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Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3β are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI. Unlabelled Image • A new small molecule Y006 on acute myocardial infarction rat model is identified. • Y006 affects 11 proteins by a proteomics assay, including inflammation and apoptosis proteins. • Y006 exerts myocardial protection effects via blocking PLCG1, RhoA, and PI3K pathways. [ABSTRACT FROM AUTHOR]

TGF-β-induced alveolar epithelial cells apoptosis were involved in idiopathic pulmonary fibrosis (IPF). This study aimed to explore potential targets and mechanisms of IPF. mRNA and microRNA arrays were used to analyze differentially expressed genes and miRNAs. Several essential targets of TGF-β-SMADs and TGF-β-PI3K-AKT pathways were detected. miR-31 and miR-184 expression levels were positively correlated with smad6 and smad2/akt expression levels in IPF patients. TGF-β could induce miR-31 and suppress miR-184 levels in A549 cells. miR-31 was confirmed to bind to the smad6 -3′UTR and functionally suppress its expression. Down-regulated SMAD6 enhanced SMAD2/SMAD4 dimer formation and translocation due to its failure to prevent SMAD2 phosphorylation. In contrast, anti-fibrotic functions of miR-184 were abolished due to TGF-β directly suppressing miR-184 levels in A549 cells. When A549 was stimulated by TGF-β combined with or without miR-31 inhibitor/miR-184 mimic, it was showed that depleted miR-31 and/or increased miR-184 significantly ameliorated TGF-β-induced viability of A549 cells, as well as inhibited the expression of profibrotic factors, MMP7 and RUNX2. Inhibiting miR-31 and/or promoting miR-184 protect against TGF-β-induced fibrogenesis by respectively repressing the TGF-β-SMAD2 and TGF-β-PI3K-AKT signaling pathways, implying that miR-31/184 are potential targets and suggesting a new management strategy for IPF. Summary of the present study: Roles of miR-31 and miR-184 in TGF-β-induced -SMAD2 and –AKT-NF-κB pathways. TGF-β via its receptors activates SMAD2 and AKT (phosphorylation). Activated SMAD2 (p-SMAD2) and AKT (p-AKT) further transfer signals by forming a heterodimer with SMAD4 and phosphorylating NF-κBp65. In the nucleus, p-SMAD2/SMAD4 and NF-κBp65 bind to target gene promoters such as runx2 and mmp7 and promote gene expression, which results in pro-fibrosis effects. In addition, TGF-β and p-SMAD2/SMAD4 can respectively suppress miR-184 and elevate miR-31 expression. Upregulated miR-31 inhibits SMAD6 expression via binding to the 3′UTR of smad6 , and downregulated miR-184 becomes dysfunctional in suppressing both smad2 and akt expression, and all of these changes result in enhancing the activity of the TGF-β-SMAD2 and TGF-β-AKT-NF-κB pathways, and finally aggravate the process of pulmonary fibrosis. Unlabelled Image • miR-31 and miR-184 are involved in IPF through TGF-β-SMAD2 and AKT-NF-κB signaling pathways. • In IPF patients, expression of miR-31 and miR-184 is negatively correlated with smad6 and smad 2 , respectively. • miR-31 and miR-184 improve TGF-β-induced alveolar epithelial cells apoptosis. [ABSTRACT FROM AUTHOR]