Florofangchinoline inhibits proliferation of osteosarcoma cells via targeting of histone H3 lysine 27 trimethylation and AMPK activation

Purpose: To investigate the effect of florofangchinoline on osteosarcoma cell growth in vitro, and the underlying mechanism of action.Methods: Changes in the viability of KHOS and Saos-2 cells were measured using water soluble tetrazolium salt (WST) assay, while apoptosis was determined using Annexin V/PI staining and flow cytometry. Increases in mtDNA, and expressions of PGC-1α and TFAM were assayed with immunoblot analysis and quantitative real-time polymerase chain reaction (qPCR), respectively.Results: Microscopic examination of florofangchinoline-treated cells showed significant decrease in cell density, relative to control cells (p < 0.05). Treatment with 10 μM florofangchinoline increased apoptosis in KHOS and Saos-2 cells to 56.32 and 63.75 %, respectively (p < 0.05). Florofangchinoline treatment markedly enhanced cleavage of caspase-3, caspase-8, caspase-9 and PARP. It elevated Bax level and reduced Bcl-2 in KHOS and Saos-2 cells. Moreover, florofangchinoline increased p21 and p-AMPKα levels, and mtDNA counts in KHOS and Saos-2 cells (p < 0.05). Moreover, in florofangchinoline-treated KHOS cells, the expressions of EED, EZH2 and SUZ12 were significantly suppressed (p < 0.05).Conclusion: Florofangchinoline inhibits osteosarcoma cell viability by activation of apoptosis. Moreover, it activates AMPK and down-regulates  histone H3 lysine 27 trimethylation in osteosarcoma cells. Therefore, florofangchinoline has potentials for development as a therapeutic drug forosteosarcoma. Keywords: Osteosarcoma, Histone H3, Florofangchinoline, Apoptosis, Chemotherapeuti

Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice

Dry skin pruritus is common in the elderly. Recent reports show that T-cell signal path is involved in dry skin pruritus. Zeta-chain-associated protein kinase 70 (ZAP70), as a T-cell receptor, may induce interleukin 2 (IL-2) secretion and promote nerve growth factor (NGF) secretion in skin. This study aimed to detect the alteration of ZAP70 in a mice model with dry skin pruritus. The C57BL mice with 5 months and 22 months were used as experimental animal. Following a 5-day period of treatment of back with a mixture of acetone-diethyl-ether-water (AEW), mice exhibited a significant increase in spontaneous scratching behavior directed to the treated back compared to control animals in which back was similarly treated with water only (W). After AEW process, spontaneous scratching in 22-month AEW mice was increased compared to 5-month AEW mice. Western blot and real-time quantitative PCR data analysis showed that ZAP70 expression was significantly increased in 22-month AEW mice compared with 5-month AEW mice. ELISA data showed that secretions of IL-2 and NGF in 22-month AEW mice were higher than 5-month AEW mice. Our results indicate that increased ZAP70 is involved in dry skin in elderly pruritus. Increased secretion of IL-2 and NGF may induce dry skin itch

Microstructured graphene arrays for highly sensitive flexible tactile sensors

A highly sensitive tactile sensor is devised by applying microstructured graphene arrays as sensitive layers. The combination of graphene and anisotropic microstructures endows this sensor with an ultra-high sensitivity of –5.53 kPa−1, an ultra-fast response time of only 0.2 ms, as well as good reliability, rendering it promising for the application of tactile sensing in artificial skin and human–machine interface