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ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.
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Objective@#To explore the dose-response relationship between pre-pregnancy body mass index (BMI) and gestational diabetes mellitus (GDM), so as to provide insights into the cut-off values of pre-pregnancy BMI and optimizing GDM prevention and control strategies. @*Methods@#Pregnant women that admitted to Zhengzhou Central hospital in 2021 were recruited, and demographics, family history, pregnancy and delivery history and blood glucose levels during pregnancy were collected. The dose-response relationship between pre-pregnancy BMI and GDM was analyzed using restricted cubic spline (RCS) analysis. The predictive ability of pre-pregnancy BMI for GDM risk was evaluated using receiver operating characteristic (ROC) curve. @*Results@#A total of 2 279 participants were included in the study. The median age was 29.0 (interquartile range, 5.0) years. The median pre-pregnancy BMI was 21.1 (interquartile range, 3.8) kg/m2. There were 312 underweight women (13.69%), 825 women with low-normal weight (36.20%), 730 women with high-normal weight (32.03%), 345 overweight women (15.14%) and 67 obese women (2.94%).The prevalence of GDM was 17.20%. RCS analysis suggested a linear dose-response relationship between age, pre-pregnancy BMI and GDM (P<0.05). When pre-pregnancy BMI was higher than 21.1 kg/m2, the risk of GDM increased with pre-pregnancy BMI (P<0.05). When women aged over 29.0 years, the risk of GDM increased with age, and the dose-response relationship of GDM caused by pre-pregnancy BMI was stronger in the women aged over 29.0 years than in the women aged 29.0 years and below (P<0.05). The area under curve (AUC) was 0.654 (95%CI: 0.624-0.684). If the cut-off value of pre-pregnancy BMI was 23.0 kg/m2, the Youden index, sensitivity and specificity was 0.238, 0.472 and 0.766, respectively. If it was 24.0 kg/m2, the Youden index, sensitivity and specificity was 0.195, 0.342 and 0.853, respectively. If it was 21.1 kg/m2, the Youden index, sensitivity and specificity was 0.213, 0.676 and 0.537, respectively.@* Conclusions @# There is a linear dose-response relationship between pre-pregnancy BMI and GDM, and higher than 21.1 kg/m2 of the pre-pregnancy BMI could increase the risk of GDM.
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SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.