肝癌是全球癌症相关死亡的第三大原因,存在早期诊断困难、治疗选择受限及复发率高的问题。因此,深入研究肝癌的分子机制,发现新的治疗靶点和方法,对改善肝癌诊断和预后具有重要意义。Tribbles假激酶(TRIB1、TRIB2、TRIB3)因其在调节炎...肝癌是全球癌症相关死亡的第三大原因,存在早期诊断困难、治疗选择受限及复发率高的问题。因此,深入研究肝癌的分子机制,发现新的治疗靶点和方法,对改善肝癌诊断和预后具有重要意义。Tribbles假激酶(TRIB1、TRIB2、TRIB3)因其在调节炎症、代谢和癌症中的独特作用已经成为研究热点。它们通过调控细胞周期在肝癌中起关键作用,并可能影响治疗抵抗性和免疫逃逸机制。文章总结近年来Tribbles假激酶家族在肝癌中作用机制的研究进展,旨在为肝癌的诊断、治疗和预后提供新的思路和策略。Liver cancer is the third leading cause of cancer-related deaths globally, characterized by difficulties in early diagnosis, limited treatment options, and high recurrence rates. Therefore, in-depth research on the molecular mechanisms of liver cancer to discover new therapeutic targets and methods is crucial for improving liver cancer diagnosis and prognosis. Tribbles pseudokinases (TRIB1, TRIB2, TRIB3) have become research hotspots due to their unique roles in regulating inflammation, metabolism, and cancer. They play a key role in liver cancer by regulating the cell cycle and may also influence treatment resistance and immune evasion mechanisms. This paper summarizes recent research progress on the mechanisms of the Tribbles pseudokinase family in liver cancer, aiming to provide new ideas and strategies for liver cancer diagnosis, treatment, and prognosis.展开更多
目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NA...目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)中的表达变化进行研究并探讨他们在NAFLD中的作用.方法:将30只Wistar大鼠随机分为正常组和NAFLD模型组,每组各15只.模型组大鼠采用高脂高糖饮食诱导NAFLD,正常组大鼠则给予普通饲料喂养,造模时间总计为16 wk.血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白(highdensity lipoprotein,HDL)和低密度脂蛋白(lowdensity lipoprotein,LDL)的含量采用全自动生化分析仪进行检测;应用PCR技术对肝脏中TRB3及CHOP m RNA水平的改变进行检测;应用免疫组织化学技术对肝脏中TRB3及CHOP蛋白水平的改变进行检测;采用流式细胞仪检测细胞凋亡改变.结果:模型组大鼠血清中TC、TG和LDL含量较正常组大鼠显著升高(P<0.05),而HDL则明显低于正常组(P<0.05);与正常组相比,模型组大鼠肝脏中TRB3及CHOP m RNA水平均显著增加(P<0.05或P<0.01);免疫组织化学结果显示模型组大鼠肝脏中TRB3及CHOP蛋白表达水平较正常组大鼠显著升高(P<0.01);此外流式细胞仪对大鼠肝细胞凋亡进行检测发现,模型组大鼠肝细胞凋亡与正常组相比明显增多.结论:TRB3和CHOP在基因及蛋白水平表达上调可能与高脂高糖诱导的NAFLD的发生发展有关.展开更多
The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of ...The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.展开更多
目的探讨母胎外周循环系统和母胎界面组织中Tribbles同源蛋白3(TRB-3)的表达水平与妊娠期糖尿病(GDM)的相关性,为阐明GDM发病的分子机制及其临床诊断提供新的依据。方法选取2022年1—12月于深圳市龙华区人民医院产科行择期剖宫产术的32...目的探讨母胎外周循环系统和母胎界面组织中Tribbles同源蛋白3(TRB-3)的表达水平与妊娠期糖尿病(GDM)的相关性,为阐明GDM发病的分子机制及其临床诊断提供新的依据。方法选取2022年1—12月于深圳市龙华区人民医院产科行择期剖宫产术的32例GDM产妇及同期32例行剖宫产术的健康孕产妇,采集其分娩前48 h外周血、分娩时脐静脉血、胎盘组织和脐带组织,用于制作石蜡切片并进行TRB-3免疫组织化学检测;采用酶联免疫吸附试验(ELISA)测定母体外周血及脐静脉血中的TRB-3水平。结果TRB-3主要表达在母胎界面的滋养层细胞及脐静脉内皮细胞;GDM组的胎盘及脐带组织中TRB-3的表达水平高于健康对照组;GDM组外周血浆及其胎儿的脐静脉血中TRB-3的水平高于健康对照组;母体外周血TRB-3水平与孕妇年龄、1 h餐后血糖(PBG)水平、2 h PBG呈正相关关系,与糖化血红蛋白水平、新生儿体重呈负相关关系;孕妇分娩孕周和PBG与脐静脉组织TRB-3的表达呈正相关关系,新生儿体重与脐静脉组织TRB-3表达呈负相关关系。结结论母胎外周血的TRB-3及胎盘组织、脐静脉组织中TRB-3在临床诊断GDM中具有一定的参考意义和应用价值。展开更多
文摘肝癌是全球癌症相关死亡的第三大原因,存在早期诊断困难、治疗选择受限及复发率高的问题。因此,深入研究肝癌的分子机制,发现新的治疗靶点和方法,对改善肝癌诊断和预后具有重要意义。Tribbles假激酶(TRIB1、TRIB2、TRIB3)因其在调节炎症、代谢和癌症中的独特作用已经成为研究热点。它们通过调控细胞周期在肝癌中起关键作用,并可能影响治疗抵抗性和免疫逃逸机制。文章总结近年来Tribbles假激酶家族在肝癌中作用机制的研究进展,旨在为肝癌的诊断、治疗和预后提供新的思路和策略。Liver cancer is the third leading cause of cancer-related deaths globally, characterized by difficulties in early diagnosis, limited treatment options, and high recurrence rates. Therefore, in-depth research on the molecular mechanisms of liver cancer to discover new therapeutic targets and methods is crucial for improving liver cancer diagnosis and prognosis. Tribbles pseudokinases (TRIB1, TRIB2, TRIB3) have become research hotspots due to their unique roles in regulating inflammation, metabolism, and cancer. They play a key role in liver cancer by regulating the cell cycle and may also influence treatment resistance and immune evasion mechanisms. This paper summarizes recent research progress on the mechanisms of the Tribbles pseudokinase family in liver cancer, aiming to provide new ideas and strategies for liver cancer diagnosis, treatment, and prognosis.
文摘目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)中的表达变化进行研究并探讨他们在NAFLD中的作用.方法:将30只Wistar大鼠随机分为正常组和NAFLD模型组,每组各15只.模型组大鼠采用高脂高糖饮食诱导NAFLD,正常组大鼠则给予普通饲料喂养,造模时间总计为16 wk.血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白(highdensity lipoprotein,HDL)和低密度脂蛋白(lowdensity lipoprotein,LDL)的含量采用全自动生化分析仪进行检测;应用PCR技术对肝脏中TRB3及CHOP m RNA水平的改变进行检测;应用免疫组织化学技术对肝脏中TRB3及CHOP蛋白水平的改变进行检测;采用流式细胞仪检测细胞凋亡改变.结果:模型组大鼠血清中TC、TG和LDL含量较正常组大鼠显著升高(P<0.05),而HDL则明显低于正常组(P<0.05);与正常组相比,模型组大鼠肝脏中TRB3及CHOP m RNA水平均显著增加(P<0.05或P<0.01);免疫组织化学结果显示模型组大鼠肝脏中TRB3及CHOP蛋白表达水平较正常组大鼠显著升高(P<0.01);此外流式细胞仪对大鼠肝细胞凋亡进行检测发现,模型组大鼠肝细胞凋亡与正常组相比明显增多.结论:TRB3和CHOP在基因及蛋白水平表达上调可能与高脂高糖诱导的NAFLD的发生发展有关.
基金supported by National Key R&D Program of China(Grant No.2017YFA0205400,China)the National Natural Science Foundation of China(Grant Nos.81530093 and 81773781,China)+43 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)CAMS Central Public-interest Scientific Institution Basic Research Fund(Grant No.2017PT3104,China)supported by grants of the National Natural Science Foundation of China(Grant No.81874316,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-008,China)supported by grants of from the BBSRC and NWCR(Grant Nos.1088 and 1097,UK)supported by grants of NSF(Grant No.IOS-1456023,USA)NIH(Grant No.NIH R21 CA197317,USA)supported by grants of Ministry of Education,Singapore(Grant Nos.MOE2014-T2-1-012 and 2012-T1-001-036,Singapore)supported by grants from the Health Research Council of New Zealandsupported by a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealandsupported by Funda??o para a Ciência e a Tecnologia(FCT)Research Center Grant UID/BIM/04773/2013 Centre for Biomedical Research 1334a research grant from Liga Portuguesa Contra o Cancro–Núcleo Regional do Sul(LPCC/NRS,Portugal)a FCT 2014 research grant SFRH/BPD/100434/2014a Pro Regem grant PD/BD/114258/2016(Portugal)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)Innovation Network and the British Heart Foundation(PG/16/44/32146,UK)supported by grants from The Howat Foundation Ltd.(UK),Children with Cancer UK,Bloodwise and the Friends of Paul O'Gorman(UK)supported by grants of P-CREATE from Japan Agency for Medical Research and Developmentsupported by grants from the NIH(NIAID,USA),Alex's Lemonade Stand Foundation(USA)and the Samuel Waxman Cancer Research Foundation(USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)the "Fondation Centaure"(RTRS),which supports a French transplantation research network,the IHU-Cesti project,the DHU Oncogreffefinancial support managed by the National Research Agency via the"Investment into the Future" program(Grant Nos.ANR-10-IBHU-005and ANR-11-LABX-0016-01,France)supported by Nantes Métropole and Région Pays de la Loire(France)supported by grants of the British Heart Foundation(PG/16/44/32146,UK)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by a joint Ph.D studentship beween the A*Star Institute and the University of Sheffield(UK)supported by funding from the National Institutes of Health National Heart,Lung,and Blood Institute(R01HL141745,USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITNProject TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by the National Natural Science Foundation of China(Grant No.81503128,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-008,China)supported by National Institute of Health(NS R01-035546,USA)supported by the National Natural Science Foundation of China(Grant No.81400140,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-011,China)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by Spanish Ministry of Economy and Competitiveness(MINECO)and Fondo Europeo de desarrollo Regional(FEDER)(Grant No.INNPACTO/IPT-2012-0614-010000,Spain)supported by the National Natural Science Foundation of China(Grant Nos.81400286 and 81530093,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-010,China)supported by the National Natural Science Foundation of China(Grant Nos.81472717 and 81673474,China)Beijing Natural Science Foundation(Grant No.7162133,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)supported by the National Natural Science Foundation of China(Grant No.81703564,China)supported by the National Natural Science Foundation of China(Grant No.81603129,China)
文摘The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.
文摘目的探讨母胎外周循环系统和母胎界面组织中Tribbles同源蛋白3(TRB-3)的表达水平与妊娠期糖尿病(GDM)的相关性,为阐明GDM发病的分子机制及其临床诊断提供新的依据。方法选取2022年1—12月于深圳市龙华区人民医院产科行择期剖宫产术的32例GDM产妇及同期32例行剖宫产术的健康孕产妇,采集其分娩前48 h外周血、分娩时脐静脉血、胎盘组织和脐带组织,用于制作石蜡切片并进行TRB-3免疫组织化学检测;采用酶联免疫吸附试验(ELISA)测定母体外周血及脐静脉血中的TRB-3水平。结果TRB-3主要表达在母胎界面的滋养层细胞及脐静脉内皮细胞;GDM组的胎盘及脐带组织中TRB-3的表达水平高于健康对照组;GDM组外周血浆及其胎儿的脐静脉血中TRB-3的水平高于健康对照组;母体外周血TRB-3水平与孕妇年龄、1 h餐后血糖(PBG)水平、2 h PBG呈正相关关系,与糖化血红蛋白水平、新生儿体重呈负相关关系;孕妇分娩孕周和PBG与脐静脉组织TRB-3的表达呈正相关关系,新生儿体重与脐静脉组织TRB-3表达呈负相关关系。结结论母胎外周血的TRB-3及胎盘组织、脐静脉组织中TRB-3在临床诊断GDM中具有一定的参考意义和应用价值。
