KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.
1 January 2023 in International Journal of Heart Failure
Introduction: Pump-controlled retrograde trial off has recently been introduced as an effective method for weaning from veno-arterial extracorporeal membrane oxygenation in pediatric patients. However, studies on pump-controlled retrograde trial off in adults are still lacking. Thus, this study aimed to examine the outcomes of pump-controlled retrograde trial off for weaning from veno-arterial extracorporeal membrane oxygenation in adult patients. Methods: Between January 2018 and July 2019, 87 consecutive adult patients underwent veno-arterial extracorporeal membrane oxygenation support, of whom 47 (54.0%) underwent pump-controlled retrograde trial off for weaning from extracorporeal membrane oxygenation and were enrolled in this study. The pump-controlled retrograde trial off results, extracorporeal membrane oxygenation reapplication rate, and clinical outcomes were analyzed. Results: Of the 47 patients, 38 (80.9%) were weaned from veno-arterial extracorporeal membrane oxygenation on the first attempt of pump-controlled retrograde trial off, 5 (10.6%) on the second attempt, and 4 (8.5%) on the third attempt. Three patients were converted to venovenous extracorporeal membrane oxygenation by desaturation but had stable blood pressure during pump-controlled retrograde trial off. No extracorporeal membrane oxygenation reapplication was performed within 3 days after removal, and two patients underwent veno-arterial extracorporeal membrane oxygenation during follow-up. No complications associated with pump-controlled retrograde trial off occurred during the weaning process, including thromboembolic events. Five in-hospital deaths (10.6%) occurred after weaning from extracorporeal membrane oxygenation. Conclusion: Pump-controlled retrograde trial off is an effective method to safely wean from veno-arterial extracorporeal membrane oxygenation in adult patients. It is simple and can be easily implemented without additional invasive procedures and may help prevent deterioration of the cardiovascular system after weaning from veno-arterial extracorporeal membrane oxygenation.