Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N -acetyl- l -tryptophan ( l -NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases. Objective: This study investigates the protective effect of l -NAT against HIRI and explores the potential underlying mechanisms. Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l -NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H 2 O 2 with or without 10 µM l -NAT for 6 h. Results: After l -NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls ( p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H 2 O 2 groups when compared with the controls; however, these levels were significantly decreased after l -NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H 2 O 2 group when compared with the controls, after l -NAT intervention. Conclusions: Our findings indicated that l -NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l -NAT to be a potential effective drug against HIRI during clinical practice.

Hepatic ischemia-reperfusion injury (HIRI) is one of the major sources of mortality and morbidity associated with hepatic surgery. Ac2-26, a short peptide of Annexin A1 protein, has been proved to have a protective effect against IRI. However, whether it exerts a protective effect on HIRI has not been reported. The HIRI mice model and the oxidative damage model of H2O2-induced AML12 cells were established to investigate whether Ac2-26 could alleviate HIRI by regulating the activation of IL-22/IL-22R1/STAT3 signaling. The protective effect of Ac2-26 was measured by various biochemical parameters related to liver function, apoptosis, inflammatory reaction, mitochondrial function and the expressions of IL-22, IL-22R1, p-STAT3Tyr705. We discovered that Ac2-26 reduced the Suzuki score and cell death rate, and increased the cell viability after HIRI. Moreover, we unraveled that Ac2-26 significantly decreased the number of apoptotic hepatocytes, and the expressions of cleaved-caspase-3 and Bax/Bcl-2 ratio. Furthermore, HIRI increased the contents of malondialdehyde (MDA), NADP+/NADPH ratio and reactive oxygen species (ROS), whereas Ac2-26 decreased them significantly. Additionally, Ac2-26 remarkably alleviated mitochondria dysfunction, which was represented by an increase in the adenosine triphosphate (ATP) content and mitochondrial membrane potential, a decrease in mitochondrial DNA (mtDNA) damage. Finally, we revealed that Ac2-26 pretreatment could significantly inhibit the activation of IL-22/IL22R1/STAT3 signaling. In conclusion, this work demonstrated that Ac2-26 ameliorated HIRI by reducing oxidative stress and inhibiting the mitochondrial apoptosis pathway, which might be closely related to the inhibition of the IL-22/IL22R1/STAT3 signaling pathway.

BackgroundThe best choice between first‐line aspiration and stent retriever for acute basilar artery occlusion remains controversial. This study aims to perform a systematic review and meta‐analysis comparing the stent retriever and direct aspiration about reported recanalization rates and periprocedural complications.MethodPubMed, Embase, Web of Science, Cochrane, and Clinical Trials were searched for the studies evaluating the efficacy and safety of first‐line aspiration versus stent retriever for acute basilar artery occlusion. A standard software program (Stata Corporation) was used for end‐point analyses. Statistical significance was defined as a p‐value less than .05.ResultsA total of 11 studies were involved in the current study, including 1014 patients. Regarding postoperative recanalization, the pooled analysis identified a significant difference in successful recanalization (odds ratio [OR] = 1.642; 95% confidence interval (95% CI): 1.099–2.453; p = .015) and complete recanalization (OR = 3.525; 95% CI: 1.306–2.872; p = .001) between the two groups in favor of the first‐line aspiration. Concerning the complications, the first‐line aspiration could achieve a lower rate of total complication (OR = .359; 95% CI: .229–.563; p < .001) and hemorrhagic complication (OR = .446, 95% CI: .259–.769; p = .004) than stent retriever. No significant difference was observed in postoperative mortality (OR = .966; p = .880), subarachnoid hematoma (OR = .171; p = .094), and parenchymal hematoma (OR = .799; p = .720). In addition, the pooled results revealed a significant difference in procedure duration between the two groups in favor of aspiration (WMD = −27.630, 95% CI: −50.958 to −4.302; p = .020). However, there was no significant difference in favorable outcome (OR = 1.149; p = .352) and rescue therapy (OR = 1.440; p = .409) between the two groups.ConclusionGiven that the first‐line aspiration was associated with a higher rate of postoperative recanalization, a lower risk of postoperative complication, and a faster duration of the procedure, these findings support the aspiration may be more secure than a stent retriever.

Inflammation is one of the most crucial mechanism underlying hepatic ischemia-reperfusion injury (HIRI). Several studies have shown that Ac2-26, the active N-terminal peptide of Annexin A1, could modulate anti-inflammatory processes and protect the organs from ischemia-reperfusion injury (IRI). However the effects of Ac2-26 on an HIRI model have not been reported to date. The purpose of the present study was to determine whether Ac2-26 pretreatment could protect hepatocytes against acute HIRI by inhibiting neutrophil infiltration through regulation of the high mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. To this end, a total of 72 adult C57BL/6 mice were randomly divided into sham operation (sham), ischemia-reperfusion (I/R), I/R + Ac2-26 and Ac2-26 groups. The HIRI model was established by occluding the branch of the hepatic pedicle to the left and median liver lobes with an atraumatic vascular clamp for 45 min, followed by reperfusion for 24 h. The expression of HMGB1, TLR4, NF-κB, IκBα and lymphocyte antigen 6 complex locus G6D (Ly6G) was detected using reverse transcription-quantitative PCR, western blotting and immunohistochemical staining; serum levels of HMGB1 were evaluated using an enzyme-linked immunosorbent assay. Flow cytometry was used to detect the proportion of neutrophil. The results indicated that Ac2-26 preconditioning rescued hepatocyte dysfunctions induced by HIRI. In addition, HIRI was associated with a significant increase in HMGB1 expression and release, accompanied by increased expression of TLR4, which was significantly inhibited by Ac2-26. Furthermore, the expression of phosphorylated (p)-NF-κB and the ratio of p-NF-κB to NF-κB were markedly increased, while the expression of IκBα was decreased in the I/R group compared with those in the sham group; however, these effects were reversed by Ac2-26 administration. Additionally, Ac2-26 administration significantly inhibited neutrophil infiltration and resulted in low levels of neutrophils and Ly6G as well as reduced myeloperoxidase activity. Taken together, these results indicated that Ac2-26 pretreatment serves a protective role against HIRI by regulating the HMGB1/TLR4/NF-κB signaling pathway and inhibiting neutrophil infiltration.

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