Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury

Background and aim Hepatic ischemia–reperfusion injury(IRI)is a significant challenge in liver transplantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors.Materials and methods This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.Results Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating therapeutic potential.Conclusions Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Fully umbilical cord-derived adhesive materials enable to recruit and segregate immune cells for the reversal of acute liver failure

Inflammatory cytokine storms can trigger disease exacerbation and even death and have reached a consensus in the clinical treatment of acute organ failure.However,the existing strategies remain a great challenge to efficiently suppress inflammatory cytokine storms for promoting organ repair and regeneration.Herein,fully human umbilical cord(UC)-derived adhesive materials(UCAM)that integrate decellularized extracellular matrix(ECM)nanofiber hydrogel and homologous mesenchymal stem cells(MSCs)are demonstrated to greatly suppress inflammatory cytokine storms,demonstrating high efficacy in treating acute liver failure(ALF)in rats with 90%hepatectomy.The UC-derived adhesive materials have the capacity to secrete a significant quantity of cytokines by MSCs to recruit activated immune cells to migrate into their ECM nanofiber networks,segregating them away from the infection area and thereby greatly suppressing the inflammatory cytokine storms.As expected,the UC-derived adhesive materials can significantly promote hepatocyte proliferation to achieve functional recovery and regeneration of the liver,significantly improving the survival rate in rats.Our fully human UC-derived adhesive materials provide a new avenue in suppressing inflammatory cytokine storms for promoting organ regeneration that would be really utility in clinical organ transplantation-related treatment.