Skimmin ameliorates cardiac function via the regulation of M2 macrophages in a myocardial infarction mouse model.

PURPOSE: Myocardial infarction (MI) is a coronary artery disorder with several complications, such as inflammation, oxidative stress, and cardiac fibrosis. The current study is aimed to explore the protective effect of skimmin (SKI) on impaired heart tissues in MI. METHODS: A mouse model of MI was induced by ligation of the left anterior descending artery. SKI was intragastric administration for 7 days after MI. Masson staining was then conducted to measure the area of fibrosis in the myocardium. The expression levels of collagen I and collagen III were analyzed using Western blot. The levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory factor were also detected. The expression of M1 polarization markers and M2 polarization markers in mice and LPS-induced RAW264.7 cells were detected using RT-qPCR and Western blot, respectively. Finally, the migration and proliferation of vascular smooth muscle cells (VSMCs) in vitro were analyzed using transwell and EDU, respectively. RESULTS: SKI improved cardiac function and cardiac fibrosis in mice with MI. SKI also decreased collagen I and collagen III expression, and inhibited inflammatory factor TNF-α, IL-1ß, and IL-6 levels. SKI decreased the levels of MDA and increased the levels of GSH and SOD. Meanwhile, SKI could promote M2 macrophage polarization in vivo and in vitro. SKI could also repress the migration and proliferation of VSMCs. CONCLUSIONS: SKI may ameliorate inflammation, oxidative stress, and cardiac fibrosis of MI by promoting M2 polarization.

Rational Design and Optimization of Trypsin Inhibitory Peptides with Antibacterial Activity.

Small natural or synthetic peptides have been reported to exhibit potent inhibitory capability against trypsin, some of which were also found to have antibacterial potency. Here, we described a successful application of in silico-in vitro integrated approach to rationally design and optimize bifunctional peptides with both trypsin inhibitory and antimicrobial activities. In the procedure, computer-aided methods including protein docking, peptide redocking, molecular dynamics simulations and binding free energy calculations were employed to model and analyze the intermolecular interaction between human trypsin (hT) and natural trypsin inhibitors (TIs). Based on the modeled hT-TI complex structures a number of promising peptide fragments were derived from the trypsin inhibitory loop of TIs, which were then tested experimentally to determine their inhibitory potency on recombinant hT protein as well as their antibacterial potency against three clinical strains. Consequently, few peptides were found to possess a good profile of trypsin inhibitory and antibacterial bi-functionality. Structural visualization and noncovalent examination of hT complex with a potent peptide revealed that the hydrophobic forces and van der Waals contacts between the peptide nonpolar residues and the hydrophobic pocket around hT active site confer significant stability to the complex architecture, while few specific hydrogen bonds and cation-π interactions at the complex interface contribute to peptide selectivity for hT.