Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier.

Sepsis-induced acute lung injury (SALI) is the common complication of sepsis, resulting in high incidence and mortality rates. The primary pathogenesis of SALI is the interplay between acute inflammation and endothelial barrier damage. Studies have shown that kaempferol (KPF) has anti-sepsis properties. Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway's significance in acute lung damage and S1P receptor 1 (S1PR1) agonists potential in myosin light chain 2 (MLC2) phosphorylation are documented. Whether KPF can regulate the SphK1/S1P/S1PR1/MLC2 signaling pathway to protect the lung endothelial barrier remains unclear. This study investigates the KPF's therapeutic effects and molecular mechanisms in repairing endothelial cell barrier damage in both LPS-induced sepsis mice and human umbilical vein endothelial cells (HUVECs). KPF significantly reduced lung tissue damage and showed anti-inflammatory effects by decreasing IL-6 and TNF-α synthesis in the sepsis mice model. Further, KPF administration can reduce the high permeability of the LPS-induced endothelial cell barrier and alleviate lung endothelial cell barrier injury. Mechanistic studies showed that KPF pretreatment can suppress MLC2 hyperphosphorylation and decrease SphK1, S1P, and S1PR1 levels. The SphK1/S1P/S1PR1/MLC2 signaling pathway controls the downstream proteins linked to endothelial barrier damage, and the Western blot (WB) showed that KPF raised the protein levels. These proteins include zonula occludens (ZO)-1, vascular endothelial (VE)-cadherin and Occludin. The present work revealed that in mice exhibiting sepsis triggered by LPS, KPF strengthened the endothelial barrier and reduced the inflammatory response. The SphK1/S1P/S1PR1/MLC2 pathway's modulation is the mechanism underlying this impact.

Quantifiable Effect of Interparticle Plasmonic Coupling on Sensitivity and Tuning Range for Wavelength-Mode LSPR Fiber Sensor Fabricated by Simple Immobilization Method.

Herein a gold nanosphere (AuNS)-coated wavelength-mode localized surface plasmon resonance (LSPR) fiber sensor was fabricated by a simple and time-saving electrostatic self-assembly method using poly(allylamine hydrochloride). Based on the localized enhanced coupling effect between AuNSs, the LSPR spectrums of the AuNS monolayer with good dispersity and high density exhibited a favourable capability for refractive index (RI) measurement. Based on the results obtained from the optimization for AuNS distribution, sensing length, and RI range, the best RI sensitivity of the fiber modified by 100 nm AuNS reached up to about 2975 nm/RIU, with the surrounding RI range from 1.3322 to 1.3664. Using an 80 nm AuNS-modified fiber sensor, the RI sensitivity of 3953 nm/RIU was achieved, with the RI range increased from 1.3744 to 1.3911. The effect of sensing length to RI sensitivity was proven to be negligible. Furthermore, the linear relationship between the RI sensitivity and plasma resonance frequency of the bulk metal, which was dependent on the interparticle plasmon coupling effect, was quantified. Additionally, the resonance peak was tuned from 539.18 nm to 820.48 nm by different sizes of AuNSs-coated fiber sensors at a RI of 1.3322, which means the spectrum was extended from VIS to NIR. It has enormous potential in hypersensitive biochemistry detection at VIS and NIR ranges.