32 research outputs found

    Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals

    Get PDF
    In the present study genipin crosslinked chitosan (CHI) hydrogels, which had been constructed and reported in our previous studies (Lei Gao, et al. Colloids Surf. B Biointerfaces. 2014, 117: 398), were further evaluated for their advantage as a carrier for silver sulfadiazine (AgSD) nanocrystal systems. Firstly, AgSD nanocrystals with a mean particle size of 289 nm were prepared by wet milling method and encapsulated into genipin crosslinked CHI hydrogels. AgSD nanocrystals displayed a uniform distribution and very good physical stability in the hydrogel network. Swelling-dependent release pattern was found for AgSD nanocrystals from hydrogels and the release profile could be well fitted with Peppas equation. When AgSD nanocrystals were encapsulated in hydrogels their fibroblast cytotoxicity decreased markedly, and their antibacterial effects against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were still comparable to unencapsulated AgSD nanocrystals. In vivo evaluation in excision and burn cutaneous wound models in mice showed that AgSD nanocrystal hydrogels markedly decreased the expression of inflammatory cytokine IL-6, but increased the levels of growth factors VEGF-A and TGF-β1. Histopathologically, the wounds treated by hydrogels containing AgSD nanocrystals showed the best healing state compared with commercial AgSD cream, hydrogels containing AgSD bulk powders and blank hydrogels. The wounds treated by AgSD nanocrystal hydrogels were dominated by marked fibroblast proliferation, new blood vessels and thick regenerated epithelial layer. Sirius Red staining assay indicated that AgSD nanocrystal hydrogels resulted in more collagen deposition characterized by a large proportion of type I fibers. Our study suggested that genipin-crosslinked CHI hydrogel was a potential carrier for local antibacterial nanomedicines

    Peptide Hydrolysis by Metal-Cyclen Complexes and Their Analogues: Insights from Theoretical Studies

    No full text
    In the present DFT study, mechanisms of peptide hydrolysis by Co­(III)- and Cu­(II)-containing complexes of 1,4,7,10-tetraazacyclododecane (cyclen), <b>1-Co</b> and <b>1-Cu</b>, respectively, and 1-oxa-4,7,10-triazacyclododecane (oxacyclen), <b>2-Co</b> and <b>2-Cu</b>, respectively, and their analogues have been investigated. In addition, the effects of the ligand environment, pendant (an organic group containing a recognition site) and metal ion (Co­(III), Cu­(II), Ni­(II), Zn­(II), Cd­(II), and Pd­(II)), on the energetics of this reaction have been elucidated. The reactant of the <b>1-Co</b> complex exists in the <i>syn–anti</i> conformation, while that of <b>1-Cu</b> in the <i>syn–syn</i> form. For both these complexes, stepwise and concerted mechanisms were found to occur with similar barriers. The substitution of one of the nitrogen atoms in the cyclen macrocycle to create oxacyclen should occur at position 10 in the Co­(III) case and at position 4 in the Cu­(II) case. A comparison between the barriers using the common conformation (<i>syn–anti</i>) of <b>1-Co</b> and <b>2-Co</b> showed that both complexes hydrolyze the peptide bond with similar barriers, i.e., 39.8 kcal/mol for the former and 40.1 kcal/mol for the latter. This result is in line with the measured data that suggest that the oxacyclen complex exhibits just four times greater activity than the cyclen complex. The removal of the pendant (−C<sub>2</sub>H<sub>5</sub>) group in the Co­(III)- and Cu­(II)-cyclen complexes (<b>1</b>′<b>-Co</b> and <b>1</b>′<b>-Cu</b>, respectively) reduced the barriers by 9.3 and 3.0 kcal/mol, respectively. For <b>1</b>′<b>-Co</b>, the barrier of 30.5 kcal/mol is in agreement with the experimental value of 25.9 kcal/mol for the cleavage of myoglobin at pH 9.0 and 50 °C. The reactants of <b>1</b>′<b>-Cu</b>,<b> 1</b>′<b>-Zn</b>,<b> 1</b>′<b>-Pd</b>, and <b>1</b>′<b>-Cd</b> adopt the <i>syn–syn</i> conformation, whereas <b>1</b>′<b>-Ni</b> and <b>1</b>′<b>-Co</b> exist in the <i>syn–anti</i> geometry. The barriers for <b>1</b>′<b>-Ni</b> (triplet spin state), <b>1</b>′<b>-Cu</b> (doublet spin state), <b>1</b>′<b>-Cd</b> (singlet spin state), <b>1</b>′<b>-Co</b> (singlet spin state), and <b>1</b>′<b>-Zn</b> (singlet spin state) are similar, i.e., 27.2, 29.7, 30.5, 30.5, and 31.9 kcal/mol, respectively, and the highest barrier (41.5 kcal/mol) is computed for <b>1</b>′<b>-Pd</b> (singlet spin state)

    Mechanistic Insights into Metal (Pd<sup>2+</sup>, Co<sup>2+</sup>, and Zn<sup>2+</sup>)−β-Cyclodextrin Catalyzed Peptide Hydrolysis: A QM/MM Approach

    No full text
    In this study, mechanistic insights into the hydrolysis of an extremely stable tertiary peptide bond (Ser–Pro) in the Ser-Pro-Phe sequence by an artificial enzyme, metal (Pd<sup>2+</sup>, Co<sup>2+</sup>, or Zn<sup>2+</sup>)−β-cyclodextrin (CD) complex, have been provided. In particular, the exact reaction mechanism, the location of CD (number of −CH<sub>2</sub> groups downstream from the metal center), conformation of CD (primary or secondary rim of CD facing the substrate), the number of CD (one or two), and the optimum metal ion (Pd<sup>2+</sup>, Co<sup>2+</sup>, or Zn<sup>2+</sup>) have been suggested using a state-of-the-art hybrid quantum mechanics/molecular mechanics (QM/MM: B3LYP/Amber) approach. The QM/MM calculations suggest that the internal delivery mechanism is the most energetically feasible for the peptide hydrolysis. The inclusion of a CD ring at two CH<sub>2</sub> groups downstream from the metal center can provide 3 × 10<sup>5</sup> times acceleration in the activity, while the replacement of Pd<sup>2+</sup> with Co<sup>2+</sup> enhances the rate activity another 3.7 × 10<sup>4</sup> times

    Correlation between <i>Txnrd1</i> gene expression and audiological measurements.

    No full text
    <p><sup>*</sup> denotes statistical significance at 0.05 level;</p><p><sup>**</sup> at the 0.01 level;</p><p><sup>***</sup> at the 0.001 level.</p

    Correlation between Gpx6 gene expression and audiological measurements.

    No full text
    <p><sup>*</sup> denotes statistical significance at 0.05 level;</p><p><sup>**</sup> at the 0.01 level.</p

    A): For both GeneChip and real-time PCR, fold changes of <i>Hspb1</i> gene expression in the cochleae of middle age, old mild hearing loss, and old severe hearing loss groups showed upregulation with age and hearing loss.

    No full text
    <p>B): For both GeneChip and real-time PCR, fold changes of <i>Gpx</i>6 gene expression in cochlea samples showed upregulation in all age groups compared to the young group. C): For both GeneChip and real-time PCR, fold changes of <i>Txnrd1</i> gene expression in the cochleae of middle age, old mild hearing loss, and old severe hearing loss groups showed downregulation with age and hearing loss.</p

    Additional file 1: Figure S1. of DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding

    No full text
    Work flow diagram. Figure S2. Serum uric acid is regulated by B1 methylation level and NRBP1 expression. a A marginal significant negative association between DNA methylation of B1 and serum uric acid (P value = 0.08). b A significant positive association between NRBP1 expression and serum uric acid (P value = 0.03). Figure S3. Decreased DNA methylation at the promoter region of NRBP1 in gout patients. a The DNA sequence at the promoter region of NRBP1 gene. The CpG sites, designated as B1 to B6, are highlighted in red. b The methylation level for each CpG site indicated in a, was investigated by bisulfite pyrosequencing. Data are represented as mean ± SEM. (*P value <0.01, **P value <0.001, Student’s t test, unpaired, two-sided). (PPTX 1077 kb
    corecore