ABSTRACT
Ras-related C3 botulinum toxin substrate 1 (Rac1) is a member of the small Rho guanosine triphosphatase (GTPase) family, having GTPase activity and serving as a " molecular switch" in a variety of cell signal transduction processes.It is involved in cell migration, adhesion, proliferation and apoptosis.Rac1 can affect the migration of neural crest cells through regulating the actin polymerization of neural crest cells and the formation of membrane protrusions, possibly leading to disorders related to abnormal neural crest migration, such as congenital megacolon and cardiac outflow tract defects.In this article, the main biological functions of Rac1 and its role in the mechanism of ente-ric neural crest cell development were described.
ABSTRACT
Hirschsprung's disease(HSCR)is a kind of complex digestive system disease with structural abnor-malities,implicated a genetic,polygenic,multifactorial disease. Etiology and pathogenesis of HSCR are not clear,now re-search shows there is complex,multiple and abnormal signal transduction with development of HSCR. The variable phe-notypic of HSCR may be the result of some gene mutation interfering with ganglion cell migration in signal pathway. Re-cently study has found that there are several signal transduction pathways strongly relevant to HSCR. Now,the research progress in primarily signal pathways relevant to HSCR were reviewed.
ABSTRACT
Hirschsprung's disease (HD) is one of the most common gastrointestinal malformations in pediatric surgery.HD may be one complex disease due to interaction of multiple genes with the environment,which is a disease closely related to intestinal neural crest cell migration disorders,but the actual pathogenesis was not yet clear.Even if the surgical resection of intestinal lesions,but the postoperative complications still occur in different degrees.In recent years,with the continuous improvement of surgical methods,the radical resection techniques of HD has made great progress,and the vast majority of children can get better results after operation.However,part of the distal internal sphincter has been retained by all the existing radical resection technology,which may result in postoperative constipation,abdominal distension and enterocolitis,seriously affect the quality of life in children.Most of these complications are related to the residual of rectal muscle sheath,therefore,how to improve the therapeutic effect of HD,more accurate treatment of rectal muscle sheath,is the goal of pediatric surgeons to pursue.
ABSTRACT
Biliary atresia (BA) is a common neonatal liver disease characterized by inflammation and fibrosis of the extrahepatic biliary ducts,leading to cholestasis and biliary cirrhosis.It is also a severe liver disease in infants.The pathogenesis of BA is associated with multiple genes and gene polymorphism,virus infections,epigenetic,immune abnormalities,and so on.With the development of genetic technology,it provides a new method to determine the susceptibility genes in BA.Now,more and more doctors pay attention to the change and regulation of genes in BA.
ABSTRACT
Objective To explore the expressions and distributions of glial cell line -derived neurotrophic factor (GDNF)and itstyrosine kinase receptor RET in the terminal rectums of fetal rats with congenital anorectal malfor-mations (ARM)at different gestationalage,and to explore their effects on the enteric nervous system in the terminal rectum of ARMfetal rats.Methods Thirty -five SD pregnancy rats were divided into a saline group (n =1 0)and an ethylenethiourea experiment group (n =25)by simple randomized study.The fetal rats were removed from the pregnant rats at the gestational 1 6 d,1 8 d and 20 d.The fetal rats were divided into the saline control group,the ethylenethiourea control group (fetal rats without ARM)and the ethylenethiourea malformation group (ARM fetal rats)by the naked eye and dissecting microscope.HE staining was used to observe the morphology and the intestinal ganglion cells in the terminal rectum were counted.The immunohistochemical staining and Western blot methods were used to observe the distributions of GDNF and RET in the rectum at the gestational 1 6 d,1 8 d and 20 d.The quantitative real -time poly-merase chain reaction (qRT -PCR)was used to detect the expression of GDNF mRNA in the fetal rats in the terminal rectum at the gestational 1 6 d,1 8 d and 20 d.Results HE staining:the development of anorectal terminal in 3 groups of fetal rats was unclear at the gestational 1 6 d.A small amount of scattered nerve plexuses were observed in the muscu-lar layer.The nuclei were small and sparse.The axons and cytoplasms were less.The serosal layer,muscular layer,sub-mucosa,mucosal layer and glands in the terminal rectum were gradually clear in the saline control group and the ethyle-nethiourea control group at the gestational 1 8 d and 20 d.The intermuscular submucosal nerve plexuses increased gra-dually (1 1 .400 ±3.1 34 and 1 1 .200 ±3.425 at the gestational 1 8 d;66.1 00 ±4.954 and 67.600 ±5.481 at the gesta-tional 20 d).While,the layer was unclear in the ethylenethiourea malformation group and the nerve plexus was less (7.800 ±1 .989 at the gestational 1 8 d,and 25.200 ±3.048 at the gestational 20 d),and the difference was statistical-ly significant compared with 2 control groups (F =7.591 ,271 .833,all P 0.05);the expressions of GDNF and RET protein were 1 03.624 ±27.533 and 1 05.1 84 ±1 9.634 at the ges-tational 1 8 d;1 51 .496 ±33.622 and 1 50.738 ±21 .423 at the gestational 20 d in 2 control groups.Compared with the ethylenethiourea malformation group (79.1 69 ±1 1 .697 at the gestational 1 8 d;94.873 ±1 1 .309 at the gestational 20 d),and the difference were statistically significant (all P <0.05).Conclusions The expressions of GDNF and its tyrosine kinase receptor RET had a certain temporal correlation in the terminal rectum of normal fetal rats at different gestational ages and ARM.Moreover,the abnormal expressions of GDNF and its tyrosine kinase receptor RET in the dis-tal rectum of ARMfetal rats can affect the development of enteric nervous system.
ABSTRACT
Regulatory non -coding RNA is a kind of non -ncoding RNA which has regulatory effect,play an important role in the development and plasticity of the human nervous system,and related to the pathogenesis of nervous system diseases.Hirschsprung′s disease(HD)is the the most common diseases associated with digestive tract pediatric deformity,at present the causes are not clear,generally considered the etiology of HD is the enteric nervous system (ENS)abnormal development of embryonic period,through the in -depth research of regulatory non -coding RNA in human nervous system development,finding that there is a close relationship between the regulatory non -coding RNA and nosogenesis of HD.This provides a basis for studying of the pathogenesis of HD.In this paper,research progress on regulatory non -coding RNA in the pathogenesis of HD are reviewed and this paper explore the role of RNA in HD,it provides a new target in the early diagnosis and treatment of HD.
ABSTRACT
Glial cell line-derived neurotrophic factor(GDNF) is a kind of protein factor which can regulate the enteric nervous system in survival,differentiation,colonization and injury repair.It has been confirmed in the disorders of the enteric nervous system,such as hirschsprung and anorectal malformations,but the specific mechanism in regulation of this factor is still unknown.Studies have found that GDNF/GFRa1/RET and GDNF/GFRa1 / NCAM pathway may be involved in the growth and maturation of the enteric nervous system,the disorders of those pathways above may lead to diseases by affecting the differentiation,proliferation and migration of intestinal neural stem cells,causing dysfunctions in the anatomical structure and function of the intestinal neurons.