Gang Wang

Sichuan University, Hua-yang, Sichuan, China

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Publications (70)192.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to improve the transfection efficiency (TE) as well as biocompatibility, a series of hyperbranched cationic polymers were synthesized by ring-opening polymerization between diepoxide and several polyamines. These materials can condense plasmid DNA efficiently into nanoparticles, which have much lower cytotoxicity than those derived from bPEI. In vitro transfection experiments showed that polymers prepared form branched or cyclic polyamine (P1 and P5) exhibited several times higher TE than 25KDa bPEI. More significantly, serum seemed to have no negative effect on P1-P5 mediated transfection. On the contrary, the TE of P1 improved even the serum concentration reached 70%. Several assays demonstrated the excellent serum tolerance of such kind of polycationic vectors: Bovine serum albumin (BSA) adsorption assay revealed considerably lower protein adsorption of P1-P5 than PEI; P1 showed better DNA protection ability from degradation by DNase I than PEI; Flow cytometry results suggested that any concentration of serum may not decrease the cellular uptake of P1/DNA polyplex; Confocal laser scanning microscope also found that serum has little effect on the transfection. By using specific cellular uptake inhibitors, it was found that the polyplexes enter the cells mainly via caveolae and microtubule-mediated pathways. We believe that this ring-opening polymerization may be an effective synthetic approach toward gene delivery materials with high biological activity.
    ACS Applied Materials & Interfaces 09/2014; · 5.90 Impact Factor
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    ABSTRACT: Hydrophilic-hydrophobic-hydrophilic triblock copolymers, such as Pluronic L64, P85 and P105, have attracted more attention due to their enhancement in muscular gene delivery. In the present study, a new kind of electroneutralized triblock copolymer, LPL: dendron G2(L-lysine-Boc)-PEG2k-dendron G2(L-lysine-Boc), was designed and investigated. This hydrophobic-hydrophilic-hydrophobic copolymer is composed of a structure reverse to L64, one of the most effective materials for intramuscular gene delivery so far. Our results showed that LPL exhibited good in vivo biocompatibility after intramuscular and intravenous administration. LPL mediated higher reporter genes expression than L64 in assays of β-galactosidase (LacZ), luciferase and fluorescent protein E2-Crimson. Furthermore, LPL-mediated mouse growth hormone expression significantly accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene expression in skeletal muscle exhibits the potential of successful gene therapy. The current study also presented an innovative way to design and construct new electroneutralized triblock copolymers for safe and effective intramuscular gene delivery.
    ACS Applied Materials & Interfaces 08/2014; · 5.90 Impact Factor
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    ABSTRACT: It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma exacerbations is not systematically assessed. This study was designed to systematically explore the evidence for montelukast, as first-line or add-on therapy, in preventing and treating asthma exacerbations in adult patients with asthma. Randomized controlled trials were searched in PubMed, CENTRAL, Web of Science, Embase, and OVID up to March 2013, where montelukast prevented or treated asthma exacerbations in adults. Primary outcomes were the number of patients experiencing exacerbations in chronic asthma and hospitalizations in acute asthma. Odds ratio (OR) with 95% confidence intervals (CI), risk difference, and number needed to treat (NNT) were calculated and pooled. Adverse events were also assessed in chronic asthma. Twenty trials for chronic asthma and six for acute asthma were identified. In comparison with placebo, adults with chronic asthma receiving montelukast had significantly reduced number of exacerbations (OR = 0.60 and 95% CI, 0.49, 0.74; NNT = 17 and 95% CI, 12, 29). However, montelukast was inferior to inhaled corticosteroids (ICSs) (OR = 1.63; 95% CI, 1.29, 2.0) and ICS plus long-acting beta2-agonist (LABA; OR = 3.94; 95% CI, 1.64, 9.48) as the first-line therapies and LABA (OR = 1.22; 95% CI, 1.05, 1.42) as the add-on therapies in reducing asthma exacerbations. In acute asthma, montelukast could statistically improve peak expiratory flow percent predicted (p = 0.008) and reduce systemic corticosteroid intake (p = 0.005). Montelukast had low risk in hoarseness and insomnia. Our meta-analysis suggests that montelukast significantly reduces mild, moderate, and part of severe exacerbations in chronic mild to moderate asthma, but it has inferior efficacy to ICS or ICS plus LABA.
    Allergy and Asthma Proceedings 08/2014; 35(4). · 2.19 Impact Factor
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    ABSTRACT: A novel pH-sensitive polymeric micelle was reported. Methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer with citraconic amide as pH-sensitive bond was synthesized (mPEG-pH-PCL). The copolymers self-assembled into micelles to encapsulate anticancer drug doxorubicin (DOX). The morphology, size and size distribution, drug release profile and in vitro anticancer activity of the DOX loaded mPEG-pH-PCL micelles were studied. The results showed that the mean size of the micelles was around 120nm, the drug loading content and encapsulation efficiency of the mPEG-pH-PCL micelles were 6.8% and 54.3%, respectively. The mean diameter and size distribution of the mPEG-pH-PCL micelles increased significantly when soaking in medium with pH 5.5. The drug release of micelles in pH 5.5 was much faster than that in pH 7.4. The confocal laser microscopy and flow cytometry measurements indicated that the weak acidity of endosomes broke the citraconic amide bonds in the copolymer backbones and triggered the fast release of DOX. The in vitro IC50 of the drug loaded mPEG-pH-PCL micelles was lower than that of drug loaded polymeric micelles without pH-sensitivity to both HepG2 and 4T1 cancer cells.
    International journal of pharmaceutics. 05/2014;
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    ABSTRACT: Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic(®) L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1α(tri)/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1α(tri)), improved the expression of stable HIF-1α, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1α(tri)/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia.
    International Journal of Nanomedicine 01/2014; 9:3439-52. · 4.20 Impact Factor
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    ABSTRACT: A control-based asthma assessment is recommended by guidelines, but questions remain about how to assess the level of asthma control, and how current control status relates to future risks and biomarkers of disease pathogenesis. This review summarizes recent published data relating to asthma control and describes the challenges created by currently available instruments. The current literature continues to show the widespread use of various assessment instruments for asthma control, in particular those with composite scores. However, poor correlations exist between the different assessment tools, and these instruments lack diagnostic accuracy to differentiate uncontrolled asthma. Whereas the concept of asthma control has been extended to add an assessment of future risks to the clinical control, clinical asthma control as measured by current available assessment tools does not necessary relate to the intrinsic disease activity which is typically characterized by inflammation in asthma. The application of asthma control assessment represents an improvement in asthma management. The measurement of underlying disease activity potentially by biomarkers to assess disease control will lead to an improved assessment of the overall control of asthma, and further studies addressing this are needed.
    Current opinion in pulmonary medicine 01/2014; 20(1):1-7. · 3.12 Impact Factor
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    ABSTRACT: The purpose of asthma management is to achieve a total asthma control that involves current control and future risk. It has proven efficacy in reducing asthma exacerbations, but the effect size of zafirlukast for asthma exacerbations of various severity is not systematically explored.
    Multidisciplinary respiratory medicine 01/2014; 9(1):30. · 0.05 Impact Factor
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    ABSTRACT: The aim of this study was to develop a new polymeric micelle delivery system for antitumor drugs. An amphiphile of methoxypoly(ethylene glycol)-histidine-di(cinnamic acid) (PEGHC) with a small lipophilic moiety instead of a hydrophobic biodegradable polymer chain was synthesized and characterized. The PEGHC self-assembled into micelles. The critical micelle concentration (CMC) was tested. 9-Nitro-20(s)-camptothecin (9-NC) was used as a model drug for encapsulation. The size and morphology of both blank and 9-NC loaded micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release profile of 9-NC loaded micelles was studied. HepG2 liver cancer cells were incubated with the drug-loaded micelles to investigate the in vitro anticancer efficiency. The results showed that the 9-NC loaded micelles exhibited high accumulated release rate (>85%) and efficient in vitro anticancer activity.
    Colloids and surfaces B: Biointerfaces 10/2013; · 4.28 Impact Factor
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    ABSTRACT: Abstract Objective. To investigate if maternal asthma is associated with an increased risk of maternal and placental complications in pregnancy. Methods. Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between 1975 and March 2012 were considered for inclusion. 40 publications met the inclusion criteria, reporting at least one maternal or placental complication in pregnant women with and without asthma. Relative risk (RR) with 95% confidence intervals (CI) was calculated. Results. Maternal asthma was associated with a significantly increased risk of cesarean section (RR=1.31, 95%CI=[1.22, 1.39]), gestational diabetes (RR=1.39, 95%CI=[1.17, 1.66]), hemorrhage (antepartum: RR=1.25, 95%CI=[1.10, 1.42]; postpartum: RR=1.29, 95%CI=[1.18, 1.41]), placenta previa (RR=1.23, 95%CI=[1.07, 1.40]), placental abruption (RR=1.29, 95%CI=[1.14, 1.47]), and premature rupture of membranes (RR=1.21, 95%CI=1.07, 1.37). Moderate to severe asthma significantly increased the risk of cesarean section (RR=1.19, 95%CI=[1.09, 1.31]) and gestational diabetes (RR=1.19, 95%CI=[1.06, 1.33]) compared to mild asthma. Bronchodilator use was associated with a significantly lowered risk of gestational diabetes (RR=0.64, 95%CI=[0.57, 0.72]). Conclusions. Pregnant women with asthma are at increased risk of maternal and placental complications, and women with moderate/severe asthma may be at particular risk. Further studies are required to elucidate whether adequate control of asthma during pregnancy reduces these risks.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2013; · 1.36 Impact Factor
  • Rui Liang, Lei Wang, Gang Wang
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    ABSTRACT: Asthma is a heterogeneous disease for which a strong genetic basis has been firmly established. Until now no studies have been undertaken to systemically explore the network of asthma-related genes using an internally developed literature-based discovery approach. This study was to explore asthma-related genes by using literature-based mining and network centrality analysis. Literature involving asthma-related genes were searched in PubMed from 2001 to 2011. Integration of natural language processing with network centrality analysis was used to identify asthma susceptibility genes and their interaction network. Asthma susceptibility genes were classified into three functional groups by gene ontology (GO) analysis and the key genes were confirmed by establishing asthma-related networks and pathways. Three hundred and twenty-six genes related with asthma such as IGHE (IgE), interleukin (IL)-4, 5, 6, 10, 13, 17A, and tumor necrosis factor (TNF)-alpha were identified. GO analysis indicated some biological processes (developmental processes, signal transduction, death, etc.), cellular components (non-structural extracellular, plasma membrane and extracellular matrix), and molecular functions (signal transduction activity) that were involved in asthma. Furthermore, 22 asthma-related pathways such as the Toll-like receptor signaling pathway, hematopoietic cell lineage, JAK-STAT signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interaction, and 17 hub genes, such as JAK3, CCR1-3, CCR5-7, CCR8, were found. Our study provides a remarkably detailed and comprehensive picture of asthma susceptibility genes and their interacting network. Further identification of these genes and molecular pathways may play a prominent role in establishing rational therapeutic approaches for asthma.
    Chinese medical journal 07/2013; 126(13):2472-9. · 0.90 Impact Factor
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    ABSTRACT: Novel nonviral gene vectors of alkaline amino acids such as arginine- (Arg), histidine- (His), and lysine- (Lys) modified chitosans (AAA-CSs) are developed to simulate the components of viral envelopes to enhance transfection efficiency. The structures of the modified chitosans are characterized using 1H NMR spectroscopy. Acid-base titration results indicate that the modified chitosans exhibit strong buffering capacity. The morphology of the AAA-CSs/pDNA complexes is observed by use of transmission electron microscopy and atomic force microscopy. The complexes are spherical nanoparticles with a mean size around 100 nm. Zeta potential tests reveal that the complexes are positively charged and their zeta potentials vary from +0.1 to +19.5 mV. The MTT assay and agarose gel electrophoresis demonstrate that the AAA-CSs are non-cytotoxic and have excellent DNA condensation and protection abilities. Cellular uptake investigation of the AAA-CSs/pDNA complexes demonstrates that Arg-CS and His-CS have better cellular internalization property than the unmodified chitosan. The in vitro gene transfection is evaluated in HEK293 and NIH3T3 cell lines and in vivo transfection is carried out in tibialis anterior muscles. The results reveal that the arginine-modified chitosan could significantly enhance gene-transfection efficiency both in vitro and in vivo.
    Advanced Functional Materials 06/2013; 23(21). · 10.44 Impact Factor
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    ABSTRACT: Peptide dendrimers represent superior drug carriers for their unique nanoarchitectures, excellent degradability and biocompatibility. In this research, poly(L-glutamic acid) dendrimers with polyhedral oligomeric silsesquioxane (POSS) as cores were synthesized. Tumor targeting moiety (biotin) and therapeutic drug doxorubicin (DOX) were immobilized on the dendrimers via pH-sensitive hydrazone bonds. The size distribution and morphology of the drug-dendrimer conjugates were characterized by DLS, AFM, and TEM. The drug release profiles, cellular uptake, in vitro and in vivo anti-tumor activities of the conjugates were investigated. The results revealed that the conjugates aggregated nanoparticles with the size around 100 nm. The drug-dendrimer conjugates could be internalized in mice breast cancer 4T1 cells efficiently. The IC of the conjugates was comparable to that of DOX·HCl. The in vivo experiments were carried out in mice xerograft breast cancer models, the results indicated that the inhibition efficiency of the DOX-dendrimer conjugates was much better than that of free DOX·HCl.
    Biomaterials 05/2013; 34(14):3658-66. · 8.31 Impact Factor
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    ABSTRACT: Heparin drug conjugates are currently investigated as excellent candidates for drug delivery vehicles. In this study, we report the preparation and characterization of dendronized heparin-doxorubicin (heparin-DOX) conjugate as pH-sensitive drug delivery vehicle by combination of the features of dendrimer and heparin. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the dendronized heparin-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.0 wt% (weight percent) of doxorubicin (DOX) showed pH-sensitive property due to the faster drug release rate at pH 5.0 and slow release rate at pH 7.4 aqueous. The nanoparticles were shown to effectively kill cancer cells in vitro. Notablely, the nanoparticles resulted in strong antitumor activity, high antiangiogenesis effects and induced apoptosis on the 4T1 breast tumor model due to the evidences from mice weight shifts, tumor weights, tumor growth curves, immunohistochemical assessment and histological analysis. It's also noteworthy that dendronized heparin and its nanoparticle with drug demonstrated no significant toxicity to healthy organs of both tumor-bearing and healthy mice, which was confirmed by histological analysis compared with free drug DOX. The dendronized heparin-DOX conjugate based nanopatilce with high antitumor activity and low side effects may be therefore a potential nanoscale drug delivery vehicle for breast cancer therapy.
    Biomaterials 01/2013; · 8.31 Impact Factor
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    ABSTRACT: The fabrication and drug delivery of novel polypseudorotaxane micelles with small molecule coumarin derivative as hydrophobic segment were reported. 7-Carboxymethoxy coumarin was immobilized on the terminal hydroxyl groups of poly(ethylene glycol) (PEG). The modified PEG chains were threaded in α-cyclodextrins (α-CDs) to form polypseudorotaxanes. The polypseudorotaxanes self-assembled into supramolecular micelles driven by hydrophobic interaction and polypseudorotaxane crystallization. Anti-tumor drug doxorubicin (DOX) was trapped in the micelles. The structure, morphology, drug release profile and cytotoxicity of the micelles were investigated. The in vitro anti-tumor studies including cellular uptake and inhibition efficiency were performed on mice cancer cell lines of TC1 lung cancer cells and B16 melanoma cells. The results revealed that the 7-carboxymethoxy coumarin modified PEG could thread into the cavity of α-CDs to form necklace-like polypseudorotaxanes. The polypseudorotaxanes self-assembled into spherical micelles with the mean size of 30 nanometers, and the size was increased to about 80 nanometers after the drug was loaded. The drug loading content of the micelles was decreased with increasing the chain length of PEG. The sustaining release of DOX could last for 32 hours. The polypseudorotaxane micelles were non-toxic to both TC1 and B16 cells. The IC50 of the DOX loaded polypseudorotaxane micelles with PEG2k was lower than that of micelles with PEG4k or PEG6k both in TC1 and B16 cells.
    Nanoscale 12/2012; · 6.73 Impact Factor
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    ABSTRACT: Nanoparticles, such as dendritic polymers, are currently investigated as excellent candidates for drug delivery vehicles. In this study, we report the preparation and characterization of mPEGylated peptide dendron-doxorubicin (dendron-DOX) conjugate based vehicle carrying 14.0 wt% (weight percent) of doxorubicin (DOX). Dynamic light scattering (DLS), scanning electron microscope (SEM) and transmission electron microscope (TEM) studies demonstrated the dendron-DOX conjugate self-assembled into nanoscale particles with neutral charged surface. The globular morphology and compact nanoparticle with diameter around 80 nm were observed by SEM and TEM. The release rates of DOX from the nanoparticle at pH 5.0 were much faster than those at pH 7.4 due to the pH-sensitive cleavage of the hydrazone bonds. The nanoparticle was shown to effectively kill cancer cells in vitro. Importantly, the nanoparticle resulted in strong antitumor activity and induced apoptosis on the 4T1 breast tumor model. In vivo toxicity evaluation demonstrated that drug-free dendron and drug-loading nanoparticle provided good biosafety in healthy or tumor-bearing mice, because no significant systematic toxicity was revealed via histological analysis. The functionalized peptide dendron-DOX conjugate based nanoparticle may be therefore a potential candidate for drug delivery vehicle for cancer therapy.
    Biomaterials 11/2012; · 8.31 Impact Factor
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    ABSTRACT: Apart from chemical molecules, physical regulations also greatly determine the efficiency of healing in regenerating functional tissues. In this study, we fabricated superparamagnetic nano-composite scaffolds for tissue engineering and investigated their effects on different bone cells without an external magnetic field. Poly(lactic-co-glycolic acid) (PLGA) and hydrophobic superparamagnetic magnetite nanoparticles (MNPs) were combined together with different mass ratios in order to construct composite scaffolds using an electrospinning method for the first time. The diameters of the fibers were 400–600 nm with the MNPs uniformly dispersed in them, as shown by transmission (TEM) and scanning (SEM) electron microscopy observations. All composite scaffolds retained superparamagnetism at room temperature, but the saturation magnetization did not increase linearly as the magnetite content increased. The composite scaffolds with different MNP content showed excellent biocompatibility and significantly promoted cell proliferation compared with PLGA nanofibrous scaffold without an external magnetic field. Cell cycle analysis proved that the composite scaffolds decreased cell numbers in G0/G1 phase while increasing those in S phase, which resulted in positive effects on cell proliferation. However, the composite scaffolds had no effect on the differentiation of MC3T3-E1 cells because of the different impact mechanism between proliferation and differentiation. Therefore, the composite scaffolds composed of superparamagnetic MNPs could be considered as an ideal substrate for accelerating osteoblast cell proliferation and tissue repair.
    RSC Advances 11/2012; 2(33):13007-13017. · 3.71 Impact Factor
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    ABSTRACT: BACKGROUND: Currently, the cornerstone of asthma management is the achievement and maintenance of optimal asthma control, but the diagnostic performances of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) have not been evaluated systematically. OBJECTIVE: We explored the diagnostic performances of and statistically compared the ACT and ACQ. METHODS: Studies that examined the accuracy of the ACT, ACQ, or both in the assessment of asthma control were found by searching PubMed, CENTRAL, Web of Science, Ovid, and Embase. Summary estimates of sensitivity, specificity, and diagnostic odds ratios for the different levels of asthma control were determined by using bivariate random-effects models and hierarchical summary receiver operating characteristic models. RESULTS: Twenty-one studies with 11,141 subjects assessed with the ACT and 12,483 assessed with the ACQ were identified. The ACT had good diagnostic accuracy for assessment of controlled and not well-controlled asthma, and the ACQ (ACQ-7 and ACQ-6) had good diagnostic accuracy for assessment of not well-controlled asthma at prespecified cutoff points. The ACT and ACQ had significant differences in the assessment of controlled and not well-controlled asthma after adjusting for potential factors (P = .001 and P = .015). For assessment of uncontrolled asthma, the ACT had poor accuracy, with a hierarchical summary receiver operating characteristic area under the curve of 0.69, and the cutoff point for the ACQ has not been established. CONCLUSION: The ACT is preferable to the ACQ in clinical practice, and the ACQ requires further cross-validation. Moreover, neither the ACT nor the ACQ is useful for the assessment of uncontrolled asthma.
    The Journal of allergy and clinical immunology 10/2012; · 12.05 Impact Factor
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    ABSTRACT: The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up. This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n = 290). The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations. The subjects were divided into three groups, which were uncontrolled (U, n = 128), partly-controlled (PC, n = 111), and well controlled (C, n = 51) asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75, respectively), unplanned visits (OR 8.03 and OR 8.21, respectively) and emergency visits (OR 20.00 and OR 22.60, respectively) over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P < 0.05). The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%. Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.
    Chinese medical journal 09/2012; 125(17):2986-93. · 0.90 Impact Factor
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    ABSTRACT: The quest for highly efficient and safe gene delivery systems has become the key factor for successful application of gene therapy. Peptide dendrimers are currently investigated as excellent candidates for non-viral gene delivery vectors. In this study, we report the synthesis and characterization of arginine functionalized peptide dendrimer-based vectors ranging from 5th generation (G5A) to 6th generation (G6A) via click chemistry, and their use for gene transfection in vitro and in vivo. The dendrimers can condense plasmid DNA (pDNA) and protect pDNAs from nuclease digestion. Both atomic force microscopy (AFM) and dynamic light scattering (DLS) revealed that the sizes of dendrimer/DNA particles were within 180-250 nm range. In vitro studies showed that the functionalized peptide dendrimers provided serum independent and high transfection efficiency on all studied cells, as over 2 fold higher than that of branched polyetherimide (PEI) in the presence of serum. Dendrimer G5A with molecular weight of 17 kDa demonstrated 6-fold transfection activity than PEI in breast tumor models, as well as good biosafety proved by in vitro and in vivo toxicity evaluation. However, G6A with molecular weight of 46 kDa showed much higher cytotoxicity. The functionalized dendrimer G5A with optimal generation may be therefore a potential candidate for gene delivery vehicle.
    Biomaterials 04/2012; 33(19):4917-27. · 8.31 Impact Factor
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    ABSTRACT: Effective gene transfection without serum deprivation is a prerequisite for successful stem cell-based gene therapy. Polyethylenimine (PEI) is an efficient nonviral gene vector, but its application has been hindered by serum sensitivity and severe cytotoxicity. To solve this problem, a new family of lipopolyplexes was developed by coating PEI/DNA polyplexes with three serum-resistant cationic lipids, namely, lysinylated, histidylated, and arginylated cholesterol. The physical properties, transfection efficiency, cellular uptake, subcellular distribution, and cytotoxicity of the lipopolyplexes was investigated. The outer coat composed of lysinylated or histidylated cholesterol remarkably improved the transfection efficiency of the polyplex with a low PEI/DNA ratio of 2 in the presence of serum. The resulting lysinylated and histidylated cholesterol lipopolyplexes were even more efficient than the best performing polyplex with a high PEI/DNA ratio of 10. Results from cellular uptake and subcellular distribution studies suggest that their higher transfection efficiency may result from accelerated DNA nuclear localization. The superiority of the lipopolyplexes over the best performing polyplex was also confirmed by delivering the therapeutic gene, hVEGF(165). Equally importantly, the lipid coating removed the necessity of introducing excess free PEI chains into the transfection solution for higher efficiency, generating lipopolyplexes with no signs of cytotoxicity. Noncovalent modification of polyplexes with lysinylated and histidylated cholesterol lipids can simultaneously improve efficiency and reduce the toxicity of gene delivery under serum conditions, showing great promise for genetic modification of bone marrow stem cells.
    International Journal of Nanomedicine 01/2012; 7:4637-48. · 4.20 Impact Factor

Publication Stats

337 Citations
192.41 Total Impact Points

Institutions

  • 2003–2014
    • Sichuan University
      • • National Engineering Research Center for Biomaterials
      • • Department of Respiratory Medicine
      • • Department of Integrated Traditional Chinese and Western Medicine
      Hua-yang, Sichuan, China
  • 2010
    • Central South University
      Ch’ang-sha-shih, Hunan, China
    • Beijing Information Science and Technology University
      Peping, Beijing, China
  • 2007
    • Chengdu University Of Traditional Chinese Medicine
      Hua-yang, Sichuan, China