Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understandin...Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.展开更多
Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in...Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.展开更多
The microRNA-21 （miR-21） is known to play a major role in cancer progression; however, its function in the cardiovascular system appears to be even more complex and conflicting. To characterize miR-21 expression in ...The microRNA-21 （miR-21） is known to play a major role in cancer progression; however, its function in the cardiovascular system appears to be even more complex and conflicting. To characterize miR-21 expression in the plasma of individuals with or without metabolic syndrome （MetS）, 58 MetS cases and 96 non-MetS controls were investigated.展开更多
BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis....BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.展开更多
<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when pe...<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“<i></i></span><i><i><span>after</span></i><span> </span><i><span>we</span></i><span> </span><i><span>have</span></i><span> </span><i><span>gone</span></i></i><span>”). </span><b><span>Objective</span></b><b><span>:</span></b><span> From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. </span><b><span>Methods</span></b><b><span>:</span></b><span> A cross-sectional Italian national study was carried out. An <i></i></span><i><i><span>ad</span></i><span> </span><i><span>hoc</span></i></i><span> questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. </span><b><span>Results</span></b><b><span>:</span></b><span> 136 family members and health professionals were involved. Most of </span><span>the </span><span>people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). </span><b><span>Conclusions</span></b><b><span>:</span></b><span> </span><span>The a</span><span>ging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming </span><span>“</span><span>in emergency</span><span>”</span><span>, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.</span>展开更多
文摘目的:评估外周血microRNA(miR)-21、血浆聚腺苷二磷酸核糖聚合酶1[poly(ADP-ribose)polymerase-1,PARP-1]在过敏性鼻炎(allergic rhinitis,AR)和过敏性鼻炎-哮喘综合征(combined allergic rhinitis and asthma syndrome,CARAS)中的诊断价值。方法:收集44例CARAS患者、31例AR患者和42例健康对照的外周血,采用RT-qPCR法检测外周血中miR-21的表达水平,采用ELISA法检测血浆中PARP-1蛋白水平。应用Pearson进行相关性分析。受试者工作特征(receiveroperatingcharacteris-tic,ROC)曲线判断miR-21和PARP-1的诊断灵敏度与特异度。结果:CARAS组患者外周血miR-21的表达较健康对照组升高。AR组患者血浆PARP-1的水平较CARAS组和健康对照组升高。Pearson相关性分析结果显示,外周血miR-21的表达水平在AR患者中与嗜酸性粒细胞计数相关,在CARAS患者中与鼻呼出气一氧化氮(fractionalnasalnitricoxide,FnNO)水平相关;血浆PARP-1在AR患者中与1秒钟用力呼气量占预计值百分比(forced expiratory volume in onesecond percent predicted,FEV1%pred)相关,在CARAS患者中与FEV1%pred及1秒钟用力呼气量(forced expiratory volume in one second,FEV1)/用力肺活量(forced vital capacity,FVC)(FEV1/FVC)相关。ROC曲线分析显示,外周血miR-21作为CARAS的诊断标志物时,灵敏度为51.35%,特异度为80.95%。血浆PARP-1作为AR的诊断标志物时,灵敏度为90.32%,特异度为54.76%。血浆PARP-1作为AR进展为CARAS的诊断标志物时,灵敏度为45.45%,特异度为90.32%。结论:AR和CARAS患者外周血miR-21、PARP-1存在差异表达,外周血miR-21可作为CARAS的诊断标志物,PARP-1可作为AR的诊断标志物及AR进展为CARAS的生物标志物。这对寻求AR和CARAS的诊治靶点有十分重要的价值。
基金supported by Shenzhen Science and Technology Planning Project(Grant No.JCYJ20210324093209024)Stable Support Project of Shenzhen(Grant No.20220812182215001).
文摘Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.
基金the Brain Research Trust,the Wellcome Trust,the UK Medical Research Council and the AnEUploidy grant from Framework Programme 6 from the European Union Commission for funding
文摘Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.
基金supported by Qianjiang Talents Project of Science Technology Department of Zhejiang Province(project number 2013R10078)(http://www.zjkjt.gov.cn/)Medical and Health Science Research Fund of Zhejiang Province(project number 2013KYB053,2008A034,2007A035,2006A019)(http://www.zjwst.gov.cn)
文摘The microRNA-21 （miR-21） is known to play a major role in cancer progression; however, its function in the cardiovascular system appears to be even more complex and conflicting. To characterize miR-21 expression in the plasma of individuals with or without metabolic syndrome （MetS）, 58 MetS cases and 96 non-MetS controls were investigated.
文摘BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.
文摘<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“<i></i></span><i><i><span>after</span></i><span> </span><i><span>we</span></i><span> </span><i><span>have</span></i><span> </span><i><span>gone</span></i></i><span>”). </span><b><span>Objective</span></b><b><span>:</span></b><span> From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. </span><b><span>Methods</span></b><b><span>:</span></b><span> A cross-sectional Italian national study was carried out. An <i></i></span><i><i><span>ad</span></i><span> </span><i><span>hoc</span></i></i><span> questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. </span><b><span>Results</span></b><b><span>:</span></b><span> 136 family members and health professionals were involved. Most of </span><span>the </span><span>people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). </span><b><span>Conclusions</span></b><b><span>:</span></b><span> </span><span>The a</span><span>ging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming </span><span>“</span><span>in emergency</span><span>”</span><span>, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.</span>
