Objective To investigate the mechanism via which artesunate regulates the invasion and metastasis of colon cancer cells and the expression of members of the TGF-β1/Smad4 signaling pathway. Methods The cell counting kit 8 (CCK8), nude mouse xenograft model, Transwell invasion assay, and flow cytometry were used to investigate the effect of artesunate on the invasion and metastasis of colon cancer cells. Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of TGF-β1 and Smad4 proteins and mRNA, respectively. Results Artesunate inhibited the growth of transplanted tumor, cell proliferation, and invasion and promoted apoptosis. It inhibited TGF-β1 expression and promoted Smad4 expression. TGF-β1 inhibitors reversed the inhibitory effect of artesunate. Conclusion Artesunate can inhibit the growth of xenograft tumor in nude mice and its mode of action may be related to the TGF-β1/Smad4 signaling pathway.

Objective To investigate the effect oftopiramate on NACHT-LRR-PYD-containing protein 3 (NALP3) inflammasome and intedeukin (IL)-1β levels in trigeminal ganglion of migraine rats.Methods Forty adult male Sprague Dawley rats were randomly divided into blank group,saline group,model group,prevention control group,10 mg/kg topiramate group,30 mg/kg topiramate group,60 mg/kg topiramate group,and 90 mg/kg topiramate group (n=5).Inflammatory soup was used to stimulate the dual matter of rats repeatedly to induce migraine models:rats in the blank group were without any treatment,those in the saline group were given saline to stimulate the dual matter,different concentrations of topiramate group were given to migraine models of the 10 mg/kg topiramate group,30 mg/kg topiramate group,60 mg/kg topiramate group,and 90 mg/kg topiramate group,respectively,and migraine models of the prevention control group were given saline containing 1％ Tween80.Three h after the last treatment,the expressions of NALP3,caspase-1 precursor (pro-caspase-1),caspase-1 and IL-1β in trigeminal ganglion of rats were detected by Western blotting,and the best concentration oftopiramate was chosen for subsequent immunofluorescence experiments.Ten healthy male adult SD rats were randomly divided into control group and topiramate group (n=5);the expression levels of NALP3,caspase-1 and IL-1β in trigeminal ganglion of the two groups were detected by immunofluorescence.Results The expression levels ofNALP3,pro-caspase-1,caspase-1 and IL-1β were not significantly different between saline group and blank group (P＞0.05);the expression levels ofNALP3,pro-caspase-1,caspase-1 and IL-1β in the model group were significantly higher than those in the saline group (P＜0.05).The expression levels of NALP3,pro-caspase-1,caspase-1 and IL-1β in 60 mg/kg topiramate group and 90 mg/kg topiramate group were significantly lower than those in the prevention control group (P＜0.05).The fluorescence intensity ofNALP3,caspase-1 and IL-1β in topiramate group was significantly lower than that in control group.Condusion Topiramate can inhibit the expression of NALP3 inflammasome and IL-1β in the trigeminal ganglion of migraine rat models,and it is likely to be one of the important mechanisms for the prevention of migraine.

OBJECTIVE:To explore the association between the mitochondrial DNA(mtDNA)3537A/G,5351A/G variant and type 2diabetes mellitus(T2DM)in northem Chinese population.METHODS:The subjects including 614 patients with T2DM in Dalian City,61 of them were collected from family survey,497 of them were collected from Department of Endocrine,Dalian Municipal Central Hospital,and the remained 56 were selected from diverging T2DM patients in Dalian City.Additional 344 cases with normal carbohydrate toierance were served as controls.The mtDNA 3537A/G.5351A/G variants in 614 patients with T2DM and 334 healthy control subjects were examined.By sequencing the mtDNA in 24 cases and 26 controls,2 candidate SNPs in mtDNA were determined,and then genotyping was carried out by using PCR restriction fragment length polymorphism(PCR-RFLP)analysis.RESULTS:The frequency of mtDNA A3537G and A5351G mutation was 2.0%and 2.6% in T2DM patients,respectively,which was 2.1%and 4.2% in the control group.No significant difference had been observed between case and control(P＞0.05).After stratifying by body mass index and blood pressure,we found that the frequency of A5351 G in obesity patients with T2DM was 1.61%,and in obesity control was 15.38%,which had significant difference(P_(Fisher)=0.02,OR=2.76),however,A3537G stili showed no significant difference in all groups(P＞0.05).CONCLUSION:5351A/G in mtDNA ND2 gene may be a variance associated with T2DM in northem Chinese.