O6-methylguanine DNA methyltransferase(MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expre...O6-methylguanine DNA methyltransferase(MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expression and methylation levels in the early embryo and in different embryonic stages, as well as the relationship between MGMT and neural tube defects. Spina bifida aperta was induced in rats by a single intragastric administration of all-trans retinoic acid on embryonic day(E) 10, whereas normal control rats received the same amount of olive oil on the same embryonic day. DNA damage was assessed by detecting γ-H2 A.X in spina bifida aperta rats. Real time-polymerase chain reaction was used to examine mRNA expression of MGMT in normal control and spina bifida aperta rats. In normal controls, the MGMT mRNA expression decreased with increasing embryonic days, and was remarkably reduced from E11 to E14, reaching a minimum at E18. In the spina bifida aperta model, γ-H2 A.X protein expression was increased, and mRNA expression of MGMT was markedly decreased on E14, E16, and E18. Bisulfite sequencing polymerase chain reaction for MGMT promoter methylation demonstrated that almost all CpG sites in the MGMT promoter remained unmethylated in both spina bifida aperta rats and normal controls, and there was no significant difference in methylation level between the two groups on either E14 or E18. Our results show that DNA damage occurs in spina bifida aperta rats. The mRNA expression of MGMT is downregulated, and this downregulation is independent of promoter DNA methylation.展开更多
Leukemia inhibitory factor receptor(LIFR),as a neuroregulatory cytokine receptor,generally shows a neuroprotective effect in central nervous system injuries.In this study,to understand the effect of LIFR on pathogenes...Leukemia inhibitory factor receptor(LIFR),as a neuroregulatory cytokine receptor,generally shows a neuroprotective effect in central nervous system injuries.In this study,to understand the effect of LIFR on pathogenesis of neural tube defects,we explored spatiotemporal expression of LIFR at different stages of fetal development in normal and neural tube defect embryos.Spina bifida aperta was induced with all-trans retinoic acid on embryonic day 10 in rats,and the spatiotemporal expression of LIFR was investigated in spina bifida aperta rats and healthy rats from embryonic day 11 to 17.Real time-polymerase chain reaction and western blot assay were used to examine mRNA and protein expression of LIFR in healthy control and neural tube defect embryos.Results of the animal experiment demonstrated that expression of LIFR protein and mRNA in the spinal cords of normal rat embryos increased with embryonic development.LIFR was significantly downregulated in the spinal cords of spina bifida aperta rats compared with healthy rats from embryonic days 11 to 17.Immunohistochemical staining showed that the expression of LIFR in placenta and spinal cord in spina bifida aperta rat embryos was decreased compared with that in control embryos at embryonic day 15.Results from human embryo specimens showed that LIFR mRNA expression was significantly down-regulated in spinal cords of human fetuses with neural tube defects compared with normal controls at a gestational age of 24 to 33 weeks.The results were consistent with the down-regulation of LIFR in the animal experiments.Our study revealed spatiotemporal changes in expression of LIFR during embryonic neurulation.Thus,LIFR might play a specific role in neural tube development.All animal and human experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University,China(approval No.2016PS106K)on February 25,2016.展开更多
Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administrat...Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administration,education and communication campaigns.New approaches are required to advance helminth control.Methods:An ecohealth study was conducted on two Mekong islands in Southern Laos.Demographic and behavioural data were collected by questionnaire.Human and animal reservoir stools were examined.Bithynia spp.and Neotricula aperta snails were examined using shedding.Fresh water fish were examined using digestion technique.Multivariate random-effects analysis was used to find risk factors associated with helminth infections.Results:Human infection rates with O.viverrini,hookworm,S.mekongi,Trichuris trichiura,Ascaris lumbricoides and Taenia spp.were 60.7%,44.1%,22.2%,4.1%,0.6%and 0.1%,respectively.Heavy intensity infections were 4.2%,3.6%and 1.8%for O.viverrini,S.mekongi and hookworm,respectively.O.viverrini and S.mekongi infection rates among dogs and cats were 25.0%and 14.7%,respectively.Of the cats tested,53.1%were infected with O.viverrini.Prevalence of O.viverrini and S.mekongi in snails was 0.3%and 0.01%,respectively.Overall prevalence of O.viverrini infection in fresh water fish was 26.9%,with the highest infection rates occurring in Hampala dispa(87.1%),Cyclocheilichthys apogon(85.7%)and Puntius brevis(40.0%).Illiteracy and lower socioeconomic status increased the risk of O.viverrini infection,while those aged 10-16 years and possessing latrines at home were less likely to be infected.Household dogs and cats that consumed raw fish were significantly and positively associated with O.viverrini infection of the household members.For S.mekongi,children under 9 years old were exposed significantly to this infection,compared to older age groups.Conclusions:There is a pressing need to design and implement an integrated helminth control intervention on the Mekong Islands in southern Lao PDR.Given the highly dynamic transmission of O.viverrini,S.mekongi,STH and extended multiparasitism,annual mass-drug administration is warranted along with environmental modifications,health education and improved access to clean water and adequate sanitation to consolidate morbidity control and move towards elimination.Trail registration number:Our findings presented here are from a cross-sectional study,therefore,it has not been registered.展开更多
基金supported by the National Natural Science Foundation of China,No.81671469,81171072(to ZWY)the National Basic Research Program of China(973 Program),No.2013CB945402(to ZWY)the Program for Liaoning Innovative Research Team in University of China,No.LT2013016(to ZWY)
文摘O6-methylguanine DNA methyltransferase(MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expression and methylation levels in the early embryo and in different embryonic stages, as well as the relationship between MGMT and neural tube defects. Spina bifida aperta was induced in rats by a single intragastric administration of all-trans retinoic acid on embryonic day(E) 10, whereas normal control rats received the same amount of olive oil on the same embryonic day. DNA damage was assessed by detecting γ-H2 A.X in spina bifida aperta rats. Real time-polymerase chain reaction was used to examine mRNA expression of MGMT in normal control and spina bifida aperta rats. In normal controls, the MGMT mRNA expression decreased with increasing embryonic days, and was remarkably reduced from E11 to E14, reaching a minimum at E18. In the spina bifida aperta model, γ-H2 A.X protein expression was increased, and mRNA expression of MGMT was markedly decreased on E14, E16, and E18. Bisulfite sequencing polymerase chain reaction for MGMT promoter methylation demonstrated that almost all CpG sites in the MGMT promoter remained unmethylated in both spina bifida aperta rats and normal controls, and there was no significant difference in methylation level between the two groups on either E14 or E18. Our results show that DNA damage occurs in spina bifida aperta rats. The mRNA expression of MGMT is downregulated, and this downregulation is independent of promoter DNA methylation.
基金supported by the National Natural Science Foundation of China,No.81601292(to DA),No.81671469(to ZWY)the National Basic Research Program of China(973 Program),No.2013CB945402(to ZWY)the National Key Research and Development Program of China,No.2016YFC1000505(to ZWY)
文摘Leukemia inhibitory factor receptor(LIFR),as a neuroregulatory cytokine receptor,generally shows a neuroprotective effect in central nervous system injuries.In this study,to understand the effect of LIFR on pathogenesis of neural tube defects,we explored spatiotemporal expression of LIFR at different stages of fetal development in normal and neural tube defect embryos.Spina bifida aperta was induced with all-trans retinoic acid on embryonic day 10 in rats,and the spatiotemporal expression of LIFR was investigated in spina bifida aperta rats and healthy rats from embryonic day 11 to 17.Real time-polymerase chain reaction and western blot assay were used to examine mRNA and protein expression of LIFR in healthy control and neural tube defect embryos.Results of the animal experiment demonstrated that expression of LIFR protein and mRNA in the spinal cords of normal rat embryos increased with embryonic development.LIFR was significantly downregulated in the spinal cords of spina bifida aperta rats compared with healthy rats from embryonic days 11 to 17.Immunohistochemical staining showed that the expression of LIFR in placenta and spinal cord in spina bifida aperta rat embryos was decreased compared with that in control embryos at embryonic day 15.Results from human embryo specimens showed that LIFR mRNA expression was significantly down-regulated in spinal cords of human fetuses with neural tube defects compared with normal controls at a gestational age of 24 to 33 weeks.The results were consistent with the down-regulation of LIFR in the animal experiments.Our study revealed spatiotemporal changes in expression of LIFR during embryonic neurulation.Thus,LIFR might play a specific role in neural tube development.All animal and human experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University,China(approval No.2016PS106K)on February 25,2016.
基金We are grateful to the International Development Research CentreForeign Affairs,Trade and Development Canada(through the Global Health Research Initiative)the Australian Agency for International Development for funding support。
文摘Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administration,education and communication campaigns.New approaches are required to advance helminth control.Methods:An ecohealth study was conducted on two Mekong islands in Southern Laos.Demographic and behavioural data were collected by questionnaire.Human and animal reservoir stools were examined.Bithynia spp.and Neotricula aperta snails were examined using shedding.Fresh water fish were examined using digestion technique.Multivariate random-effects analysis was used to find risk factors associated with helminth infections.Results:Human infection rates with O.viverrini,hookworm,S.mekongi,Trichuris trichiura,Ascaris lumbricoides and Taenia spp.were 60.7%,44.1%,22.2%,4.1%,0.6%and 0.1%,respectively.Heavy intensity infections were 4.2%,3.6%and 1.8%for O.viverrini,S.mekongi and hookworm,respectively.O.viverrini and S.mekongi infection rates among dogs and cats were 25.0%and 14.7%,respectively.Of the cats tested,53.1%were infected with O.viverrini.Prevalence of O.viverrini and S.mekongi in snails was 0.3%and 0.01%,respectively.Overall prevalence of O.viverrini infection in fresh water fish was 26.9%,with the highest infection rates occurring in Hampala dispa(87.1%),Cyclocheilichthys apogon(85.7%)and Puntius brevis(40.0%).Illiteracy and lower socioeconomic status increased the risk of O.viverrini infection,while those aged 10-16 years and possessing latrines at home were less likely to be infected.Household dogs and cats that consumed raw fish were significantly and positively associated with O.viverrini infection of the household members.For S.mekongi,children under 9 years old were exposed significantly to this infection,compared to older age groups.Conclusions:There is a pressing need to design and implement an integrated helminth control intervention on the Mekong Islands in southern Lao PDR.Given the highly dynamic transmission of O.viverrini,S.mekongi,STH and extended multiparasitism,annual mass-drug administration is warranted along with environmental modifications,health education and improved access to clean water and adequate sanitation to consolidate morbidity control and move towards elimination.Trail registration number:Our findings presented here are from a cross-sectional study,therefore,it has not been registered.
