KDM6A is required in chondrogenic differentiation of PDLSCs by demethylation of H3K27me3, and EZH2 inhibitor could rescue chondrogenesis of PDLSCs after knockdown of KDM6A. It could be inferred that upregulation of KDM6A or application of EZH2 inhibitor might improve mesenchymal stem cell mediated cartilage regeneration in inflammatory tissue destruction such as osteoarthritis.
Insulin
resistance (IR) is one of the essential conditions in the
development of type 2 diabetes mellitus (T2DM). IR occurs in hepatic
cells when the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol
3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is downregulated;
thus, activating this pathway can significantly improve insulin sensitivity
and ameliorate T2DM. Tetrahedral framework nucleic acids (tFNAs),
a DNA nanomaterial, are synthesized from four single-stranded DNA
molecules. tFNAs possess excellent biocompatibility and good water
solubility and stability. tFNAs can promote cell proliferation, cell
autophagy, wound healing, and nerve regeneration by activating the
PI3K/Akt pathway. Herein, we explore the effects and underlying mechanisms
of tFNAs on IR. The results displayed that tFNAs could increase glucose
uptake and ameliorate IR by activating the IRS-1/PI3K/Akt pathway
in glucosamine (GlcN)-stimulated HepG2 cells. By employing a PI3K
inhibitor, we confirmed that tFNAs reduce IR through the PI3K/Akt
pathway. Moreover, tFNAs can promote hepatic cell proliferation and
inhibit GlcN-induced cell apoptosis. In a T2DM mouse model, tFNAs
reduce blood glucose levels and ameliorate hepatic IR via the PI3K/Akt pathway. Taken together, tFNAs can improve hepatic
IR and alleviate T2DM through the PI3K/Akt pathway, making contribution
to the potential application of tFNAs in T2DM.
It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHR1-luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants.
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