Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
Aluminum is the primary structural material in nuclear engineering,and its cross section induced by 14-MeV neutrons is of great significance.To address the issue of insufficient accuracy for the^(27)Al(n,2n)^(26)Al re...Aluminum is the primary structural material in nuclear engineering,and its cross section induced by 14-MeV neutrons is of great significance.To address the issue of insufficient accuracy for the^(27)Al(n,2n)^(26)Al reaction cross section,the activation method and accelerator mass spectrometry(AMS)technique were used to determine the^(27)Al(n,2n)^(26)Al cross section,which could be used as a D-T plasma ion temperature monitor in fusion reactors.At the China Academy of Engineering Physics,neutron activation was performed using a K-400 neutron generator produced by the T(d,n)4He reaction.The^(26)Al∕^(27)Al isotope ratios were measured using the newly installed GYIG 1 MV AMS at the Institute of Geochemistry,Chinese Academy of Sciences.The neutron flux was monitored by measuring the activity of 92mNb produced by the 93Nb(n,2n)92mNb reaction.The measured results were compared with available data in the experimental nuclear reaction database,and the measured values showed a reasonable degree of consistency with partially available literature data.The newly acquired cross-sectional data at 12 neutron energy points through systematic measurements clarified the divergence,which has two different growth trends from the existing experimental values.The obtained results are also compared with the corresponding evaluated database,and the newly calculated excitation functions with TALYS−1.95 and EMPIRE−3.2 codes,the agreement with CENDL−3.2,TENDL-2021 and EMPIRE−3.2 results are generally acceptable.A substantial improvement in the knowledge of the^(27)Al(n,2n)^(26)Al reaction excitation function was obtained in the present work,which will lay the foundation for the diagnosis of the fusion ion temperature,testing of the nuclear physics model,evaluation of nuclear data,etc.展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
基金the Open Project of Guangxi Key Laboratory of Nuclear Physics and Nuclear Technology(NLK 2022-04)the Central Government Guidance Funds for Local Scientific and Technological Development,China(No.Guike,ZY22096024)+1 种基金the National Natural Science Foundation of China(12065003)Guangxi Key R&D Project(2023AB07029).
文摘Aluminum is the primary structural material in nuclear engineering,and its cross section induced by 14-MeV neutrons is of great significance.To address the issue of insufficient accuracy for the^(27)Al(n,2n)^(26)Al reaction cross section,the activation method and accelerator mass spectrometry(AMS)technique were used to determine the^(27)Al(n,2n)^(26)Al cross section,which could be used as a D-T plasma ion temperature monitor in fusion reactors.At the China Academy of Engineering Physics,neutron activation was performed using a K-400 neutron generator produced by the T(d,n)4He reaction.The^(26)Al∕^(27)Al isotope ratios were measured using the newly installed GYIG 1 MV AMS at the Institute of Geochemistry,Chinese Academy of Sciences.The neutron flux was monitored by measuring the activity of 92mNb produced by the 93Nb(n,2n)92mNb reaction.The measured results were compared with available data in the experimental nuclear reaction database,and the measured values showed a reasonable degree of consistency with partially available literature data.The newly acquired cross-sectional data at 12 neutron energy points through systematic measurements clarified the divergence,which has two different growth trends from the existing experimental values.The obtained results are also compared with the corresponding evaluated database,and the newly calculated excitation functions with TALYS−1.95 and EMPIRE−3.2 codes,the agreement with CENDL−3.2,TENDL-2021 and EMPIRE−3.2 results are generally acceptable.A substantial improvement in the knowledge of the^(27)Al(n,2n)^(26)Al reaction excitation function was obtained in the present work,which will lay the foundation for the diagnosis of the fusion ion temperature,testing of the nuclear physics model,evaluation of nuclear data,etc.
