OBJECTIVE: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantation failure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluate the endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrial expressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) in patients with RIF compared to control subjects.
METHODS: This case-control study was carried out between June 2021-July 2022. Subjects included 17 patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referred to the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopy and Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulation in all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The student\'s t test, chi-square, Mann-Whitney U, and analysis of covariance (ANCOVA) were used for data analyses.
RESULTS: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions of miR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased in patients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrial miR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF.
CONCLUSIONS: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can be reliable, novel biomarkers for diagnosis of RIF.

Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD.
We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs.
Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction.
The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.

Purpose: To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the miR-143/145 cluster with Type 2 diabetes mellitus (T2DM) risk. Methods:A total of 1200 subjects were genotyped using the ARMS-PCR method. Results: The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in p-values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. Conclusions: Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.

We analyzed the relationship between plasma miR-143/145 and serum MMP-9 in patients with unruptured or ruptured intracranial aneurysms (IAs) to identify new biomarkers for predicting rupture in IAs.
We prospectively enrolled 24 consecutive patients, including seven patients without IAs as a control group, nine patients with unruptured IAs, and eight patients with ruptured IAs (enrolled within 3 days after rupture). Plasma miR-143/145 and MMP-9 were measured in blood samples collected from the femoral artery. Spearman ρ values were used for correlation analyses.
The level of plasma miR-143/145 in patients with ruptured IAs was significantly lower than that of the control group. Moreover, patients with ruptured IAs had a significantly higher level of serum MMP-9 compared with that in patients with unruptured IAs and in control patients. A lower level of plasma miR-143 was significantly correlated with a lower level of plasma miR-145 (Spearman ρ = 0.771; P <  0.0001).
These findings showed that a lower of plasma miR-143/145 is potentially associated with IA formation, while higher serum MMP-9 levels may be associated with IA rupture and could serve as a useful biomarker for the evaluation of IA rupture.

BACKGROUND: Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells.
METHODS: DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05.
RESULTS: DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR-145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase.
CONCLUSIONS: DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

To date, acupuncture has been widely used despite a lack of solid clinical evidence in the East and West. However, there are few validated in vitro models for the mechanistic studies of acupuncture. We hypothesized that adenosine could be used as a probing tool in the mechanistic studies of acupuncture because of its critical role in the action of acupuncture. Subsequently, we tested this hypothesis using both in vitro and in vivo experiments. First, we found that adenosine stimulation mimicked the effect of acupuncture on microRNA profiling (including miR-339, miR-145 and miR-451) and protein level (including Sirt2) in nerve growth factor-induced differentiated PC12 cells. These miRNA and proteins have been found to be regulated by acupuncture treatment in the brain of spontaneously hypertensive rats. Next, we found that adenosine stimulation downregulated miR-339 expression through adenosine A1 receptor-mediated pathway. Finally, we showed that the concentration of adenosine was actually decreased in the brain of spontaneously hypertensive rats after acupuncture treatment at Taichong acupoint. Taken together, these findings suggest that adenosine could be used as a useful probing tool for acupuncture mechanistic studies, while more validation studies are certainly warranted.