Mutations and altered expression of deubiquitinating enzymes (DUBs) have been found associated with many human diseases including cancers. In this study, Ubiquitin specific protease 1 (USP1) expression was found significantly increased in some colorectal cancers (CRC). The elevated USP1 level was associated with short overall survival of patients and with advanced stages of cancers. In cultured CRC cells, knockdown of USP1 induced growth arrest at G 2 /M of cell cycle and reduced the expression of anti-apoptotic proteins Bcl-2 and Mcl-1. Its knockdown also led to reduction of DNA-repair related substrates FANCD2 and ID1. Further investigations found that small molecular inhibitor of USP1 ML323 sensitized CRC cells to DNA-targeting chemotherapeutics, including doxorubicin, TOPI/II inhibitors, and PARP inhibitor, but not to 5-Fu. These results indicate that USP1 plays a critical in colorectal cancer cell survival and is a promising target for anti-colorectal cancer chemotherapy. Targeting USP1 may represent an effective strategy to regulate the DNA-repairing system.
This work reports a facile and effective approach for preparing graphene quantum dots co-doped with nitrogen and sulfur (N-S/GQDs). The proposed method comprised pyrolysis of citric acid with glutathione and dialysis treatment. The fabricated N-S/GQDs exhibited blue luminescence and a high fluorescence quantum yield of 36.3%. N-S/GQDs can be sensitively quenched by Fe 3+ , which was absorbed on the edge of N-S/GQDs through the coordination interaction between Fe 3+ and N, S elements. The subsequent introduction of pyrophosphate ion (PPi) resulted in the recovery of the fluorescence of Fe 3+-quenched N-S/GQDs. The stronger coordination reactivity between Fe 3+ and PPi induced changes in fluorescence. PPi concentration was facilely quantified through the recovered amplitudes of the fluorescence intensities of N-S/GQDs. Under the optimized experimental condition, increased fluorescence intensity showed a linear relationship to PPi concentration (1 μM to 1000μM) in serum samples. Additionally, the proposed method featured sensitive and selectivity for the detection of PPi in synovial fluid, suggesting the potential application for simple and accurate clinical diagnosis of arthritic diseases.
ObjectivesThere is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA.MethodsWe investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared.ResultsThe results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = −0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency.ConclusionWe conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.
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