Background & Aims
Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome.
Methods
C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, i.p.) was administered for seven days and 30 min before and after MCAO. Their brain tissues were evaluated for NLRP3 inflammasome and Sirtuin-1 (Sirt-1) expression. An intracerebroventricular injection of Sirt-1 siRNA was administered to assess the activation of the NLRP3 inflammasome.
Results
Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation.
Conclusion
Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.
ADP-ribosylation factor 3 (ARF3) has confirmed participate in diverse biological processes in many cancers. However, the expression patterns and roles of ARF3 in gastric cancer (GC) remains largely unknown. In our study, by using qRT-PCR and western blot, we found that, in In GC tissues and cells, the expression of ARF3 was significantly down-regulated. Functional experiments demonstrated that ARF3 inhibited proliferation, induced cycle arrest and enhanced apoptosis of GC cells. Moreover, by performing western blot, we found that ARF3 could regulate the protein expression of key factors of AKT and ERK pathway. Using orthotopic xenograft mouse models, it is showed that ARF3 could inhibit GC tumorigenesis in vivo. To sum up, ARF3 may suppress proliferation, induced cycle arrest and promotes apoptosis of GC by modulating AKT and ERK pathway. It might act as a potential biomarker for GC prognosis.
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