SUMMARYIntroduction: To investigate the cardioprotective effect of MicroRNA-21 (miR-21) in murine myocardial infarction (MI). Methods: Forty C57BL/6 male mice were divided into sham group, MI group, LV-GFP group, and miR-21 group. Mice in the MI group, LV-GFP group, and miR-21 group were subjected to MI by left anterior descending artery (LAD) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR-21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR-21 and lentivirus that did not express miR-21 were transfected into mice left ventricular cavity of miR-21 group and LV-GFP group, respectively. Cardiac function, MI size, miR-21 expression, collagen I level, fibronectin content, number of a-SMA-positive cells, number of apoptotic cells, apoptosis-related factors were compared between the three groups. Results: Compared with sham group, miR-21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in the miR-21 group improved compared to the LV-GFP group. In miR-21 group, myocardial infarct size reduced by 36.9% in comparison with LV-GFP group. Compared to sham group, miR-21 expression in the miR-21 group and LV-GFP group decreased significantly. In the miR-21 group, collagen I level, fibronectin content and number of a-SMA-positive cells of miR-21 decreased significantly compared to the LV-GFP group. The number of apoptotic cells in the MI areas of the miR-21 group was significantly less than the LV-GFP group. Compared with the LV-GFP group, Bcl-2 level and the ratio of Bcl-2 to Bax were significantly increased, and the levels of Bax and Caspase-3 decreased. Conclusions: Our results suggest miR-21 is an important regulatory molecule in the pathophysiology of MI.

Limited circulating tumor cells (CTCs) capturing efficiency and lack of regulation capability on CTC-supportive metastatic niches (MNs) are two main obstacles hampering the clinical translation of conventional liposomes for the treatment of metastatic breast cancers. Traditional delivery strategies, such as ligand modification and immune modulator co-encapsulation for nanocarriers, are inefficient and laborious. Here, a multifunctional Rg3 liposome loading with docetaxel (Rg3-Lp/DTX) was developed, in which Rg3 was proved to intersperse in the phospholipid bilayer and exposed its glycosyl on the liposome surface. Therefore, it exhibited much higher CTC-capturing efficiency via interaction with glucose transporter 1 (Glut1) overexpressed on CTCs. After reaching the lungs with CTCs, Rg3 inhibited the formation of MNs by reversing the immunosuppressive microenvironment. Together, Rg3-Lp/DTX exhibited excellent metastasis inhibition capacity by CTC (“seeds”) neutralization and MN (“soil”) inhibition. The strategy has great clinical translation prospects for antimetastasis treatment with enhanced therapeutic efficacy and simple preparation process.

Poor water solubility limits the clinical use of andrographolide and its derivatives. In an attempt to develop potent hepatoprotective drugs, a strategy was proposed to improve the aqueous solubility of andrographolide. Ten andrographolide derivatives were designed, synthesized, evaluated for aqueous solubility and in vivo hepatoprotective activity against CCl4 -induced liver injury in mice. As expected, the aqueous solubility of synthetic derivatives was effectively improved. All compounds demonstrated the effect of different degrees in improving the liver enzyme (ALT and AST) activity, especially the most promising compound 9d significantly improved liver enzyme activity, with high potency to be a new lead.