肥胖导致男性不育的表观遗传机制研究进展

肥胖引发表观遗传改变可导致男性出现不育表型。关于肥胖与男性不育的关系问题,早期研究多集中于内分泌方面。近年研究发现肥胖还可以引发机体表观遗传改变,如DNA甲基化,残余组蛋白修饰,小RNA等,影响精子成熟发育。DNA甲基化是胞嘧啶-磷酸-鸟嘌呤二核苷酸的胞嘧啶残基上的调节标记,肥胖导致DNA甲基化异常,并改变mRNA表达丰度,还可以影响印记基因表达出现印记基因病。残余组蛋白修饰方式包括甲基化、乙酰化等,它们可以相互作用或协同作用,以保证精子正常生长发育。肥胖可以改变甲基化酶及乙酰化酶活性,直接影响残余组蛋白的甲基化和乙酰化;还可以影响精子小RNA的表达,导致精子缺陷。本文就肥胖引起的表观遗传学改变及导致男性不育的作用机制做逐一综述。     

表观遗传学与肝癌关系的研究进展

肝细胞肝癌（Hepatocellular carcinoma,HCC）简称肝癌,是人类最常见的恶性肿瘤之一.我国是肝癌的高发区,发病人数居首位,死亡率在各种恶性肿瘤中占据第二位.它是一种容易侵袭转移的恶性肿瘤,临床就诊者多属中晚期病人,手术切除率低.未经治疗的肝癌患者5年生存率极低,大约0～14％[1],即使早期切除,术后5年复发率也在60％以上,小肝癌仍达40％ ～ 50％[2].其主要发病原因是肝炎病毒（HBV、HCV）感染,黄曲霉毒素、过量酒精摄入及遗传性肝硬化也可导致肝癌发生,但发病机制尚不清楚.过去认为环境因素作用导致遗传学改变是肿瘤发生的主要原因,但大量的研究表明,在肝癌发生过程中,只有少数癌基因或抑癌基因发生突变.近年来,表观遗传学（Epigenetics）的兴起为解答这些问题提供了新思路.本文就DNA甲基化、组蛋白修饰和miRNA调控与肝癌关系的研究进展作一综述.     

药物成瘾的表观遗传机制

背景 奖赏脑区基因表达异常是药物成瘾的关键基因机制,但决定药物成瘾的表观遗传学机制并不清楚.目的 研究慢性外源性药物暴露转变为药物成瘾的表观遗传发病机理.内容 综述有关DNA甲基化与组蛋白表观遗传调节药物依赖或成瘾的证据. 趋向 这些表观遗传变异介导药物滥用与依赖的新颖见解,将为改善药物成瘾的治疗提供新途径.     

前列腺癌的表观遗传学研究进展

前列腺癌是男性最常见的恶性肿瘤之一,其病因和发病机制尚不清楚。表观遗传参与了前列腺癌病程的各个阶段,与前列腺癌的发生、发展及转移密切相关,其中DNA甲基化和组蛋白修饰是前列腺癌中最为重要的两种表观遗传表现形式。DNA异常甲基化对肿瘤发生影响机制主要有:基因组广泛性低甲基化、局部过度甲基化、基因突变热点,与前列腺癌DNA损伤修复、激素应答、肿瘤细胞浸润/转移、细胞周期调控等过程密切相关。而组蛋白修饰的异常则将引起相应染色体结构和基因转录水平改变,影响细胞周期、分化和凋亡,导致前列腺癌的发生。目前已有一些针对前列腺癌表观遗传改变的治疗,主要有DNA甲基化转移酶和组蛋白去乙酰化酶抑制剂,并取得了一定的效果。相信随着对表观遗传学研究的深入,必将为前列腺癌的治疗开辟一条新思路。     

骨质疏松症与表观遗传学

骨质疏松症是老年人常见的退行性疾病,老龄化的社会结构也使得骨质疏松症具有广泛的发病人群,其继发骨折的风险较高,危害性大。骨质疏松症以骨强度下降,骨折风险增加为特征的一种全身性骨骼系统疾病,它受年龄、性别、体内性激素水平、遗传、环境等多方面因素的影响。近年来,随着基因技术的发展,遗传因素与骨质疏松症的相关研究也逐渐增加,其热点之一为表观遗传学。表观遗传是不同于传统孟德尔遗传定律,不通过改变DNA序列所致的可遗传的基因表达变化,它包括DNA甲基化、组蛋白修饰、微小RNA(miRNA)、染色质重塑等。本文就骨质疏松症与表观遗传学的研究现状进行阐述,旨在揭示骨质疏松症在表观遗传学方面可能的发病机制。     

表观遗传学在骨性关节炎研究中的进展

骨性关节炎(osteoarthritis,OA)是一种最常见的以关节软骨退变为主要病理改变的年龄相关性退化疾病,可表现为不同程度的关节软骨丢失、骨质增生、软骨下骨改变和滑膜炎等.近年来越来越多的证据表明表观遗传修饰在OA发生发展中扮演着非常重要的作用.表观遗传学研究与DNA序列无关的基因表达调控,包括DNA甲基化、组蛋白修饰、miRNA、基因印记等.表观遗传调控可以作为研究OA发病机制的一个新思路.本文就表观遗传学与OA的相关性做一综述.     

肝细胞肝癌异质性与表观遗传学研究进展

肿瘤异质性是恶性肿瘤普遍存在的现象之一,肝细胞肝癌异质性显著。尽管早期行根治性手术切除、化疗、放疗等治疗,肝细胞肝癌患者预后仍不理想,这与肝细胞肝癌异质性密切相关。因此,探究肝细胞肝癌的异质性的特点,对改善肝细胞肝癌治疗效果有重要临床意义。本文拟从表观遗传学角度对肝细胞肝癌异质性进行综述,探讨肝细胞肝癌异质性的内在的表观遗传学分子机制。     

神经病理性疼痛的表观遗传学发展方向

背景 神经病理性疼痛(neuropathic pain,NP)是由神经系统的损害或炎症引起的一种常见而特殊的慢性疼痛,以痛觉过敏、异常痛敏和自发痛为特征.目前发病机制不清,发病率逐年上升,处理非常棘手而且目前的治疗方法疗效不佳,是医学领域的挑战性研究课题. 目的 综述表观遗传学在疼痛中的研究状况. 内容 主要对表观遗传学的基本原理、生物学作用以及表观遗传学在疼痛中的研究进展进行综述. 趋向 表观遗传学在NP中的作用将为人们进一步深入阐明疼痛机制提供新的思路,为NP的治疗提供新的策略.     

组蛋白甲基化与慢性疼痛关系的研究进展

慢性疼痛是一种复杂的病症,其发生、发展机制目前尚不十分清楚,临床治疗效果欠佳.越来越多的研究表明,表观遗传调控参与了慢性疼痛的发生、发展过程,组蛋白甲基化是一种重要的表观遗传修饰方式,其在慢性疼痛中起着重要的作用.文章旨在总结组蛋白甲基化与慢性疼痛的关系,阐述组蛋白甲基化的生物学效应.进一步探讨组蛋白甲基化在慢性疼痛中...     

肝细胞癌的表观遗传学研究进展

肝细胞癌简称肝癌(hepatocellular carcinoma)的发病率、病死率呈逐年上升趋势,尽管几种主要危险致病因素已经比较明确,但是肝癌发生的确切的分子生物学机制尚不完全清楚.近年来越来越多的证据表明,表观遗传修饰(epigenetics)在肝癌的发生发展中具有非常重要的作用.本文将就DNA的异常甲基化、组蛋白异常修饰与肝癌的关系,肝癌的表观遗传学检测及表观遗传学治疗现状做一综述.     

DNA甲基化与肝细胞癌

肝细胞癌是原发性肝癌的主要类型,也是常见的恶性肿瘤之一,具有较高的发病率和病死率。然而在分子和细胞水平,肝癌的发病机制仍然不清楚。一般来说,肿瘤形成通常被认为是抑癌基因失活或原癌基因激活致DNA突变而诱导人类正常细胞向恶性细胞转化的过程。近年来随着对肿瘤研究的不断深入,人们发现表观遗传学改变与肝癌发生发展密切相关。其中DNA甲基化是人类基因组发生最为常见的一种表观遗传学事件,也是表观遗传学研究最为深入的一种机制。本文将就DNA甲基化在肝癌中的研究进展作一综述。     

肝细胞癌表观遗传学改变和重编程

肝细胞癌是世界范围内常见的恶性肿瘤.研究表明,由遗传学和表观遗传学改变引起的细胞恶性改变是肿瘤发生的重要原因.近年来,人们发现表观遗传学异常在肿瘤的发生、发展过程中也起到非常重要的作用.表观遗传修饰主要包括组蛋白乙酰化和DNA甲基化,组蛋白乙酰化和DNA低甲基化可促进基因表达,反之,则可抑制基因表达.在肝细胞癌的发生发展过程中,抑癌基因的甲基化特别是高甲基化起着重要作用,与肝细胞癌的形成有密切关系.肝癌的表观遗传学研究对肝癌的早期诊断和病情预后的监测及其防治具有重要意义.     

组蛋白修饰与糖尿病肾病

糖尿病肾病(diabetic nephropathy,DN)是一种以持续性蛋白尿和肾功能进行性下降为特征的临床综合征,是一种典型的肾小球疾病,发病率逐年上升,已成为终末期肾病最常见的原因.明确DN的发病机制显得尤为重要,越来越多的证据表明,DN的发病不仅受经典信号通路的调控,还受组蛋白修饰、DNA甲基化和非编码IRNA...     

Recent Advances in Epigenetic Biomarkers and Epigenetic Targeting in Prostate Cancer

ContextIn addition to genetic alterations, epigenetic alterations play a crucial role during prostate cancer progression. A better understanding of the epigenetic factors that promote prostate cancer progression may lead to the design of rational therapeutic strategies to target prostate cancer more effectively.ObjectiveTo systematically review recent literature on the role of epigenetic factors in prostate cancer and highlight key preclinical and translational data with epigenetic therapies.Evidence acquisitionWe performed a systemic literature search in PubMed. At the request of the editors, we limited our search to articles published between January 2015 and August 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Clinical trials targeting epigenetic factors were retrieved from clinicaltrials.gov.Evidence synthesisWe retrieved 1451 articles, and 62 were finally selected for review. Twelve additional foundational studies outside this time frame were also included. Findings from both preclinical and clinical studies were reviewed and summarized. We also discuss 12 ongoing clinical studies with epigenetic targeted therapies.ConclusionsEpigenetic mechanisms impact prostate cancer progression. Understanding the role of specific epigenetic factors is critical to determine how we may improve prostate cancer treatment and modulate resistance to standard therapies. Recent preclinical studies and ongoing or completed clinical studies with epigenetic therapies provide a useful roadmap for how to best deploy epigenetic therapies clinically to target prostate cancer.Patient summaryEpigenetics is a process by which gene expression is regulated without changes in the DNA sequence itself. Oftentimes, epigenetic changes influence cellular behavior and contribute to cancer development or progression. Understanding how epigenetic changes occur in prostate cancer is the first step toward therapeutic targeting in patients. Importantly, laboratory-based studies and recently completed and ongoing clinical trials suggest that drugs targeting epigenetic factors are promising. More work is necessary to determine whether this class of drugs will add to our existing treatment arsenal in prostate cancer.     

大肝癌的外科治疗策略

Hepatocellular carcinoma (HCC) with a diameter > 5 cm is defined as large HCC. Hepatic resection is the first choice for solitary large HCC with intact capsule and without satellite nodules. The key to successful large HCC resection is to judge the resectability and estimate the remnant liver function preoperatively. Moreover, the liver must be exposed and dissociated adequately, and familiarity with the anatomy of the liver is crucial. Choosing the right technique of hepatic blood flow occlusion and avoiding excessive resection of the liver are important elements. Special attention should be paid to the efficacy of liver transplantation for patients with large HCC exceeding Milan criteria, h is advisable to resect large HCC actively.The hepatic resection is safe and feasible in selected patients with large HCC.     

Epigenetic transgenerational toxicology and germ cell disease

The ability of an environmental exposure (i.e. endocrine disruptor) during sex determination to reprogramme the male germline and promote an epigenetic transgenerational disease phenotype suggests that environmental factors and compounds may permanently alter the germline epigenome. This epigenetic transgenerational phenomenon will be discussed with respect to adult-onset germline disease (e.g. testicular cancer). A thorough literature review is not provided, rather a perspective is provided on how this epigenetic transgenerational toxicology should be considered in germ cell disease and testicular cancer.     

肝癌手术治疗进展

The incidence of hepatocellular carcinoma (HCC) has increased worldwide over the past two decades. Surgical resection and liver transplantation have been demonstrated as potentially curative treatment options, which could be considered in 30% -40% of HCC patients. Recent advancements of surgical treatment have focused not only on the surgical techpiques, but also the hepatic functional reserve evaluation, resectability assessment and the effects of biological characteristics of tumor on prognosis. There is no single variable to evaluate the hepatic functional reserve accurately. Combined Child-Pugh classification, ICGI5, portal vein pressure detection and remanent liver volume measurement are required prior to liver resection. The 5-year survival rate after liver resection for HCC is about 50%. The results are acceptable for some selected patients that underwent tumor resection with thrombectomy, including HCC with portal vein tumor thrombus or bile duct thrombosis. The choice of local resection or regular hepatectomy is still controversial although the former is commonly performed to treat HCC with cirrhosis, and the latter is applied to HCC patients without liver cirrhosis. The results of liver transplanta-tion for HCC are better than liver resection, and the Milan criteria is generally accepted. Any attempts to expand the selection criteria should be cautious because of organ shortage. Salvage transplantation for intrabepatic recurrence after liver resection may be a good choice in some resectable HCC. The recurrence and metastasis after surgical treatment are the main obstacles to achieve better results. Identification of predictive factors could be helpful to develop prevention strategies. Due to the importance of biological characteristics in tumor recurrence and metastasis, a molecular classification to predict prognosis of HCC patients will lead to a more personalized medicine. Targeting key molecules of biological pathways could optimize the therapeutic modality in HCC.     

肝细胞癌治疗理念与策略的转变

With the progress in muhimodality therapy, the management of hepatocellular carcinoma (HCC) comes to an era of diversification. Dudng the last 2 decades, the increased understanding of biological behaviors of HCC and innovations of various treatment modalities has led to dramatic changes in concepts and strategies of treatment for HCC. The changes include the shifts from experience-based medicine to evidence-based medicine, from rough treatment to precise treatment and from single therapy to integrated therapy. The implementation of these concepts and therapies will further improve the chance of survival and the quality of life for HCC patients.     

SMYD3在肝癌中的研究进展

组蛋白甲基转移酶SMYD3是一种具有组蛋白甲基化功能的蛋白,在转录调控中具有重要作用.研究发现SMYD3可抑制癌细胞凋亡、促进细胞增殖、侵袭及转移.越来越多的数据显示SMYD3在肝癌中高度表达,而在正常组织中表达较低甚至检测不到.SMYD3水平与肿瘤预后显著相关,另外在SMYD3基因沉默实验中发现肿瘤细胞生长受到明显抑制.可见,SMYD3与肝癌的发生、发展及预后密切相关,提示人们可以通过抑制SMYD3表达来阻碍肿瘤细胞生长、迁移并改善肿瘤预后,为未来的抗癌治疗提供新的目标与方向.