Efficient Upconversion by Highly Water-Soluble Cationic Sensitizer and Emitter in Aqueous Solutions with DNA

Highly water-soluble cationic palladium porphyrin as a sensitizer and 9,10-bis­(4-trimethylammoniumphenyl)­anthracene as an emitter were newly synthesized. They were shown to be bound and immobilized in DNA double helix assembly from absorption, fluorescence, phosphorescence, and circular dichroism spectra. Upon excitation at 532 nm in deaerated aqueous solutions, they showed weak blue upconversion fluorescence, the efficiency of which increased dramatically in the presence of DNA. The threshold power density between the second-order and first-order power dependence of upconversion fluorescence decreased to less than a half upon addition of DNA. The emitter triplet lifetime estimated from time dependences of upconversion fluorescence at low power ns pulsed laser was found to considerably increase in the presence of DNA. From these results, DNA was concluded to work effectively in concentrating both sensitizer and emitter and in migrating excited triplet states, resulting in efficient upconversion

Table1_miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress.docx

The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.</p