RESUMEN
The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.
RESUMEN
In this work the encapsulation of an α-helical peptide in single carbon nanotubes (CNTs) with similar diameter and length but different geometry (armchair and zigzag) was investigated through molecular dynamics simulations and free energy calculations. Our simulation results showed that in vacuo it makes no evident difference whether the investigated peptide is encapsulated in armchair or zigzag CNTs; however, in aqueous solution the armchair CNT encapsulates the peptide remarkably easier than the zigzag CNT does. A detailed analysis revealed that the equilibrium conformation of the water molecules inside the CNTs with varying geometry mediates the peptide encapsulation. It suggests that the water molecules play an important role in regulating behaviors of biomolecules in bio-systems. Then the impact of the CNT geometry on the conformational changes of the confined peptide was studied. Analyses of secondary structures showed the α-helix of the peptide could be better maintained in the zigzag CNT.