GCN5 regulates ZBTB16 through acetylation, mediates osteogenic differentiation, and affects orthodontic tooth movement.

In the process of orthodontic tooth movement (OTM), periodontal ligament fibroblasts (PDLFs) must undergo osteogenic differentiation. OTM increased the expression of Zinc finger and BTB domain-containing 16 (ZBTB16), which is implicated in osteogenic differentiation. Our goal was to investigate the mechanism of PDLF osteogenic differentiation mediated by ZBTB16. The OTM rat model was established, and PDLFs were isolated and exposed to mechanical force. Hematoxylin-eosin staining, Alizarin Red staining, immunofluorescence, and immunohistochemistry were carried out. The alkaline phosphatase (ALP) activity was measured. Dual-luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted. In OTM models, ZBTB16 was significantly expressed. Additionally, there was an uneven distribution of PDLFs in the OTM group, as well as an increase in fibroblasts and inflammatory infiltration. ZBTB16 interference hindered PDLF osteogenic differentiation and decreased Wnt and ß-catenin levels. Meanwhile, ZBTB16 activated the Wnt/ß-catenin pathway. ZBTB16 also enhanced the expression of the osteogenic molecules osterix, osteocalcin (OCN), osteopontin (OPN), and bone sialo protein (BSP) at mRNA and protein levels. The interactions between Wnt1 and ZBTB16, as well as GCN5 and ZBTB16, were also verified. The adeno-associated virus-shZBTB16 injection also proved to inhibit osteogenic differentiation and reduce tooth movement distance in in vivo tests. ZBTB16 was up-regulated in OTM. Through acetylation modification of ZBTB16, GCN5 regulated the Wnt/ß-catenin signaling pathway and further mediated PDLF osteogenic differentiation.

Construction of heteroaryl-bridged NIR AIEgens for specific imaging of lipid droplets and its application in photodynamic therapy.

As a kind of subcellular organelle, lipid droplets (LDs) play a critical role in the body's normal metabolism. LDs have gained increasing attention as a fluorescent photodynamic target site. Near-infrared (NIR) organic light-emitting luminescent materials, with aggregation-induced emission (AIE)-active feature, preeminent LD-imaging ability, and effective reactive oxygen species (ROS) production property, have been widely used for photodynamic therapy (PDT) in diagnostic therapeutics, but its application remains challenging. In the present work, three novel NIR organic compounds with AIE-active feature, namely, TPET-Is, TPET-Fu, and TPEF-Is, were developed and synthesized. These heteroaryl-bridged molecules possess a donor-donor-π-acceptor structure and strong intramolecular charge transfer character. These AIEgens are capable of high-fidelity LD imaging in living cells (Pearson's coefficient values: 0.94, 0.96, 0.97) due to their biocompatibility, good photostability, and strong lipophilicity (LogP values: 9.39, 7.89, 8.03), respectively. Moreover, they can be also applied in bright imaging the LDs of oil-rich plant tissues, such as those of sunflower seeds. The respective AIEgens TPET-Fu of these compounds can also produce ROS in the condition of white light to effectively kill live Hela cells. The present study thus provides a potential strategy through heteroaryl-bridged molecular engineering for LD-targeted imaging and PDT application.

Effects of the extract of Ginkgo biloba on the differentiation of bone marrow mesenchymal stem cells in vitro.

The balance of osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) is disrupted in osteoporosis. This study was designed to investigate the effects of extract of Ginkgo biloba (EGB) on proliferation, osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells in vitro. The effect of EGB on proliferation was evaluated by CCK-8 assay and flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red S staining and Alkaline phosphatase assay. Adipogenic differentiation was evaluated by Oil Red O staining. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the expression of osteogenic specific genes (BMP-2, Runx2 and Colla1) and adipogenic specific genes (ap2, PPARγ). EGB did not significantly affect proliferation of BMSCs. However, it increased the calcium accumulation and significantly promoted the activity of alkaline phosphatase, especially when the concentration of EGB reached 150 µg/mL. EGB dose-dependently inhibited the adipogenic ability of BMSCs. The osteogenic-related genes (BMP-2, Runx2, Colla1) were overexpressed while the expression of genes involved in adipogenesis, such as PPAR-γ and ap2, was decreasing with the increase of EGB concentration. Our data proves that EGB inhibited adipocyte differentiation and enhanced osteogenic differentiation in BMSCs, but had no effect on the proliferation of BMSCs.