A repeated sequence DNA fragment, L5B-4, was cloned from the 5 kb BamHI DNA fragments of rat genomic DNA. The expressions of the L5B-4 DNA fragment are different in liver and hepatoma cells. The amounts of transcripts...A repeated sequence DNA fragment, L5B-4, was cloned from the 5 kb BamHI DNA fragments of rat genomic DNA. The expressions of the L5B-4 DNA fragment are different in liver and hepatoma cells. The amounts of transcripts in hepatoma cells are lower in nucleus and higher in cytoplasm, especially in polysomal RNA, as compared with that in liver cells. The alteration shown in polysomal RNA of hepatoma cells seems to be specific. These results are discussed with respect to the possible function of this repeated DNA and its variation in hepatoma cells.展开更多
To explore the relationship between the expression of E-cadherin and the apoptosis in intrahepatic bile duct epithelial cells in biliary atresia (BA).Methods The E-cadherin expression was demonstrated by immunohistoch...To explore the relationship between the expression of E-cadherin and the apoptosis in intrahepatic bile duct epithelial cells in biliary atresia (BA).Methods The E-cadherin expression was demonstrated by immunohistochemical staining for the liver specimens from 38 children with BA and 16 normal children.The apoptotic intrahepatic bile duct epithelial cells in these specimens were visualized by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay,and the apoptotic index (AI) was calculated from the percentage of apoptotic cells in total cells.Results The intensity of E-cadherin expression in bile duct epithelial cells in BA group was lower than that in the normal control group (0.33±0.12 vs 0.62±0.20,P<0.01).On the other hand,the AI in BA group was significant higher than that in control group (51.74±19.93 vs 12.34±19.32,P<0.01).An inverse correlation was detected between the intensity of E-cadherin and the AI in the liver from children with BA.Conclusion The abnormal decrease of E-cadherin may lead to an increase of the apoptosis of intrahepatic bile epithelial cells in BA,resulting in developmental disorder of intrahepatic bile duct and ductal plate malformation in the liver.12 refs,4 figs,1 tab.展开更多
Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is ...Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is well-established,the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+T cell-mediated antitumor immunity remain unclear.Our findings indicate that depleting SRSF1 in CD8+T cells improve antitumor immune function,glycolytic metabolism,and the efficacy of adoptive T cell therapy.The inactivation of SRSF1 in tumor cells reduces transcription factors,including c-Jun,c-myc,and JunB,facilitating glycolytic metabolism reprogramming,which restores CD8+T cell function and inhibits tumor growth.The small-molecule inhibitor TN2008 targets SRSF1,boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models.We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+T cells.展开更多
文摘A repeated sequence DNA fragment, L5B-4, was cloned from the 5 kb BamHI DNA fragments of rat genomic DNA. The expressions of the L5B-4 DNA fragment are different in liver and hepatoma cells. The amounts of transcripts in hepatoma cells are lower in nucleus and higher in cytoplasm, especially in polysomal RNA, as compared with that in liver cells. The alteration shown in polysomal RNA of hepatoma cells seems to be specific. These results are discussed with respect to the possible function of this repeated DNA and its variation in hepatoma cells.
文摘To explore the relationship between the expression of E-cadherin and the apoptosis in intrahepatic bile duct epithelial cells in biliary atresia (BA).Methods The E-cadherin expression was demonstrated by immunohistochemical staining for the liver specimens from 38 children with BA and 16 normal children.The apoptotic intrahepatic bile duct epithelial cells in these specimens were visualized by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay,and the apoptotic index (AI) was calculated from the percentage of apoptotic cells in total cells.Results The intensity of E-cadherin expression in bile duct epithelial cells in BA group was lower than that in the normal control group (0.33±0.12 vs 0.62±0.20,P<0.01).On the other hand,the AI in BA group was significant higher than that in control group (51.74±19.93 vs 12.34±19.32,P<0.01).An inverse correlation was detected between the intensity of E-cadherin and the AI in the liver from children with BA.Conclusion The abnormal decrease of E-cadherin may lead to an increase of the apoptosis of intrahepatic bile epithelial cells in BA,resulting in developmental disorder of intrahepatic bile duct and ductal plate malformation in the liver.12 refs,4 figs,1 tab.
基金funded by the National Natural Science Foundation of China(Grant No.).This research was supported by grants from the National Natural Science Foundation of China(Grant Nos.82073217,82403555,82073218,82003084)the National Key Research and Development Program of China(Grant No.2018YFC1312100)+3 种基金the Shanghai Municipal Key Clinical Specialty,and the CAMS Innovation Fund for Medical Sciences(CIFMS 2019-I2M-5-058)the Leading Project of the Science and Technology Commission of Shanghai Municipality(No.21Y21900100)the Project of the Shanghai Municipal Health Commission This research was also supported by the Outstanding Resident Clinical Postdoctoral Program at Zhongshan Hospital,Fudan University,and the China Postdoctoral Science Foundation(KLF152165,202140269)The authors appreciated for the technical assistance in the virtual screening job described in this study by Prof.Renxiao Wang,School of Pharmacy,Fudan University.
文摘Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is well-established,the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+T cell-mediated antitumor immunity remain unclear.Our findings indicate that depleting SRSF1 in CD8+T cells improve antitumor immune function,glycolytic metabolism,and the efficacy of adoptive T cell therapy.The inactivation of SRSF1 in tumor cells reduces transcription factors,including c-Jun,c-myc,and JunB,facilitating glycolytic metabolism reprogramming,which restores CD8+T cell function and inhibits tumor growth.The small-molecule inhibitor TN2008 targets SRSF1,boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models.We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+T cells.
