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Yu F.,No. 98 Hospital of PLA | Huang X.,Shanghai Institute of Phamaceutical Industy | Miao J.,Shuguang Hospital | Guo L.,No. 98 Hospital of PLA | Tao D.,No. 98 Hospital of PLA
Endocrine Journal | Year: 2013

The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of osteoprotegerin gene (OPG) with bone mineral density (BMD) and osteoporosis. A total of 338 Chinese postmenopausal women with primary osteoporosis and 367 healthy controls were enrolled. The lumbar spine (L2-4), total hip and femoral neck hip of BMD were assessed by dual-energy X-ray absorptiometry (DEXA). OPG genetic variants were genotyped through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods. In this study, the g.18861A>G and g.25548C>T SNPs were detected and our data suggested that the significant differences of spine BMD, femoral neck hip BMD and total hip BMD were found among different g.18861A>G genotype, subjects with the AA genotype were significantly higher than those of AG and GG genotypes (p < 0.05). The g.25548C>T variant was not significantly associated with spine BMD, femoral neck hip BMD and total hip BMD (p > 0.05), while almost reached at the significant level in total hip BMD (p = 0.061). These findings suggeste that OPG gene variants are related to BMD and osteoporosis in Chinese postmenopausal women. ©The Japan Endocrine Society.


Sun G.,Shanghai University of Traditional Chinese Medicine | Sun G.,China University of Technology | Lin X.,Shanghai University of Traditional Chinese Medicine | Wang Z.,Shanghai University of Traditional Chinese Medicine | And 3 more authors.
Journal of Biomaterials Science, Polymer Edition | Year: 2011

Although poly(ethylene glycol) and polysaccharide have been widely used as pharmaceutical carriers for decades, they both have some disadvantages. In order to overcome these shortcomings, this study was conducted to prepare and assess a novel polymeric carrier, PEGylated inulin. Three conjugates, with an average of 1.4 PEG (20 kDa), 3.1 PEG (20 kDa) and 5.5 PEG (5 kDa) residues per single inulin (5 kDa) molecule, respectively, were prepared through the reaction of hydroxyl-activated inulin with amino-terminated methoxy-PEGs. Their pharmacokinetic properties were evaluated in rats following i.v. and s.c. administration. These conjugates, following i.v. administration, displayed multi-compartmental pharmacokinetics with the mean retention times being 9.8, 80 and 90 h, respectively. When given subcutaneously, they were well absorbed with the absolute bioavailability ranging from 66% to 79% and the mean retention times being 35, 155 and 179 h, respectively. Both the small size and the long circulation lifetime suggest their potential application as a pharmaceutical carrier to enhance the delivery of various agents to their targets by the enhanced permeability and retention (EPR) effect. © Koninklijke Brill NV, Leiden, 2011.


Yu F.,Changzheng Hospital | Miao J.,Shuguang Hospital | Liao X.,Changzheng Hospital | Wang X.,Changzheng Hospital | And 2 more authors.
European Spine Journal | Year: 2013

Study design: A retrospective review of prospectively collected data in an academic institution. Objective: To evaluate the safety and efficacy of a new type of titanium mesh cage (TMC) in single-level, anterior cervical corpectomy and fusion (ACCF). Methods: Fifty-eight patients consecutive with cervical spondylotic myelopathy (CSM) from cervical degenerative spondylosis and isolated ossification of the posterior longitudinal ligament were treated with a single-level ACCF using either a new type of TMC (28 patients, group A) or the traditional TMC (30 patients, group B). We evaluated the patients for TMC subsidence, cervical lordosis (C2-C7 Cobb and Cobb of fused segments) and fusion status for a minimum of 30 months postoperatively based on spine radiographs. In addition, neurologic outcomes were evaluated using the Japanese Orthopedic Association (JOA) scores. Neck pain was evaluated using a 10-point visual analog scale (VAS). Results: The loss of height of the fused segments was less for group A than for group B (0.8 ± 0.3 vs. 2.8 ± 0.4 mm) (p < 0.01); also, there was a lower rate of severe subsidence (≥3 mm) in group A (4 %, 1/28) than in group B (17 %, 5/30) (p < 0.01). There were no differences in the C2-C7 Cobb and Cobb of fused segments between the groups preoperatively or at final follow-up (p > 0.05), but the Cobb of fused segments immediately postoperative were significantly less for group B than for group A (p < 0.01). All patients, however, had successful fusion (100 %, each). Both groups had marked improvement in the JOA score after operation (p < 0.01), with no significant differences in the JOA recovery ratio (p > 0.05). The postoperative VAS neck pain scores for group A were significantly less than that for group B (p < 0.05); severe subsidence was correlated with neck pain. Conclusions: The new type of TMC provides comparable clinical results and fusion rates with the traditional TMC for patients undergoing single-level corpectomy. The new design TMC decreases postoperative subsidence (compared to the traditional TMC); the unique design of the new type of TMC matches the vertebral endplate morphology which appears to decrease the severity of subsidence-related neck pain in follow-up. © 2013 Springer-Verlag Berlin Heidelberg.


Huang Y.,Shanghai University | Feng H.,Hebei Medical University | Kan T.,Shanghai University | Huang B.,Shanghai University | And 7 more authors.
PLoS ONE | Year: 2013

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy. © 2013 Huang et al.


Yang J.,Baylor College of Medicine | Lin S.-C.,Baylor College of Medicine | Chen G.,Baylor College of Medicine | Chen G.,Huazhong University of Science and Technology | And 6 more authors.
Journal of the American Society of Nephrology | Year: 2013

Bone marrow-derived fibroblasts may contribute substantially to the pathogenesis of renal fibrosis through the excessive production and deposition of extracellular matrix. However, the mechanisms underlying the accumulation and activation of these fibroblasts are not understood. Here, we used a mouse model of tubulointerstitial fibrosis to determine whether adiponectin, which is elevated in CKD and is associated with disease progression, regulates monocyte-to-fibroblast transition and fibroblast activation in injured kidneys. In wild-type mice, the expression of adiponectin and the number of bone marrow-derived fibroblasts in the kidney increased after renal obstruction. In contrast, the obstructed kidneys of adiponectin-knockout mice had fewer bone marrow-derived fibroblasts. Adiponectin deficiency also led to a reduction in the number ofmyofibroblasts, the expression of profibrotic chemokines and cytokines, and the number of procollagen-expressing M2 macrophages in injured kidneys. Consistent with these findings, adiponectin-deficiency reduced the expression of collagen I and fibronectin. Similar results were observed in wild-type and adiponectin-knockout mice after ischemia-reperfusion injury. In cultured bone marrow-derived monocytes, adiponectin stimulated the expression of a-smooth muscle actin (SMA) and extracellular matrix proteins and activated AMP-activated protein kinase (AMPK) in a time- and dose-dependent manner. Furthermore, specific activation of AMPK increased the expression of α-SMA and extracellular matrix proteins, while inhibition of AMPK attenuated these responses. Taken together, these findings identify adiponectin as a critical regulator of monocyte-to-fibroblast transition and renal fibrosis, suggesting that inhibition of adiponectin/AMPK signaling may represent a novel therapeutic target for fibrotic kidney disease. Copyright © 2013 by the American Society of Nephrology.

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