The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadheri...The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadherin 1（Cdh1）,and catenin beta 1（Ctnnb1） are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization（IVF） mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin（HMG）（GnRH agonist group）,GnRH antagonist plus HMG（GnRH antagonist group）,and HMG alone（HMG group）.The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.展开更多
Objective: The main purpose was to investigate expression of CDH11 in pancreatic tissues and analyze its relations with clinical characteristics of patients with pancreatic cancer (PC). Methods: Expression of CDH11 in...Objective: The main purpose was to investigate expression of CDH11 in pancreatic tissues and analyze its relations with clinical characteristics of patients with pancreatic cancer (PC). Methods: Expression of CDH11 in cancerous tissues and cancer adjacent tissues were detected by immunohistochemistry staining, and their associations with clinical characteristics were analyzed. The text mining methods were used to assist the study of the effect of CDH11 on prognosis. Results: A total of 79 patients with PC were enrolled in the study, including 51 (64.6%) men and 28 (35.4%) women with a median age of 62 (41 - 84). The CDH11 expression in cancerous tissues was higher than that in adjacent tissues and the expression of CDH11 in both tissues was positively correlated (P 0.999;stage II vs III & IV, P = 0.308). A higher level of CDH11 expression correlated with worse overall survival (OS) time (P = 0.015). Conclusion: CDH11 may be involved in the development of early PC and lead to poor prognosis and could be a new target molecule for early diagnosis and treatment of PC.展开更多
Importance:Cadherin-11(CDH11),a cell-to-cell adhesion molecule,is implicated in the fibrotic process of several organs.Biliary atresia(BA)is a common cholestatic liver disease featuring cholestasis and progressive liv...Importance:Cadherin-11(CDH11),a cell-to-cell adhesion molecule,is implicated in the fibrotic process of several organs.Biliary atresia(BA)is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children.Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies.Currently,the role of CDH11 in cholestatic liver fibrosis remains unclear.Objective:This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.Methods:The expression ofCDH11 in BA livers was evaluated by database analysis and immunostaining.Seven BA liver samples were used for immunostaining.The wild type(Wt)andCDH11 knockout(CDH11^(-/-))mice were subjected to bile duct ligation(BDL)to induce cholestatic liver fibrosis.The serum biochemical analysis,liver histology,and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β(TGF-β)/Smad pathway.The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.Results:Analysis of public RNA-seq datasets showed thatCDH11 expression levels were significantly increased in livers of BA,and CDH11 was correlated with liver fibrosis in BA.BDL-induced liver injury and liver fibrosis were attenuated inCDH11^(-/-)mice compared to Wt mice.The protein expression levels of phosphorylated Smad2/3 were decreased in livers ofCDH11^(-/-)BDL mice compared to Wt BDL mice.CDH11 knockdown inhibited the activation of LX-2 cells.Interpretation:CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease,such as BA.展开更多
基金supported by a grant from the Major State Basic Research Development Program of China (973 Program)(No. 2007-CB948100)
文摘The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadherin 1（Cdh1）,and catenin beta 1（Ctnnb1） are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization（IVF） mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin（HMG）（GnRH agonist group）,GnRH antagonist plus HMG（GnRH antagonist group）,and HMG alone（HMG group）.The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.
文摘Objective: The main purpose was to investigate expression of CDH11 in pancreatic tissues and analyze its relations with clinical characteristics of patients with pancreatic cancer (PC). Methods: Expression of CDH11 in cancerous tissues and cancer adjacent tissues were detected by immunohistochemistry staining, and their associations with clinical characteristics were analyzed. The text mining methods were used to assist the study of the effect of CDH11 on prognosis. Results: A total of 79 patients with PC were enrolled in the study, including 51 (64.6%) men and 28 (35.4%) women with a median age of 62 (41 - 84). The CDH11 expression in cancerous tissues was higher than that in adjacent tissues and the expression of CDH11 in both tissues was positively correlated (P 0.999;stage II vs III & IV, P = 0.308). A higher level of CDH11 expression correlated with worse overall survival (OS) time (P = 0.015). Conclusion: CDH11 may be involved in the development of early PC and lead to poor prognosis and could be a new target molecule for early diagnosis and treatment of PC.
基金National Natural Science Foundation of China(Grant/Award Number:81770517)。
文摘Importance:Cadherin-11(CDH11),a cell-to-cell adhesion molecule,is implicated in the fibrotic process of several organs.Biliary atresia(BA)is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children.Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies.Currently,the role of CDH11 in cholestatic liver fibrosis remains unclear.Objective:This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.Methods:The expression ofCDH11 in BA livers was evaluated by database analysis and immunostaining.Seven BA liver samples were used for immunostaining.The wild type(Wt)andCDH11 knockout(CDH11^(-/-))mice were subjected to bile duct ligation(BDL)to induce cholestatic liver fibrosis.The serum biochemical analysis,liver histology,and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β(TGF-β)/Smad pathway.The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.Results:Analysis of public RNA-seq datasets showed thatCDH11 expression levels were significantly increased in livers of BA,and CDH11 was correlated with liver fibrosis in BA.BDL-induced liver injury and liver fibrosis were attenuated inCDH11^(-/-)mice compared to Wt mice.The protein expression levels of phosphorylated Smad2/3 were decreased in livers ofCDH11^(-/-)BDL mice compared to Wt BDL mice.CDH11 knockdown inhibited the activation of LX-2 cells.Interpretation:CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease,such as BA.
