目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,...目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,研究组采用宣白承气汤联合强化胰岛素治疗。治疗7 d后记录两组治疗前后3 d的空腹血糖(FPG)、早餐后2 h血糖(2 h PG)、空腹血糖与夜间最低点血糖净增值(∂glucose1)、早餐后2 h血糖与空腹血糖净增值(∂glucose2)、日内平均血糖(MBG)、日内血糖波动幅度(MAGE)。通过TCMSP数据库筛选宣白承气汤关键活性成分,利用Cytoscape3.7.2软件构建中药—活性成分—靶点网络图。采用Maestro11.5软件构建Nr1D1虚拟靶点模型,与宣白承气汤活性成分进行分子对接。结果两组治疗后FPG、2 h PG、∂glucose1、MBG、MAGE均较治疗前降低,且观察组低于对照组(P均<0.05)。观察组低血糖发生率低于对照组(P<0.05)。筛选出宣白承气汤45种活性成分,其中,15个活性成分与Nr1D1具有较好的结合活性。其中,来自大黄的5个成分(MOL000554、MOL002280、MOL002260、MOL002259、MOL002288)主要作用于PHE111、ARG172、GLY174、TYR113、LYS122、ARG126、TYR113、GLY174、GLU119、PHE173、SER109、HID112等氨基酸残基组合的活性位点。结论宣白承气汤联合强化胰岛素治疗可显著抑制2型糖尿病患者黎明现象,减少日间血糖波动。宣白承气汤君药大黄中的活性成分可能通过与Nr1D1结合,进而发挥治疗作用。展开更多
OBJECTIVE To study the dysregulation of metallothioneins(MT)and circadian genes in achieved human hepatocellular carcinoma(HCC),Peri-HCC tissues as compared to normal human livers,which may open up a new avenue for ta...OBJECTIVE To study the dysregulation of metallothioneins(MT)and circadian genes in achieved human hepatocellular carcinoma(HCC),Peri-HCC tissues as compared to normal human livers,which may open up a new avenue for targeting circadian clock to prevent and treatment of HCC.METHODS Total RNA was extracted,purified,and reverse transcribed.Realtime quantitative polymerase chain reaction(RT-q PCR)was performed to determine the expression of genes of metallothionein-1(MT-1),MT-2,and metal transcription factor-1(MFT-1)and circadian clock genes including core clock genes,circadian locomotor output cycles kaput(Clock)and brain and muscle Arnt-like protein 1(Bmal1),the clock feedback control genes,period(Per1,Per2)and cryptochrome(Cry1,Cry2),and clock target genes,nuclear orphan receptor factor protein(Nr1d1)and D-box-binding protein(Dbp)in human HCC,Peri-HCC and normal livers.RESULTS The expression of MT-1,MT-2,MFT-1 in human HCC was decreased,which were previously shown to have circadian rhythms.Similarly,the expression of the core clock genes(Bmal1,Clock),the clock feedback genes(Per1,Per2,Cry1and Cry2)was decreased in human HCC,as compared to Peri-HCC and normal livers.However,the expression of clock target genes(Nr1d1and Dbp)was increased in human HCC,as compared to Peri-HCC and normal livers.CONCLUSION These data clearly demonstrated the dysregulation of MTs and circadian clock genes in HCC,which could provide new insights into the relationship of circadian clock disruption and loss of MT in hepatocarcinogenesis,and could help a new strategy of targeting MT and circadian clock in the prevention and treatment of HCC.展开更多
文摘目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,研究组采用宣白承气汤联合强化胰岛素治疗。治疗7 d后记录两组治疗前后3 d的空腹血糖(FPG)、早餐后2 h血糖(2 h PG)、空腹血糖与夜间最低点血糖净增值(∂glucose1)、早餐后2 h血糖与空腹血糖净增值(∂glucose2)、日内平均血糖(MBG)、日内血糖波动幅度(MAGE)。通过TCMSP数据库筛选宣白承气汤关键活性成分,利用Cytoscape3.7.2软件构建中药—活性成分—靶点网络图。采用Maestro11.5软件构建Nr1D1虚拟靶点模型,与宣白承气汤活性成分进行分子对接。结果两组治疗后FPG、2 h PG、∂glucose1、MBG、MAGE均较治疗前降低,且观察组低于对照组(P均<0.05)。观察组低血糖发生率低于对照组(P<0.05)。筛选出宣白承气汤45种活性成分,其中,15个活性成分与Nr1D1具有较好的结合活性。其中,来自大黄的5个成分(MOL000554、MOL002280、MOL002260、MOL002259、MOL002288)主要作用于PHE111、ARG172、GLY174、TYR113、LYS122、ARG126、TYR113、GLY174、GLU119、PHE173、SER109、HID112等氨基酸残基组合的活性位点。结论宣白承气汤联合强化胰岛素治疗可显著抑制2型糖尿病患者黎明现象,减少日间血糖波动。宣白承气汤君药大黄中的活性成分可能通过与Nr1D1结合,进而发挥治疗作用。
文摘OBJECTIVE To study the dysregulation of metallothioneins(MT)and circadian genes in achieved human hepatocellular carcinoma(HCC),Peri-HCC tissues as compared to normal human livers,which may open up a new avenue for targeting circadian clock to prevent and treatment of HCC.METHODS Total RNA was extracted,purified,and reverse transcribed.Realtime quantitative polymerase chain reaction(RT-q PCR)was performed to determine the expression of genes of metallothionein-1(MT-1),MT-2,and metal transcription factor-1(MFT-1)and circadian clock genes including core clock genes,circadian locomotor output cycles kaput(Clock)and brain and muscle Arnt-like protein 1(Bmal1),the clock feedback control genes,period(Per1,Per2)and cryptochrome(Cry1,Cry2),and clock target genes,nuclear orphan receptor factor protein(Nr1d1)and D-box-binding protein(Dbp)in human HCC,Peri-HCC and normal livers.RESULTS The expression of MT-1,MT-2,MFT-1 in human HCC was decreased,which were previously shown to have circadian rhythms.Similarly,the expression of the core clock genes(Bmal1,Clock),the clock feedback genes(Per1,Per2,Cry1and Cry2)was decreased in human HCC,as compared to Peri-HCC and normal livers.However,the expression of clock target genes(Nr1d1and Dbp)was increased in human HCC,as compared to Peri-HCC and normal livers.CONCLUSION These data clearly demonstrated the dysregulation of MTs and circadian clock genes in HCC,which could provide new insights into the relationship of circadian clock disruption and loss of MT in hepatocarcinogenesis,and could help a new strategy of targeting MT and circadian clock in the prevention and treatment of HCC.
