Objective: To investigate the effects of adiponectin (APN, also known as ADIPOQ) -related miR- 371b-5p with differential expressions in the epicardial adipose tissue (EAT) and plasma in the patients with coronary artery disease CAD) on the secretions of APN, KruppelTike factor 4(KLF4), interleukin-6 (IL-6) and monocyte chemokine 1 (MCP-1), and to elucidate the mechanism of action of miR-371b-5p in CAD. Methods: The EAT and blood samples were collected from the patients with CAD (CAD group, n= 34) and non-CAD (non-CAD group, n=16). Real-time quantitative PCR qRT-PCR) was used to detect the expression levels of miR-371b-5p in the EAT and plasma of the patients in two groups. The successfully induced 3T3-L1 preadipocytes were divided into (without any treatment), miR-371b-5p over-expression group (transfected with miR-371b-5p mimics) and miR- 371b-5p inhibitor group (transfected with miR-371b-5p inhibitor). The relative expression levels of APN, KLF4, IL-6 and MCP-1 mRNA in the 3T3-L1 preadipocytes were detected by qRT-PCR method. The miR-371b-5p was analyzed by bioinformatics. Results: The expression levels of miR-371b-5p in the EAT and plasma of the patients in CAD group were higher than those in non-CAD group (P<0. 01). Compared with blank control group, the expression levels of APN and KLF4 mRNA in 3T3-L1 preadipocytes in miR-371b-5p over-expression group were decreased (P=0. 043, P=0. 045), and the expression levels of IL-6 and MCP-1 mRNA in 3T3-L1 preadipocytes in miR-371b-5p over-expression group were increased (P=0. 037, P=0. 041). Compared with blank control group, the expression levels of APN and KLF4 in 3T3-L1 preadipocytes in miR-371b-5p inhibitor group were increased (P=0. 025, P=0. 027), and the expression levels of IL-6 and MCP-1 mRNA in 3T3-L1 preadipocytes in miR-371b- 5p inhibitor group were decreased (P= 0.039, P= 0.041). The target genes predicted by miR-371b-5p were enriched in multiple biological functions and processes. The KEGG pathway was mainly enriched in the signaling pathways such as adipocytokines The protein interaction results showed that the target genes APN, leptin (LEP) and AKT1 encoded proteins predicted by miR-371b-5p were located at the core of the interaction network. Conclusion: The expression levels of anti-inflammatory factors in the cells with over-expression of miR-371b-5p in EAT of the patients with CAD are decreased, the expression levels of inflammatory factors are increased, and miR- 371b-5p is expected to become a new target for CAD treatment.

Objective : To explore the epicardial adipose tissue ( EAT) of patients with coronary heart disease , KLF7 stimulates macrophages to secrete inflammatory factors and promotes the differentiation and maturation of adipocytes through the NF⁃κB signaling pathway , and to clarify the mechanism of KLF7 in the occurrence and development of CAD. Methods : 30 patients with coronary heart disease ( CAD group) and 30 patients without coronary heart disease (non⁃CAD group) were collected , and general data and biochemical indicators were collected. qRT⁃PCR was used to detect the expression levels of KLF7 , APN , IL⁃6 , and TNF⁃α mRNA in EAT. Human THP⁃1 cells were cultured in vitro and induced into M1 type macrophages and 3T3 ⁃L1 preadipocytes. The cells were divied into 3 groups : KLF7 up⁃regulated group ( transfected with KLF7 mimic) , KLF7 down⁃regulated group ( transfected with siRNA knockdown KLF7 ) , NC group ( transfected oligopeptide sequence) , transfected two kinds of cells. qRT⁃PCR was used to detect the expression of APN , MCP⁃1 , IL⁃6 and TNF⁃α mRNA in M1 type macrophages , and the protein expression levels of key factors in the NF⁃κB signaling pathway were detected by Westren blot. The qRT⁃PCR method was used to detect APN , KLF4 , IL⁃6 , MCP⁃1 mRNA and adipocyte differentiation marker peroxisome proliferator⁃activated receptor⁃γ (PPARγ) in 3T3 ⁃L1 preadipocytes 24 h after transfection. CCAAT/enhancer binding protein α (C/EBPα ) , fatty acid binding protein 4 (FABP4) mRNA relative expression levels , and Westren blot was used to detect protein expression levels. Results : Compared with the non⁃CAD group , the expression of CAD group decreased , APN decreased , IL⁃6 and TNF⁃α increased significantly , and the difference was statistically significant (P < 0. 01) . KLF7 was highly expressed in human THP⁃1 derived M1 macrophages induced by inflammatory stimuli (LPS) . In M1 macrophages derived from human THP⁃1 , knocking down KLF7 could inhibit the release of inflammatory factors. Transfection with KLF7 ⁃siRNA could significantly inhibit LPS⁃induced phosphorylation of JNK⁃MAPKs , the level of p⁃p65 and the activation of p ⁃IκBa (P < 0. 05) . In 3T3 ⁃L1 preadipocytes , upregulation of KLF7 increased the expression of adipocyte differentiation markers PPARγ , C/EBPa , FABP4 mRNA , and promoted the differentiation of 3T3 ⁃L1 preadipocytes into adipocytes (P < 0. 05) . Conclusion The expression of KLF7 in EAT in CAD patients increases. KLF7 activates the activation of macrophages mediated by the JNK⁃NF⁃KB signaling pathway in EAT , promotes inflammation in EAT in CAD patients , and promotes the differentiation and maturation of adipocytes , thereby promoting the development of CAD. It indicates that KLF7 may be a potential therapeutic target for cardiovascular diseases (such as CAD) .

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.