Background The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC. Methods The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities. Conclusion Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

Pulmonary artery hypertension (PAH) is a disease with high morbidity and mortality. Cyanidin-3-O-β-glucoside (Cy-3-g), a classical anthocyanin, has a variety of biological effects. The present study evaluated whether Cy-3-g attenuated PAH, and explored the potential mechanism of action. Rats were injected with monocrotaline (MCT; 60 mg per kg of body weight) and then treated with Cy-3-g (200 or 400 mg per kg of body weight) for 4 weeks. Protein expression was determined in vitro in transforming growth factor-β1 (TGF-β1)-mediated human pulmonary arterial smooth muscle cells (SMCs). The results indicated that Cy-3-g significantly inhibited the mean pulmonary artery pressure, right ventricular systolic pressure and right ventricular hypertrophy index, as well as vascular remodeling induced by MCT in PAH rats. Further experiments showed that Cy-3-g suppressed the expression of pro-inflammatory factors and enhanced the levels of anti-inflammatory factors. Cy-3-g blocked oxidative stress and improved vascular endothelial injury. Cy-3-g also reduced the proliferation of SMCs. Furthermore, the MCT-and TGF-β1-induced increase in TGF-β1, phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) and p-cAMP-response element binding protein (CREB) expression was blocked by Cy-3-g treatment in vivo and in vitro. These results indicated that Cy-3-g could prevent vascular remodeling in PAH via inhibition of the TGF-β1/p38 MAPK/CREB axis.

Background Chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, chemoresistance frequently occurs, making the treatment of NSCLC more difficult. Method We combined clinical and experimental studies to establish the role of microRNA (miR)-34c in NSCLC metastasis and chemoresistance. Results MiR-34c expression was significantly decreased in patients with NSCLC who showed a poor chemoresponse and metastasis. Overexpression of miR-34c sensitized NSCLC cells to paclitaxel and cisplatin both in vitro and in vivo. Furthermore, we found that NOTCH1 was target of miR-34c in NSCLC cells and played a key role in the effects of miR-34c on NSCLC. Conclusion NSCLC metastasis and chemoresistance are suppressed though the miR-34c/NOTCH1 axis. MiR-34c has important implications in the development of therapeutic strategies for metastasis and chemoresistance in NSCLC.

Poor prognosis in patients with glioma is primarily due to rapid tumor growth and cell invasion and migration. In addition, microRNA (miR)-27b is decreased in metastatic glioma. The present study investigated whether sevoflurane inhibited glioma cell progression by targeting miR-27b. Cell proliferation was analyzed using a Cell Counting Kit-8 assay and a wound healing assay was used to detect cell migration. Western blotting and reverse transcription-quantitative PCR analysis were performed to determine the protein and mRNA expression levels. A dual luciferase assay was used to determine the relationship between vascular epithelial growth factor (VEGF) and miR-27b. VEGF was identified to be a direct target of miR-27b. Moreover, sevoflurane treatment increased the expression of miR-27b and decreased the expression of VEGF in U251 and U87 cells. Compared with the control group, sevoflurane inhibited the proliferation and migration of U251 and U87 cells, as well as the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were subsequently abolished by pre-treatment with an miR-27b inhibitor. The present results indicated the potential use of sevoflurane by anesthesiologists for the surgical resection of glioma, which may improve patient outcomes in the clinical setting.

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Objective: Little is known about how renal aquaporin-2 (AQP2) expression is affected by right heart failure caused by pulmonary heart disease (PHD). Therefore, we examined the expression of AQP2 in a rat model of PHD induced by monocrotaline (MCT). Methods: After 4 weeks of treatment, urine and blood samples were collected from shamtreated and MCT-treated rats. Plasma arginine vasopressin (AVP) levels were measured by radioimmunoassay, and kidney Aqp2 mRNA expression was detected by reverse transcription (RT)-PCR. Kidney AQP2 protein expression was quantified by immunohistochemistry and western blotting assays. The concentration of urine AQP2 was determined by indirect enzyme-linked immunosorbent assay. Results: We successfully established an animal model of MCT-induced PHD in rats. MCT-treated rats had significantly higher mRNA and protein levels of AQP2 in their kidney tissue. Following MCT treatment, rats also had markedly increased concentrations of both urine AQP2 and plasma AVP. Conclusions: AQP2 expression was significantly increased in the kidney tissues and urine of rats with PHD induced by MCT. Our findings suggest that the evaluation of AQP2 expression contributes to an early diagnosis of PHD, and may also be an important reference to improve PHD therapeutics.

Aims Myeloid differentiation protein 1 (MD1) was shown to ameliorate pressure overload-induced cardiac hypertrophy and fibrosis by negatively regulating the MEK-ERK1/2 and NF-κB pathways. However, whether MD1 modulates cardiac function and whether the Akt pathway mediates the benefits of MD1 in pressure overload-induced cardiac remodelling remain unclear. Methods and Results Male cardiac-specific transgenic MD1 (MD1-TG) mice, MD1-knockout (KO) mice and wild-type (WT) littermates aged 8-10 weeks were subjected to sham operation and aortic banding (AB) for 4 weeks. Then, left ventricular (LV) hypertrophy, fibrosis and function of the mice were assessed. When compared with WT-AB mice, MD1-TGs showed decreased cross-sectional area (CSA) of cardiomyocytes (P < 0.001), mRNA expression of β-myosin heavy chain (β-MHC) (P < 0.02), ratios of heart weight/body weight and heart weight/tibia length (P < 0.04) and collagen volume fraction (P < 0.001). The LV end-diastolic diameter was reduced, and LV ejection fraction and fractional shortening were improved in MD1-TG-AB mice than in WT-AB mice (P < 0.05). In cultured H9C2 cells, adenovirus vector-mediated MD1 overexpression decreased angiotensin II-induced mRNA expression of brain natriuretic peptide (BNP) and β-MHC and cell CSA (P < 0.002), whereas knockdown of MD1 by shRNA exhibited opposite effects (P < 0.04). Mechanistically, MD1 suppressed pathological cardiac remodelling at least partly by blocking Akt pathway. Akt inactivation by MK2206 largely offset the pro-hypertrophic effects of MD1 deficiency in angiotensin II-stimulated cardiomyocytes. Conclusions The Akt pathway mediates the protective effects of MD1 in pressure overload-induced cardiac remodelling in mice. Targeting MD1 may provide therapeutic strategy for the treatment of pathological cardiac remodelling and heart failure.

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