[Intervention Effect and Mechanism of Regulating MiR-155 on Young Rats with Dysfunction of Blood Coagulation].

OBJECTIVE: To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation. METHODS: Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models. Twenty-four rats successfully established models and were randomly divided into three groups: model group, up-regulated miR-155 group and down-regulated miR-155 group, with 8 rats in each group. The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction. The changes of coagulation factors and coagulation indicators were observed. Liver pathological tissues were observed by HE staining. The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot. RESULTS: Compared with model group, the expressions of HMGB1, RAGE, TLR2, TLR4 and NF-κB were significantly increased in up-regulated miR-155 group (all P < 0.05), while decreased in down-regulated miR-155 group (all P < 0.05). Compared with model group, the expressions of coagulation factor Ⅱ, Ⅶ, Ⅸ, and Ⅹ were significantly decreased in up-regulated miR-155 group (all P < 0.05), while increased in down-regulated miR-155 group (P < 0.05). There was no significant difference in the expression of coagulation factor Ⅺ among the three groups (P >0.05). Compared with model group, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower and fibrinogen (FIB) was higher in up-regulated miR-155 group (all P < 0.05), while in the down-regulated miR-155 group they were opposite. CONCLUSION: Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy, and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.

MiR-185-5p measurement assists in reflecting Th1/Th2 cell imbalance, inflammatory cytokine production, and exacerbation risk for childhood asthma.

BACKGROUND: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma. METHODS: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay. RESULTS: MiR-185-5p was increased in childhood asthma patients versus HCs [median (interquartile range (IQR)): 2.315 (1.770-3.855) versus 1.005 (0.655-1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1ß (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1ß or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070-4.905) versus 1.900 (1.525-2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010). CONCLUSION: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients.