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Feng W.,China Medical University at Heping | Feng W.,Key Laboratory of Reproductive Health and Medical Genetics | Feng W.,Key Laboratory of Reproductive Health of Liaoning | Xin Y.,China Medical University at Heping | And 3 more authors.
Digestive Diseases and Sciences | Year: 2015

Background: Recently Cyclophilin A (CypA) was identified as a candidate target protein in gastric carcinoma. However, the role of CypA in gastric cancer (GC) has not been investigated extensively so far. Aim: The purpose of this study was to determine the expression pattern of CypA in human GC, and to explore the effects of suppressed CypA expression on cell proliferation and xenografted tumor growth of gastric cancer. Methods: In the present study, we detected the expression pattern of CypA in human GC by immunohistochemistry analysis. Further, the RNAi method was used to silence CypA, and colony formation assay, growth curves, cell cycle and mouse xenograft were analysed. Results: An elevated expression of CypA in GC tissues compared with normal gastric mucosa was observed, especially in TNM stage-I and intestinal type of tumor. CypA was overexpressed in most GC cell lines and endogenous expression of CypA correlated with cell growth phenotypes. Transient suppression of CypA reduced the proliferation of BGC-823 and SGC-7901 GC cell lines. Exogenous CypA promoted the proliferation of NCI-N87 GC cells in a concentration dependent manner. Further study revealed that stable CypA silencing inhibited the proliferation, prevented cell cycle and reduced autophagy of BGC-823 GC cells in vitro through suppressing the ERK1/2 signal pathway. Stable CypA silencing also inhibited the growth of xenografted tumor of BGC-823 GC cell in nude mice. Conclusions: These results indicate a special function mode for CypA of playing more important roles in the early stage of gastric tumorigenesis and suggest CypA as a new molecular target of diagnosis and treatment for GC patients. © 2015, Springer Science+Business Media New York. Source


Yang L.,Key Laboratory of Reproductive Health and Medical Genetics | Yang L.,Liaoning Research Institute of Family Planning | Yang L.,University of Sichuan | Li J.,Key Laboratory of Reproductive Health and Medical Genetics | And 4 more authors.
Polymers | Year: 2016

The degradation of the poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-co-CL)) networks cross-linked by 0.01 and 0.02 mol % 2,2'-bis(trimethylene carbonate-5-yl)-butylether (BTB) was carried out in the conditions of hydrolysis and enzymes in vitro and subcutaneous implantation in vivo. The results showed that the cross-linked PTMC networks exhibited much faster degradation in enzymatic conditions in vitro and in vivo versus in a hydrolysis case due to the catalyst effect of enzymes; the weight loss and physical properties of the degraded networks were dependent on the BTB amount. The morphology observation in lipase and in vivo illustrated that enzymes played an important role in the surface erosion of cross-linked PTMC. The hydrolytic degradation rate of the cross-linked P(TMC-co-CL) networks increased with increasing ε-caprolactone (CL) content in composition due to the preferential cleavage of ester bonds. Cross-linking is an effective strategy to lower the degradation rate and enhance the form-stability of PTMC-based materials. © 2016 by the authors. Source


Yang L.,University of Sichuan | Yang L.,Key Laboratory of Reproductive Health and Medical Genetics | Yang L.,Liaoning Research Institute of Family Planning | Li J.,Key Laboratory of Reproductive Health and Medical Genetics | And 6 more authors.
Polymer Degradation and Stability | Year: 2014

The cross-linked poly(ε-caprolactone) (PCL) implants were directly prepared via the ring-opening polymerization of CL with cross-linker (BTB). The in vitro enzymatic degradation of the resulting implants was performed with Thermomyces lanuginosus lipase. We saw that the cross-linked PCL implants degraded in lipase via the surface erosion mechanism. The higher the molar ratio of monomers to catalyst or the higher the cross-linker amount in feeding dose, the slower the degradation rate of the cross-linked PCL implants. Moreover, the degradation rate of the cross-linked PCL implants was lower than that of the uncross-linked ones, which could markedly reduce the acidic degradation products. The macroscopic observation results indicated that the cross-linked PCL implants had good form-stability. The changes in thermal properties showed that the degradation occurred in both amorphous and crystalline regions. The results implied that the highly cross-linked PCL implants had great potential as controlled drug release agents. © 2014 Elsevier Ltd. All rights reserved. Source


Yang L.,University of Sichuan | Yang L.,Key Laboratory of Reproductive Health and Medical Genetics | Yang L.,Liaoning Research Institute of Family Planning | Li J.,Key Laboratory of Reproductive Health and Medical Genetics | And 8 more authors.
Polymer (United Kingdom) | Year: 2014

To improve the form-stability and lower the degradation rate of poly(trimethylene carbonate) (PTMC) in biomedical fields, the cross-linked PTMC networks (PTMC-Ns) with controllable properties were prepared via chemical cross-linking. We report higher gel percentage and lower swelling degree as well as enhanced thermal and mechanical properties of the PTMC-Ns by increasing the initial molecular weight and by increasing the cross-linker amount. The PTMC-Ns cross-linked by bis(trimethylene carbonate) (BTB) had similar properties to that of counterparts cross-linked by 2, 2-bis(ε-CL-4-yl)-propane (BCP), indicating that BTB can be used interchangeably with BCP. Through in vitro enzymatic degradation, the 0.05 mol% BTB cross-linked PTMC with an initial molecular weight of 256 kDa displayed a mass loss of 34% and an erosion rate of 6.94 μm/d after 12 weeks - this was markedly slower than that of the uncross-linked samples. The PTMC-Ns have potential as biomedical implants because of their better form-stability and lower erosion rate than that of PTMC. © 2014 Elsevier Ltd. Source


Yang L.,University of Sichuan | Yang L.,Key Laboratory of Reproductive Health and Medical Genetics | Yang L.,Liaoning Research Institute of Family Planning | Li J.,Key Laboratory of Reproductive Health and Medical Genetics | And 12 more authors.
Polymer (United Kingdom) | Year: 2014

The degradation behavior of P(TMC-co-CL) in different compositions was investigated via subcutaneous implantation in vivo. To clarify the role of enzymes in the degradation behavior of the copolymers, hydrolytic and enzymatic degradation were also performed. The mass loss, changes in molecular weight and polydispersity, as well as the variation in composition were monitored with degradation. The changes in thermal and mechanical properties of the specimens were also studied. The results showed that the preferred cleavage of ester bonds resulted in faster degradation in both the hydrolytic and enzymatic cases. Furthermore, the P(TMC-co-CL) had a higher degradation rate in the presence of lipase because it cleaves ester bonds as well as the role of surfactants in the diffusion of the degradation products into water. In vivo, the degradation behavior of the P(TMC-co-CL) depended on their composition - copolymers with a higher TMC content degraded primarily via surface erosion. Bulk degradation was observed for those with a higher CL content. After degradation the mechanical properties and thermal stabilities of the copolymers deteriorated, but the Tm and crystallinity increased via preferred degradation of the amorphous regions. The P(TMC-co-CL) had a tunable degradation rate and remains a promising candidate for clinical subcutaneous implants especially through form-stabilization work. © 2014 Elsevier Ltd. All rights reserved. Source

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