Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototox...Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.展开更多
目的对一个常染色体显性遗传的Van der Hoeve综合征家系进行详尽的临床表型分析及基因突变检测,明确该家系的致病基因突变位点及该突变对基因编码的影响。方法对收集到的Van der Hoeve综合征家系进行包括病史、体格检查及辅助检查在内...目的对一个常染色体显性遗传的Van der Hoeve综合征家系进行详尽的临床表型分析及基因突变检测,明确该家系的致病基因突变位点及该突变对基因编码的影响。方法对收集到的Van der Hoeve综合征家系进行包括病史、体格检查及辅助检查在内的临床资料的收集及外周血液样本的采集,并对22位家系成员进行外显子组测序以及Sanger测序,利用生物信息学软件分析数据。结果该家系共五代,各代连续发病,且每一代男女均可患病,符合常染色体显性遗传特点。该家系中12例患者均自出生时巩膜即呈蓝色且身材矮小,8例患者有骨折病史,可正常愈合,3例患者考虑有Van der Hoeve综合征所致的听力下降,12例患者的COL1A1基因第17号外显子有一个碱基的缺失(c.1128delT),使第376位后的氨基酸编码改变,在第539位提前结束氨基酸编码,该家系中10例无症状者无此突变。结论该家系患者确定为由COL1A1基因c.1128delT突变导致的Van der Hoeve综合征。展开更多
文摘Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.
文摘目的对一个常染色体显性遗传的Van der Hoeve综合征家系进行详尽的临床表型分析及基因突变检测,明确该家系的致病基因突变位点及该突变对基因编码的影响。方法对收集到的Van der Hoeve综合征家系进行包括病史、体格检查及辅助检查在内的临床资料的收集及外周血液样本的采集,并对22位家系成员进行外显子组测序以及Sanger测序,利用生物信息学软件分析数据。结果该家系共五代,各代连续发病,且每一代男女均可患病,符合常染色体显性遗传特点。该家系中12例患者均自出生时巩膜即呈蓝色且身材矮小,8例患者有骨折病史,可正常愈合,3例患者考虑有Van der Hoeve综合征所致的听力下降,12例患者的COL1A1基因第17号外显子有一个碱基的缺失(c.1128delT),使第376位后的氨基酸编码改变,在第539位提前结束氨基酸编码,该家系中10例无症状者无此突变。结论该家系患者确定为由COL1A1基因c.1128delT突变导致的Van der Hoeve综合征。
