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Although aggravated liver injury has been reported in aged livers post‐ischemia and reperfusion (IR), the underlying mechanism of innate immune activation of aged macrophages is not well understood. Here, we investigated whether and how Stimulator of interferon genes (STING) signaling regulated macrophage proinflammatory activation and liver IR injury. Mice were subjected to hepatic IR in vivo. Macrophages isolated from IR‐stressed livers and bone marrow‐derived macrophages (BMDMs) from young and aged mice were used for in vitro studies. Enhanced nucleotide‐binding domain and leucine‐rich repeat containing protein 3 (NLRP3) activation was found in both livers and macrophages of aged mice post‐IR. NLRP3 knockdown in macrophages inhibited intrahepatic inflammation and liver injury in both young and aged mice. Interestingly, enhanced activation of the STING/ TANK‐binding kinase 1 (TBK1) signaling pathway was observed in aged macrophages post‐IR and mitochondria DNA (mtDNA) stimulation. STING suppression blocked over‐activation of NLRP3 signaling and excessive secretion of proinflammatory cytokines/chemokines in the mtDNA‐stimulated BMDMs from aged mice. More importantly, STING knockdown in macrophages abrogated the detrimental role of aging in aggravating liver IR injury and intrahepatic inflammation. Finally, peripheral blood from the recipients undergoing liver transplantation was collected and analyzed. The results showed that the elderly recipients had much higher levels of TNF‐α, IL‐6, IL‐1β, and IL‐18 post‐transplantation, indicating increased NLRP3 activation in lR‐stressed livers of elderly recipients. In summary, our study demonstrated that the STING‐NLRP3 axis was critical for the proinflammatory response of aged macrophages and would be a novel therapeutic target to reduce IR injury in elderly patients., Liver IR triggered mtDNA release from stressed hepatocytes. Aging promoted STING over‐activation, leading to enhanced NLRP3 inflammasome activation and increased proinflammatory cytokines/chemokines production of macrophages, which ultimately aggravated IR injury.

Background and Aim: Our previous studies have shown that regulatory T cells (Tregs) are reduced and Th17 cells are elevated in liver insults. Recent studies have indicated the critical role of endoplasmic reticulum (ER) stress of Kupffer cells (KCs) in evoking liver inflammation following reperfusion. The objective of this study was to investigate the role of ER stress of KCs in the conversion of Tregs to Th17 cells and the effect on liver ischemia-reperfusion injury. Methods: The partial warm liver ischemia-reperfusion injury mouse model was adopted. ER stress of KCs and the frequency of Tregs and Th17 cells following reperfusion were analyzed. Apart from depletion and adoptive transfer of KCs, KCs were isolated from ischemic lobes and co-cultured with Tregs to study the effect of KCs on Tregs and Th17 cells. Results: It was found that KCs induced ER stress, decreased natural Tregs (nTregs), and increased Th17 cells after reperfusion. Depletion of KCs modulated the reduction of nTregs and elevation of Th17 cells. Co-culture with stressed KCs led to the reduction in nTregs and elevation of Th17 cells. This effect was suppressed by anti-interleukin-6. Adoptive transfer of these stressed KCs resulted in the reduction in nTregs and elevation of Th17 cells and caused liver injury. Conclusion: Endoplasmic reticulum stress of KCs contributed to the conversion of nTregs to Th17 cells due to interleukin-6, resulting in the worsening of liver insult.

A high-permeability polyacrylonitrile membrane was used for hemodialysis in experimental animals with induced liver ischemia and for acute treatment of 39 patients with fulminant hepatic failure. Measurements were made of amino acids and other relevant compounds; nine patients survived. In long-term studies, the polyacrylonitrile membrane was used for hemofiltration in ten clinical cases of fulminant hepatic failure and coma. Five patients, including two pregnant women, survived.

Objective Finding of a significant replaced left hepatic artery (RLHA) during esophagectomy is relatively rare, with an incidence of approximately 5%. Sparing of the artery may be required to avoid complications of liver ischemia. Robotic assistance during esophagectomy may provide a technically superior method of artery preservation with minimally invasive approaches. Methods This is a retrospective case series of patients undergoing robotic-assisted minimally invasive esophagectomy (RAMIE) identified to have a significant RLHA at time of surgery. Results Five patients with a significant RLHA were identified from a series of over 100 RAMIE operations. Preservation of RLHA was accomplished in all cases without need for conversion, no intra-operative complications, and no post-operative liver dysfunction. The stomach was suitable and used for conduit reconstruction in all patients. Conclusions Sparing of the RLHA during RAMIE is feasible and effective. The robotic assisted approach may obviate the need for open conversion during these complex minimally invasive operations.

Autophagy clears dysfunctional proteins and organelles in a timely manner. Defective autophagy and subsequent mitochondrial dysfunction is a key mechanism of I/R injury to the liver. Sirtuin 1 (SIR...

The effect of the scavenger compound disulfiram (Antabus) on postischemic cell injury was investigated. Rats were subjected to 90 min of liver ischemia and 3 h of reperfusion. The extent of cell injury was evaluated morphologically by a dye exclusion test and a histochemical stain for calcium. It was found that pretreatment with disulfiram significantly reduced the number of injured cells compared to untreated controls.