Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis.

Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 µM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.

Determination of Phenolic Compounds in Environmental Water by HPLC Combination with On-Line Solid-Phase Extraction Using Molecularly Imprinted Polymers.

A novel molecularly imprinted polymer (MIP) was synthesized using halloysite nanotubes (HNT) as matrix, ß-cyclodextrin (ß-CD) and methyl propyl acid (MAA) as functional monomers, and 2,4,6-TCP as template molecule by graft copolymerization. Infrared spectroscopy and transmission electron microscopy (TEM) were used to characterize the as-synthesized imprinted polymer. The selective recognizability of the MIP towards four phenolic analogs were determined and the recognition coefficients for 2,4,6-TCP, 2,6-DCP, 4-CP and phenol were found to be 2.17, 1.85, 2.02 and 1.36, respectively. Using as the packing material of solid-phase extraction, the imprinted polymer has been applied to on-line extraction of the four phenolic compounds in environmental water. The corresponding analytical methods to determine these four phenolic compounds have been developed. Good linear relationships were obtained over the range of 0.05-5.0 mg x L(-1). The average recoveries for spiked samples were in the range of 74.8-97.2%, and the detection limits for 2,4,6-TCP, 2,6-DCP, p-chlorophenol, phenol were 0.19, 0.20, 0.75, 0.73 mg x L(-1), respectively. The method is rapid, accurate and high selectivity. It was feasible for the determination of trace level phenolic compounds in environmental samples.