Objective: Period1 (PER1), a core circadian gene, not only modulates circadian rhythm but may also play an important role in other biological processes, including pathways involved in the proliferation and apoptosis of tumor cells. In this study, we investigated the mechanism by which the downregulated expression of PER1 promotes the apoptosis of wild-type P53 human glioma U343 cells exposed to X-rays. Methods:U343 cells were exposed to 6 mV 10 Gy X-ray irradiation after infection with an shRNA lentivirus to reduce the expression of PER1 and were analyzed by SCGE analysis, flow cytometry, qRT-PCR, and western blotting. Result: SCGE analysis revealed that compared with the controls, U343 cells expressing low levels of PER1 showed minor DNA damage when exposed to X-ray irradiation (P<0.05), and the flow cytometry assay showed lower death rates (P<0.05). RT-PCR and western blot analysis both revealed decreased expression of CHK2 and P53, which regulate DNA damage and repair via the CHK2-P53 pathway, and decreased expression of C-MYC, which is related to cell apoptosis. Conclusion:Our research suggests that PER1 may play an important role in tumor radiotherapy, which is attributable to enhanced chk2-P53 signaling and proapoptotic processes. These findings provide a new target for the clinical treatment of glioma and a reliable basis for postradiation therapy and gene therapy for glioma and other cancers.

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Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the elderly population and significantly impacts the normal life of OA patients. It has been reported that the development of pathological cell senescence in chondrocytes is involved in the pathogenesis of OA. Celecoxib is a common non-steroidal anti-inflammatory drug, and it has been recently reported to exert therapeutic effects on OA. However, its underlying mechanism is still unclear. The present study intends to explore its mechanism and provide fundamental evidence for the application of Celecoxib in the treatment of clinical OA. Tumor necrosis factor-α (TNF-α) was utilized to establish an in vitro model of chondrocytes senescence. The elevated reactive oxygen species (ROS) generation, increased cell cycle arrest in G0/G1 phase, reduced telomerase activity, and upregulated senescence-associatedβ-galactosidase (SA-β-Gal) staining were all observed in TNF-α-treated chondrocytes, which were then dramatically reversed by 10 and 20 μM Celecoxib. In addition, the upregulated DNA damage biomarkers, p-ATM, and p-CHK2, observed in TNF-α-treated chondrocytes were significantly downregulated by 10 and 20 μM Celecoxib. Lastly, the expression level of p21 and p53 was greatly elevated in chondrocytes by stimulation with TNF-α which was then pronouncedly repressed by treatment with Celecoxib. Taken together, our data reveal that Celecoxib ameliorated TNF-α-induced cellular senescence in human chondrocytes.

Paraquat (PQ) is a potent toxicant for humans, and poisoning with PQ is associated with high mortality. Patients with severe PQ-induced poisoning may die of multiple organ failure involving the circulatory and respiratory systems. Death resulting from epilepsy-like convulsions, which are infrequently noted reported with PQ poisoning, is observed clinically with this condition. This study presents the clinical data of five patients with severe PQ-induced poisoning who died of epilepsy-like convulsions, and related publications were reviewed in order to investigate the pathogenesis, clinical manifestations, and prognosis of these convulsions. Our results may help prevent this event and improve the success of treatment.