表观遗传学在口腔鳞状细胞癌分子机制中的研究进展

口腔鳞状细胞癌（oral sqaumous cell carcinoma,OSCC）是来源于口腔粘膜不同程度鳞状分化的上皮性恶性肿瘤.找到OSCC发生的根本原因是提高生存率和减少发生率的关键,而分子标志物的筛查成为早发现早诊断的重要依据,表观遗传学是肿瘤标志物的研究方法之一.表观遗传学在口腔鳞癌分子机制研究中的应用历经了DNA甲基化、组蛋白修饰、染色质重塑、组蛋白变体和非编码RNA（microRNA）等调控模式的变迁,近来新出现的lncRNA对肿瘤等各种疾病的调控模式在表观遗传学中越来越重要.本文就表观遗传学在口腔鳞癌发生机制探索中的研究内容做一全面综述,展望表观遗传学在口腔鳞癌领域的应用前景.     

DNA甲基化和组蛋白乙酰化对人口腔鳞癌细胞中KLF4基因的调控研究

目的：探讨人口腔鳞癌中DNA甲基化和组蛋白乙酰化对KLF4基因的调控作用。方法体外培养人口腔鳞癌细胞系SCC-6,分别用DNA甲基化抑制剂5-氮-2’-脱氧胞苷(DAC)、组蛋白去乙酰化酶抑制剂曲古抑菌素A( TSA)处理SCC-6细胞,并据此将SCC-6分为4组,阴性对照组(不做处理)、DAC处理组、TSA处理组、DAC+TSA联合处理组,采用荧光定量PCR方法检测SCC-6细胞经DAC或/和TSA处理前后KLF4 RNA水平的变化;用免疫细胞化学方法检测SCC-6细胞经DAC或/和TSA处理前后KLF4蛋白的变化。结果 SCC-6细胞DAC处理组、TSA处理组、DAC+TSA 组的KLF4 RNA水平与阴性对照组相比均有显著升高(P<0.01)。另外,DAC处理组KLF4 RNA水平均高于其他3组(P<0.01)。 SCC-6细胞DAC处理组中KLF4蛋白表达明显升高,均高于其他3组(P<0.01)。 TSA处理组与DAC+TSA联合组KLF4蛋白表达也都高于阴性对照组(P<0.01);TSA处理组与DAC+TSA处理组间无显著差异(P>0.05)。结论在口腔鳞状细胞癌SCC-6细胞中导致KLF4基因沉默的主要原因可能为DNA甲基化,此外组蛋白乙酰化可能也参与了KLF4表达的调控,但组蛋白乙酰化在提高KLF4表达方面与去甲基化无明显协同作用。     

口腔微生物共聚的研究进展

共聚是不同属(种)微生物表面分子间的特异性识别,在口腔微生物定植于宿主以及菌斑生物膜形成和成熟过程中起着重要作用,与龋病、牙周病等口腔感染性疾病的发生发展密切相关。笔者就近期口腔微生物共聚的关系、相关性生物分子及研究方法三方面作一综述,旨在揭示其共聚的特征及本质,为有效控制菌斑及防治口腔疾病提供依据。     

口腔微生物与消化系统疾病关系的研究进展

人类微生物组计划使人们对口腔微生物的认识更加深入。口腔微生物不仅在龋病、牙周病、口腔癌等口腔疾病的病程中发挥重要作用,还与其他全身系统疾病关系密切。口腔微生物与消化系统疾病间存在紧密的相关性,可以促进结直肠癌的发生和发展。本文对口腔微生物与消化系统疾病的研究进展、口腔微生物在消化系统疾病进程中的重要作用以及口腔微生物作用于消化系统多脏器的途径进行综述,为口腔微生物与全身系统疾病的进一步研究提供参考。     

牙周膜干细胞表观遗传学研究进展

牙周膜干细胞(periodontal ligament stem cells,PDLSCs)是牙周膜组织中的间充质干细胞,是牙周组织再生和修复的重要细胞群,牙周微环境的变化会影响牙周膜干细胞的生物学特性.表观遗传(epigenetics)是指不基于DNA序列的变化,而出现稳定可遗传的基因表达水平及功能的改变.环境因素是影响表观遗传的重要因素之一,暴露环境的不同可以引起表观修饰改变,进而影响基因表达.表观遗传是干细胞生物学特性的重要内源性调控机制,在干细胞中的变化稳定可遗传,并具有可逆性.近年来牙周膜干细胞的表观遗传调控已成为研究热点,本文通过对表观遗传调控对牙周膜干细胞生物学特性的影响进行综述,以期使牙周膜干细胞更好地应用于牙周再生修复.     

口腔微生物名称

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口腔鳞状细胞癌的表观遗传学研究现状和进展

口腔鳞状细胞癌(OSCC)是最常见的口腔颌面部恶性肿瘤之一,但目前对于OSCC的具体发病机制并不十分清楚。当前的研究认为在OSCC发生发展中的基因变化因素主要包括基因突变与表观遗传修饰异常。表观遗传修饰是可遗传、可逆转的生物学行为,主要包括DNA甲基化、组蛋白修饰、非编码RNA调控等。近来研究发现,表观遗传修饰的改变尤其是DNA甲基化对OSCC的发病过程意义重大。对于表观遗传学修饰改变的进一步探索将有助于我们理解OSCC的发病机制,该机制将为OSCC的诊断、治疗、预后提供一个新的研究思路,并且为新型抗肿瘤药物的研发工作,提供了新的理论基础。     

Advances in oral bacteria influencing host epigenetic regulation

表观遗传是指非基因序列改变所导致的基因表达水平的稳定改变,微生物能通过表观遗传途径调节宿主炎症,从而逃避或者扩大免疫反应。口腔细菌作为人体微生物的重要组成部分,目前已发现多种表观遗传调控机制可影响宿主对口腔细菌的反应。本文就细菌调控表观遗传的常见途径以及不同疾病中口腔细菌对宿主表观遗传的调控进行综述,以期为口腔疾病中表观遗传相关机制研究提供参考。     

DNA hypermethylation as an epigenetic mark for oral cancer diagnosis

J Oral Pathol Med (2011) 40 : 665–676 Oral cancer is the largest group of cancers which fall into the head and neck category. While genetic alterations in oral cancer have long been documented, the effect of epigenetic changes is more recent. The recent explosion in science of how chromatin organization modulates the gene expression has highlighted the epigenetic mechanism of oral cancer pathogenesis. DNA methylation, which is an important epigenetic marker, is perhaps the best characterized chemical modification of mammalian DNA and provides a stable, heritable, and critical component of epigenetic regulation. This review attempts to decipher the epigenetic aspects of oral cancer by evaluating the DNA methylation status through its various stages from normal to potentially malignant to malignant states. In doing so, we emphasize DNA methylation as a novel biomarker in oral cancer research, thus opening newer avenues in oral cancer research.     

微结构芯片对石墨粉吸附及3种口腔微生物黏附行为的影响

目的 通过制备精确控制微结构的材料样品,比较不同尺寸无生命物质的吸附行为及不同尺寸微生物的黏附行为,探讨微结构影响微生物黏附增殖的机制.方法 聚二甲基硅氧烷(PDMS)翻制羟磷灰石(HA)芯片上的23个微结构,并分别与不同尺寸的石墨粉和不同尺寸的口腔微生物共培养,观察并比较微结构大小及形状对石墨粉吸附和微生物黏附的影响...     

Brain abscesses caused by oral infection

Abstract— Brain abscesses are rare but can be life-threatening infections. Recent progress in microbiological classification and identification has indicated that they are sometimes caused by oral infection and dental treatment. It has been postulated that oral microorganisms may enter the cranium by several pathways: 1) by direct extension, 2) by hematogenous spread, 3) by local lymphatics, and 4) indirectly, by extraoral odontogenic infection. In the direct extension, oral infections spread along the fascial planes. Hematogenous spreading occurs along the facial, angular, ophthalmic, or other veins which lack valves, through the cavernous sinus and into the cranium. Another hematogenous pathway is through the general circulation. Oral bacteria may cause systemic infections, e.g., endocarditis, and then indirectly initiate brain abscess. Microbiota, complications, and the prevention and management of odontogenic brain abscesses are also discussed in this review.     

Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study

Introduction

We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13-gene panel.

Methods

Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value.

Results

Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups.

Conclusion

Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis.     

Epigenetic gene regulation by histone demethylases: emerging role in oncogenesis and inflammation

Histone N‐terminal tails of nucleosomes are the sites of complex regulation of gene expression through post‐translational modifications. Among these modifications, histone methylation had long been associated with permanent gene inactivation until the discovery of Lys‐specific demethylase (LSD1), which is responsible for dynamic gene regulation. There are more than 30 members of the Lys demethylase (KDM) family, and with exception of LSD1 and LSD2, all other KDMs possess the Jumonji C (JmjC) domain exhibiting demethylase activity and require unique cofactors, for example, Fe(II) and α‐ketoglutarate. These cofactors have been targeted when devising KDM inhibitors, which may yield therapeutic benefit. KDMs and their counterpart Lys methyltransferases (KMTs) regulate multiple biological processes, including oncogenesis and inflammation. KDMs’ functional interactions with retinoblastoma (Rb) and E2 factor (E2F) target promoters illustrate their regulatory role in cell cycle progression and oncogenesis. Recent findings also demonstrate the control of inflammation and immune functions by KDMs, such as KDM6B that regulates the pro‐inflammatory gene expression and CD4⁺ T helper (Th) cell lineage determination. This review will highlight the mechanisms by which KDMs and KMTs regulate the target gene expression and how epigenetic mechanisms may be applied to our understanding of oral inflammation.     

口腔微生物与肠道微生物的关系

口腔和肠道是人体消化道的重要组成部分。口腔微生物和肠道微生物的相互关系和致病共性已成为近年来人体微生物组研究的热点。本文结合近期研究进展,对口腔微生物和肠道微生物群落结构和功能,相互定植和致病作用,以及两者与系统性疾病的相关性进行综述。     

Systemic diseases caused by oral microorganisms

Abstract Human endodontic and periodontal infections are associated with complex microfloras in which approximately 150, (in apical periodontitis) and 350 (in marginal periodontitis) bacterial species have been encountered. These infections are predominantly anaerobic, with gram-negative rods being the most common isolates. The anatomic closeness of this microflora to the bloodstream can facilitate bacteremia and systemic spread of bacterial by-products and immunocomplexes. A variety of clinical procedures such as tooth extraction, periodontal and endodontic treatment, may cause translocation of microorganisms from the oral cavity to the bloodstream. The microorganisms that gain entrance to the blood circulate throughout the body, but are usually eliminated by the host (reticuloendothelial system) within minutes. However, in patients with ineffective heart valves or vascular diseases, bacteremia can be a potential danger, leading most commonly to infective endocarditis and myocardial or cerebral infarction. Other forms of systemic diseases such as brain abscesses, hematological infections and implant infections have also been related to oral microorganisms.