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.
Topographical cues of DMLS surfaces have greater potential for the induction of osteogenic differentiation of BMSCs than SLA and Ti surfaces both in vitro and in vivo. A potential epigenetic mechanism is that the appropriate topography allows rapid H3K27 demethylation and an increased H3K4me3 level at the promoter region of osteogenesis-associated genes during the osteogenic differentiation of BMSCs.
Background and Objective This study investigated the effects and underlying mechanisms of azithromycin (AZM) treatment on the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) after their stimulation with TNF-α in vitro. Methods. PDLSCs were isolated from periodontal ligaments from extracted teeth, and MTS assay was used to evaluate whether AZM and TNF-α had toxic effects on PDLSCs viability and proliferation. After stimulating PDLSCs with TNF-α and AZM, we analyzed alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red staining to detect osteogenic differentiation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the mRNA expression of osteogenic-related genes, including RUNX2, OCN, and BSP. Western blotting was used to measure the NF-κB signaling pathway proteins p65, phosphorylated p65, IκB-α, phosphorylated IκB-α, and β-catenin as well as the apoptosis-related proteins caspase-8 and caspase-3. Annexin V assay was used to detect PDLSCs apoptosis. Results TNF-α stimulation of PDLSCs decreased alkaline phosphatase and alizarin red staining, alkaline phosphatase activity, and mRNA expression of RUNX2, OCN, and BSP in osteogenic-conditioned medium. AZM enhanced the osteogenic differentiation of PDLSCs that were stimulated with TNF-α. Western blot analysis showed that β-catenin, phosphorated p65, and phosphorylated IκB-α protein expression decreased in PDLSCs treated with AZM. In addition, pretreatment of PDLSCs with AZM (10 μg/ml, 20 μg/ml) prevented TNF-α-induced apoptosis by decreasing caspase-8 and caspase-3 expression. Conclusions Our results showed that AZM promotes PDLSCs osteogenic differentiation in an inflammatory microenvironment by inhibiting the WNT and NF-κB signaling pathways and by suppressing TNF-α-induced apoptosis. This suggests that AZM has potential as a clinical therapeutic for periodontitis.
We reviewed the outcome for 211 women undergoing a planned en caul (within intact membranes) cesarean section and for 836 control women with conventional lower segment section, in the period 2001-2010 at a university-affiliated hospital in China, where the former technique has been practiced. Of the intended en caul sections there were 141 successful deliveries (66.8%), and 70 that failed and were converted to conventional lower segment cesarean section. Maternal blood loss was similar for both operation types, but the rate of asphyxia was significantly lower among preterm infants delivered by the en caul method than in the control cases. Multivariate logistic regression revealed that the volume of amniotic fluid, a low Bishop score and high birthweight were associated with failed en caul deliveries. Cesarean section en caul can be a safer option than lower segment section when preterm delivery is required.
A novel dual-drug delivery system (DDDS) for cancer chemotherapy has been established by employing highly purified and mildly oxidized large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) as the vector. The LID-MWCNTs were modified with the antitumor drugs, cisplatin (CDDP) and doxorubicin (DOX). CDDP was encapsulated inside the nanotube vectors by a wet-chemical approach while DOX was attached to the external surfaces through non-covalently interaction. The loading efficiencies of CDDP and DOX were as high as 84.56 and 192.67%, respectively. Notably, after CDDP was encapsulated inside the nanotubes, a three-level blocking strategy, which included polyethylene glycol, folic acid and DOX, was employed to block the CDDP exits at different levels. The pH-sensitive release profile of CDDP was demonstrated using a modified characterization method, as well as that of DOX. Finally, the anticancer activity of the DDDS on MCF-7 cells was tested and a synergistic effect was recorded. This work is part of our LID-MWCNTs based drug delivery system studies, and provides a basis for developing a novel comprehensive antitumor treatment that combines chemotherapy and photothermal therapy.
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