Natural emodin reduces myocardial ischemia/reperfusion injury by modulating the RUNX1/miR­142­3p/DRD2 pathway and attenuating inflammation.

Acute myocardial infarction is one of the leading causes of death worldwide. Although timely reperfusion could attenuate myocardial ischemia injury and reduce mortality, it causes severe secondary injury to the myocardium known as myocardial ischemia/reperfusion injury (MIRI) with unmet clinical needs. Emodin has a protective effect on MIRI in rodents. However, the precise mechanism underlying its pharmacological effect remains poorly understood. Accordingly, the present study used mRNA and microRNA (miRNA) sequencing based on MIRI mouse models to determine the mechanism involved. Emodin was found to prevent MIRI and attenuate the inflammation of myocardium in the MIRI model. In addition, by using an interdisciplinary approach, the present study uncovered that emodin suppressed the runt-related transcription factor 1 (RUNX1), which is a transcription factor of miR-142-3p, in either MIRI or the hypoxia/reoxygenation injury model. Furthermore, miR-142-3p can negatively regulate dopamine receptor D2 (DRD2), which acted as an anti-inflammatory factor to suppress NF-κB-dependent inflammation and prevent MIRI. These results were demonstrated by both cellular hypoxia/reoxygenation and mouse MIRI models. Overall, the present study provided an unrevealed molecular mechanism for emodin function. Emodin could inhibit NF-κB-triggered inflammation in MIRI by regulating the RUNX1/miR-142-3p/DRD2 pathway. Therefore, the RUNX1/miR-142-3p/DRD2 pathway presented a novel target for MIRI treatment, and the application of emodin in clinical practice may improve the treatment of MIRI.

Effect of pidotimod combined with azithromycin on children with mycoplasma pneumonia and the expression levels of IL-10 and G-CSF in serum.

This study explored the effect of pidotimod combined with azithromycin on children with mycoplasma pneumonia and the expression of interleukin-10 (IL-10) and granulocyte colony-stimulating factor (G-CSF) in serum. The clinical data of 149 children with mycoplasma pneumonia from May 2014 to May 2018 in Zhangqiu District Maternal and Child Health Care Hospital were collected. Among them, 70 children treated with azithromycin sequential therapy were the control group, and 79 children treated with the combination of pidotimod and azithromycin were the observation group. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to determine the expression levels of IL-10 and G-CSF in serum before and after treatment. Pearson's correlation coefficient was used to analyze the correlation between IL-10 and G-CSF in serum. The total effective rate in the observation group (94.94%) was significantly higher than that in the control group (81.43%) (P<0.05). There was no significant difference in the expression levels of IL-10 and G-CSF between the two groups before treatment (P>0.05). The expression levels of IL-10 and G-CSF in the two groups after treatment were significantly lower than those before treatment (P<0.05). After treatment, the expression levels of IL-10 and G-CSF in serum in the observation group were significantly lower than those in the control group. There was a significant positive correlation between the expression levels of IL-10 and G-CSF before and after treatment in the observation group (P<0.05), and a significant positive correlation between the expression levels of IL-10 and G-CSF before and after treatment in the control group (P<0.05). Compared with sequential treatment with azithromycin alone, pidotimod combined with azithromycin significantly reduced the expression levels of IL-10 and G-CSF in serum of children with mycoplasma pneumonia, improved the curative effect and reduced the occurrence of adverse reactions, which has high application value in clinic.

TGF-ß1 induces airway smooth muscle cell proliferation and remodeling in asthmatic mice by up-regulating miR-181a and suppressing PTEN.

Several studies have shown that transforming growth factor ß1 (TGF-ß1) plays a crucial role in remodeling and proliferation of airway smooth muscle cells (ASMCs). However, its molecular mechanism needs to be further studied. TGF-ß1 can up-regulate the level of miR-181a in multiple cells, while miR-181a is expressed in asthma. We asked whether TGF-ß1 plays a role in asthma through regulation of miR-181a. For this purpose, ASMCs were stimulated with TGF-ß1 and the expression level of miR-181a and extracellular matrix (ECM) protein were measured by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The cell proliferation and migration ability of TGF-ß1-induced ASMCs were detected by Cell Counting Kit-8 (CCK-8) and transwell method, respectively. Luciferase assay was used to verify whether PTEN is a direct target of miR-181a in ASMCs. miR-181a expression level was increased in TGF-ß1-induced ASMCs and miR-181a could inhibit the cell proliferation, migration, and excessive secretion of ECM. The results of the luciferase assay showed that miR-181a plays a role in TGF-ß1-induced ASMCs targeting PTEN and the results of western blotting indicated that TGF-ß1 could activate Akt/mTOR signaling pathway by up-regulating miR-181a and down-regulating siPTEN. In conclusion, TGF-ß1 may induce airway smooth muscle cell proliferation and airway remodeling of asthma by up-regulating miR-181a and suppressing PTEN, and miR-181a inhibitor may function as an inhibitor of ASMCs proliferation through inactivation of the Akt/mTOR pathway.