UTMD targeting intraplaque neovascularization was found to inhibit atherosclerotic plaque in a mouse model of atherosclerosis, suggesting the potential of microbubble-mediated ultrasound technology in aiding drug delivery for atherosclerosis treatment.

Objective. Ribonucleotide reductase M2 (RRM2) as an enzyme that catalyzes the deoxyreduction of nucleosides to deoxyribonucleoside triphosphate (dNTP) has been extensively studied, and it plays a crucial role in regulating cell proliferation. However, its role in ischemia-reperfusion injury (I/RI) is still unclear. Methods. SD rats were used as the research object to detect the expression of RRM2 in the myocardium by constructing an I/RI model. At the same time, primary SD neonatal rat cardiomyocytes were extracted, and hypoxia/reoxygenation (H/R) treatment simulated the I/RI model. Using transfection technology to overexpress RRM2 in cardiomyocytes, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of RRM2, Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and immunofluorescence staining was used to detect Ki67 and EdU-positive cells. Western blot (WB) technology was used to detect YAP and its phosphorylation expression. Results. qRT-PCR results indicated that the expression of RRM2 was inhibited in the model group, and cardiomyocytes overexpressing RRM2 can obviously promote the proliferation of primary cardiomyocytes and improve the damage of cardiac structure and function caused by I/R. At the same time, RRM2 can promote the increase of YAP protein expression and the increase of Cyclin D1 mRNA expression. Conclusion. RRM2 expression was downregulated in myocardial tissue with I/R. After overexpression of RRM2, cardiomyocyte proliferation was upregulated and the Hippo-YAP signaling pathway was activated.

In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has certain characteristics, which are generally low in the south and high in the north, and they tend to be younger and growing. Permanent pacemaker implantation is currently the most effective means of treating arrhythmia and preventing sudden death. To explore the clinical application value of metoprolol in patients after permanent pacemaker implantation. Ninety patients with permanent dual-chamber pacemaker implantation in our hospital are selected and divided into a metoprolol group and a control group according to whether metoprolol is used one week after the operation and 45 patients in each group. After one postoperative week, the LVEF%, LVEDd, LAD, and E/A of the metoprolol and the control groups had no statistically significant differences p > 0.05 . Twelve months postoperatively, the E/A of the metoprolol group is higher than that of the control group p < 0.05 , and LVEDd and LAD are lower than those of the control group (P < 0.05). The NT-proBNP and hs-CRP levels between the metoprolol and control groups had no significant differences p > 0.05 in the values recorded immediately postoperatively. The NT-proBNP of the metoprolol group is lower than that of the control group p < 0.05 at 12 months following pacemaker implantation. At one week after surgery, QTd, Pd, and Tp-Te are not significantly different (P > 0.05) between the metoprolol group and the control group, whereas the QTd and Pd times in the metoprolol group are lower than those in the control group p < 0.05 at the 12-month follow-up. At one week postoperatively, the SDNN, SDANN, and RMSSD between the metoprolol and control groups did not show any statistically significant differences p > 0.05 . The SDANN of the metoprolol group is higher than that in the control group p < 0.05 in the 12-month evaluation. One week after the operation, the serum IL-6 and TNF-α levels are not significantly different between the metoprolol and control groups p > 0.05 . At 12 months after surgery, the serum IL-6 and TNF-α levels in the metoprolol group are lower than those in the control group p < 0.05 . The incidence of adverse events in the metoprolol group is 9.30% lower than 26.83% in the control group within 12 months after the operation p < 0.05 . The use of metoprolol in patients with permanent pacemaker implantation after surgery can reduce the expansionary remodeling of the left atrium and have less impact on the QT-dispersion and Pd time.

Abnormal expression of miR-155 is related to degree of myocardial fibrosis in myocarditis. This study mainly explored the role of miR-155 in myocardial fibrosis and possible mechanisms. Forty Balb/c mice were randomly separated into blank group, model group, miR-155 group, and DMSO group (n = 10). Fibrosis area and expression of TGF-β and α-SMA in each group were observed. Fibroblasts were then isolated and miR-155mRNA expression, expression of Collagen I, α-SMA, Th17 cell number, Treg cell number, and expressions of IL-6, IL-10, IL-17, STAT3, RORγt, and Foxp3 were also investigated. The model group and DMSO group had the highest fibrosis area, while the blank group and miR-155 group had the lowest fibrosis area. However, the fibrosis area for miR-155 group was higher than the blank group (P >0.05). No significant difference was found between model group and DMSO group (P >0.05). Compared to blank and miR-155 groups, expressions of TGF-β and α-SMA in the model and DMSO group were significantly up-regulated (P <0.05). No significant difference was found between the model and DMSO groups, or between blank and miR-155 groups P < 0.05). Compared to blank and miR-155 groups, the levels of Collagen I, α-SMA, IL-6, IL-10, IL-17, STAT3, RORγt, and Foxp3 in the model and DMSO groups were significantly up-regulated (P > 0.05). No significant difference was found between model and DMSO groups, or between blank and miR-155 groups (P < 0.05). The number of Th17 cells was significantly increased, while Treg cells were significantly decreased in the model and DMSO groups (P < 0.05). In contrast, Th17 cells were significantly decreased, while Treg cells were significantly increased in the blank and miR-155 groups (P < 0.05). No significant difference was found between the model and DMSO groups, or between blank and miR-155 groups (P < 0.05). Moreover, miR-155 inhibited myocarditis and myocardial fibrosis. The mechanism is mainly related to Th17/Treg signaling pathway, where miR-155 decreased Th17 cells, increased Treg cells, inhibited the secretion of Collagen I and α-SMA, and reduced the levels of fibroblast molecules. The miR-155 also interacted with STAT3 pathway to stimulate the activity of inflammatory cells, inhibit the secretion of inflammatory factors, further improving the inflammatory response of myocarditis, and ultimately improving the degree of myocarditis myocardial fibrosis.

Materials and MethodsLigand conjugation of microbubbles. One vial (800 μL) of streptavidin-labeled ultrasound microbubbles (MBs) USphere™ Labeler-LS (TRUST Bio-sonics, Zhubei, Taiwan, ROC) was 4761 This article is freely accessible online.