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。     

肺癌与慢性阻塞性肺病的表观遗传学

肺癌是严重影响人类健康的恶性肿瘤之一,影响肺癌发病的表观遗传学机制已成为近年来的研究热点.慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)不但是肺癌的常见合并症,而且可能是肺癌的独立风险因素.肺癌和COPD在表观遗传学水平的改变主要涉及DNA甲基化、组蛋白修饰和非编码RNA调控等.探讨肺癌与COPD在表观遗传学水平的改变及其相互关系,可为肺癌及COPD的发病机制、疾病进展、疾病预后等提供更为广阔的视角,并为疾病的治疗开辟新的方向.     

表观遗传学及其研究进展

本文概述了表观遗传学(epigenetics)作为分子生物学的一个分支学科的基本内容,并着重讨论DNA甲基化、组蛋白修饰、染色体重塑在生物体分化发育期间引起基因表型效果与表达机制及影响因素。该研究进展有助于指导疾病治疗与新药开发。     

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。     

表观遗传调控与骨质疏松症的研究进展

表观遗传指所有不通过DNA序列改变就能影响基因表达的、可遗传的调控方式,包括DNA甲基化、组蛋白修饰、染色质重塑和微小RNA(miRNA)等。骨质疏松的发生与环境和遗传因素的相互作用密不可分,其中涉及多种表观遗传调控机制。     

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,...     

抑郁症的表观学遗传改变的研究进展

抑郁症是以快感缺失、持续心境低落为特征,伴睡眠、饮食、认知与记忆障碍的精神心理疾病.据WHO报道2030年抑郁症将成为全球疾病负担的首要疾病,造成了极大的医疗、经济与社会负担.表观遗传是指在基因序列不改变的条件下使基因表达水平发生变化,包括DNA甲基化、组蛋白修饰、染色体重塑和非编码RNA调控等,主要通过对基因转录或翻...     

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.     

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...     

Pathogenesis of chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) could develop following long-term exposure of individuals to cigarette smoke, toxic gases, and particulate matter, resulting in airway flow limitation, pulmonary failure, multiple systemic effects, and, eventually, death. The disease is associated with pulmonary inflammation with its own specific characteristics, and could be exacerbated by multiple factors such as microbial infection. COPD is chronic and progressive in nature, and multiple pulmonary inflammatory cells are detected at different stages of the disease, with a possible network of interactions with parenchymal cells. The pathological changes in the lung of COPD patients are characterized by an excess of extracellular matrix deposition, yet, loss of extracellular matrix in alveoli, increased thickness of airway walls, mucus hypersecretions, and destruction of alveolar septae, resulting in narrowing of airway diameters, reduced functional lung parenchyma, and decreased elastic tethering forces to maintain airway patency. Multiple factors, such as inflammatory cytokines, proteolytic proteinases, and oxidative stress molecules are suspected to be responsible, each at some degree, for these structural changes leading to airway obstruction. Because not everyone exposed to cigarette smoke will develop the disease, it is reasonable to think that multiple risk factors are involved and that COPD could be developed along a variety of pathways. Our current understanding of pulmonary changes associated with COPD, its similarity and differences with asthma, the nature of inflammatory cells associated with the disease, and the capacity of different molecules to induce a variety of these structural alterations are discussed to advance a cellular and molecular look at the pathogenesis of COPD.     

表观遗传调控在肥胖症研究领域中的研究进展

肥胖症被认为是一种由遗传因素和环境因素共同决定的复杂型疾病,已成为严重影响现代人类健康的公共卫生问题.在肥胖症的发生和发展过程中,表观遗传调控发挥了极其重要的作用.表观遗传主要的调控方式包括DNA的甲基化修饰,非编码RNA和组蛋白翻译后修饰,近年来组蛋白修饰方向的研究获得了较大突破.在此基础上,本文对表观遗传领域的肥胖症相关研究现状和进展进行了简要综述.     

miRNAs在慢性阻塞性肺疾病中的研究进展

微小RNAs(microRNAs,miRNAs)是一种非编码小分子单链RNAs,其通过与靶mRNA完全或部分结合,从而在转录后水平调控基因的表达。近年来,诸多研究显示miRNAs与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的发生发展密切相关。本文就miRNAs与烟草烟雾、肺气肿、炎症的关系进行综述,并侧重阐述miRNAs参与调控COPD作用机制及其临床应用前景。     

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.     

CD8 chemokine receptors in chronic obstructive pulmonary disease

Increased lung CD8 cells and their expression of chemokine receptors CXCR3 and CCR5 have been previously reported in chronic obstructive pulmonary disease (COPD). Alterations of CD8-CCR3 and -CCR4 expression and their ligands in COPD patients have not been fully investigated. The objective of this study was to assess in COPD patients: (i) broncho-alveolar lavage (BAL) CD8 CCR3 and CCR4 expression in COPD patients; and (ii) airway levels of the CCR3 ligands, CCL11 and CCL5. Multi-parameter flow cytometric analysis was used to assess BAL CD3 and CD8-chemokine receptor expression in COPD patients, smokers and healthy non-smokers (HNS). CCL5 and CCL11 levels were measured in BAL, and from the supernatants of lung resection explant cultures. CD8-CCR3 and -CCR5 expression (means) were increased in COPD patients (22% and 46% respectively) and smokers (20% and 45%) compared with HNS (3% and 22%); P < 0.05 for all comparisons. CD3CXCR3 expression was raised in smokers and COPD while CD8CXCR3 and CD3 and CD8 CCR4 expression was similar between groups. CD8CCR5 expression correlated to smoking pack years (r = 0.42, P = 0.01). COPD explants released more CCL5 compared with smokers (P = 0.02), while there was low level CCL11 production. CD8CCR3 and CCR5 expression appear to be regulated by cigarette smoke exposure. We show that COPD lung tissue released more CCL5, suggesting a role for CCL5-CCR3 signalling in pulmonary CD8 recruitment in COPD.     

Analysis of microbiota in stable patients with chronic obstructive pulmonary disease

To identify the bacterial diversity (microbiota) in expectorated sputum, a pyrosequencing method that investigates complex microbial communities of expectorated sputum was done in 19 stable chronic obstructive pulmonary disease patients (mean (SD) FEV1: 47 (18%) of predicted value). Using conventional culture, 3 phyla and 20 bacterial genera were identified, whereas the pyrosequencing approach detected 9 phyla and 43 genera (p < 0.001). In sputum the prevalent genera with pyrosequencing approach were Streptococcus, Actinomyces, Neisseria, Haemophilus, Rothia, Fusobacterium, Gemella, Granulicatella, Porphyromonas, Prevotella and Veillonella. Enterobacteriaceae, detected frequently in conventional culture, were not significantly detected with pyrosequencing methods. In addition, we found that important pathogens such as Haemophilus and Moraxella were detected more frequently with the new genetic procedures. The presence of Enterobacteriaceae is probably overestimated with conventional culture, whereas other difficult cultivable pathogens are underestimated. These studies open a new perspective for evaluating the role of bacterial colonization in chronic obstructive pulmonary disease pathogenesis and progression.     

Palliative care for patients with chronic obstructive pulmonary disease: current perspectives

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory illness with a myriad of disabling symptoms and a decline in the functional parameters that affect the quality of life. The mortality and morbidity associated with severe COPD is high and the patients are mostly housebound and in need of continuous care and support. The uncertain nature of its prognosis makes the commencement of palliative care and discussion of end-of-life issues difficult even in the advanced stage of the disease. This is often compounded by inadequate communication and counseling with patients and their relatives. The areas that may improve the quality of care include the management of dyspnea, oxygen therapy, nutritional support, antianxiety, and antidepressant treatment, and advance care planning. Hence, it is necessary to pursue a holistic care approach for palliative care services along with disease-specific medical management in all such patients to improve the quality of life in end-stage COPD.     

Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V_CW) = rib cage (V_RC) + abdomen (V_AB)] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III) underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim) at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE) V_CW increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V_CW regulation as EEV_CW increased non-linearly in 17/30 “hyperinflators” and decreased in 13/30 “non-hyperinflators” (P < 0.05). EEV_AB decreased slightly in 8 of the “hyperinflators”, thereby reducing and slowing the rate of increase in end-inspiratory (EI) V_CW (P < 0.05). In contrast, decreases in EEV_CW in the “non-hyperinflators” were due to the combination of stable EEV_RC with marked reductions in EEV_AB. These patients showed lower EIV_CW and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05). Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV_CW regardless of the presence or absence of dynamic hyperinflation (P < 0.001). However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid) their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.