疼痛的表观遗传学机制研究进展

<正>疼痛的定义是与实际或潜在组织损伤相关联的不愉快的感觉和情感体验[1],是人体第五大生命特征。一方面,疼痛可以作为一种警戒信号,提示机体可能发生组织损伤,继而引发机体一系列防御反应,是生命的重要保护功能;另一方面,若疼痛长期持续便对机体构成难以忍受的折磨,无论是躯体感觉还是精神状态,最终导致生活质量的下降。表观遗传学是不涉及DNA序列改变的基因表达和调控的可逆、可遗传性修饰,这种修饰可以改变基因活性,调控基因表达,影响个体发育和表型。其主要内容为DNA甲基化、组蛋白修饰、非编码RNA等[2,3]。近些年来,关于疼痛发生发展和维持的机制研究越来越多,随着表观遗传学飞速发展,疼痛的表观遗传学机制研究也逐步深入,本文对疼痛的表观遗传学机制研究进展作一综述。     

肿瘤表观遗传学

表观遗传学(epigenetics)是指不涉及核苷酸序列的改变、但以通过有丝分裂和减数分裂进行遗传的生物现象为内容的生命学科.表观遗传修饰异常广泛存在于肿瘤的发生、发展过程中,所以近年来备受研究者们的关注.     

慢性阻塞性肺疾病与肺癌在表观遗传学上的研究进展

肺癌与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是全球发病率与死亡率最高的疾病之一.COPD与肺癌存在共同的致病因素,包括环境因素与遗传因素,其中环境因素中由吸烟介导的氧化应激反应导致基因组发生表观遗传改变,较个体间的遗传易感性差异更受关注.表观遗传机制在许多复杂疾病中发挥巨大作用,并且表观遗传变化也是COPD与肺癌临床诊断上的重要生物标记物,主要包括DNA甲基化、组蛋白共价修饰和MicroRNAs.本文重点就DNA甲基化与组蛋白共价修饰在COPD与肺癌中的联系进行讨论.     

表观遗传调控在阻塞性睡眠呼吸暂停综合征中的作用研究进展

慢性间歇性低氧在阻塞性睡眠呼吸暂停综合征(OSA)的各种不良反应的发生机制中发挥重要作用.表观遗传过程通过影响慢性间歇性低氧条件下的适应潜能和表型变异,参与OSA及并发症的发生和发展.所以,了解表观遗传调控对OSA的作用有助于为OSA的临床表型和靶向治疗提供新的思路.     

产科抗磷脂综合征的表观遗传学研究进展

产科抗磷脂综合征（APS）是一种系统性自身免疫性疾病,临床以早期复发性流产、早产、死胎、胎盘功能不全、子痫前期等病理妊娠为主要表现,主要病因是抗磷脂抗体持续阳性引发的动静脉血栓形成和免疫炎症反应。目前关于产科APS的研究多集中在实验室检测和临床特点上,缺少对其确切发病机制的深入探讨。众所周知,中性粒细胞、单核细胞、内皮细胞、血小板、滋养细胞的功能障碍是产科APS发生、发展的关键因素,近年来研究显示这些细胞的表观遗传学改变（主要包括DNA甲基化、组蛋白修饰、非编码RNA）涉及产科APS发病中免疫炎症反应、血栓形成和病理妊娠的基因表达和沉默。鉴于表观遗传学标志物作为产科APS诊断性标志物或治疗靶点的潜力,本文就产科APS发生、发展的表观遗传学机制作一综述。     

表观遗传学与肺癌的研究进展

表观遗传学是分子生物学研究领域内的一个新的研究内容。表观遗传改变调控基因表达并不改变DNA的序列，但又能够通过细胞分裂在代与代之间传递。本文主要阐述了DNA甲基化、组蛋白的共价修饰以及RNA介导的基因沉默以及microRNA等表观遗传相关因素在生物体生长发育过程中对基因表达的重要调控作用以及表观遗传事件对肺癌发生的作用。     

表观遗传学修饰与阿尔茨海默病的关系

阿尔茨海默病(Alzheimer disease,AD)是一种以进行性认知障碍和记忆力减退为主要特征的中枢神经退行性疾病.随着社会老龄化的加剧,AD日益威胁着人类的健康及生活质量.表观遗传学是指在DNA编码序列不变的情况下,通过影响基因转录活性调控基因转录水平进而调控基因的表达.现今,随着表观遗传学的研究方法日益成熟,...     

结直肠癌的表观遗传学研究新进展

结直肠癌(CRC)是最常见的消化道肿瘤之一,现已成为全球第三大癌症.由于该病早期症状不明显,大多数患者就诊即是晚期,目前对于该病的诊断和治疗很局限.随着对CRC发病机制的研究深入,该病的诊治也有了不断突破,现有研究表明,CRC产生和迁徙的关键由表观遗传学控制,其可以针对性地预防和治疗CRC.表观遗传修饰包括之前研究充分...     

树突状细胞分化发育及功能的表观遗传学调控机制的研究进展

树突状细胞（DCs）是体内功能最强的专职抗原提呈细胞,具有摄取、加工、处理和呈递抗原以及激活初始T淋巴细胞的功能。近年来研究发现,DNA甲基化、组蛋白修饰、染色质重塑、基因组印记以及非编码RNA等表观遗传学修饰能调控相关基因的表达,同时树突状细胞的分化发育及功能也受到表观遗传学调控。研究从DNA甲基化修饰、组蛋白修饰和非编码RNA,了解近年来很有必要树突状细胞的分化发育及功能的表观遗传学调控机制很有意义。     

The role of epigenetics in aging and age-related diseases

The role of epigenetics in aging and age-related diseases is a key issue in molecular physiology and medicine because certain epigenetic factors are thought to mediate, at least in part, the relationship between the genome and the environment. An active role for epigenetics in aging must meet two prior conditions: there must be specific epigenetic changes during aging and they must be functionally associated with the aged phenotype. Assuming that specific epigenetic modifications can have a direct functional outcome in aging, it is also essential to establish whether they depend on genetic, environmental or stochastic factors, and if they can be transmitted from one generation to the next. Here we discuss current knowledge about these matters and future directions in the field.     

胸腺五肽辅助治疗慢性阻塞性肺病的疗效观察

目的观察胸腺五肽辅助治疗慢性阻塞性肺病(COPD)的疗效。方法将78例COPD患者随机分为2组,对照组给予常规治疗,治疗组加用胸腺五肽,观察比较2组患者症状体征缓解时间、平均住院时间以及3个月内再入院率。结果治疗组症状体征缓解时间、平均住院时间均较对照组显著缩短(P<0.05),治疗组3个月内再入院率较对照组显著降低(P<0.05)。结论胸腺五肽可增强COPD患者的免疫功能,缩短平均住院时间,降低再发风险,提高患者生活质量。     

Severe chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) exacts a heavy toll on society, yet its prevention, diagnosis and treatment receives inadequate attention from both the medical community and from society at large. Guidelines released in 2001 from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) are aimed at redressing this inequity. In this review, we integrate information from the GOLD guidelines with recent updates on the prevention, treatment and management as related specifically to the most severe form of this disease. In order to help distinguish COPD from other disorders that may mimic or confound its treatment, we place particular emphasis on the definition, underlying pathophysiology and diagnosis of COPD. In addition, we discuss future directions in pharmacotherapy.     

Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease

ObjectivesIt is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage.MethodsWhole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142).ResultsA total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated.DiscussionRecurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.     

Prediction of exacerbation onset in chronic obstructive pulmonary disease patients

The objective of this study was to develop an algorithm for prediction of exacerbation onset in Chronic Obstructive Pulmonary Disease (COPD) patients based on continuous self-monitoring of physiological parameters from telehome-care monitoring. 151 physiological parameters of COPD patients were monitored on a daily/weekly basis for up to 2 years. Data were segmented in 30-day periods leading up to an exacerbation (exacerbation episode) and starting from a 14-day recovery period post-exacerbation (control episode) and tested in 6 intervals to predict exacerbation onset using k-nearest neighbour (k?=?1, 3, 5). A classifier with sensitivity of 73%, specificity of 74%, positive predictive value of 69%, negative predictive value of 78% and an accuracy of 74% was achieved using data intervals consisting of 5 days. Intelligent processing of physiological recordings have potential for predicting exacerbation onset.     

慢性阻塞性肺疾病小鼠模型制备方法的比较研究

目的:采用香烟烟雾(cigarette smoke,CS)暴露、肺炎克雷伯杆菌(Klebsiella pneumoniae,KP)感染、聚肌胞苷酸(polyinosinic-polycytidylic acid,Poly I:C)滴鼻、CS暴露联合KP感染和CS暴露联合Poly I:C滴鼻5种方法,建立并比较慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)小鼠模型。方法:将288只雄性BALB/c小鼠随机分为正常组(normal组)、CS组、KP组、CS+KP组、Poly I:C组及CS+Poly I:C组,每组48只。第1～8周造模,分别于第4、8、16和24周末取材。观察小鼠肺组织平均肺泡数(mean alveolar number,MAN)、肺泡平均截距(mean linear intercept,MLI)、肺功能呼气峰流速(peak expiratory flow,PEF)和50%潮气量呼气流量(50%tidal volume expiratory flow,EF50)的变化,检测肺组织中肿瘤坏死因子α(tumor nec...     

Toll样受体4在慢性阻塞性肺疾病中作用的研究进展

Toll样受体(TLRs)是一类最早发现的固有免疫受体,其中TLR4是介导来源于革兰阴氏菌细胞壁外膜脂多糖反应中的主要信号转导分子,参与多种疾病炎症过程.TLR4参加对抗细菌感染是常见的慢性阻塞性肺疾病(COPD)的防御机制之一.把TLR4作为靶点将是COPD临床治疗中一种新的潜在的治疗方法.     

An operational definition of epigenetics

A recent meeting (December 2008) regarding chromatin-based epigenetics was hosted by the Banbury Conference Center and Cold Spring Harbor Laboratory. The intent was to discuss aspects of epigenetic control of genomic function, and to arrive at a consensus definition of “epigenetics” to be considered by the broader community. It was evident that multiple mechanistic steps lead to the stable heritance of the epigenetic phenotype. Below we provide our view and interpretation of the proceedings at the meeting.