2016

It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown. To investigate the role of verapamil in antagonizing TNF-α-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-α, in the presence or absence of verapamil. Inflammation-associated cytokines, including IL-1, IL-6, inducible nitric oxide synthase 2 (NOS-2), and cyclooxygenase-2 (COX-2), were assessed, and verapamil suppressed TNF-α-induced expression of inflammatory cytokines. Furthermore, collagen-induced arthritis (CIA) mice models were established, and arthritis progression was evaluated by clinical and histological signs of arthritis. Treatment of verapamil attenuated inflammation as well as joint destruction in arthritis models. In addition, activity of NF-kB signaling pathway was determined both in vitro and in mice arthritis models, and verapamil inhibited TNF-α-induced activation of NF-kB signaling both in vitro and in mice models. Collectively, chronic calcium channel blocker verapamil may shed light on treatment of inflammatory arthritis and provide a potential therapeutic instrument for RA in the future. © 2016 Springer Science+Business Media New York


Chen G.,Shandong University | Zhang J.,The Third Peoples Hospital of Jinan | Zhang H.,Shandong University | Xiao Y.,Shandong University | And 3 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Emodin, a major bioactive extract of several Chinese herbs, has been shown to have a number of biological activities including antiviral, anti-inflammatory, anti-tumor, anti-fibrosis etc. In the present study, we investigated the effects of emodin as an anti-inflammatory agent on lipopolysaccharide (LPS) induced keratitis in Wistar rats. Clinical score, slit-lamp microscope were used to determine corneal inflammatory response. Corneal structure was observed by hematoxylin-eosin staining and transmission electron microscopy. Messenger ribonucleic acid levels of tight junction protein and cytokines were determined by reverse transcription- polymerase chain reaction. The activation of nuclear factor-kappa B (NF-κB) was detected with Western blot. We found that disorganized corneal tissue and cellular structures were observed in keratitis rats and emodin could deduce inflammatory response and improve corneal structure. Pretreated with emodin could up-regulate and down-regulate the mRNA expression of occludin and Interleukin-6. The activation of NF-κB could be inhibited partly after emodin treatment. In conclusion, emodin reduced corneal inflammation in LPS-induced keratitis in Wistar rats due to its capability of inhibition in NF-κB activation. © 2015, E-Century Publishing Corporation. All rights reserved.


Shao S.,The Third Peoples Hospital of Jinan | Li B.,The Third Peoples Hospital of Jinan | Xue H.-M.,The Third Peoples Hospital of Jinan | Huang H.-Y.,Shandong University | And 2 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

To evaluate the effects of alveolar ridge preservation with Bio-Oss bone substitute (Geistlich Pharma) on delayed implant osseointegration. The 3rd and 4th left and right mandibular premolars were extracted from four adult healthy male and female dogs. For the experimental group, we randomly selected two extraction sockets in each dog to be filled with Bio-Oss bone substitute (Geistlich Pharma). The two remaining extraction sockets remained untreated and served as the control group. Three months after Bio-Oss placement, dental implants were inserted into the alveolar bone of the experimental group and the control group. The osteogenic activity of the bone around the implants was assessed by evaluating the histological morphology and by estimating histomorphometric parameters at 3 and 6 months after delayed implantation. At 3 months, Goldner’s trichrome staining analysis showed that the bone-implant contact rate and mineralised bone area around the implant were significantly higher in the experimental group (75.98% ± 8.97% and 69.52% ± 9.63%, respectively) than in the control group (56.13% ± 8.18% and 52.82% ± 7.25%, respectively; P < 0.05). However, at 6 months, the two groups showed no significant difference. Fluorescence microscopy analysis revealed that the average mineralisation apposition rate of the bone tissue around the dental implant in the experimental group at 3 and 6 months was 6.80 ± 0.43 μm and 8.38 ± 0.84 μm, respectively, which was significantly higher than the rate in the control group (P < 0.05). These data indicated that alveolar ridge preservation by using Bio-Oss placement can promote osseointegration of delayed implantation. This may be a promising option for clinical use. © 2015, E-Century Publishing Corporation. All rights reserved.


Wang W.-D.,The Third Peoples Hospital of Jinan | Teng J.-R.,2Clinical Laboratory | Xing L.,The Third Peoples Hospital of Jinan | Li S.,The Third Peoples Hospital of Jinan | And 2 more authors.
Journal of Shanghai Jiaotong University (Medical Science) | Year: 2014

Objective: To observe variations of functions of islet β cells during the short-term insulin pump intensive treatment for patients with type 2 diabetes mellitus. Methods: A total of 120 cases of type 2 diabetes mellitus were randomly divided into the observation group and control group with 60 cases in each group. Patients of the control group administrated oral antidiabetic drugs to control the blood glucose, while patients of the observation group were treated by the intensive insulin pump. After 4 weeks of therapy, the blood glucose, blood lipid, and relevant indicators of insulin function of two groups before and after the treatment were compared. Results: After treatment, fasting blood glucose (FPG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and insulin resistance index (HOMA-IR) of two groups were significantly lower than those before the treatment (P〈0.05), while fasting C peptide (FCP), 2 h postprandial C peptide (CP2h), high density lipoprotein cholesterol (HDL-C), and insulin secretion index (HOMA-β) were significantly higher than those before the treatment (P〈0.05). After treatment, the FPG, 2hPG, HbA1c, TC, TG, and LDL-C of the observation group were all significantly lower than those of the control group (P〈0.05), while the FCP, CP2h, and HDL-C were significantly higher than those of the control group (P〈0.05). The HOMA-IR of the observation group was significantly lower than that of the control group (P〈0.05), while the HOMA-β was significantly higher than that of the control group (P〈0.05). Conclusion: The short-term intensive insulin pump treatment can quickly stabilize the blood glucose level of patients with type 2 diabetes mellitus, contribute to recovering functions of islet β cells, and alleviate the insulin resistance and lipid metabolism disorder. ©, 2014, Editorial Department of Journal of Shanghai Second Medical University. All right reserved.

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