OBJECTIVE: To study the expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis (LN). METHODS: A total of 92 children with LN who were admitted from January 2016 to May 2019 were enrolled as the LN group, among whom 17 had type II LN, 15 had type III LN, 36 had type IV LN, 18 had type V LN, and 6 had type VI LN. Forty healthy children who underwent physical examination were enrolled as the healthy control group. According to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the 92 children with LN were further divided into a stable LN group with 34 children (SLEDAI score <10) and an active LN group with 58 children (SLEDAI score ≥10). RT-PCR was used to measure the expression of miR-145 and miR-183 in plasma. The receiver operating characteristic (ROC) curve was used to analyze the value of plasma miR-145, miR-183, and anti-dsDNA antibody in the diagnosis of LN. Pearson correlation analysis was used to investigate the correlation of the expression levels of miR-145 and miR-183 in plasma with laboratory markers. RESULTS: The LN, active LN, and stable LN groups had significantly higher levels of anti-dsDNA antibody, C-reactive protein, serum creatinine (Scr), and blood urea nitrogen (BUN) than the control group (P<0.05). The active LN group had significantly higher SLEDAI score, anti-dsDNA antibody, Scr, and BUN than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower levels of complement C3, complement C4, and serum albumin (Alb) than the control group (P<0.05). The active LN group had a significantly lower level of Alb than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01). The active LN group had significantly lower plasma levels of miR-145 and miR-183 than the stable LN group (P<0.01). The children with difference types of LN had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01), and the type V-VI group and the type IV group had significantly lower plasma levels of miR-145 and miR-183 than the type II-III group (P<0.01). The ROC curve analysis showed that the optimal cut-off values of plasma miR-145, miR-183, and anti-dsDNA antibody were 1.05, 0.62, and 186.30 IU/mL respectively, in the diagnosis of LN, and the combination of these three indices had the largest area under the ROC curve of 0.896 (95%CI: 0.835-0.955), with a sensitivity of 90.5% and a specificity of 84.2%. In the children with LN, the plasma levels of miR-145 and miR-183 were negatively correlated with SLEDAI score, anti-dsDNA antibody, Scr, and BUN (P<0.05) and were positively correlated with complement C3, complement C4, and Alb (P<0.05). CONCLUSIONS There are significant reductions in the expression levels of miR-145 and miR-183 in plasma in children with LN, which are correlated with the activity level and pathological typing of LN. Combined measurement of miR-145, miR-183, and anti-dsDNA antibody has a high value in the diagnosis of LN.
Biomarkers ; Child ; Complement C4 ; Humans ; Lupus Nephritis ; genetics ; MicroRNAs ; genetics ; ROC Curve

OBJECTIVE: To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. METHODS: Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. RESULTS: Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). CONCLUSIONS Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; MicroRNAs ; Rats ; Triterpenes