Background:Cholangiocarcinoma(CCA)is a cancer type that builds in the bile ducts that carry digestive fluid,bile.These ducts connect the liver to the gallbladder and the small intestine.The disease is often diagnosed ...Background:Cholangiocarcinoma(CCA)is a cancer type that builds in the bile ducts that carry digestive fluid,bile.These ducts connect the liver to the gallbladder and the small intestine.The disease is often diagnosed at an advanced stage,resulting in a low 5-year survival rate.This study aims to evaluate the concentrations of serum thiol/disulfide in CCA patients and healthy volunteers and investigate the association between oxidative activity and clinical and pathological characteristics in CCA patients.By examining the relationship between reduced thiol/disulfide measures and tumorigenesis of the disease,we can potentially identify an unfavourable prognosis in CCA patients.Methods:To assess the status of thiol/disulfide in the blood of Cholangiocarcinoma patients using a novel automated homeostasis assay,we recruited 55 individuals for this study(CCA patients,n=27;healthy volunteers,n=28).We measured the levels of serum total thiol(TT)(–SH+–S-S–),native thiol(NT)(–SH),and disulfide(DD)(–S-S–)in both the CCA group and the control group.Additionally,we calculated the ratio of thiol/disulfide(–SH/–S-S–).Results:We explored the relationship between oxidative activity and clinical and pathological characteristics in CCA patients.The study found no significant differences in age and sex between CCA patients and controls.NT and TT levels were higher in the control group compared to the CCA group.However,the disulfide level did not significantly differ between the two groups.Pearson's correlation matrix analysis revealed positive correlations between TT and NT levels and negative correlations between NT/TT%,DD level,and DD/TT%.Conclusion:Our findings suggest a statistical difference in serum thiol/disulfide parameters.As a marker of total oxidant status,thiol and disulfide levels have decreased in patients with CCA.However,no correlation was found between the tumour markers CEA and CA19-9 and thiol levels.A decrease in blood thiol and disulfide concentrations or the ratio of thiol to disulfide may indicate an increase in oxidative stress and decreased antioxidant capacity.As an indication of the prognosis of cholangiocarcinoma disease in the early period,it may be used to determine the effectiveness of medical interventions.The NT/TT%,disulfide/native thiol percentage,and DD/TT%ratios did not significantly change between the groups.Therefore,measuring serum thiol levels could be a helpful marker for assessing prognosis in the early stages of CCA.Nevertheless,further studies must validate these results and investigate the underlying mechanisms.展开更多
As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoreti...As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect（i.e. conjugation and hyper-conjugation effects） becomes important when the steric hindrance is insignificant.展开更多
文摘Background:Cholangiocarcinoma(CCA)is a cancer type that builds in the bile ducts that carry digestive fluid,bile.These ducts connect the liver to the gallbladder and the small intestine.The disease is often diagnosed at an advanced stage,resulting in a low 5-year survival rate.This study aims to evaluate the concentrations of serum thiol/disulfide in CCA patients and healthy volunteers and investigate the association between oxidative activity and clinical and pathological characteristics in CCA patients.By examining the relationship between reduced thiol/disulfide measures and tumorigenesis of the disease,we can potentially identify an unfavourable prognosis in CCA patients.Methods:To assess the status of thiol/disulfide in the blood of Cholangiocarcinoma patients using a novel automated homeostasis assay,we recruited 55 individuals for this study(CCA patients,n=27;healthy volunteers,n=28).We measured the levels of serum total thiol(TT)(–SH+–S-S–),native thiol(NT)(–SH),and disulfide(DD)(–S-S–)in both the CCA group and the control group.Additionally,we calculated the ratio of thiol/disulfide(–SH/–S-S–).Results:We explored the relationship between oxidative activity and clinical and pathological characteristics in CCA patients.The study found no significant differences in age and sex between CCA patients and controls.NT and TT levels were higher in the control group compared to the CCA group.However,the disulfide level did not significantly differ between the two groups.Pearson's correlation matrix analysis revealed positive correlations between TT and NT levels and negative correlations between NT/TT%,DD level,and DD/TT%.Conclusion:Our findings suggest a statistical difference in serum thiol/disulfide parameters.As a marker of total oxidant status,thiol and disulfide levels have decreased in patients with CCA.However,no correlation was found between the tumour markers CEA and CA19-9 and thiol levels.A decrease in blood thiol and disulfide concentrations or the ratio of thiol to disulfide may indicate an increase in oxidative stress and decreased antioxidant capacity.As an indication of the prognosis of cholangiocarcinoma disease in the early period,it may be used to determine the effectiveness of medical interventions.The NT/TT%,disulfide/native thiol percentage,and DD/TT%ratios did not significantly change between the groups.Therefore,measuring serum thiol levels could be a helpful marker for assessing prognosis in the early stages of CCA.Nevertheless,further studies must validate these results and investigate the underlying mechanisms.
基金NSFC (No. 21202006)FRFCU (No. FRF-TP14-015A2) for financial supports and Super-computer Center of Shanghai and Shenzhen for technical supports
文摘As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect（i.e. conjugation and hyper-conjugation effects） becomes important when the steric hindrance is insignificant.
