Li Li

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (10)22.62 Total impact

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    ABSTRACT: Previous studies showed that the Ca(2+)-activated Cl(-) channel (CaCC) was involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13 (IL-13). However, the mechanisms underlying the process were unknown. Recently, transmembrane protein 16A (TMEM16A) was identified as the channel underlying the CACC current. The aim of the current study was to investigate whether the TMEM16A channel is part of the mechanism underlying IL-13-induced mucus hypersecretion. We observed that both TMEM16A mRNA and protein expression were significantly up-regulated after treatment with IL-13 in human bronchial epithelial 16(HBE 16) cells, which correlated with an increase in mucus production. Additionally, mucus hypersecretion in rat airways was induced by intratracheal instillation of IL-13 and similar increases were observed in the expression of TMEM16A mRNA and protein in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC, markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A overexpression clearly promoted mucus production, IκBα phosphorylation, and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition of mucus production, and the TMEM16A-mediated production of MUC5AC was significantly blocked by a nuclear factor-kappa B (NF-κB) inhibitor. Therefore, the TMEM16A channel acts upstream of NF-κB in the regulation of mucus production. This is the first demonstration that the TMEM16A-NF-κB pathway is positively involved in IL-13-induced mucus production, which provides novel insight into the molecular mechanism of mucin overproduction. Copyright © 2015. Published by Elsevier Inc.
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    Dataset: paper 4
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    Dataset: paper 4
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    ABSTRACT: Background Human cells release nano-sized vesicles called exosomes, containing mRNA, miRNA and specific proteins. Exosomes from one cell can be taken up by another cell, which is a recently discovered cell-to-cell communication mechanism. Also, exosomes can be taken up by different types of cancer cells, but the potential functional effects of mast cell exosomes on tumor cells remain unknown.Methods and resultsExosomes were isolated from the human mast cell line, HMC-1, and uptake of PKH67-labelled exosomes by the lung epithelial cell line, A549, was examined using flow cytometry and fluorescence microscopy. The RNA cargo of the exosomes was analyzed with a Bioanalyzer and absence or presence of the c-KIT mRNA was determined by RT-PCR. The cell proliferation was determined in a BrdU incorporation assay, and proteins in the KIT-SCF signaling pathway were detected by Western blot. Our result demonstrates that exosomes from mast cells can be taken up by lung cancer cells. Furthermore, HMC exosomes contain and transfer KIT protein, but not the c-KIT mRNA to A549 cells and subsequently activate KIT-SCF signal transduction, which increase cyclin D1 expression and accelerate the proliferation in the human lung adenocarcinoma cells.Conclusions Our results indicate that exosomes can transfer KIT as a protein to tumor cells, which can affect recipient cell signaling events through receptor-ligand interactions.
    Cell Communication and Signaling 10/2014; 12(1):64. DOI:10.1186/PREACCEPT-1817458803126023 · 4.67 Impact Factor
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    ABSTRACT: c-Kit and epidermal growth factor receptor (EGFR) have critical roles in cell proliferation and differentiation in patients with non-small cell lung cancer (NSCLC). The present study aimed to investigate the prognostic impact of c-Kit and/or EGFR expression in tumor tissue samples from 146 patients with NSCLC. c-Kit expression was analyzed using immunohistochemistry and the expression of EGFR was assessed using fluorescence in situ hybridization. Univariate and multivariate analyses identified that c-Kit is a significant negative prognostic factor. The expression of c-Kit was correlated with poor differentiation, pleura involvement and smoking history (P=0.043, 0.007 and 0.032, respectively). Furthermore, patients with c-Kit-positive expression were associated with a significantly lower overall survival compared with those exhibiting c-Kit-negative expression (P=0.048). The median follow-up time was 19 months post-surgery. EGFR gene amplification as a result of polysomy of chromosome 7 was found to be negatively correlated with poor differentiation and smoking history (P=0.023 and 0.044, respectively). The findings of the present study indicate that c-Kit and EGFR expression is a strong, independent, negative prognostic factor in NSCLC.
    Oncology letters 08/2014; 8(2):582-588. DOI:10.3892/ol.2014.2173 · 0.99 Impact Factor
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    ABSTRACT: We established a novel gene expression analysis platform, Multiplex Competitive RT-PCR Using Fluorescent Universal Primers (MCF-PCR), to study multi-gene expression patterns simultaneously. This platform combines fluorescent universal primers, multiplex competitive RT-PCR, and capillary electrophoretic separation, which ensures MCF-PCR a reliable, medium-throughput, cost-effective technology for gene expression profiling. With cloned standard DNAs, the detection limits, precision, and sensitivity of MCF-PCR were evaluated and compared with that of the assay without adding competitive templates and real-time PCR, respectively. The results showed that detection limit was 3.125 × 10(3) to 3.2 × 10(6) copies, and 10 % copy differences between two samples can be detected by MCF-PCR. To validate MCF-PCR, we analyzed expression profile of five genes in interleukin (IL)-4/IL-13 pathway in peripheral blood of 20 healthy adults and 20 allergic dermatitis patients; three genes including IL-4, IL-13, and STAT6 were found differentially expressed in the two sample groups, which maybe key players in IL-4/IL-13 immunological signaling pathway and need further function analysis.
    Analytical and Bioanalytical Chemistry 12/2012; 405(4). DOI:10.1007/s00216-012-6518-1 · 3.58 Impact Factor
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    ABSTRACT: Celastrol has been found to be a potent anti-inflammatory and antitumor plant derivative recently. Herein we established an accurate reverse phase HPLC (RP-HPLC) determination method of celastrol, and prepared an effective nanoscale drug delivery system from the optimized formulations of celastrol-loaded carboxyl functioned poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)(PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles. Rotatable central composite design (RCCD) and response surface methodology (RSM) were applied to improve the celastrol entrapment efficiency (EE), drug loading percentage (DLP), and decrease the particle size. The characteristics of the optimized micelles including particle size distribution, morphology, zeta potential and in vitro release of celastrol from micelles were carried out. Results showed that RP-HPLC method was successfully applied to detect and qualify the celastrol. The drug quantification range of the method was 20-200 microg/mL with a linear correlation coefficient of greater than 0.999. The average accuracy (99.763%), the precision (0.521%) and recovery (99.63%) for this method were good. The optimal conditions for the preparation of celastrol-loaded polymeric nanomicelles were found to be: the celastrol/polymer weight ratio 8.5-9 mg/25 mg, hydration volume 11-17 mL. Under the optimal conditions, the EE was 100.3 +/- 4.3%, DLP was 22.8 +/- 1.0%, the average particle size was 117.3 +/- 1.27 nm and the zeta potential was -2.19 +/- 0.15 mV. Transmission electron micrograph (TEM) showed the micelles to be oval and rodlike shaped, with mean diameter around 20 nm. The in vitro experiments proved that celastrol in polymeric nanomicelles released gradually over the period of 24 h. These results showed that the RCCD and RSM could efficiently be applied for optimized preparation of celastrol-loaded polymeric nanomicelles.
    Journal of Biomedical Nanotechnology 06/2012; 8(3):491-9. DOI:10.1166/jbn.2012.1398 · 7.58 Impact Factor
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    ABSTRACT: The immunoglobulin E (IgE) high-affinity receptor FcεRI expressed on mast cells and basophils plays a critical role in triggering allergic disease. The co-aggregation of the FcεRI and FcγRIIb receptors is inhibitory to FcεRI signaling and holds great potential for the treatment of IgE-mediated allergies. In China, Dermatophagoides farinae is a common anaphylaxis trigger. Therefore, in this study, the FcγRIIb-mediated immunomodulating activity of recombinant Fcγ-Der f2 fusion protein was tested in a Der f2-allergic murine model. Following the treatment, bronchoalveolar lavage fluid (BALF) was collected to measure the expression of several Th1/Th2-type cytokines (IL-5, TNF-α, IL-12p70, IL-4, IL-10, IFN-γ and IL-18) and histamine, while blood was used to detect the specific IgE and IgG-types anti-Der f2 antibodies, for measurement. In contrast to the saline-treated allergic mice, the levels of Der f2-specific IgE, cytokines and histamine were lowered in the Fcγ-Der f2-treated allergic mice, in addition to the rare inflammatory cell infiltration in the airways and blood vessels revealed by histopathological examination. The recombinant Fcγ-Der f2 protein was demonstrated to function as an effective immunotherapeutic agent, suggesting that chimeric human Fcγ-allergen proteins could be used in the development of antigen-specific immunotherapy for human allergic diseases.
    Immunologic Research 04/2012; 52(3):276-83. DOI:10.1007/s12026-012-8339-x · 3.53 Impact Factor
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    ABSTRACT: The high-affinity receptor for immunoglobulin E (IgE) plays a central role in allergy diseases. Previous studies have reported the association of variants in the proximal promoter of FCER1A with IgE levels as well as allergy disorders. Another promoter gene polymorphism that is located upstream of exon 1 has not been investigated. We investigated the association of variants in the promoter located upstream of FCER1A exon 1 with serum IgE levels and allergy diseases in a Han Chinese population. A total of 97 patients with atopic dermatitis (AD), 123 patients with chronic urticaria (CU), 286 children with asthma, and control groups were screened for polymorphisms in the promoter region located upstream of FCER1A exon 1 by the polymerase chain reaction-ligation detection reaction method. Total serum IgE levels were tested in groups. The rare allele A of the rs2427837 A/G polymorphism was significantly different in the AD group compared with the controls. No association with the polymorphism was observed in the CU group. In asthmatic patients, IgE levels were higher in the mutation genotypes GA of rs2427837 and TC of rs2251746 compared with normal genotype individuals. The minor allele of rs2427837 and rs2251746 in FCER1A is a genetic risk factor of high IgE levels.
    Human immunology 03/2012; 73(3):301-5. DOI:10.1016/j.humimm.2011.12.001 · 2.28 Impact Factor
  • Xia Peng, Li Li
    Academic Journal of Second Military Medical University 01/2011; 31(1):96-100. DOI:10.3724/SP.J.1008.2011.00096