Nie W.,The 425th Hospital of PLA |
Meng L.,Shanghai JiaoTong University |
Wang X.,Shanghai University |
Xiu Q.,Shanghai University
Journal of Investigational Allergology and Clinical Immunology | Year: 2014
Background: Results regarding the association between the interferon-γ (IFN-γ) +874A/T polymorphism and asthma risk are controversial and ambiguous. The aim of this study was to determine with greater precision the relationship between the IFN-γ +874A/T polymorphism and asthma using a meta-analysis.Methods: Published literature was retrieved from 5 databases (PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure [CNKI] and Weipu). ORs with 95% CIs were used to assess the strength of association.Results: Ten case-control studies involving 697 cases and 1049 controls were identified. In the overall analysis, a significant association between the +874A/T polymorphism and asthma susceptibility was found for AA vs AT + TT (OR, 1.89; 95% CI, 1.37-2.62; P=.0001). In the subgroup analysis by ethnicity, significant associations were found among whites (OR, 1.42; 95% CI, 1.04-1.93; P=.03) and Asians (OR, 2.52; 95% CI, 1.49-4.25; P=.0006). The sensitivity analysis and cumulative meta-analysis further strengthened the validity of this association. No publication bias was observed in this study.Conclusion: The results of this meta-analysis suggest that the IFN-γ +874A/T polymorphism is a risk factor for asthma. © 2014 Esmon Publicidad.
Fan W.,Shanghai University |
Fan W.,The 425th Hospital of PLA |
Wu X.,Shanghai University |
Ding B.,Jiaxing University |
And 9 more authors.
International Journal of Nanomedicine | Year: 2012
Background: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake. Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether- Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers. Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophiliclipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus. Conclusion: This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future. © 2012 Fan et al, publisher and licensee Dove Medical Press Ltd.
PubMed | The 425th Hospital of PLA, Nankai Hospital and Shanghai University
Type: Journal Article | Journal: Drug delivery | Year: 2016
Bone is the primary site of skeletal metastasis in prostate cancer (PCa). Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence endogenous genes involved in PCa metastatic tumor cell growth. However, we hope that the delivery system can target PCa cells to reduce damage to the bone tissue and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a ligand to target PCa cells that express prostate-specific membrane antigen (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE-based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To observe the targeted delivery and transfection efficiency of ATE-APT in PSMA-overexpressing cells, luciferase activity and biodistribution of nanoparticles in Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was investigated using the survival times of human PCa bone metastasis mice model. Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells showed that the transfection efficiency of the synthesized DNA/ATE-APT complex was higher than that of the DNA/ATE complex. The anticancer efficacy of miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of PCa cells in bone metastatic foci.
PubMed | Fudan University, The 425th Hospital of PLA and Shanghai University
Type: Journal Article | Journal: Laboratory investigation; a journal of technical methods and pathology | Year: 2014
Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P<0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P<0.001), large tumor size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.
Wu X.,Second Military Medical University |
Wu X.,Shanghai JiaoTong University |
Tai Z.,Second Military Medical University |
Zhu Q.,Shanghai University of Traditional Chinese Medicine |
And 13 more authors.
International Journal of Nanomedicine | Year: 2014
Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa. © 2014 Wu et al.
Wu Z.,Jiaxing University |
Zhan S.,Jiaxing University |
Fan W.,The 425th Hospital of PLA |
Ding X.,Shanghai JiaoTong University |
And 10 more authors.
Nanoscale Research Letters | Year: 2016
Polyethylenimine (PEI) is considered to be a promising non-viral gene delivery vector. To solve the toxicity versus efficacy and tumor-targeting challenges of PEI used as gene delivery vector, we constructed a novel non-viral vector DR5-TAT-modified Pluronic-PEI (Pluronic-PEI-DR5-TAT), which was based on the attachment of low-molecular-weight polyethylenimine (LMW-PEI) to the amphiphilic polymer Pluronic to prepare Pluronic-modified LMW-PEI (Pluronic-PEI). This was then conjugated to a multifunctional peptide containing a cell-penetrating peptide (TAT) and a synthetic peptide that would bind to DR5—a receptor that is overexpressed in cancer cells. The vector showed controlled degradation, favorable DNA condensation and protection performance. The Pluronic-PEI-DR5-TAT/DNA complexes at an N/P ratio of 15:1 were spherical nanoparticles of 122 ± 11.6 nm and a zeta potential of about 22 ± 2.8 mV. In vitro biological characterization results indicated that Pluronic-PEI-DR5-TAT/DNA complexes had a higher specificity for the DR5 receptor and were taken up more efficiently by tumor cells than normal cells, compared to complexes formed with PEI 25 kDa or Pluronic-PEI. Thus, the novel complexes showed much lower cytotoxicity to normal cells and higher gene transfection efficiency in tumor cells than that exhibited by PEI 25 kDa and Pluronic-PEI. In summary, our novel, degradable non-viral tumor-targeting vector is a promising candidate for use in gene therapy. © 2016, Wu et al.
Chen D.,Central South University |
Chen D.,The Central Hospital of Zhuzhou City |
Gao M.,Central South University |
Fu Y.,Central South University |
And 2 more authors.
Electrochimica Acta | Year: 2015
In this paper, a facile approach to manipulating osteogenic activity of orthopedic implants by in situ electrically controlled wettability was developed. Glycosaminoglycans (GAGs), the major organic extracellular matrix (ECM) components, were electrochemically doped in nanostructured poly(3,4-ethylenedioxythiophene) (NPEDOT) on Ti-6Al-4 V orthopedic implants. The controlled wettability of NPEDOT/GAGs was achieved by in situ applying electrical stimulus. Moreover, the in situ electrically controlled wettability could be utilized to implement the manipulation of osteogenic activity of orthopedic implants. This facile strategy may open up a new avenue to electrically responsive biomedical applications. © 2015 Elsevier Ltd. All rights reserved.
Zeng G.Q.,The 425th Hospital of PLA |
Chen A.B.,The 425th Hospital of PLA |
Li W.,The 425th Hospital of PLA |
Song J.H.,The 425th Hospital of PLA |
Gao C.Y.,The 425th Hospital of PLA
Genetics and Molecular Research | Year: 2015
Our study examined the relationship between the expression of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-9 proteins and the pathogenesis of osteoarthritis (OA). We employed rigorous inclusion and exclusion criteria in computer-based bibliographic databases to extract published studies relevant to this investigation. The STATA 12.0 software was used for the statistical analyses. A total of 1408 studies were initially searched, and 10 studies with 458 OA patients and 295 healthy controls were included in this meta-analysis. The meta-analysis results suggested that the protein levels of MMP-1, MMP-2, and MMP-9 were higher in patients with OA than those in the control group. A subgroup analysis according to ethnicity showed that the protein levels of MMP-1 and MMP-2 were higher in Asian patients with OA than in controls. Caucasians showed no statistically significant differences in protein expression of MMP-1 and MMP-2 between the OA patient group and the control group. Interestingly, the protein levels of MMP-9 in patients with OA were higher than those in the control group in both Asians and Caucasians. A sample-source analysis suggested that the serum levels of MMP-2 and MMP-9 proteins were higher in patients with OA than in controls, while MMP-1 and MMP-9 protein expressions were higher in th synovial joint fluid of patients with OA than in controls. In conclusion, our meta-analysis results suggested that the increased expression of MMP-1, MMP-2, and MMP-9 proteins might be associated with the pathogenesis of OA. © FUNPEC-RP.
Wu X.,The 425th Hospital of PLA |
Liu H.,The 425th Hospital of PLA
International Journal of Clinical and Experimental Medicine | Year: 2015
Associations between Obstructive sleep apnea/hypopnea syndrome (OSAHS) and risk of glaucoma remained controversial. Therefore, we performed this meta-analysis to investigate this association. We searched Pubmed, EMBASE, and Wangfang databases for studies before Oct. 10 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. A total of 12 studies with 36909 subjects on the association between OSAHS and glaucoma risk were included for this meta-analysis. OSAHS was associated with a significantly increased risk of glaucoma (OR = 1.65; 95% CI, 1.44-1.88; I2 = 43%). In the race subgroup analysis, both Asians (OR = 1.78; 95% CI, 1.49-2.12; I2 = 0%) and Caucasians (OR = 2.03; 95% CI, 1.12-3.69; I2 = 57%) with OSAHS had increased glaucoma risk. In the subgroup analysis according to gender, both women and men were significantly associated with risk of glaucoma (OR = 1.81; 95% CI, 1.27-2.57; I2 = 22% and OR = 1.62; 95% CI, 1.29-2.03; I2 = 0%, respectively). In the subgroup analysis by glaucoma type, OSAHS patients showed increased primary open-angle glaucoma (POAG) risk (OR = 1.87; 95% CI, 1.54-2.33; I2 = 0%) but not normal tension glaucoma (NTG) risk (OR = 3.57; 95% CI, 0.89-14.43; I2 = 0%). In addition, severe OSAHS patients had an increased glaucoma risk (OR = 5.49; 95% CI, 1.04-33.83; I2 = 0%), while mild and moderate OSAHS patients did not show significantly increased glaucoma risk. This meta-analysis suggested that the OSAHS may be a risk factor for glaucoma. © 2014, E-Century Publishing Corporation. All rights reserved.
PubMed | The 425th Hospital of PLA
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2015
Our study examined the relationship between the expression of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-9 proteins and the pathogenesis of osteoarthritis (OA). We employed rigorous inclusion and exclusion criteria in computer-based bibliographic databases to extract published studies relevant to this investigation. The STATA 12.0 software was used for the statistical analyses. A total of 1408 studies were initially searched, and 10 studies with 458 OA patients and 295 healthy controls were included in this meta-analysis. The meta-analysis results suggested that the protein levels of MMP-1, MMP-2, and MMP-9 were higher in patients with OA than those in the control group. A subgroup analysis according to ethnicity showed that the protein levels of MMP-1 and MMP-2 were higher in Asian patients with OA than in controls. Caucasians showed no statistically significant differences in protein expression of MMP-1 and MMP-2 between the OA patient group and the control group. Interestingly, the protein levels of MMP-9 in patients with OA were higher than those in the control group in both Asians and Caucasians. A sample-source analysis suggested that the serum levels of MMP-2 and MMP-9 proteins were higher in patients with OA than in controls, while MMP-1 and MMP-9 protein expressions were higher in the synovial joint fluid of patients with OA than in controls. In conclusion, our meta-analysis results suggested that the increased expression of MMP-1, MMP-2, and MMP-9 proteins might be associated with the pathogenesis of OA.