Alcohol consumption is one of the leading causes of death worldwide.Adolescence is a critical period of structural and functional maturation of the brain.Adolescent alcohol use can alter epigenetic modifications.Howev...Alcohol consumption is one of the leading causes of death worldwide.Adolescence is a critical period of structural and functional maturation of the brain.Adolescent alcohol use can alter epigenetic modifications.However,little is known on the long-term effects of alcohol consumption during adolescence on RNA epigenetic modifications in brain.Herein,we systematically explored the long-term effects of alcohol exposure during adolescence on small RNA modifications in adult rat brain tissues by comprehensive liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS)analysis.We totally detected 26 modifications in small RNA of brain tissues.Notably,we observed most of these modifications were decreased in brain tissues.These results suggest that alcohol exposure during adolescence may impose a long-lasting impact on RNA modifications in brain tissues.This is the first report that alcohol use during adolescence can alter RNA modifications in adult brain.Collectively,this study suggests a long-term adverse effects of alcohol consumption on brain from RNA epigenetics angle by comprehensive mass spectrometry analysis.展开更多
Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that...Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that alcohol-induced changes of DNA cytosine methylation(5-methyl-2-deoxycytidine, 5 m C) in genomes play an important role in the development of diseases. However, systemic investigation of the effects of adolescent alcohol exposure on DNA and RNA modifications is still lacked. Especially, there hasn’t been any report to study the effects of alcohol exposure on RNA modifications. Similar to DNA modifications,RNA modifications recently have been identified to function as new regulators in modulating numbers of biological processes. In the current study, we systematically investigated the effects of alcohol exposure on both DNA and RNA modifications in peripheral blood of adolescent rats by liquid chromatographyelectrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) analysis. The developed LC-ESI-MS/MS method enabled the sensitive and accurate determination of 2 DNA modifications and 12 RNA modifications. As for the alcohol exposure experiments, the adolescent rats were intraperitoneally injected with ethanol with an interval of one day for a total 14 days. The quantification results by LC-ESI-MS/MS analysis showed that adolescent alcohol exposure could alter both DNA and RNA modifications in peripheral blood. Specifically, we observed an overall decreased trend of RNA modifications. The discovery of the significant alteration of the levels of DNA and RNA modifications under alcohol exposure indicates that alcohol consumption may increase the risk of the incidence and development of diseases through dysregulating DNA and RNA modifications.展开更多
In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully vali...In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.展开更多
Objective: Determine the effectiveness of an intervention to reduce prenatal alcohol exposure in the Congo. Methods: We utilized a screening tool validated in the Congo to identify women who were drinking during pregn...Objective: Determine the effectiveness of an intervention to reduce prenatal alcohol exposure in the Congo. Methods: We utilized a screening tool validated in the Congo to identify women who were drinking during pregnancy. The intervention was implemented by prenatal care providers comparing 162 women receiving the intervention with 58 (controls) who did not. The study endpoints were proportion of women who quit drinking, drinking days per week, drinks per drinking day, most drinks on any day, and number of binge episodes per week. Results: In the control group 36% of the women quit drinking compared to 54% in the intervention group (Chi-square 5.61;p = 0.02). The number of drinking days per week for the controls decreased by 50.1% compared to 68% for the intervention group (p = 0.008);drinks per drinking day for the controls decreased by 37% compared to 60.1% for the intervention group (p = 0.001);and most drinks on any occasion in the controls decreased by 38% compared to 61% for the intervention group (p = 0.004). Conclusions: This study demonstrates the effectiveness of a low cost in-office intervention to reduce prenatal alcohol exposure in the Congo. At $1.50 per beer, the reduction in drinks per week would more than pay for the cost of the intervention. In addition to efforts to reduce alcohol use prior to pregnancy in the Congo, providers can now offer an evidence based intervention to reduce exposure for women who continue to drink during pregnancy.展开更多
Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytr...Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.展开更多
目的探讨孕期酒精暴露致子代小鼠心肌致密化不全样改变的关系。方法对孕期3.5~18.5 d的母鼠用56%酒精以5 m L/kg的剂量灌胃,收集孕期第19.5天子代小鼠心脏标本,电子透射显微镜观察肌丝、线粒体及肌浆网等心肌细胞超微结构,HE染色观察心...目的探讨孕期酒精暴露致子代小鼠心肌致密化不全样改变的关系。方法对孕期3.5~18.5 d的母鼠用56%酒精以5 m L/kg的剂量灌胃,收集孕期第19.5天子代小鼠心脏标本,电子透射显微镜观察肌丝、线粒体及肌浆网等心肌细胞超微结构,HE染色观察心室肌层结构,小鼠心脏超声心动图观察成年鼠心脏舒缩功能及心室肌层改变。结果实验组子代心脏电镜下发现肌丝排列紊乱、溶解的现象;31.25%子代小鼠(5/16)的左心室肌呈非致密化样改变[病变组N/C值为(2.49±0.68),对照组N/C值为(0.62±0.23);t=10.397,P=0.000],且心脏体积变小,病变室腔明显扩大;成年后心脏超声提示实验组小鼠心功能减退、室间隔/左室后壁增厚。结论孕期大量酒精暴露可致子代小鼠心室肌出现高度肌小梁化及心肌压实缺乏等改变,孕期酗酒可能是子代心肌致密化不全的病因之一。展开更多
目的:评价急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)对酒依赖者线索暴露诱导的饮酒迫促性的作用。方法:采用随机双盲交叉对照的方法,选择符合ICD-10和DSM-Ⅳ诊断标准的男性酒依赖患者12名,并排除任一符合DSM-Ⅳ轴Ⅰ诊断的其他精神障碍。...目的:评价急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)对酒依赖者线索暴露诱导的饮酒迫促性的作用。方法:采用随机双盲交叉对照的方法,选择符合ICD-10和DSM-Ⅳ诊断标准的男性酒依赖患者12名,并排除任一符合DSM-Ⅳ轴Ⅰ诊断的其他精神障碍。在签署知情同意书的情况下,每位受试者间隔至少7d分别在实验当天禁食的情况下给予含人体必需的16种氨基酸的氨基酸饮料(BLANCE)或缺失色氨酸、苯丙氨酸和酪氨酸的氨基酸饮料(CMD),实验的前一天低蛋白饮食,实验当天结束后给予高蛋白饮食。实验当天,在给予氨基酸饮料前后进行Tiffany饮酒迫促性量表、焦虑可视模拟标尺、抑郁可视模拟标尺、副反应量表测查以及血压、心率检测。给予氨基酸饮料6h后进行非酒精(纯净水)相关线索和酒精(白酒)相关线索暴露,并评价暴露前后饮酒迫促性、焦虑可视模拟标尺分、抑郁可视模拟标尺分和血压、心率的变化。结果:CMD组在非酒精相关线索和酒精相关线索暴露后饮酒意愿(Intention/desire to drinking)和舒张压均增加,差异具有显著性(P=0.0217,0.038),而BLANCE组在非酒精相关线索和酒精相关线索暴露后饮酒意愿、舒张压差异均无显著性。焦虑可视模拟标尺分、抑郁可视模拟标尺分、收缩压、心率在两组中的非酒精相关线索和酒精相关线索暴露前后的差异无显著性。在安全性方面,所有受试者中有1名出现腹泻,但是病人尚能耐受。其余少见的副反应主要有恶心、头晕、困倦等,皆为轻度或中度。结论:急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)后酒依赖患者在非酒精和酒精相关线索暴露后的饮酒意愿增加,舒张压增高,但是对焦虑和抑郁情绪没有影响。口服氨基酸饮料的副反应少且轻微。展开更多
Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around ...Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around seven years of age. The most severe outcome in cases of FASD is mortality. The purpose of this scoping review is to 1) use a systematic review to provide an estimated mortality proportion for children with FASD, and 2) update a study published in 2014 by reviewing published reports of mortality in individuals diagnosed with FASD. Method: A search of PubMed, CINAHL, and Google Scholar for reports published between 2013 and 2023 on mortality in individuals with FASD. Results: Three population-based studies have reported on all-cause mortality rates, finding a combined mortality rate of 10.9%, a 2.63 fold (95% CI: 2.61 to 2.65) increase in mortality risk over the general population. Since 2016, this review identified only eight new cases meeting the study inclusion criteria. The reported causes of death were five cases of pneumonia, and one case each of failure to thrive and dehydration, intestinal dilatation and asphyxiation caused by overeating due to pica, and acute gastric volvulus. Discussion: While current research suggests a diagnosis of FASD is associated with a 2.6-fold increase in mortality risk, this is likely an underestimation, as most cases of FASD-related mortality go unreported. Globally, about 1 new case is reported every 15 months. However, in the United States alone, between 1752 to 4400 FASD related deaths occur annually. Our review suggests that FASD is rarely identified as a causal or contributing factor in deaths of children and adolescents, resulting in a substantial undercount of FASD-related deaths. Increased attention to the role of FASD in infant and child mortality case reviews, child death review committee reports, and mortality reviews is needed.展开更多
基金the National Key R&D Program of China(Nos.2022YFA0806601,2022YFC3400700)the National Natural Science Foundation of China(Nos.22277093,22074110,21721005)+1 种基金the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCGW-2022-008)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNJC202208).
文摘Alcohol consumption is one of the leading causes of death worldwide.Adolescence is a critical period of structural and functional maturation of the brain.Adolescent alcohol use can alter epigenetic modifications.However,little is known on the long-term effects of alcohol consumption during adolescence on RNA epigenetic modifications in brain.Herein,we systematically explored the long-term effects of alcohol exposure during adolescence on small RNA modifications in adult rat brain tissues by comprehensive liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS)analysis.We totally detected 26 modifications in small RNA of brain tissues.Notably,we observed most of these modifications were decreased in brain tissues.These results suggest that alcohol exposure during adolescence may impose a long-lasting impact on RNA modifications in brain tissues.This is the first report that alcohol use during adolescence can alter RNA modifications in adult brain.Collectively,this study suggests a long-term adverse effects of alcohol consumption on brain from RNA epigenetics angle by comprehensive mass spectrometry analysis.
基金supported by the National Natural Science Foundation of China (Nos. 22074110, 21635006, 21721005, 31771193)the Fundamental Research Funds for the Central Universities (No.2042021kf0212)。
文摘Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that alcohol-induced changes of DNA cytosine methylation(5-methyl-2-deoxycytidine, 5 m C) in genomes play an important role in the development of diseases. However, systemic investigation of the effects of adolescent alcohol exposure on DNA and RNA modifications is still lacked. Especially, there hasn’t been any report to study the effects of alcohol exposure on RNA modifications. Similar to DNA modifications,RNA modifications recently have been identified to function as new regulators in modulating numbers of biological processes. In the current study, we systematically investigated the effects of alcohol exposure on both DNA and RNA modifications in peripheral blood of adolescent rats by liquid chromatographyelectrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) analysis. The developed LC-ESI-MS/MS method enabled the sensitive and accurate determination of 2 DNA modifications and 12 RNA modifications. As for the alcohol exposure experiments, the adolescent rats were intraperitoneally injected with ethanol with an interval of one day for a total 14 days. The quantification results by LC-ESI-MS/MS analysis showed that adolescent alcohol exposure could alter both DNA and RNA modifications in peripheral blood. Specifically, we observed an overall decreased trend of RNA modifications. The discovery of the significant alteration of the levels of DNA and RNA modifications under alcohol exposure indicates that alcohol consumption may increase the risk of the incidence and development of diseases through dysregulating DNA and RNA modifications.
文摘In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.
文摘Objective: Determine the effectiveness of an intervention to reduce prenatal alcohol exposure in the Congo. Methods: We utilized a screening tool validated in the Congo to identify women who were drinking during pregnancy. The intervention was implemented by prenatal care providers comparing 162 women receiving the intervention with 58 (controls) who did not. The study endpoints were proportion of women who quit drinking, drinking days per week, drinks per drinking day, most drinks on any day, and number of binge episodes per week. Results: In the control group 36% of the women quit drinking compared to 54% in the intervention group (Chi-square 5.61;p = 0.02). The number of drinking days per week for the controls decreased by 50.1% compared to 68% for the intervention group (p = 0.008);drinks per drinking day for the controls decreased by 37% compared to 60.1% for the intervention group (p = 0.001);and most drinks on any occasion in the controls decreased by 38% compared to 61% for the intervention group (p = 0.004). Conclusions: This study demonstrates the effectiveness of a low cost in-office intervention to reduce prenatal alcohol exposure in the Congo. At $1.50 per beer, the reduction in drinks per week would more than pay for the cost of the intervention. In addition to efforts to reduce alcohol use prior to pregnancy in the Congo, providers can now offer an evidence based intervention to reduce exposure for women who continue to drink during pregnancy.
基金the Natural Science Foundation of Henan Province in China,No.102102310156the Foundation of Xinxiang Technology Bureau in China,No.ZG14004
文摘Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.
文摘目的探讨孕期酒精暴露致子代小鼠心肌致密化不全样改变的关系。方法对孕期3.5~18.5 d的母鼠用56%酒精以5 m L/kg的剂量灌胃,收集孕期第19.5天子代小鼠心脏标本,电子透射显微镜观察肌丝、线粒体及肌浆网等心肌细胞超微结构,HE染色观察心室肌层结构,小鼠心脏超声心动图观察成年鼠心脏舒缩功能及心室肌层改变。结果实验组子代心脏电镜下发现肌丝排列紊乱、溶解的现象;31.25%子代小鼠(5/16)的左心室肌呈非致密化样改变[病变组N/C值为(2.49±0.68),对照组N/C值为(0.62±0.23);t=10.397,P=0.000],且心脏体积变小,病变室腔明显扩大;成年后心脏超声提示实验组小鼠心功能减退、室间隔/左室后壁增厚。结论孕期大量酒精暴露可致子代小鼠心室肌出现高度肌小梁化及心肌压实缺乏等改变,孕期酗酒可能是子代心肌致密化不全的病因之一。
文摘目的:评价急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)对酒依赖者线索暴露诱导的饮酒迫促性的作用。方法:采用随机双盲交叉对照的方法,选择符合ICD-10和DSM-Ⅳ诊断标准的男性酒依赖患者12名,并排除任一符合DSM-Ⅳ轴Ⅰ诊断的其他精神障碍。在签署知情同意书的情况下,每位受试者间隔至少7d分别在实验当天禁食的情况下给予含人体必需的16种氨基酸的氨基酸饮料(BLANCE)或缺失色氨酸、苯丙氨酸和酪氨酸的氨基酸饮料(CMD),实验的前一天低蛋白饮食,实验当天结束后给予高蛋白饮食。实验当天,在给予氨基酸饮料前后进行Tiffany饮酒迫促性量表、焦虑可视模拟标尺、抑郁可视模拟标尺、副反应量表测查以及血压、心率检测。给予氨基酸饮料6h后进行非酒精(纯净水)相关线索和酒精(白酒)相关线索暴露,并评价暴露前后饮酒迫促性、焦虑可视模拟标尺分、抑郁可视模拟标尺分和血压、心率的变化。结果:CMD组在非酒精相关线索和酒精相关线索暴露后饮酒意愿(Intention/desire to drinking)和舒张压均增加,差异具有显著性(P=0.0217,0.038),而BLANCE组在非酒精相关线索和酒精相关线索暴露后饮酒意愿、舒张压差异均无显著性。焦虑可视模拟标尺分、抑郁可视模拟标尺分、收缩压、心率在两组中的非酒精相关线索和酒精相关线索暴露前后的差异无显著性。在安全性方面,所有受试者中有1名出现腹泻,但是病人尚能耐受。其余少见的副反应主要有恶心、头晕、困倦等,皆为轻度或中度。结论:急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)后酒依赖患者在非酒精和酒精相关线索暴露后的饮酒意愿增加,舒张压增高,但是对焦虑和抑郁情绪没有影响。口服氨基酸饮料的副反应少且轻微。
文摘Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around seven years of age. The most severe outcome in cases of FASD is mortality. The purpose of this scoping review is to 1) use a systematic review to provide an estimated mortality proportion for children with FASD, and 2) update a study published in 2014 by reviewing published reports of mortality in individuals diagnosed with FASD. Method: A search of PubMed, CINAHL, and Google Scholar for reports published between 2013 and 2023 on mortality in individuals with FASD. Results: Three population-based studies have reported on all-cause mortality rates, finding a combined mortality rate of 10.9%, a 2.63 fold (95% CI: 2.61 to 2.65) increase in mortality risk over the general population. Since 2016, this review identified only eight new cases meeting the study inclusion criteria. The reported causes of death were five cases of pneumonia, and one case each of failure to thrive and dehydration, intestinal dilatation and asphyxiation caused by overeating due to pica, and acute gastric volvulus. Discussion: While current research suggests a diagnosis of FASD is associated with a 2.6-fold increase in mortality risk, this is likely an underestimation, as most cases of FASD-related mortality go unreported. Globally, about 1 new case is reported every 15 months. However, in the United States alone, between 1752 to 4400 FASD related deaths occur annually. Our review suggests that FASD is rarely identified as a causal or contributing factor in deaths of children and adolescents, resulting in a substantial undercount of FASD-related deaths. Increased attention to the role of FASD in infant and child mortality case reviews, child death review committee reports, and mortality reviews is needed.
