Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Role of Intrahepatic Regional Immunity in Post-Transplant Cancer Recurrence

Hepatic malignancy is a major indication for liver transplantation;however,post-tra ns plant cancer recurrence is an emerging clinical challenge affecting long-term outcomes.Pre-tra ns plant tumor biology,staging,and post-transplant immunosuppression regimens have been elucidated as risk factors for recurrent liver cancer.However,increasing evidence indicates that hepatic ischemia and reperfusion(IR)injury to allografts are crucial to providing a favorable immunologic microenvironment for cancer cell invasiveness and metastasis after liver transplantation.The association of severe graft injury in marginal grafts,such as small-for-size or fatty grafts,with lower recurrence-free survival rates in living donor liver transplantations,substantiates the correlation between hepatic IR injury and cancer recurrence.IR has been demonstrated to trigger intrahepatic immunological microenvironment remodeling,including pro-inflammatory responses exacerbating graft injury and anti-inflammatory responses promoting tissue repair.However,the role of regional immunity in post-transplant cancer recurrence is not comprehensively understood.This review describes the up-to-date evidence of the intrahepatic humoral microenvironment and regional regulatory immunological microenvironment induced by IR injury,as well as their roles in cancer recurrence after liver transplantation.A comprehensive understanding of regional immunity will provide novel precise diagnostic,therapeutic,and prognostic strategies for post-transplant cancer recurrence.

A green light-enhanced cytosolic protein delivery platform based on BODIPY-protein interactions

Development of cytosolic protein delivery platforms brings new possibilities for various incurable diseases.Strategies based on polymer/protein self-assembly have shown their potential in protein delivery.However,versatile photocontrolled platforms based on self-assembly for protein delivery are seldom reported.Herein,we report a boron-dipyrromethene(BODIPY)-modified polyamidoamine(PAMAM)with excellent photo-controllability and efficiency for the cytosolic delivery of various proteins.High serum stability was achieved by coating hyaluronic acid and human serum albumin on the surface of BODIPY-modified PAMAM/protein nanoparticles.The nanoparticles under green light irradiation allowed efficient intracellular delivery of multiple cargo proteins with different charges and molecular weights and promoted endosome escape.The study provides valuable guidance for the development of BODIPY derivative-based protein delivery systems and advances the research in intracellular protein delivery.