Background: The protective effect of metformin (MET) on abdominal aortic aneurysm (AAA) has been reported. However, the related mechanism is still poor understood. In this study, we deeply investigated the role of metformin in AAA pathophysiology. Methods: Angiotensin II (Ang-II) was used to construct the AAA model in ApoE −/− mice. The related mechanism was explored using Western blot and quantitative real time PCR (qRT-PCR). We also observed the morphological changes in the abdominal aorta and the influence of metformin on biological behaviors of rat abdominal aortic VSMCs. Results: The PI3K/AKT/mTOR pathway was activated in aneurysmal wall tissues of AAA patients and rat model. Treatment with metformin inhibited the breakage and preserved the elastin structure of the aorta, the loss of collagen, and the apoptosis of aortic cells. In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II. Moreover, PI3K inhibitors enhanced the effect of metformin while PI3K agonists largely reversed this effect. Interestingly, the cell proliferation, apoptosis, migration and autophagy of vascular smooth muscle cells (VSMCs) induced by Ang-II were also decreased following metformin treatment. PI3K inhibitors and agonists strengthened and weakened the effects of metformin in VSMCs, respectively. Conclusions: Metformin represses the pathophysiology of AAA by inhibiting the activation of PI3K/AKT/mTOR/ autophagy pathway. This repression may be useful as a new therapeutic strategy for AAA.

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Background Early diagnosis of asymptomatic carotid artery stenosis (ACAS) is important to prevent the incidence of cerebrovascular events. This study aimed to investigate the circulating expression of microRNA-92a (miR-92a) in ACAS patients and evaluate its diagnostic value for ACAS and predictive value for cerebrovascular events. Methods Circulating expression of miR-92a was measured using quantitative real-time PCR. Chi-square test was used to analyze the association of miR-92a with ACAS patients’ clinical characteristics. A receiver operating characteristic (ROC) was used to evaluate the diagnostic value of miR-92a, and the Kaplan-Meier method and Cox regression analysis were used to assess the predictive value of miR-92a for cerebrovascular events. Results Serum expression of miR-92a was higher in ACAS patients than that in the healthy controls (P <  0.001), and associated with patients’ degree of carotid stenosis (P = 0.013). The elevated miR-92a expression could distinguish ACAS patients from healthy individual, and was an independent predictive factor for the occurrence of cerebrovascular events (P = 0.015). Conclusion The data from this study indicated that circulating increased miR-92a may serve as a noninvasive diagnostic biomarker for ACAS and a potential risk factor for the future onset of cerebrovascular events.

Hepatocellular carcinoma (HCC) is the primary and most frequently occurring type of malignant liver cancer, accounting for 70-85% of total liver cancer cases worldwide. It has previously been demonstrated that the aberrant expression of microRNAs (miR) contributes to carcinogenesis and progression of various human malignancies, including HCC. However, mechanisms underlying the differential expression and specific roles of miR‑187 in HCC remain to be elucidated, particularly regarding how the modulation of malignant phenotypes in HCC cells occurs. The present study demonstrated that miR‑187 was significantly downregulated in HCC tissues and cell lines. Restoration of miR‑187 expression inhibited cell proliferation, migration and invasion in HCC. Furthermore, insulin‑like growth factor 1 receptor (IGF‑1R) was demonstrated to act as a direct target gene of miR‑187 in HCC. IGF‑1R knockdown mimicked the effects of miR‑187 overexpression in HCC, resulting in a significant inhibition of cell proliferation, migration and invasion. The results of the present study demonstrated that miR‑187 acted as a tumor suppressor in HCC progression via direct targeting of IGF‑1R. miR‑187 may therefore exhibit the potential to act as a novel and therapeutic target for HCC treatment in the future.

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Summary: Background:We investigated the association of the 5A/6A polymorphism in the promoter region at -1612 of the matrix metalloproteinase-3 gene (MMP-3-1612) and deep venous thrombosis (DVT). Patients, materials and methods: The distribution of the MMP-3 (-1612 5A/6A) polymorphism in the case and control groups was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum MMP-3 level of two groups was detected using enzyme-linked immunosorbent assay (ELISA). HepG2 cells containing MMP-3-1612 recombinant plasmid were cultured in vitro and the MMP-3 level was defined by luminescence intensity of luciferase. A DVT rat model was built. Serum MMP-3 level in the rats' wounded vein at different time points was detected by ELISA and recorded for investigation of the association between MMP-3 and DVT. Statistical data analysis was conducted with SPSS18.0. Results: On the basis of the observation of MMP-3-1612 genotype frequency and allele frequency in the case and control groups, we identified significantly higher MMP-3-1612 5A allele frequency and higher serum MMP-3 level in the case group than in the control group (both P < 0.05). According to in vitro luciferase measurements, the 5A allele had higher transcriptional activity than the 6A allele. As observed in the rat model, serum MMP-3 level increased with time passing and thrombosis formation after modelling. Conclusions: The MMP-3-1612 5A/6A polymorphism may effect serum MMP-3 level and over-expression of serum MMP-3 level may be a risk factor for DVT formation.