Background/Aims: Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. And it is tightly related to chronic inflammation. Interleukin-38 (IL-38) represents a new member of anti-inflammatory cytokines. Thus we studied the important role of IL-38 in hyperlipidemia development and treatment. Methods: The mRNA level of IL-38 in PBMCs (peripheral blood mononuclear cells) and serum IL-38 levels in hyperlipidemia patients and healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA). The hyperlipidemia patients were further divided into two groups (Sensitive and Resistant Group) according to their clinical response to Atorvastatin therapy. Finally, the effects of IL-38 on hyperlipidemia was evaluated in the mice model. Results: Data showed that the IL-38 mRNA and serum protein levels were higher in patients with hyperlipidemia compared with healthy controls. And the IL-38 mRNA and serum protein levels were higher in patients sensitive to Atorvastatin therapy than the resistant group. In vitro, IL-38 inhibited the production of IL-6, IL-1β and CRP in PBMCs of patients with hyperlipidemia. In the mice model of hyperlipidemia, IL-38 was also elevated during the hyperlipidemia development. Furthermore, the IL-38 over-expressed by adeno-associated virus significantly inhibited the hyperlipidemia development, inflammatory factor secretion and also the atherosclerosis process. Conclusion: Thus our data showed that IL-38 might present protective effects on hyperlipidemia treatment.
Background: Dysregulation of the proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial cause of atherosclerosis. MiR-637 exerts an antiproliferative effect on multiple human cells. Its impact on atherosclerosis remains largely unexplored. Methods: Real-time PCR was used to determine miR-637 expression in samples from atherosclerosis patients and animal models. Its expression in VSMC dysfunction models (induced by ox-LDL) was also measured. The proliferation and migration of VSMCs were respectively tested using CCK-8 and Transwell assays, and apoptosis was measured using flow cytometry. The Targetscan database was used to predict the target genes of miR-637. Interaction between miR-637 and the potential target gene was validated via real-time PCR, western blotting and a luciferase reporter assay. Results: MiR-637 expression was significantly lower in atherosclerosis patient and animal model samples. It also decreased in a dose-and time-dependent manner in animal models with ox-LDL-induced atherosclerosis. Transfection with miR-637 mimics suppressed the proliferation and migration of VSMCs while promoting apoptosis, while transfection with miR-637 inhibitors had the opposite effects. We also validated that insulin-like growth factor-2 (IGF-2), a crucial factor in the pathogenesis of atherosclerosis, serves as a target gene for miR-637. Conclusion: MiR-637 targeting IGF-2 contributes to atherosclerosis inhibition and could be a potential target for this disease.
The aim of the study is to investigate the impact of SELP and IL-6 genetic single-nucleotide polymorphisms (SNPs) and its gene-gene interaction on cardiovascular disease (CVD) risk based on Chinese population. A total of 1082 subjects (519 males, 563 females), with a mean age of 53.9 ± 13.1 years, were selected, including 540 CVD patients and 542 normal control participants. Logistic regression model was used to examine the association between six SNPs and CVD risk. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the gene-gene interaction. CVD risk was significantly higher in carriers with rs1800805-A allele than those with GG genotype (GA + AA vs. GG), adjusted OR (95% CI) = 1.69 (1.31-2.16), and CVD risk was also higher in carriers with rs6136-AC or CC genotype than those with AA genotype (AC + CC vs. AA), adjusted OR (95% CI) = 1.78 (1.28-2.26), and higher in carriers with rs1800796-GC or CC genotype than those with GG genotype (CC + GC vs. GG), adjusted OR (95% CI) = 1.67 (1.25-2.14). GMDR analysis suggested a significant two-locus model (p = 0.0010) involving rs1800805 and rs1800796. Overall, the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.17%, and participants with rs1800805-GA or AA and rs1800796-GC or CC genotype have the highest CVD risk, compared to participants with rs1800805-GG and rs1800796-GG genotypes, and OR (95% CI) was 2.52 (1.81-2.66). Our results support an important association of rs1800805, rs6136 minor allele of SELP gene, rs1800796 within IL-6 gene, and additional interaction between rs1800805 and rs1800796 with increased risk of CVD.
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, and its mortality rate is 10% to 20%. However, there are currently only a few markers to predict the prognosis in patients with TTP. We aimed to identify several clinical indices and laboratory parameters for predicting the prognosis of TTP at admission. A single-centre observational cohort study that included patients with TTP from the First Affiliated Hospital of Zhengzhou University in China was conducted from January 1, 2012 to November 30, 2018. The primary outcome was prognosis, including in-hospital mortality, major thromboembolic events, or failure to achieve remission at discharge. We used the random forest method to identify the best set of predictors. Eighty-seven patients with TTP were identified, of whom 12 died during the treatment. The total number of patients within-hospital mortality, major thromboembolic events, and failure to achieve remission at discharge was 58. The machine learning method showed that the D-dimer level was the strongest predictor of the primary outcome. Receiver operating characteristic (ROC) analysis demonstrated that the sensitivity and specificity of the D-dimer level alone for identifying high-risk patients were 78% and 81%, respectively, with an optimum diagnostic cut-off value of 770 ng/mL. The area under the ROC curve (AUC) was 0.80, and the 95% confidence interval (CI) was 0.70 to 0.90. This study found that the D-dimer level exhibited a good predictive ability for prognosis in patients with TTP. These findings may aid in the development of new and intensive treatment strategies to achieve remission among high-risk patients. However, external validation is necessary to confirm the generalizability of our approach across populations and treatment practices.
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