ABSTRACT
Intracerebral hemorrhage (ICH), known as non-traumatic cerebrovascular rupture and hemorrhage, often occurs in the deep basal brain segment. It is known for its high morbidity and mortality rates. Subarachnoid hemorrhage (SAH) is a clinical syndrome caused by the rupture of blood vessels at the base or surface of the brain that allows blood to flow directly into the subarachnoid space. It progresses quickly and typically manifests at younger ages compared with ICH. ICH and SAH are both devastating events in the category of hemorrhagic strokes and are attracting increasing attention from researchers. Flavonoids, being important natural molecules, have remarkable anti-inflammatory and antioxidant effects. Flavonoids have extensive biological activities in inflammation and oxidative stress (OS), and have protective effects in vascular function associated with cerebrovascular diseases. They have an impact on the onset of ICH and SAH by targeting various pathways, including the suppression of inflammation and OS. Recently, the role of flavonoid compounds in ICH and SAH has also received increasing interest. Thus, to serve as a resource for the prevention and treatment of ICH and SAH, the present review provided an overview of the research on flavonoid compounds in the prevention of brain damage after these two conditions have occurred.
ABSTRACT
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.
Subject(s)
Acute Lung Injury , Cardiac Myosins , Human Umbilical Vein Endothelial Cells , Kaempferols , Lung , Lysophospholipids , Mice, Inbred C57BL , Myosin Light Chains , Sepsis , Signal Transduction , Sphingosine , Animals , Sepsis/drug therapy , Sepsis/complications , Sepsis/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Acute Lung Injury/etiology , Acute Lung Injury/pathology , Humans , Myosin Light Chains/metabolism , Signal Transduction/drug effects , Mice , Lysophospholipids/metabolism , Kaempferols/pharmacology , Kaempferols/therapeutic use , Sphingosine/analogs & derivatives , Sphingosine/metabolism , Sphingosine/pharmacology , Male , Human Umbilical Vein Endothelial Cells/metabolism , Cardiac Myosins/metabolism , Lung/pathology , Lung/drug effects , Lung/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors , Lipopolysaccharides , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Receptors, Lysosphingolipid/metabolism , Interleukin-6/metabolism , Sphingosine-1-Phosphate Receptors/metabolismABSTRACT
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.