Objective To investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

Objective: To observe the inlfuence of simvastatin combining ezetimibe on blood levels of glucose and lipids in patients of acute coronary syndrome (ACS) with impaired glucose tolerance (IGT).
Methods: A total of 316 patients with ACS and IGT were randomly divided into 2 groups: Treatment group, the patients received simvastatin 20 mg/day with ezetimibe 10 mg/day,n=160 and Control group, the patients received simvastatin 20 mg/day,n=156. All patients were treated for 24 months. Blood levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were observed at 6, 12 and 24 months of medication; fasting blood glucose (FBG), 2 hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c) and the number of patients with new onset diabetes were examined at 6 days and 12, 24 months of medication.
Results:①In Treatment group, at 6 months of medication, blood levels of TC (mmol/L) and LDL-C (mmol/L) were (3.5 ± 0.5) and (2.1 ± 0.4) which were both lower than baseline levels (5.2±1.2) and (3.5±0.5),P<0.05; at 12 and 24 months, TC and LDL-C were (3.1 ± 1.0), (1.8 ± 0.6) and (3.0 ± 0.6), (1.8 ± 0.5), TC and LDL-C were consistently decreased, all P<0.05. In Control group, at 6 months of medication, TC and LDL-C were (4.0 ± 0.5) and (2.4 ± 0.5) which were both lower than baseline levels (5.3 ± 0.8) and (3.1 ± 0.4),P<0.05; at 12 and 24 months, TC and LDL-C were (3.8 ± 0.6), (2.3 ± 0.6) and (3.7 ± 0.5), (2.1 ± 0.7), allP<0.05. TC and LDL-C levels in Treatment group were lower than Control group at 6, 12 and 24 months of medication, allP<0.05.②In Treatment group, FBG (mmol/L) levels at 12 and 24 months were similar to 6 days,P>0.05; HbA1c at 12 and 24 months were similar to baseline,P>0.05; 2hPG (mmol/L) level at 24 months was higher than 6 days (9.5 ± 1.1) vs (8.7 ± 1.0),P<0.05; there were 26 patients with new onset diabetes at 24 months after medication. In Control group, 2hPG level at 24 months was higher than 6 days (9.6 ± 0.8) vs (8.7±0.7); there were 25 patients with new onset diabetes at 24 months after medication. The levels of FBG, 2hPG, HbA1c and the number of patients with new onset diabetes were similar between 2 groups, allP>0.05.
Conclusion: Ezetimibe combining simvastatin may better reduce blood lipids, while it had no real effect on blood glucose metabolism in patients with ACS and IGT.