Salvianolic Acid A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Neutrophil NETosis.

Salvianolic acid A (SAA) is one of bioactive polyphenol extracted from a Salvia miltiorrhiza (Danshen), which was widely used to treat cardiovascular disease in traditional Chinese medicine. SAA has been reported to be protective in cardiovascular disease and ischemia injury, with anti-inflammatory and antioxidative effect, but its role in acute lung injury (ALI) is still unknown. In this study, we sought to investigate the therapeutic effects of SAA in a murine model of lipopolysaccharide- (LPS-) induced ALI. The optimal dose of SAA was determined by comparing the attenuation of lung injury score after administration of SAA at three different doses (low, 5 mg/kg; medium, 10 mg/kg; and, high 15 mg/kg). Dexamethasone (DEX) was used as a positive control for SAA. Here, we showed that the therapeutic effect of SAA (10 mg/kg) against LPS-induced pathologic injury in the lungs was comparable to DEX. SAA and DEX attenuated the increased W/D ratio and the protein level, counts of total cells and neutrophils, and cytokine levels in the BALF of ALI mice similarly. The oxidative stress was also relieved by SAA and DEX according to the superoxide dismutase and malondialdehyde. NET level in the lungs was elevated in the injured lung while SAA and DEX reduced it significantly. LPS induced phosphorylation of Src, Raf, MEK, and ERK in the lungs, which was inhibited by SAA and DEX. NET level and phosphorylation level of Src/Raf/MEK/ERK pathway in the neutrophils from acute respiratory distress syndrome (ARDS) patients were also inhibited by SAA and DEX in vitro, but the YEEI peptide reversed the protective effect of SAA completely. The inhibition of NET release by SAA was also reversed by YEEI peptide in LPS-challenged neutrophils from healthy volunteers. Our data demonstrated that SAA ameliorated ALI via attenuating inflammation, oxidative stress, and neutrophil NETosis. The mechanism of such protective effect might involve the inhibition of Src activation.

A Stable Quaternized Chitosan-Black Phosphorus Nanocomposite for Synergetic Disinfection of Antibiotic-Resistant Pathogens.

Antibiotics are widely used for treatment of bacterial infections, and their overuse has contributed to microbial resistance. Currently, an alternative antibiotic-free therapy for inactivating bacteria is of great interest. Black phosphorus (BP), a biocompatible and nontoxic rising-star two-dimensional layered material, has gained remarkable interest in many bioapplications including biosensing, cancer therapy, drug delivery, and also antibacterial treatment. However, BP nanosheets suffer from instability in ambient environments due to rapid oxidation and degradation. To address this issue, BP nanosheets were modified with quaternized chitosan (QCS) by electrostatic adsorption to prepare a BP-QCS composite for photothermal/pharmaco treatment of bacterial infection. The BP-QCS has obviously enhanced solubility and chemical stability in aqueous suspensions. We have demonstrated that under near-infrared (NIR) irradiation, the BP-QCS can synergistically inactivate more than 95% methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) and Escherichia coli within 10 min with a dose of only 75 µg/mL in vitro. Meanwhile, the BP-QCS composite under NIR can synergistically inactivate 98% S. aureus in vivo. Furthermore, the BP-QCS suspensions at effective antibacterial concentrations have negligible cytotoxicity and in vivo toxicity.