E2F1-mediated Up-regulation of NCAPG Promotes Hepatocellular Carcinoma Development by Inhibiting Pyroptosis

Background and Aims:As a subunit of the condensin complex,NCAPG has an important role in maintaining chromosome condensation,but its biological function and regulatory mechanism in hepatocellular carcinoma(HCC)remains undefined.Methods:The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression analysis.ROC curves were plotted to compare the predictive ability of NCAPG and AFP.Double luciferase reporter system,and ChIP were used to investigate transcriptional potential of E2F1 to NCAPG.Pyroptosis was observed by scanning electron microscopy.Protein expression of NCAPG,E2F1,and major proteins constituting NLRP3 inflammasome was determined by western blotting and ELISA.An in vivo tumor formation assay was conducted to verify the in vitro results.Results:Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor prognosis.Serum NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP[AUROC 0.766(95%CI:0.650–0.881)vs.0.649(95%CI 0.506–0.793)].HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG.E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter,and the interaction of E2F1 and NCAPG gene was confirmed by ChIP.Silencing of E2F1 resulted in significant down-regulation of NCAPG.Knockdown of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in vitro.Conclusions:We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis,which was regulated by its upstream transactivator,E2F1.The role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

The clinical implication of gamma-glutamyl transpeptidase in COVID-19

Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.

OOCDB:A Comprehensive,Systematic,and Real-time Organs-on-a-chip Database

Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro.Organs-on-a-chip technology,as opposed to traditional two-dimensional cell culture and animal models,can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs.Despite the fact that many organs-on-a-chip-related data have been published,none of the current databases have all of the following functions:searching,downloading,as well as analyzing data and results from the literature on organs-on-a-chip.Therefore,we created an organs-on-a-chip database(OOCDB)as a platform to integrate information about organs-on-a-chip from various sources,including literature,patents,raw data from microarray and transcriptome sequencing,several open-access datasets of organs-on-a-chip and organoids,and data generated in our laboratory.OOCDB contains dozens of sub-databases and analysis tools,and each sub-database contains various data associated with organs-on-a-chip,with the goal of providing researchers with a comprehensive,systematic,and convenient search engine.Furthermore,it offers a variety of other functions,such as mathematical modeling,three-dimensional modeling,and citation mapping,to meet the needs of organs-on-a-chip.

Glycogen accumulation drives hepatocarcinogenesis by targeting the Hippo signaling pathway

Recent advances highlight accelerated glucose metabolism as one of the hallmarks of cancer cells.Normal differentiated cells usually utilize the process of mitochondrial oxidative phosphorylation to metabolize glucose into carbon dioxide(CO_(2))and adenosine triphosphate(ATP).However,the cancer cell preferentially takes advantage of aerobic glycolysis to generate lactate and ATP to support the high energy demand for rapid cancer cell proliferation even in the presence of sufficient oxygen.1 This intriguing observation was first reported by the German physiologist Otto Warburg,and thus,this process is termed“the Warburg effect”.