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
Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor o...Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor of the bacterium,having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease.From the results of various independent researcher groups,it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest,production of reactive oxygen species leading to DNA damage,promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression,and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation.In addition,the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review.Apart from affecting the gastric epithelium,HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H.pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype,possibly contributing to the persistence of the pathogen in the gastric mucosa.展开更多
Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the me...Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the mechanism of carcinogenesis. During the recent Past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme γglutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, CGT activity induced by careinogenic polycyclic aromatic hydmiarbons, viz. 7, 12-dimethylbenz(a) anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbnol (I3C) in mouse skin. DAS and 13C are constituents of garlic and cruciferous vegetables respectively. A significant iIthibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/13C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis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
Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori G...Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.展开更多
Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to ...Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione(GSH) increased markedly in piglets fed glutamine, and the response was related to dose. In treatments I and I , the levels of plasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plasma GSH in treatment I was significantly higher than that in the control at 42 days age (P<0. 05). At 49 days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of the control, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyl transpeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatmentⅡ were significantly lower than that in the control (P<0.05). The activities ofγ-GT of duodenum in treatments I and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences of the activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation increased the level of plasma GSH, and decreased γ-GT activities.展开更多
BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resec...BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resection has not been established.AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBVrelated HCC patients.METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed.GPR levels were compared with 908 non-HCC individuals.Overall survival(OS)and recurrence-free survival(RFS)were evaluated,and cox proportional hazard model analyses were performed to identify independent risk factors.Differences in characteristics were adjusted by propensity score matching(PSM).Subgroup and stratified survival analyses for HCC risks were performed,and a linear trend of the hazard ratio(HR)according to GPR levels was constructed.RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas,chronic hepatitis B and healthy control(adjusted P<0.05).Variable bias was diminished after the PSM balance test.The low GPR group had improved OS(P<0.001)and RFS(P<0.001)in the PSM analysis and when combined with other variables.Multivariate cox analyses suggested that low GPR levels were associated with a better OS(HR=0.5,95%CI:0.36-0.7,P<0.001)and RFS(HR=0.57,95%CI:0.44-0.73,P<0.001).This same trend was confirmed in subgroup analyses.Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction.Moreover,stratified survival analyses found that GPR>0.6 was associated with a worse OS and higher recurrence rate(P for trend<0.001).CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBVrelated HCC.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
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
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
Background and Aims:Chronic hepatitis B virus(HBV)infection is a serious health problem worldwide.Evaluating liver injury in patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)with detectable ...Background and Aims:Chronic hepatitis B virus(HBV)infection is a serious health problem worldwide.Evaluating liver injury in patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)with detectable HBV DNA and normal alanine aminotransferase(ALT)is crucial to guide their clinical management.We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpepti-dase-to-platelet ratio(GPR)in these patients.Methods:A total of 184 treatment-naïve HBeAg-negative CHB pa-tients with detectable HBV DNA and normal ALT were enrolled.The Scheuer scoring system was used to classify liver inflammation and fibrosis.Results:The distribution of patients with different liver inflammation grades were as follows:G0,0(0%);G1,97(52.7%);G2,68(37.0%);G3,12(6.5%);and G4,7(3.8%).The distribution of patients with different liver fibrosis stages were as follows:S0,22(12.0%);S1,72(39.1%);S2,42(22.8%);S3,19(10.3%);and S4,29(15.8%).The areas under the re-ceiver operating characteristic(AUROC)curves of GPR in predicting significant inflammation,severe inflammation,and advanced inflammation were 0.723,0.895,and 0.952,respectively.The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation.The AUROCs of GPR in predicting significant fibrosis,severe fibrosis,and cirrhosis were 0.691,0.780,and 0.803,respectively.The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on four factors(FIB-4)in identifying advanced fibrosis and cirrhosis,and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis.Conclusions:Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis.GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.展开更多
Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate t...Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.展开更多
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 Singapore National Medical Research Council,No.R182000180213
文摘Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor of the bacterium,having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease.From the results of various independent researcher groups,it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest,production of reactive oxygen species leading to DNA damage,promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression,and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation.In addition,the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review.Apart from affecting the gastric epithelium,HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H.pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype,possibly contributing to the persistence of the pathogen in the gastric mucosa.
文摘Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the mechanism of carcinogenesis. During the recent Past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme γglutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, CGT activity induced by careinogenic polycyclic aromatic hydmiarbons, viz. 7, 12-dimethylbenz(a) anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbnol (I3C) in mouse skin. DAS and 13C are constituents of garlic and cruciferous vegetables respectively. A significant iIthibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/13C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis
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.
基金Supported by Italian Ministry for University and Research(Progetto di Ricerca di Interesse Nazionale No.2009A37C8C_002,to Ricci V)Fondazione Cariplo Grant(No.2011-0485 to Ricci V)+2 种基金Second University of Naples(CIRANAD to Romano M)University of Naples "Federico Ⅱ"(Fondo d’Ateneo per la Ricercato Zarrilli R)
文摘Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.
文摘Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione(GSH) increased markedly in piglets fed glutamine, and the response was related to dose. In treatments I and I , the levels of plasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plasma GSH in treatment I was significantly higher than that in the control at 42 days age (P<0. 05). At 49 days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of the control, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyl transpeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatmentⅡ were significantly lower than that in the control (P<0.05). The activities ofγ-GT of duodenum in treatments I and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences of the activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation increased the level of plasma GSH, and decreased γ-GT activities.
基金Supported by The National Natural Science Foundation of China,No.81560535,No.81802874 and No.81072321The Self-funded Scientific Research Project of Health Commission in Guangxi Zhuang Autonomous Region,China,No.Z20210977.
文摘BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resection has not been established.AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBVrelated HCC patients.METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed.GPR levels were compared with 908 non-HCC individuals.Overall survival(OS)and recurrence-free survival(RFS)were evaluated,and cox proportional hazard model analyses were performed to identify independent risk factors.Differences in characteristics were adjusted by propensity score matching(PSM).Subgroup and stratified survival analyses for HCC risks were performed,and a linear trend of the hazard ratio(HR)according to GPR levels was constructed.RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas,chronic hepatitis B and healthy control(adjusted P<0.05).Variable bias was diminished after the PSM balance test.The low GPR group had improved OS(P<0.001)and RFS(P<0.001)in the PSM analysis and when combined with other variables.Multivariate cox analyses suggested that low GPR levels were associated with a better OS(HR=0.5,95%CI:0.36-0.7,P<0.001)and RFS(HR=0.57,95%CI:0.44-0.73,P<0.001).This same trend was confirmed in subgroup analyses.Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction.Moreover,stratified survival analyses found that GPR>0.6 was associated with a worse OS and higher recurrence rate(P for trend<0.001).CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBVrelated HCC.
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.
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。
基金funded by the National Natural Science Foundation of China(82002133)Jiangsu Provincial Medical Innovation Team(CXTDA2017005)+4 种基金Nanjing Medical Science,Technique Development Foundation(QRX17121)Yangzhou Key R&D Program(Social Development)(YZ2020101)China Postdoctoral Science Foundation for COVID-19(2020T130049ZX)Natural Science Foundation of Jiangsu Province for Young Scholars(BK20200266)Foundation Project of Jiangsu Commission of Health(Q2017003).
文摘Background and Aims:Chronic hepatitis B virus(HBV)infection is a serious health problem worldwide.Evaluating liver injury in patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)with detectable HBV DNA and normal alanine aminotransferase(ALT)is crucial to guide their clinical management.We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpepti-dase-to-platelet ratio(GPR)in these patients.Methods:A total of 184 treatment-naïve HBeAg-negative CHB pa-tients with detectable HBV DNA and normal ALT were enrolled.The Scheuer scoring system was used to classify liver inflammation and fibrosis.Results:The distribution of patients with different liver inflammation grades were as follows:G0,0(0%);G1,97(52.7%);G2,68(37.0%);G3,12(6.5%);and G4,7(3.8%).The distribution of patients with different liver fibrosis stages were as follows:S0,22(12.0%);S1,72(39.1%);S2,42(22.8%);S3,19(10.3%);and S4,29(15.8%).The areas under the re-ceiver operating characteristic(AUROC)curves of GPR in predicting significant inflammation,severe inflammation,and advanced inflammation were 0.723,0.895,and 0.952,respectively.The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation.The AUROCs of GPR in predicting significant fibrosis,severe fibrosis,and cirrhosis were 0.691,0.780,and 0.803,respectively.The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on four factors(FIB-4)in identifying advanced fibrosis and cirrhosis,and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis.Conclusions:Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis.GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.
基金This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China(2017ZX10203205 to G.Chen)National Key R&D Plan(2017YFA0104304 to Y.Yang)+6 种基金Na-tional Natural Science Foundation of China(81770648 to Y.Yang)Guangdong Natural Science Foundation(2015A030312013 to Y.Yang)Science and Technology Program of Guangdong Province(2017B020209004 and 2017B030314027 to G.Chen)Science and Technology Program of Guangzhou city(201508020262 to Y.Yang)Collaborative Innovation Major Special Projects of Guangzhou City(201604020007 to F.Yang)Project funded by China Postdoctoral Science Foundation(2019M653904XB to F.Yang)Natural Science Foundation of Xinjiang Uyghur Autonomous Region(2020D01C006 to F.Yang).
文摘Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.