Up-regulation of exosomal miR-106a may play a significant role in abdominal aortic aneurysm by inducing vascular smooth muscle cell apoptosis and targeting TIMP-2, an inhibitor of metallopeptidases that suppresses extracellular matrix degradation.

OBJECTIVE: Abdominal aortic aneurysm (AAA) rupture is a dramatic and lethal clinical condition with a high risk of death. Emerging evidence indicates a role for miRNAs in AAA pathogenesis, therefore we aimed to identify miRNAs that differently expressed in exosomes from AAA patients and explore the underlying mechanisms of how miR-106a plays its role in this disease. PATIENTS AND METHODS: Exosomes were isolated from plasma of AAA patients, as well as from the tissue-conditioned culture medium. The exosomal expression profiles of several miRNAs including miR-106a were analyzed by quantitative RT-PCR. To determine the potential role of miR-106a in the pathogenesis of AAA, miR-106a was overexpressed in vascular smooth muscle cells (VSMCs), and then cell viability and apoptosis were evaluated by performing CCK-8 assay and flow cytometry, respectively. Afterwards, enzyme-linked immunosorbent assay (ELISA) was applied to assess the expression levels of some proteins involved in the modulation of extracellular matrix (ECM) homeostasis. Furthermore, the target gene of miR-106a was predicted and verified through Dual-Luciferase reporter assay. RESULTS: MiR-106a was up-regulated in exosomes from plasma of those patients with AAA as compared with healthy peers. Likely, increased level of miR-106a was observed in exosomes released from AAA tissue in comparison to those from adjacent normal tissues. Enhanced expression of miR-106a in VSMCs suppressed cell viability but promoted cellular apoptosis, whereas inhibition of miR-106a in VSMCs resulted in a significant decrease in the percentage of apoptotic cells compared to the control group. In addition, the protein levels of matrix metalloproteinases (MMPs, including MMP-2 and MMP-12) secreted from VSMCs were significantly up-regulated, while their inhibitor TIMP-2 was down-regulated due to miR-106a overexpression. Finally, TIMP-2 was validated subsequently as the direct target of miR-106a through Dual-Luciferase reporter assay. CONCLUSIONS: In aggregate, our results suggest that increased expression of miR-106a promotes VSMC cell apoptosis and down-regulates TIMP-2 through directly targeting its 3'-UTR, which in turn restores MMP production and ultimately accelerates ECM degradation. Therefore miR-106a is proposed to play a crucial role in AAA development and this will provide an update on the understanding of the clinical value of miRNAs as novel therapeutic targets for the treatment of this disease.

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.

Analysis of a series of patients with varicose vein recurrence.

OBJECTIVE: Varicose veins of the lower extremities is a common clinical condition. Although surgical treatment is often successful, the recurrence rate remains high. This retrospective study evaluated the reasons for postoperative recurrence of varicose veins by analysing ultrasonography and venography findings in patients with recurrent disease. METHODS: A series of consecutive cases of recurrent varicose veins of the lower limbs was reviewed. Data collected included clinical characteristics, symptoms and vascular imaging. RESULTS: The study included 109 legs with recurrent varicose veins (92 patients): 101/109 legs (92.7%) showed perforating vein insufficiency and 86/109 (78.9%) showed reflux of the superficial femoral vein, of varying degrees of severity. Residual saphenous vein was recorded for 82 legs (75.2%), while 19 (17.4%) had blocked iliac veins due to post-thrombotic syndrome. CONCLUSIONS: Several factors that may contribute to varicose vein recurrence have been identified. These include failure to ligate perforating veins and initial failure to perform the appropriate surgical intervention. Prevention of varicose vein recurrence after surgical correction requires a more extensive use of preoperative imaging, to tailor surgical intervention to suit individual patients.