The study of ligand-receptor interactions is of great significance in food flavor perception.In this study,a computer simulation method was used to investigate the mechanism of interaction between umami peptides and T...The study of ligand-receptor interactions is of great significance in food flavor perception.In this study,a computer simulation method was used to investigate the mechanism of interaction between umami peptides and T1R1/T1R3-Venus-flytrap domain(VFT)receptor.The binding site,conformational changes,and binding free energy between umami peptides and T1R1/T1R3-VFT were analyzed through molecular modeling,molecular docking,and molecular dynamics simulations.The receptor model constructed using AlphaFold2 has the best rationality.The molecular docking results showed that umami peptides primarily bound to T1R1-VFT through hydrogen bonding,with key binding residues such as Thr149,Arg151,and Asp108.The binding of umami peptides led to a more stable complex system,and the positively charged amino acids contributed positively to the overall binding free energy.This study provides theoretical support for the development of a better understanding of the interaction between umami substances and the umami receptor.展开更多
目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表...目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表法将其分为对照组(n=32)与试验组(n=31),对照组给予钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)类药物治疗,试验组在对照组基础上给予二甲双胍治疗,两组患者均连续治疗12周。收集患者临床资料,对比治疗前后两组简易精神量表(MMSE)得分、蒙特利尔认知评估量表(MoCA)得分、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2小时血糖(2 hPBG)、外周单核细胞中NLRP3炎性小体蛋白表达水平、caspase-1蛋白表达水平及血清IL-8、IL-1β水平;采用Pearson线性相关分析治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG的相关性。结果治疗后,试验组MMSE、MoCA得分均增高,且明显高于对照组(P<0.05),试验组FBG、HbA1c、2 h PBG水平低于对照组(P<0.05),试验组NLRP3、caspase-1蛋白水平和IL-18、IL-1β水平较对照组明显更低(P<0.05);经Pearson线性相关分析显示,治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG呈正相关(P<0.05)。结论二甲双胍治疗能够改善T2DM合并脑卒中患者的认知功能,降低血糖水平和炎症反应,这可能与其对NLRP3/caspase-1信号通路的调节作用有关。展开更多
基金funded by the National Natural Science Foundation of China(32001824,31972198)supported by the Startup Fund for Young Faculty at SJTU(Shanghai Jiao Tong University)High Level Innovation Team and Distinguished Scholar Project of Guangxi Universities and Colleges(2020[6]).
文摘The study of ligand-receptor interactions is of great significance in food flavor perception.In this study,a computer simulation method was used to investigate the mechanism of interaction between umami peptides and T1R1/T1R3-Venus-flytrap domain(VFT)receptor.The binding site,conformational changes,and binding free energy between umami peptides and T1R1/T1R3-VFT were analyzed through molecular modeling,molecular docking,and molecular dynamics simulations.The receptor model constructed using AlphaFold2 has the best rationality.The molecular docking results showed that umami peptides primarily bound to T1R1-VFT through hydrogen bonding,with key binding residues such as Thr149,Arg151,and Asp108.The binding of umami peptides led to a more stable complex system,and the positively charged amino acids contributed positively to the overall binding free energy.This study provides theoretical support for the development of a better understanding of the interaction between umami substances and the umami receptor.
文摘目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表法将其分为对照组(n=32)与试验组(n=31),对照组给予钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)类药物治疗,试验组在对照组基础上给予二甲双胍治疗,两组患者均连续治疗12周。收集患者临床资料,对比治疗前后两组简易精神量表(MMSE)得分、蒙特利尔认知评估量表(MoCA)得分、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2小时血糖(2 hPBG)、外周单核细胞中NLRP3炎性小体蛋白表达水平、caspase-1蛋白表达水平及血清IL-8、IL-1β水平;采用Pearson线性相关分析治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG的相关性。结果治疗后,试验组MMSE、MoCA得分均增高,且明显高于对照组(P<0.05),试验组FBG、HbA1c、2 h PBG水平低于对照组(P<0.05),试验组NLRP3、caspase-1蛋白水平和IL-18、IL-1β水平较对照组明显更低(P<0.05);经Pearson线性相关分析显示,治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG呈正相关(P<0.05)。结论二甲双胍治疗能够改善T2DM合并脑卒中患者的认知功能,降低血糖水平和炎症反应,这可能与其对NLRP3/caspase-1信号通路的调节作用有关。
