Currently,60 million women of reproductive age(18-44 years old) worldwide,and approximately 3 million American women have diabetes mellitus,and it has been estimated that this number will double by 2030.Pregestational...Currently,60 million women of reproductive age(18-44 years old) worldwide,and approximately 3 million American women have diabetes mellitus,and it has been estimated that this number will double by 2030.Pregestational diabetes mellitus(PGD) is a significant public health problem that increases the risk for structural birth defects affecting both maternal and neonatal pregnancy outcome.The most common types of human structural birth defects associated with PGD are congenital heart defects and central nervous system defects.However,diabetes can induce birth defects in any other fetal organ.In general,the rate of birth defects increases linearly with the degree of maternal hyperglycemia,which is the major factor that mediates teratogenicity of PGD.Stringent prenatal care and glycemic control are effective means to reduce birth defects in PGD pregnancies,but cannot reduce the incidence of birth defects to the rate of that is seen in the nondiabetic population.Studies in animal models have revealed that PGD induces oxidative stress,which activates cellular stress signalling leading to dysregulation of gene expression and excess apoptosis in the target organs,including the neural tube and embryonic heart.Activation of the apoptosis signalregulating kinase 1(ASK1)-forkhead transcription factor 3a(Fox O3a)-caspase 8 pathway causes apoptosis in the developing neural tube leading to neural tube defects(NTDs).ASK1 activates the c-Jun-N-Terminal kinase 1/2(JNK1/2),which leads to activation of the unfolded protein response and endoplasmic reticulum(ER) stress.Deletion of the ASK1 gene,the JNK1 gene,or the JNK2 gene,or inhibition of ER stress by 4-Phenylbutyric acid abrogates diabetes-induced apoptosis and reduces the formation of NTDs.Antioxidants,such as thioredoxin,which inhibits the ASK1-Fox O3a-caspase 8 pathway or ER stress inhibitors,may prevent PGD-induced birth defects.展开更多
Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube developme...Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.展开更多
Introduction: Omphalocele is an embryopathy of the first ten weeks of gestation. It corresponds to a defect in the abdominal wall through which viscera contained in a sac constituted by the amniotic membrane and cente...Introduction: Omphalocele is an embryopathy of the first ten weeks of gestation. It corresponds to a defect in the abdominal wall through which viscera contained in a sac constituted by the amniotic membrane and centered by the umbilical cord are exteriorized. The objective of this work was to study the diagnostic modalities and the impact of our therapeutic choices on the outcome of the management. Material and Methods: We carried out a prospective study on patients with omphalocele admitted to the pediatric surgery departments of the HND, during a period spread over 4 years, between January 2017 and December 2020. Results: we collected 55 files (i.e., 13.7 cases/year). There were 38 boys and 17 girls (sex ratio 2.2) with an average age of 1.9 days. We found 15 cases (27%) of type I and 40 cases (73%) of type II according to the AITKEN classification. Fifteen cases (27%) benefited from surgical treatment and 45 cases (73%) benefited from conservative treatment (Grob). Two surgical methods were used: Primary parietal closure, which was used in 10 cases (66.7%), and the GROSS method, which was used in 5 cases (33.3%). We obtained an improvement of 40 cases (73%) and 15 cases (27%) of death. Conclusion: our work reported our experience in the management of omphalocele and the difficulties of postoperative resuscitation.展开更多
基金Supported by NIH R01DK083243,R01DK101972 and R56 DK095380(to Yang P),R01DK103024(to Yang P and Reece EA)Basic Science Award(1-13-BS-220)American Diabetes Association(to Yang P)
文摘Currently,60 million women of reproductive age(18-44 years old) worldwide,and approximately 3 million American women have diabetes mellitus,and it has been estimated that this number will double by 2030.Pregestational diabetes mellitus(PGD) is a significant public health problem that increases the risk for structural birth defects affecting both maternal and neonatal pregnancy outcome.The most common types of human structural birth defects associated with PGD are congenital heart defects and central nervous system defects.However,diabetes can induce birth defects in any other fetal organ.In general,the rate of birth defects increases linearly with the degree of maternal hyperglycemia,which is the major factor that mediates teratogenicity of PGD.Stringent prenatal care and glycemic control are effective means to reduce birth defects in PGD pregnancies,but cannot reduce the incidence of birth defects to the rate of that is seen in the nondiabetic population.Studies in animal models have revealed that PGD induces oxidative stress,which activates cellular stress signalling leading to dysregulation of gene expression and excess apoptosis in the target organs,including the neural tube and embryonic heart.Activation of the apoptosis signalregulating kinase 1(ASK1)-forkhead transcription factor 3a(Fox O3a)-caspase 8 pathway causes apoptosis in the developing neural tube leading to neural tube defects(NTDs).ASK1 activates the c-Jun-N-Terminal kinase 1/2(JNK1/2),which leads to activation of the unfolded protein response and endoplasmic reticulum(ER) stress.Deletion of the ASK1 gene,the JNK1 gene,or the JNK2 gene,or inhibition of ER stress by 4-Phenylbutyric acid abrogates diabetes-induced apoptosis and reduces the formation of NTDs.Antioxidants,such as thioredoxin,which inhibits the ASK1-Fox O3a-caspase 8 pathway or ER stress inhibitors,may prevent PGD-induced birth defects.
基金supported by the grant from Shaanxi Technology Committee of China,No.2013JM4001the China Scholarship Council(CSC)
文摘Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.
文摘Introduction: Omphalocele is an embryopathy of the first ten weeks of gestation. It corresponds to a defect in the abdominal wall through which viscera contained in a sac constituted by the amniotic membrane and centered by the umbilical cord are exteriorized. The objective of this work was to study the diagnostic modalities and the impact of our therapeutic choices on the outcome of the management. Material and Methods: We carried out a prospective study on patients with omphalocele admitted to the pediatric surgery departments of the HND, during a period spread over 4 years, between January 2017 and December 2020. Results: we collected 55 files (i.e., 13.7 cases/year). There were 38 boys and 17 girls (sex ratio 2.2) with an average age of 1.9 days. We found 15 cases (27%) of type I and 40 cases (73%) of type II according to the AITKEN classification. Fifteen cases (27%) benefited from surgical treatment and 45 cases (73%) benefited from conservative treatment (Grob). Two surgical methods were used: Primary parietal closure, which was used in 10 cases (66.7%), and the GROSS method, which was used in 5 cases (33.3%). We obtained an improvement of 40 cases (73%) and 15 cases (27%) of death. Conclusion: our work reported our experience in the management of omphalocele and the difficulties of postoperative resuscitation.
