γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:tas...γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:taste type 1 receptor 1(T1 R1)-MSG and taste type 1 receptor 2(T1 R2)-sucrose were constructed to form binding receptors.These peptides showed affinity for the two receptors,but a higher affi nity scores and more binding amino acid residues for the T1 R1-MSG receptor,implying that they may exhibit a higher umami-enhancing effect.Thereinto,γ-glutamyl alanine(γ-EA)displayed the highest affi nity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds,indicating it had the highest enhancement for umaminess and sweetness among these peptides.Sensory evaluation demonstrated the enhancement ofγ-EA on umaminess was superior to that of sweetness.Generally,γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor,and exhibited a highest umami-enhancing effect.展开更多
Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1...Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1)expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasmaγ-glutamyl transpeptidase(GGT),an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels(6 weeks vs.baseline)in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies(camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab)at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels(P<0.001).Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels(OR=1.437,95%CI=1.116-1.849,P=0.005)and 6-week difference in GGT≥0 or<0(OR=53.675,95%CI=6.379-451.669,P<0.001)were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival(PFS)and overall survival(P<0.001).Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS(HR=1.033,95%CI=1.013-1.053,P=0.001).Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.展开更多
AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stre...AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.展开更多
Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to ...Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.展开更多
目的探讨并分析急性非ST段抬高心肌梗死(NSTEMI)患者经皮冠状动脉介入治疗(PCI)术后血清纤维蛋白原/白蛋白值(FAR)、γ-谷氨酰转肽酶(γ-GGT),N端脑钠肽前体(NT-proBNP)水平对预后的预测价值。方法回顾性分析2020年2月至2023年2月邯郸...目的探讨并分析急性非ST段抬高心肌梗死(NSTEMI)患者经皮冠状动脉介入治疗(PCI)术后血清纤维蛋白原/白蛋白值(FAR)、γ-谷氨酰转肽酶(γ-GGT),N端脑钠肽前体(NT-proBNP)水平对预后的预测价值。方法回顾性分析2020年2月至2023年2月邯郸市中心医院收治的实施PCI的急性NSTEMI患者93例,根据术后30 d主要不良心血管事件(MACE)发生情况将其分为MACE组(n=21)及无MACE组(n=72)。比较术前、术后30 d MACE组及无MACE组血清FAR、γ-GGT、NT-proBNP水平,采用单因素和多因素Logistic回归分析对影响急性NSTEMI患者术后30 d MACE发生的危险因素进行分析,采用受试者操作特征(ROC)曲线分析血清FAR、γ-GGT、NT-proBNP水平对急性NSTEMI患者术后MACE发生的预测价值。结果MACE组年龄为(65.37±3.46)岁;Killip分级为Ⅰ级2例,Ⅱ级3例,Ⅲ级5例,Ⅳ级11例;病变支数双支5例,3支16例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.87±0.55)%、(53.27±3.06)U/L、(914.35±84.35)ng/mL。无MACE组的年龄为(58.71±2.86)岁;Killip分级为Ⅰ级32例,Ⅱ级27例,Ⅲ级7例,Ⅳ级6例;病变支数为双支53例,3支19例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.12±0.51)%、(44.33±3.35)U/L、(656.82±75.63)ng/mL。MACE组和无MACE组的年龄、Killip分级、病变支数及术后30 d血清FAR、γ-GGT、NT-proBNP水平比较,差异均有统计学意义(P<0.05),两组性别、吸烟史、高血压史、高血脂史、糖尿病史及术前1 d血清FAR、γ-GGT、NT-proBNP水平比较差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,血清FAR、γ-GGT、NT-proBNP升高均为影响急性期NSTEMI患者术后MACE发生的独立危险因素(OR=3.074、2.686、3.340,P均<0.05)。ROC结果显示血清FAR、γ-GGT、NT-proBNP及其联合检测预测急性NSTEMI患者术后MACE发生的曲线下面积(AUC)分别为0.681、0.690、0.733和0.790,联合检测的AUC更高(P<0.05)。结论血清FAR、γ-GGT、NT-proBNP水平升高增加了急性NSTEMI患者PCI术后MACE的发生风险,三者联合检测对患者术后不良预后有一定预测价值。展开更多
目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本...目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本汤治疗。比较两组患者的临床疗效、不良反应发生率及治疗前后中医证候积分、肝功能指标[谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartateaminotransferase,AST)、γ-谷氨酰转肽酶(γ-GT)]、胆汁生化指标[总胆红素(total bilirubin,TBIL)、总胆汁酸(total bile acid,TBA)]。结果:两组患者发热、腹痛、黄疸等中医证候积分低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。观察组有效率高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后AST、ALT以及γ-GT低于本组治疗前,且治疗后观察组低于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TBA高于本组治疗前,TBIL低于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:扶正固本汤运用于胆总管结石手术后,能明显提高临床疗效,改善患者肝功能及胆汁生化指标,降低不良反应。展开更多
基金financial support by the National Natural Science Foundation of China(31901814)Guangzhou Science and Technology program key project(202104020028)the Major State Basic Reasearch Development Program Of China(2018YFD0901003)。
文摘γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:taste type 1 receptor 1(T1 R1)-MSG and taste type 1 receptor 2(T1 R2)-sucrose were constructed to form binding receptors.These peptides showed affinity for the two receptors,but a higher affi nity scores and more binding amino acid residues for the T1 R1-MSG receptor,implying that they may exhibit a higher umami-enhancing effect.Thereinto,γ-glutamyl alanine(γ-EA)displayed the highest affi nity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds,indicating it had the highest enhancement for umaminess and sweetness among these peptides.Sensory evaluation demonstrated the enhancement ofγ-EA on umaminess was superior to that of sweetness.Generally,γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor,and exhibited a highest umami-enhancing effect.
基金Supported by a grant from the Hubei and the Huazhong University of Science and Technology Undergraduate Innovation and Entrepreneurship Training Program(No.S202110487427,DYLC2021072).
文摘Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1)expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasmaγ-glutamyl transpeptidase(GGT),an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels(6 weeks vs.baseline)in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies(camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab)at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels(P<0.001).Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels(OR=1.437,95%CI=1.116-1.849,P=0.005)and 6-week difference in GGT≥0 or<0(OR=53.675,95%CI=6.379-451.669,P<0.001)were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival(PFS)and overall survival(P<0.001).Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS(HR=1.033,95%CI=1.013-1.053,P=0.001).Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.
基金Supported by a grant: "Progetto di Ricerca Sanitaria Finalizzata,Regione Piemonte, 2003"
文摘AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.
基金This work was supported by the National Natural Science Foundation of China(21925802,21878039,21822804,21808028,22022803,22078046)and the Natural Science Foundation of China-Liaoning Joint Fund(U1908202).
文摘Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.
文摘目的探讨并分析急性非ST段抬高心肌梗死(NSTEMI)患者经皮冠状动脉介入治疗(PCI)术后血清纤维蛋白原/白蛋白值(FAR)、γ-谷氨酰转肽酶(γ-GGT),N端脑钠肽前体(NT-proBNP)水平对预后的预测价值。方法回顾性分析2020年2月至2023年2月邯郸市中心医院收治的实施PCI的急性NSTEMI患者93例,根据术后30 d主要不良心血管事件(MACE)发生情况将其分为MACE组(n=21)及无MACE组(n=72)。比较术前、术后30 d MACE组及无MACE组血清FAR、γ-GGT、NT-proBNP水平,采用单因素和多因素Logistic回归分析对影响急性NSTEMI患者术后30 d MACE发生的危险因素进行分析,采用受试者操作特征(ROC)曲线分析血清FAR、γ-GGT、NT-proBNP水平对急性NSTEMI患者术后MACE发生的预测价值。结果MACE组年龄为(65.37±3.46)岁;Killip分级为Ⅰ级2例,Ⅱ级3例,Ⅲ级5例,Ⅳ级11例;病变支数双支5例,3支16例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.87±0.55)%、(53.27±3.06)U/L、(914.35±84.35)ng/mL。无MACE组的年龄为(58.71±2.86)岁;Killip分级为Ⅰ级32例,Ⅱ级27例,Ⅲ级7例,Ⅳ级6例;病变支数为双支53例,3支19例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.12±0.51)%、(44.33±3.35)U/L、(656.82±75.63)ng/mL。MACE组和无MACE组的年龄、Killip分级、病变支数及术后30 d血清FAR、γ-GGT、NT-proBNP水平比较,差异均有统计学意义(P<0.05),两组性别、吸烟史、高血压史、高血脂史、糖尿病史及术前1 d血清FAR、γ-GGT、NT-proBNP水平比较差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,血清FAR、γ-GGT、NT-proBNP升高均为影响急性期NSTEMI患者术后MACE发生的独立危险因素(OR=3.074、2.686、3.340,P均<0.05)。ROC结果显示血清FAR、γ-GGT、NT-proBNP及其联合检测预测急性NSTEMI患者术后MACE发生的曲线下面积(AUC)分别为0.681、0.690、0.733和0.790,联合检测的AUC更高(P<0.05)。结论血清FAR、γ-GGT、NT-proBNP水平升高增加了急性NSTEMI患者PCI术后MACE的发生风险,三者联合检测对患者术后不良预后有一定预测价值。
文摘目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本汤治疗。比较两组患者的临床疗效、不良反应发生率及治疗前后中医证候积分、肝功能指标[谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartateaminotransferase,AST)、γ-谷氨酰转肽酶(γ-GT)]、胆汁生化指标[总胆红素(total bilirubin,TBIL)、总胆汁酸(total bile acid,TBA)]。结果:两组患者发热、腹痛、黄疸等中医证候积分低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。观察组有效率高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后AST、ALT以及γ-GT低于本组治疗前,且治疗后观察组低于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TBA高于本组治疗前,TBIL低于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:扶正固本汤运用于胆总管结石手术后,能明显提高临床疗效,改善患者肝功能及胆汁生化指标,降低不良反应。
