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Background and Aim Methods Results Conclusion Hepatic ischemia–reperfusion (I/R) injury is the primary cause of liver dysfunction and liver failure, commonly occurring in liver transplantation, hepatectomy, and hemorrhagic shock. Polo‐like kinase 2 (PLK2), a pivotal regulator of centriole duplication, plays a crucial role in cell proliferation and injury repair. However, the function of PLK2 in hepatic I/R remains unclear.The effect of PLK2 was investigated in the mouse hepatic I/R model and the hepatocyte hypoxia‐reoxygenation (H/R) model. Liver injury was assessed by serum transaminase and hematoxylin and eosin staining. Cell apoptosis was analyzed using TUNEL analysis and immunoblotting. Inflammatory factors were evaluated by reverse transcription‐quantitative polymerase chain reaction. Mice or cultured cells during the I/R or H/R were treated by overexpressing PLK2. ROS fluorescence staining was used to assess oxidative stress injury.PLK2 was upregulated after hepatic I/R injury. Overexpressed PLK2 significantly improved liver enzyme levels and alleviated liver histological injury. Moreover, PLK2 decreased hepatocyte apoptosis and inhibited the expression of inflammatory factors in liver. Mechanistically, PLK2 increased the phosphorylation of GSK3β and enhanced expression of the antioxidant enzyme HO‐1, leading to less ROS production. Inhibition of the HO‐1 aggravated ROS generation and abolished the protective effect of PLK2.Overall, these findings revealed that PLK2 enhanced HO‐1 expression and reduced oxidative stress damage in hepatic I/R injury, and this protective effect related to GSK3β activity. [ABSTRACT FROM AUTHOR]

Introduction: In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification., Methods: The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed., Results: A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival., Conclusions: Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)