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Mei S.,Nankai University | Liu Y.,Nankai University | Bao Y.,Nankai University | Zhang Y.,Nankai University | And 7 more authors.
PLoS ONE | Year: 2014

Introduction: Epigenetic modification plays a critical role in regulating gene expression. To understand how epigenetic modification alters miRNA expression in monocyte-derived dendritic cells (moDCs) in different environments, we analyzed the connections between H3K4me3 and H3K27me3 modification and the expression of miRNAs in LPS- and TGF-β-conditioned moDCs. Results: In moDCs, H3K4me3 modification was strongly associated with the expression of activating miRNAs, whereas H3K27me3 was related to repressive miRNAs. The regulation of miRNA expression by H3K4me3 and H3K27me3 was further confirmed by silencing or inhibiting methyltransferases or methylation- associated factors in LPS- and TGF-β-conditioned moDCs. siRNAs targeting H3K4me3-associated mixed lineage leukemia (MLL) and retinoblastoma binding protein 5 (RBBP5) reduced H3K4me3 enrichment and downregulated miRNA expression; conversely, silencing H3K27me3-associated enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) genes upregulated the DC-associated miRNAs. However, LPS-mediated miRNAs were often associated with H3K4me3 redistribution from the transcription start site (TSS) to the miRNA-coding region. Silencing LPS-associated NF-κB p65 and CBP/p300 not only inhibited H3K4m3 redistribution but also reduced miRNA expression. LPS-upregulated RBBP4 and RBBP7, which are involved in chromatin remodeling, also affected the redistribution of H3K4me3 and reduced the expression of miRNAs. Conclusion: In LPS- and TGF-β-conditioned moDCs, miRNAs may be modulated not only by H3K4m3 and H3K27me3 modification but also by redistribution of H3K4me3 around the transcriptional start site of miRNAs. Thus, H3K4me3 and H3K27me3 epigenetic modification may play an important role in regulating DC differentiation and function in the presence of tumor or inflammatory environments. © 2014 Mei et al.


Min S.,Nankai University | Li L.,Nankai University | Zhang M.,Nankai University | Zhang Y.,Nankai University | And 10 more authors.
Genes and Immunity | Year: 2012

The alterations induced in dendritic cells (DCs) in the cancer microenvironment have not been extensively explored. We found that the tumor-associated factor TGF-β may selectively upregulate the expression of miR-27a via the SP1 transcription factor. Importantly, miR-27a altered the activity of NF-κB and MAPKs (mitogen-activated protein kinases) p38, JNK (c-Jun N-terminal kinases) and ERK (extracellular signal-regulated kinase 1/2). It influences the production of proinflammatory cytokines by targeting TAB3, p38 MAPK, MAP2K4 and MAP2K7. As a consequence, miR-27a hampered the DC-mediated differentiation of Th1 and Th17 cells in vitro and in vivo, but it promoted the DC-mediated accumulation of Tr1 (CD4+ IL-10+) and Treg (CD4+ CD25+ Foxp3+) cells in vivo. The repeated infusion of miR-27a-engineered DCs into tumor tissues accelerated tumor growth, indicating that miR-27a is a potential target for tumor immunotherapy. © 2012 Macmillan Publishers Limited All rights reserved.


Li J.,Chinese Institute of Basic Medical Sciences | Zhu C.,Key Laboratory of Bioactive Materials | Yang J.,Key Laboratory of Bioactive Materials
Starch/Staerke | Year: 2015

Zwitterionic polymers are known to possess excellent protein resistance due to high hydration capacity of their zwitterionic moieties. In this study, polysaccharide-based zwitterionic polymers 3-dimethyl(propyl) ammonium propanesulfonate starches (Z-starches) with different degrees of substitution of the zwitterionic moieties (DSZM) were synthesized successfully. The value of DSZM can be controlled exactly in the range of 0-0.46. The cytotoxicity of Z-starches with different DSZM was evaluated by an MTT assay, and the Z-starch with DSZM of 0.26 promoted cell proliferation when the concentration of this polymer solution was 1-25mg/mL. The protein resistance and cell adhesion of Z-starch hydrogels were evaluated, and the amount of protein adsorption or cell adhesion on Z-starch hydrogels was decreased as the DSZM increased. The preliminary protein resistance and cell adhesion tests suggest that the Z-starches have potential applications in drug delivery carriers and coatings of implanted sensors where protein resistance is needed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Cui X.A.,Tianjin Medical University | Liu X.,Tianjin Institute of Urological Surgery | Kong D.L.,Key Laboratory of Bioactive Materials | Gu H.Q.,Tianjin Institute of Urological Surgery
IFMBE Proceedings | Year: 2013

The electrospun collagen (COL)/silk fibroin (SF) complex scaffold was investigated for the fabrication of a biocompatible and biomimetic scaffold for tissue engineering. The COL/SF complex microfibers were prepared via electrospinning COL/SF blend solutions in 1,1,1,3,3,3-hexafluoroiso propanol (HFIP), and then crosslinked by glutaraldehyde (GTA) vapor. The fiber morphology was observed by scanning electron microscopy (SEM) and the structural changes of fibers after crosslinked were analysised by Fourier transform infrared spectra (FTIR). The mechanical property of the scaffolds was examined by tensile testing. To assay the biocompatibility of the matrics, the proliferation of fibroblasts (L929) on the microfibrous scaffolds was investigated by methylthiazol tetrazolium testing (MTT). The results showed that the average diameters of complex fibers ranged from 550 to 1100 nm, increasing with the increase of SF content. The GTA vapor stabilized the microfibers especially the COL component via crosslinking and stabilized the SF component via changing the SF component to β-sheet structure. The mechanical property of the crosslinked fibers was better than that of the uncrosslinked ones, and the highest average ultimate tensile strength 8.7 MPa appeared when SF content was 70%. L929 cells grew and proliferated well on the microfibers, especially on the fibers with SF content of 70%. These results strongly support that the COL/SF microfibrous scaffolds, could be a potential candidate for biomedical applications such as wound dressing and scaffolds for skin tissue engineering. © 2013 Springer-Verlag.


Cui X.-A.,Tianjin Medical University | Liu X.,Tianjin Institute of Urological Surgery | Kong D.-L.,Key Laboratory of Bioactive Materials | Gu H.-Q.,Tianjin Medical University | Gu H.-Q.,Tianjin Institute of Urological Surgery
Chinese Journal of Biomedical Engineering | Year: 2012

This study aimed to prepare collagen/silk fibroin composite micro-nanofibers using electrospinning technique, and to evaluate their properties and cytocompatibility. Taking 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, the composite fibers were prepared according to the mass ratio of collagen/silk fibroin as 100:0, 70:30, 50:50, 30:70, 0:100, and then crosslinked by glutaraldehyde (GTA) vapor for 12 h. The fibers were characterized by combined techniques of scanning electron microscopy (SEM) , Fourier-transform infrared spectra (FTIR) , X-ray diffraction (XRD) , thermal analysis and tensile measurements. The composite fibers were inoculated with fibroblasts (3T3). The cell adhesion and proliferation were evaluated by SEM and MTT. The results showed the diameter of composite fibers ranged from 550 nm to 1100 nm, and fiber diameter was positively correlated with SF content. After crosslinking, the β-sheet structure, crystallinity and thermal stability of the nanofibers were improved. This improvement was more obvious with the SF content increases. The mechanical properties of cross-linked fibers were better than those of uncrosslinked fibers, and the best average ultimate tensile strength was (8.70 ± 1.05) MPa when SF content was 70%. The cells grew well on the surface of materials, and had the best adhesion and proliferation on the composite fibers with SF content of 70% , which might be a potential candidate for tissue engineering scaffold.

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