Dendritic cells (DC) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness in vitro. The expression of costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with their capacity to induce or suppress immune responses. Expression of these molecules is associated with NF-kB-dependent transcription of their genes. DC tolerogenicity has been associated with impaired NF-kB-dependent transcription of costimulatory genes as well as NF-kB translocation to the nucleus. In this report, we demonstrate that double-stranded oligodeoxyribonucleotides containing binding sites for NF-kB (NF-kB ODN) are efficiently incorporated by bone marrow-derived DC and specifically inhibit NF-kB-dependent transcription of a reporter gene. Moreover, exposure of DC to the oligonucleotide decoys inhibited lipopolysaccharide (LPS)-induced nitric oxide production, a marker of DC maturation. Treatment of bone marrow-derived DC progenitors with NF-kB ODN selectively suppressed the cell-surface expression of costimulatory molecules without interfering with MHC class I or class II expression. Furthermore, NF-kB ODN DC induced allogeneic donor-specific hyporesponsiveness in mixed leukocyte cultures, and this was associated with inhibition of Th1-type cytokine production. Finally, infusion of NF-kB ODN-modified bone marrow-derived DC into allogeneic recipients prior to heart transplantation resulted in significant prolongation of allograft survival in the absence of immunosuppression. Specific interference with NF-kB and other transcriptional pathways involved in immune stimulation in DC using ODN decoy approaches could be one means to promote tolerance induction in organ transplantation.
The present study compared the effect of resveratrol on HCT116 and Caco-2 human colon cancer cells. Annexin V/propidium iodide staining, MTT assay and western blot analysis revealed that resveratrol induced cycle arrest in the two cell lines, which was evidenced by cell cycle analysis and changes in the expression of the cell cycle proteins cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, proliferating cell nuclear antigen and P21. Furthermore, resveratrol was found to have a strong apoptosis-inducing effect, which was evidenced through the high percentage of annexin V positive cells and high protein expression of cleaved-caspase-7, cleaved-caspase-9 and cleaved-poly(ADP-ribose) polymerase in the resveratrol-treated cancer cells. In conclusion, these results demonstrated that resveratrol had greater growth inhibitory and cell cycle arrest effects on Caco-2 cells than HCT116 cells, through caspase-dependent and cyclin-CDK pathways.
Nitrogen-doped
carbon nanotubes (NCNTs) have demonstrated great
promise as an electrocatalyst alternative to platinum for oxygen reduction
reaction (ORR). However, there is much disagreement regarding which
N doping sites are most desirable for the reaction. Here, we report
an experimental and computational study to identify the efficient
active sites in NCNTs for ORR in alkaline media. In our experiments,
we synthesized NCNTs of similar overall N content (∼4.1%) and
carbon matrix but varying percentages of different types of N doping
species. Our results reveal a positive correlation between ORR activity
and the content of graphitic N doping. Furthermore, we performed density
functional theory calculations to predict the free energy evolution
of ORR on various N doping sites in NCNTs. Our computational results
also indicate that graphitic N doping sites exhibit higher thermodynamic
limiting potential for ORR than pyridinic N doping sites. Our combined
experimental and theoretical study concludes that graphitic N doping
sites are more efficient for ORR than pyridinic N doping in NCNTs.
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