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Articles by Kun Zhang
Total Records ( 4 ) for Kun Zhang
  Min Chen , Shun Huang , Yuan-Yuan Chang , Xi Zheng , Ren-Ping Zhou , Dong-Li Li and Kun Zhang
  Background and Objective: Curcumin is a bioactive natural polyphenol, but the poor bioavailability has limited its application. To be effective as a therapeutic drug, curcumin must be combined with other drugs to improve bioavailability. The aim of the present study was to investigate the effects and mechanisms of curcumin and piperine administered individually or in combination on lipopolysaccharide (LPS)-induced neuroinflammation. Materials and Methods: Mice were treated with curcumin (100 and 200 mg kg–1, p.o.) and piperine (20 mg kg–1, p.o.) for 21 days followed by LPS (250 μg kg–1, i.p.) administration for 7 days. Results: It is found that repeat injections of LPS induced neuronal damage and increased inflammatory cytokines release, while pretreatment with curcumin reversed these changes. In addition, co-administration of piperine with curcumin potentiated their neuroprotective effects as compared to the treatment with curcumin alone. It is further examined that the molecular mechanisms by which curcumin exerts its neuroprotective effects and inhibited the Toll-like receptor 4 (TLR4)-mediated downstream signaling and effectively lowered the production of inflammatory mediators. Conclusion: These findings led us to the conclusion that the effects of curcumin on LPS-induced neuroinflammation is mediated by modulating TLR4 pathway, which is enhanced by an adjuvant, piperine.
  Jie Bai , Xinwen Wang , Zhen Jia , YangjunZhu , YubenXu , Kun Zhang and Lisong Heng
  Background and Objective: Interferon (IFN)-γ plays crucial roles in the development of ankylosing spondylitis (AS) though regulating its sensitive response genes, but the sensitive response genes to IFN-γ dysregulation in AS are partially reported. Thus, the present study explored potential target genes for AS treatment under interferon-γ (IFN-γ) stimulated condition. Materials and Methods: The gene expression profile, GSE11886 was downloaded. The differentially expressed genes (DEGs) in non-INF-γ group and INF-γ group were revealed respectively, followed by function and pathway enrichment analyses, as well as protein-protein interaction network analysis. Furthermore, the small-molecule drugs associated with AS were identified. Finally, the data validation for DEGs in AS with non-INF-γ interference was conducted using another dataset GSE25101. Results: Totally, 317 DEGs and 394 DEGs were revealed in the INF-γ group and non-INF-γ group, respectively. Venn diagram revealed 60 overlapped DEGs. Among the 394 DEGs, nineteen genes were verified in non-INF-γ group. The DEGs in the two groups were mainly enriched in mitotic cell cycle and T cell activation, respectively. CKD1 and BUB1 were outstanding in INF-γ group, while the validated PRKCQ and SMARCA4 might be crucial with AS in non-INF-γ group. In addition, the DL-thiorphan and NS-398 had the highest negative correlation with DEGs in two groups, respectively. Conclusion: Genes like CDK1 and BUB1 might be novel INF-γ sensitive response gene for AS. The PRKCQ and SMARCA might be strongly related to the process of AS. In addition, NS-398 and DL-thiorphan might be ideal small-molecule drugs for AS treatment.
  Min Hong , Kun Zhang , Yi-Zhi Li and Jin Zhu
  The synthesis and structural chemistry of four new divalent transition metal complexes of the fluorene ligands 4,5-diazaspirobifluorene (L1) and bis-9-biphenyl-4,5-diazafluorenyl peroxide (L2), [Cu3(L1)4(NO3)6(H2O)2]·2CH3CN (1), [Cu(L1)(CH3CO2)2(H2O)]·2H2O (2), [Cd(L1)2(NO3)2]·DMF (3) (DMF=N,N-dimethylformamide) and [Zn2(L2)(μ-Cl)2Cl2] (4) are described. Single-crystal X-ray diffraction analysis reveal that the four complexes exhibit various frameworks due to diverse coordination modes and different conformations of ligands L1 or L2, as well as nitrate, acetate or chloro counterions. L1 in complexes 1, 2 and 3 present an asymmetric rigid bidentate ligand with two nitrogen atoms as the donor sites. Novel complex 4 was formed through complexation between conformationally bent shaped peroxide ligands and zinc(II) dichlorides that adopt a linear coordination geometry, which can also give rise to extended polymeric chains with a zigzag secondary structure.
  Patricia L. Taylor , Kim M. Blakely , Gladys P. de Leon , John R. Walker , Fiona McArthur , Elena Evdokimova , Kun Zhang , Miguel A. Valvano , Gerard D. Wright and Murray S. Junop
  The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria presents a significant challenge in treatment of these organisms with otherwise effective hydrophobic antibiotics. The absence of L-glycero-D-manno-heptose in the LPS molecule is associated with a dramatically increased bacterial susceptibility to hydrophobic antibiotics and thus enzymes in the ADP-heptose biosynthesis pathway are of significant interest. GmhA catalyzes the isomerization of D-sedoheptulose 7-phosphate into D-glycero-D-manno-heptose 7-phosphate, the first committed step in the formation of ADP-heptose. Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms, which together suggest that GmhA adopts two distinct conformations during isomerization through reorganization of quaternary structure. Biochemical characterization of GmhA mutants, combined with in vivo analysis of LPS biosynthesis and novobiocin susceptibility, identifies key catalytic residues. We postulate GmhA acts through an enediol-intermediate isomerase mechanism.

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