Rho kinase inhibitor Y-27632 downregulates IL-1ß expression in mice with experimental autoimmune myocarditis.

Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1ß expression in the myocardial tissue of EAM mice. Notably, IL-1ß expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1ß expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

LINC00963 silencing inhibits the proliferation and migration of high glucose-induced retinal endothelial cells via targeting miR-27b.

The association between long intergenic non-protein-coding RNA 963 (LINC00963) and diabetes has not been fully elucidated. Therefore, the present study aimed to investigate the effect of the long non-coding RNA LINC00963 on diabetic retinopathy (DR), in order to provide a new therapeutic target for this condition. Human retinal capillary endothelial cells (HRECs) were induced with high concentrations of glucose to establish a DR model. The expression levels of LINC00963, cell viability, the protein expression levels of proliferating cell nuclear antigen (PCNA) and Ki67, and the migratory capacity of HRECs were determined using reverse transcription-quantitative PCR (RT-qPCR), Cell Counting Kit-8 assay, western blot analysis, and wound healing and Transwell assays, respectively. Furthermore, the Encyclopedia of RNA Interactomes database was used to predict the binding targets of LINC00963, and luciferase reporter assay was used to verify the direct binding of microRNA (miR)-27b to LINC00963. RT-qPCR was also utilized to measure the expression levels of miR-27b, PCNA and Ki67. The results demonstrated that LINC00963 silencing inhibited glucose-induced HREC proliferation and migration, and downregulated PCNA and Ki67 expression. Following transfection with miR-27b inhibitor, cell proliferation and migration were notably enhanced, and the protein expression levels of PCNA and Ki67 were increased. Taken together, the results of the present study suggested that the LINC00963/miR-27b axis may regulate the proliferation and migration of glucose-induced HRECs. Therefore, LINC00963 may be considered as a potential therapeutic target for DR.

Liraglutide promotes the angiogenic ability of human umbilical vein endothelial cells through the JAK2/STAT3 signaling pathway.

Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and incretin mimetic used for the treatment of Type 2 diabetes mellitus. It has also been shown to have a beneficial role in the cardiovascular system. Here, we investigated the mechanism by which liraglutide promotes angiogenesis using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of liraglutide, and assessed by wound healing assay and tube formation assay as measures of angiogenesis. We found that liraglutide at 10 and 100 nmol/L greatly promoted the angiogenic ability of HUVECs. Next, we examined the JAK2/STAT3 signaling pathway and found that liraglutide treatment led to JAK2/STAT3 activation and significant increase in the angiogenic mediator expressions, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endothelial nitric oxide synthase (eNOS) in HUVECs. Treatment with JAK2 inhibitor, AG490, in HUVECs successfully reduced the observed effects of liraglutide. We conclude that liraglutide promotes the angiogenic ability of HUVECs by activating the JAK2/STAT3 signaling pathway and upregulating its downstream factors, VEGF, bFGF and eNOS. Thus, liraglutide may provide ischemic relief for diabetic patients with cardiovascular diseases in addition to glycemic control.

[Applications of ultrasound in the treatment of the complications of breast augmentation with polyacrylamide hydrogel injection].

OBJECTIVE: To search for a simple and non-invasive method to assist the treatment of the complications of breast augmentation with polyacrylamide hydrogel injection. METHODS: High-frequency ultrasound was used to examine the breast and observe the distributions of the injected polyacrylamide hydrogel. The operation procedure was predetermined according to the ultrasound information. The ultrasound results were compared with what was seen during the operation. RESULTS: 40 patients (80 breasts) were examined. The ultrasound results were coincident with the outcomes of surgery. The results of postoperative follow-up were coincident with the predicted. CONCLUSION: Ultrasound is an accurate method for examining the augmented breast with polyacrylamide hydrogel injection. It is helpful in predetermining the operation procedure, predicting postoperative results.