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Start Over Author "Wen-Tao He" Topic biochemistry
3 results on '"Wen-Tao He"'

2. Targeting of MyD88 Homodimerization by Novel Synthetic Inhibitor TJ-M2010-5 in Preventing Colitis-Associated Colorectal Cancer.

Author

Lin Xie, Feng-Chao Jiang, Li-Min Zhang, Wen-Tao He, Jian-Hua Liu, Ming-Qiang Li, Xue Zhang, Shuai Xing, Hui Guo, Ping Zhou, Xie, Lin, Jiang, Feng-Chao, Zhang, Li-Min, He, Wen-Tao, Liu, Jian-Hua, Li, Ming-Qiang, Zhang, Xue, Xing, Shuai, Guo, Hui, and Zhou, Ping

Subjects
COLON diseases, COLON cancer, COLITIS, DIMERIZATION, CHEMICAL inhibitors, TUMOR prevention, COLON tumor prevention, ANIMALS, ANTINEOPLASTIC agents, BIOCHEMISTRY, BIOLOGICAL models, CARRIER proteins, CELLULAR signal transduction, CHEMOKINES, DRUG therapy, COLON tumors, CYTOKINES, ENZYME-linked immunosorbent assay, FLOW cytometry, GENETIC techniques, HETEROCYCLIC compounds, IMMUNOHISTOCHEMISTRY, PHENOMENOLOGY, MICE, POLYMERASE chain reaction, RECTUM tumors, THIAZOLES, DISEASE complications, PHARMACODYNAMICS
Abstract

Background: The TLR/MyD88 signaling pathway is an important driver of inflammation and cancer and is a possible target for antitumor therapy.Methods: We generated a MyD88 inhibitor (TJ-M2010-5), which was designed to bind to the TIR domain of MyD88 to interfere with its homodimerization, and the TLR/MyD88 signal pathway. We utilized a mouse model of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated cancer (CAC) in combination with TJ-M2010-5 administration to investigate the anti-inflammation-related cancer effect of MyD88 inhibitor in vivo. Data were analyzed with one-way and repeated measures analysis of variance. Differences in survival between groups were compared using the log rank test. All statistical tests were two-sided.Results: TJ-M2010-5 inhibited MyD88 homodimerization in transfected HEK293 cells in a concentration-dependent manner and suppressed MyD88 signaling in LPS-responsive RAW 264.7 cells in vitro. In a 10-week CAC mouse model (n = 30 per group), TJ-M2010-5 treatment statistically significantly reduced AOM/DSS-induced colitis and completely prevented CAC development with less related body mass loss, resulted in 0% mortality of treated mice (compared with 53% mortality of control mice), decreased cell proliferation, and increased apoptosis in colon tissue. TJ-M2010-5 treatment also inhibited production of inflammatory cytokines and chemokines (TNF-α, IL-6,G-CSF, MIP-1β, TGF-β1, IL-11, IL-17A, IL-22 and IL-23) and infiltration of immune cells (macrophages, dendritic cells, neutropihls and CD(+)4 T cells) in colon tissues of mice.Conclusions: Our findings suggest that TLR/MyD88 signaling may be a therapeutic target for CAC intervention and MyD88 inhibitors may be a promising therapeutic modality for treating patients with colitis or CAC. [ABSTRACT FROM AUTHOR]

Published
2016
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3. One-pot preparation of polyethylenimine-silica nanoparticles as serum-resistant gene delivery vectors: Intracellular trafficking and transfection

Author

Wen-Tao He, Wen-Ming Liu, Na Peng, Shi-Wen Huang, Yanan Xue, and Ren-Xi Zhuo

Subjects
Polyethylenimine, Materials science, Nanoparticle, General Chemistry, Transfection, Gene delivery, chemistry.chemical_compound, chemistry, Biochemistry, Materials Chemistry, Agarose, Surface charge, Cytotoxicity, DNA, Nuclear chemistry
Abstract

Organic-inorganic hybrid silica nanoparticles (PM-1, PM-2 and PM-3) with positive surface charge and size below 200 nm were one-pot prepared viaMichael addition between 3-methacryloxypropyl- trimethoxysilane (MPTMS) and polyethylenimine (PEI), followed by hydrolysis and polycondensation of siloxanes. The nanoparticles were characterized by FT-IR, element analysis and particle size analysis. The average sizes of the nanoparticles were 130–180 nm and the surface charge was about 40 mV. The acid–base titration showed that the nanoparticles had higher buffer capacity than PEI 25 kDa. The positively charged nanoparticles can condense negatively charged DNA to form complexes and completely retard the DNA mobility in agarose gel at a weight ratio of 5. The average sizes of PM-1/DNA and PM-2/DNA complexes were below 250 nm and the surface charge of the complexes was in the range of 30–40 mV at the weight ratio of 100. An in vitro transfection assay demonstrated that the transfection efficiencies of the nanoparticles were dependent on the PEI content, and PM-1 showed improved transfection efficiency compared with PEI 25 kDa in the presence of 10% serum. The intracellular trafficking assay of PM-1 nanoparticle/Cy3-labelled DNA complexes in COS-7 cells in the presence of 10% serum indicated that a large amount of complexes crossed the cell membrane and located in the cytoplasm and only a small amount of complexes entered into the cell nucleus after 24 h incubation. The uptake of PM-1 nanoparticle/DNA complexes by COS-7 cells in the presence of serum was higher than that of PEI/DNA complexes. In addition, the cytotoxicity of PM nanoparticles was significantly lower than that of PEI 25 kDa. The results indicate that the synthesized nanoparticles will show potential in nonviral gene delivery.

Published
2011
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