Myocardial ischemia reperfusion injury is alleviated by curcumin-peptide hydrogel via upregulating autophagy and protecting mitochondrial function.

BACKGROUND: Ischemia-reperfusion injury (IRI) is an important factor limiting the success of cardiac reperfusion therapy. Curcumin has a significant cardioprotective effect against IRI, can inhibit ventricular remodeling induced by pressure load or MI, and improve cardiac function. However, the poor water solubility and low bioavailability of curcumin restrict its clinical application. METHODS: In this study, we prepared and evaluated a curcumin-hydrogel (cur-hydrogel) to reduce cardiomyocyte apoptosis and reactive oxygen species formation induced by hypoxia-reoxygenation injury, promote autophagy, and reduce mitochondrial damage by maintaining the phosphorylation of Cx43. RESULTS: Meanwhile, cur-hydrogel can restore cardiac function, inhibit myocardial collagen deposition and apoptosis, and activate JAK2/STAT3 pathway to alleviate myocardial ischemia-reperfusion injury in rats. CONCLUSIONS: The purpose of this study is to elucidate the protective effects of cur-hydrogel on myocardial ischemia-reperfusion injury by regulating apoptosis, autophagy, and mitochondrial injury in vitro and in vivo, which lays a new theoretical and experimental foundation for the prevention and reduction of IRI.

Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis.

AIM: To evaluate the efficacies of six derivatives of Compound 2, a novel YycG histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections. METHODS: The minimal inhibitory concentration (MIC) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (MBC) was obtained via sub-culturing 100 µL from each negative tube from the MIC assay onto drug-free Mueller-Hinton agar plates. Biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (CLSM). RESULTS: The derivatives potently suppressed the growth of Staphylococcus epidermidis. The MIC values of the derivatives H2-10, H2-12, H2-20, H2-29, H2-27, and H2-28 on S epidermidis ATCC 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 µg/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 µg/mL, respectively. The derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. The derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward Vero cells and human erythrocytes. CONCLUSION: The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.