1.Mechanism of KIAA1199 promoting osteosarcoma cell proliferation by regulating ferroptosis
Huisong GONG ; Jun CHENG ; Youwen DENG
Journal of Navy Medicine 2025;46(4):392-400
Objective To investigate the effect and mechanism of cell migration-induced protein(KIAA1199)on the proliferation of osteosarcoma cells.Methods The KIAA1199 gene was knocked down or overexpressed in osteosarcoma cell lines(HOS and U2OS)with high KIAA1199 expression.The expression of KIAA1199 was confirmed by RT-PCR and Western blotting.CCK-8 and colony formation assays were used to determine the effect of KIAA1199 on cell proliferation.CCK-8 and cell viability assays were used to confirm that KIAA1199 promoted osteosarcoma cell proliferation by inhibiting ferroptosis.The BODIPY 581/591 probe was used to investigate the effect of KIAA1199 on cell lipid peroxidation.The effect of KIAA1199 on PTGS2 was investigated by RT-PCR,and the level of ferroptosis related proteins(GPX4,SLC7A11,DHODH,and FSP1)were determined by Western blotting.Results KIAA1199 knockdown inhibited osteosarcoma cell proliferation,which mainly worked by promoting ferroptosis in osteosarcoma cells.Ferrostatin-1(Fer-1,a ferroptosis inhibitor)could reverse the proliferation inhibition caused by KIAA1199 knockdown.Osteosarcoma cells with KIAA1199 knockdown were more sensitive to ferroptosis inducer Erastin,and their lipid peroxidation and PTGS2 mRNA increased significantly.KIAA1199 knockdown resulted in lower expression of GPX4 and SLC7A11 proteins and a lower GSH/GSSG ratio.On the other hand,KIAA1199 overexpression promoted osteosarcoma cell proliferation,made cells more tolerant to Erastin,significantly reduced lipid peroxidation and PTGS2 mRNA levels,and obviously increased the protein expression levels of GPX4 and SLC7A11.Conclusion KIAA1199 inhibits ferroptosis through SLC7A11/GSH/GPX4 pathway,thereby promoting osteosarcoma cell proliferation.
2.High-resolution magnetic resonance angiography for assessing the correlation between plaque characteristics of middle cerebral artery stenosis and in-stent restenosis
Yu GONG ; Miao YU ; Tian TIAN ; Jiwei ZHANG ; Jun HU ; Zhixin CUI ; Xuedong BAI ; Fengwei HAN ; Huisong CHU ; Zhansen WANG ; Tiemin HU
Journal of Interventional Radiology 2024;33(12):1282-1287
Objective By using high-resolution magnetic resonance angiography to display the vascular wall imaging so as to evaluate the relationship between plaque characteristics and postoperative in-stent restenosis(ISR)in patients with middle cerebral artery stenosis.Methods A total of 66 patients with symptomatic atherosclerotic middle cerebral artery stenosis,who were admitted to the Affiliated Hospital of Chengde Medical College of China from January 2019 to March 2023,were enrolled in this study.Before stent implantation,all the 66 patients completed high-resolution magnetic resonance angiography.According to the postoperative imaging follow-up results,the patients were divided into ISR group and non-ISR group.The preoperative plaque characteristics,which were assessed by high-resolution magnetic resonance imaging,were compared between the two groups.Results ISR group had 14 patients and non-ISR group had 52 patients.Most of the plaques were located in the inferior lateral wall(37.8%)and the ventral lateral wall(28.7%),in which no statistically significant difference existed between the two groups(P>0.05).Compared with non-ISR group,in ISR group the negative remodeling degree was obviously higher and the difference between the two groups was statistically significant(x2=6.026,P=0.049).The plaque load in ISR group and non-ISR group was 79.09±8.82 and 69.46±10.49 respectively,and the difference between the two groups was statistically significant(t=3.143,P=0.003).The homocysteine level in ISR group and non-ISR group was(16.02±4.24)mol/L and(12.05±3.34)mol/L respectively,and the difference between the two groups was statistically significant(t=3.717,P<0.001).In ISR group,there were more significantly contrast-enhanced plaques(78.5%vs.42.3%),with statistically significant difference(x2=6.311,P=0.043).Multivariate logistic regression analysis showed that plaque load(OR=1.225,95%CI:1.040-1.443,P=0.015)and homocysteine level(OR=1.676,95%CI:1.150-2.442,P=0.007)were the independent risk factors for ISR.ROC curve analysis showed that in predicting ISR,the AUC,specificity and sensitivity of the plaque load were 0.765(95%CI:0.622-0.908,P=0.002),0.731 and 0.714 respectively,which of the homocysteine level were 0.767(95%CI:0.623-0.911,P=0.002),0.942 and 0.500 respectively.The combination use of plaque load and homocysteine level could achieve the best predictive effect,its AUC,specificity and sensitivity were 0.887(95%CI:0.794-0.981,P<0.001),0.904 and 0.714 respectively.Conclusion The plaque load assessed by high-resolution magnetic resonance imaging and the homocysteine level have higher specificity and sensitivity in predicting ISR in patients with middle cerebral artery stenosis.

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