白假丝酵母菌在义齿性口炎中的相关研究

义齿性口炎是一种发生在可摘义齿佩戴者口腔的常见病,其主要的特征为与义齿接触的口腔黏膜出现炎症与红斑或组织水肿样病损,发病机制仍不明确.研究表明,白假丝酵母菌与义齿性口炎的发生有着密切的关系.白假丝酵母菌主要通过其分泌的侵袭酶与黏附素及菌丝相的形成作为毒力因子,对宿主细胞进行感染.这一系列的毒力作用大多由某一种或几种分子通路来实现调控.本文就白假丝酵母菌在义齿性口炎中相关毒力因子的产生与作用,其分子通路及宿主细胞的反应等几个方面进行综述.     

Adherent interactions which may affect microbial ecology in the mouth

Bacteria attach to teeth and oral mucosal surfaces in a surprisingly selective manner, and attachment appears to be the first step in the colonization process. Attachment is thought to involve lectin-like and/or hydrophobic ligands, called adhesins, often present in bacterial surface appendages which interact with receptors on oral tissues. A variety of factors can influence bacterial attachment, and therefore have the potential to affect host-parasite interactions in the mouth. Factors discussed include salivary components, dietary lectins, and sublethal concentrations of antibiotics.     

Proteins in whole saliva during the first year of infancy

During the first year of an infant's life, the oral environment is subject to drastic changes that coincide with the eruption of teeth. Proteins in saliva are important for protecting oral surfaces and provide receptors for bacterial adhesins. The objective of this longitudinal study was to monitor the general composition and expression of proteins in whole saliva of infants, to prove the hypothesis that expression of certain proteins changes during infant development, and might be associated with tooth eruption. The results showed a remarkable constancy in the overall pattern of salivary proteins and glycoproteins during infancy. Exceptions were the mucins and albumin. The mucins are expressed differentially, with first MUC7 and later MUC5B being predominant. Albumin, a marker of serum leakage, started to rise in whole saliva preceding tooth eruption. Thus, the expression of only few proteins appears to be changed during infant development.     

Streptococcus mitis: walking the line between commensalism and pathogenesis

Streptococcus mitis is a viridans streptococcus and a normal commensal of the human oropharynx. However, S. mitis can escape from this niche and cause a variety of infectious complications including infective endocarditis, bacteraemia and septicaemia. It uses a variety of strategies to effectively colonize the human oropharynx. These include expression of adhesins, immunoglobulin A proteases and toxins, and modulation of the host immune system. These various colonization factors allow S. mitis to compete for space and nutrients in the face of its more pathogenic oropharyngeal microbial neighbours. However, it is likely that in vulnerable immune‐compromised patients S. mitis will use the same colonization and immune modulation factors as virulence factors promoting its opportunistic pathogenesis. The recent publication of a complete genome sequence for S. mitis strain B6 will allow researchers to thoroughly investigate which genes are involved in S. mitis host colonization and pathogenesis. Moreover, it will help to give insight into where S. mitis fits in the complicated oral microbiome. This review will discuss the current knowledge of S. mitis factors involved in host colonization, their potential role in virulence and what needs to be done to fully understand how a an oral commensal successfully transitions to a virulent pathogen.     

具核梭杆菌与牙周炎关系的研究进展

牙周炎是由多种微生物引起的感染性疾病。具核梭杆菌在牙周炎中有高检出率,两者有强相关性。具核梭杆菌可借助多种黏附素共聚致病菌、黏附侵入上皮细胞,利用毒力因子和代谢产物等破坏牙周组织,并可诱导宿主产生免疫反应,促进牙周疾病甚至全身系统性疾病的发生发展。但目前临床上辅助牙周基础治疗的药物并不能针对具核梭杆菌等特定牙周致病菌,可能会导致菌群失调或耐药等问题。具核梭杆菌致病机制的研究为牙周炎的预防及治疗提供了新的思路,研发针对具核梭杆菌黏附素、毒力因子、代谢产物或切断各个致病通路的材料、药物、益生菌产品,抑制其在深牙周袋中的增殖和炎症反应,保持与其他口腔微生物及宿主的动态平衡,有利于牙周炎的控制。     

Oral adhesion of yeasts

Oral adhesion of yeasts probably occurs by interaction between yeast cell adhesins and oral epithelial cell receptors. In Candida albicans mannoprotein, glucan, chitin, cell wall proteins, and lipids are possible adhesins. Mannoprotein appears as a fibrillar or floccular outermost layer in stationary-phase cells grown in sugar-rich medium. Preincubation of buccal epithelial cells (BECs) with concanavalin A inhibits adhesion, as does suppression of mannoprotein production by tunicamycin. Germ tubes adhere more easily to BECs and plastic than do blastospores. Methyl-alpha-D-mannoside may be analogous to the yeast adhesin or epithelial cell receptor because it inhibits adhesion of C. albicans to BECs. L-Fucose, N-acetyl-D-glucosamine, or D-mannose, having the same effect, may also function as epithelial cell receptors. Other factors affecting yeast adhesion may be fibronectin, hydrophobicity, s-IgA, and indigenous bacteria. Growth of yeasts to stationary phase in sugar-rich media promotes adhesion to acrylic, as do divalent cations and serum. Saliva, chlorhexidine, and Streptococcus salivarius inhibit adhesion of yeasts.     

Molecular pathways regulated by areca nut in the etiopathogenesis of oral submucous fibrosis

Many oral mucosal lesions are due to substance abuse, such as tobacco and areca nut, amongst others. There is considerable evidence that oral lesions/disorders such as some leukoplakias, most erythroplakias, and submucous fibrosis have malignant potential, with a conversion rate of 5%‐10% over a 10‐year period. There have been several reports on possible biomarkers that predict malignant conversion of the oral lesions associated with these disorders. Management of these is mostly surgical removal of the lesion followed by observation, and in some cases treatment by antioxidants and anti‐inflammatory agents. Oral submucous fibrosis is due to excessive deposition of extracellular matrix in the connective tissue plus, particularly, collagens. The deposition of collagen leads to stiffness of the affected regions and results in difficulty in mouth opening. Areca nut chewing is proposed as the most probable etiological factor in the manifestation of oral submucous fibrosis. Several studies suggest involvement of proinflammatory cytokines, dysregulated by areca nut, in the development of the disease. Amongst these, transforming growth factor‐β is in the forefront, which is also shown to be involved in fibrosis of other organs. This review addresses the molecular mechanisms involved in oral submucous fibrosis development and provides a model for the regulation of transforming growth factor‐β by areca nut. It provides an exemplar of the role of modern molecular techniques in the study of oral disease.     

Study on the adhesion of an endemic strain of Streptococcus mutans serotype C to acquired pellicle. II. Isolation and extraction of adhesins of an endemic strain of Streptococcus mutans serotype C]

Surface proteins of S. mutans WD9463 A(c) were separated by DEAE-Sephadex A25 Chromatography and Sepharose C1-6B Chromatography. The adhesins were distinguished by bacterial adhesin inhibition experiment and were identified by PAGE, SDS-PAGE, IEP-PAGE, immunol diffusion test, GTF activity test and annalization of the sorts of amino acid. The results showed P1, two proteins with molecular weight of 117 kD and 127 kD and two proteins with GTF activity could inhibit the adhesion effectively. On the other hand, another kind of GTF could improve the adhesion of the strain. These indicated that S. mutans may be many kinds of adhesins.     

Molecular force probe measurement of antigen I/II-matrix protein interactions

Viridans streptococci possess a family of immunologically and structurally related cell-surface proteins, termed antigen I/II, which may function as adhesins and enable oral streptococci to adhere to saliva-coated surfaces and matrix proteins. Here we used atomic force microscopy in the molecular force mode to measure the specific interaction forces between antigen I/II and two matrix proteins, collagen and fibronectin. These matrix proteins provide important binding sites for adherence of oral streptococcal in dentinal caries and endocarditis, respectively. Antigen I/II-coated cantilever tips were brought into contact with collagen- or fibronectin-coated silica coverslips. For the protein I/II-fibronectin interaction experiments, the mean strength of the last ruptures was 216 pN, with most of the detachments located around 125 pN. In antigen I/II-collagen interaction experiments, the mean strength of the last rupture forces corresponded to 136 pN, with the most frequent unbinding force around 75 pN. Thus, our findings definitely suggest that, under the present experimental conditions, antigen I/II binds more strongly to fibronectin than to type I collagen. This might be of relevance for the attachment of viridians streptococci to surfaces exposed to strong hydrodynamic shearing forces under in vivo conditions.     

Bacterial adhesion to oral tissues: a model for infectious diseases

The majority of bacteria which colonize humans display sharp host and tissue tropisms; consequently, relatively little is known about how they initiate colonization on mucosal surfaces. The mouth has a variety of features which have enabled it to serve as a useful model for the discovery of basic principles of host-parasite interactions occurring in mucosal environments. Early studies demonstrated that indigenous bacteria attach to surfaces of the mouth in a highly selective manner; attachment was often observed to correlate with colonization. These studies led to the recognition that bacterial attachment is an essential step for colonization in environments which contain surfaces exposed to a fluid flow. Bacterial adhesion has subsequently grown into a major area of infectious disease research. Many bacteria have been found to possess proteinaceous components, called "adhesins", on their surfaces which bind in a stereochemically specific manner to complementary molecules, or "receptors", on the tissue surface. Adhesins are often lectins which bind to saccharide receptors, but some adhesins are thought to bind to proteinaceous receptors. Studies of components of human saliva, which adsorb to hydroxyapatite (HA) surfaces similar to those of teeth, and promote the attachment of prominent plaque bacteria, have revealed that the acidic proline-rich proteins (PRPs) promote the attachment of several important bacteria. These include strains of Actinomyces viscosus, Bacteroides gingivalis, some strains of Streptococcus mutans, and others. The salivary PRP's are a unique family of molecules. However, segments of PRPs are structurally related to collagen. This may be significant, since B. gingivalis and certain cariogenic streptococci bind to collagenous substrata, and such interactions may facilitate their invasion into gingival tissues, or into dentin or cementum, respectively. Another unexpected observation was that although A. viscosus and other bacteria bind avidly to PRPs adsorbed onto apatitic surfaces, they do not interact with PRPs in solution. PRP molecules evidently undergo a conformational change when they adsorb to HA, and adhesins of A. viscosus recognize cryptic segments which are only exposed in adsorbed molecules. This provides the bacteria with a mechanism for efficiently attaching to teeth while suspended in saliva. It also offers a molecular explanation for their sharp tropisms for human teeth. It has proven convenient to refer to such hidden receptors for bacterial adhesins as "cryptitopes" (from cryptic, meaning hidden, and topo, meaning place).(ABSTRACT TRUNCATED AT 400 WORDS)     

Porphyromonas gingivalis-epithelial cell interactions in periodontitis

Emerging data on the consequences of the interactions between invasive oral bacteria and host cells have provided new insights into the pathogenesis of periodontal disease. Indeed, modulation of the mucosal epithelial barrier by pathogenic bacteria appears to be a critical step in the initiation and progression of periodontal disease. Periodontopathogens such as Porphyromonas gingivalis have developed different strategies to perturb the structural and functional integrity of the gingival epithelium. P. gingivalis adheres to, invades, and replicates within human epithelial cells. Adhesion of P. gingivalis to host cells is multimodal and involves the interaction of bacterial cell-surface adhesins with receptors expressed on the surfaces of epithelial cells. Internalization of P. gingivalis within host cells is rapid and requires both bacterial contact-dependent components and host-induced signaling pathways. P. gingivalis also subverts host responses to bacterial challenges by inactivating immune cells and molecules and by activating host processes leading to tissue destruction. The adaptive ability of these pathogens that allows them to survive within host cells and degrade periodontal tissue constituents may contribute to the initiation and progression of periodontitis. In this paper, we review current knowledge on the molecular cross-talk between P. gingivalis and gingival epithelial cells in the development of periodontitis.     

口腔癌颌骨侵犯的分子机制研究进展

口腔癌易于发生颌骨侵犯,影响患者预后,而这一现象的分子机制尚未完全阐明。目前研究发现,口腔癌细胞通过一系列信号分子的表达直接或者间接影响破骨细胞的形成和功能,有多条信号通路参与其调控,其中核因子κB受体活化因子配体/核因子κB受体活化因子/骨保护素信号通路的调节备受关注。本文就口腔癌颌骨侵犯的分子机制研究进展进行综述。     

Differential modulation of adherence of oral streptococci by human neutrophil myeloperoxidase

In this study, the modulation of adherence of hydrogen peroxide (H2O2)-producing and non-H2O2-producing strains of oral streptococci by the host leukocyte enzyme myeloperoxidase (MPO) was examined. It was found that exposure to MPO decreased adherence of many strains of oral streptococci to saliva-coated hydroxyapatite beads in the presence of exogenous H2O2 and chloride. The MPO-H2O2-Cl-system increased the adherence of one strain. In the absence of exogenous H2O2, the MPO-H2O2-Cl-system decreased the adherence of H2O2-producing strains only. Glucose increased streptococcal H2O2 production and also increased the anti-adhesive activity of MPO in the absence of exogenous H2O2. We conclude that: (1) host leukocytes can modulate the adherence of oral streptococci via MPO; (2) endogenous production of H2O2 by the oral streptococci can provide sufficient substrate H2O2 to drive this system; and (3) MPO will exert differential modulatory effects on the adherence of oral streptococci, based in part upon the level of endogenous H2O2 production and in part upon the particular characteristics of the adhesins of the bacteria.     

Invasion of dentinal tubules by root canal bacteria

Bacterial invasion of dentinal tubules and the clinical consequences have been recognized for over a century. However, while many components of the infected dentinal tubule microflora have been identified, it is likely that there are etiological agents involved in endodontic infections that have not yet been recognized. Bacterial invasion of coronal dentinal tubules occurs when the dentine is exposed to the oral environment and of radicular dentinal tubules subsequent to infection of the root canal system or as a consequence of periodontal disease. The content and architecture of a dentinal tubule can influence bacterial invasion, with tubule patency being important. This can account for regional variations in bacterial invasion and is particularly seen with dentinal sclerosis, where more advanced sclerotic changes in apical radicular tubules, especially in elderly individuals, limit bacterial invasion in this area. While several hundred bacterial species are known to inhabit the oral cavity, a relatively small and select group of bacteria are involved in invasion of dentinal tubules. Gram‐positive organisms dominate the tubule microflora in both carious and non‐carious dentine. The relatively high numbers of obligate anaerobes present, such as Eubacterium spp., Propionibacterium spp., Bifidobacterium spp., Peptostreptococcus micros, and Veillonella spp., suggests that the environment favors the growth of these bacteria. Gram‐negative obligate anaerobic rods, e.g. Porphyromonas spp., are less frequently recovered; however, with time, fastidious obligately anaerobic bacteria become established as principal components of the microflora and can be found within the deep dentine layers. In the early stages of infection, Gram‐positive bacteria dominate the microflora. The identification of adhesins that mediate these initial interactions of bacteria with dentine is important for understanding the development of tubule infection and in designing adhesion‐blocking compounds. Recent evidence suggests that streptococci and enterococci may recognize components present within dentinal tubules, such as collagen type I, which stimulate bacterial adhesion and intra‐tubular growth. Specific interactions of other oral bacteria with invading streptococci may then facilitate invasion of dentine by select bacteria. It is important therefore that the mechanisms of invasion and inter‐bacterial adhesion are understood to assist development of novel control strategies.     

Subgingival colonization by Porphyromonas gingivalis

Porphyromonas gingivalis, a gram-negative anaerobe, is a major causative agent in the initiation and progression of severe forms of periodontal disease. In order to cause periodontal disease, P. gingivalis must colonize the subgingival region, a process that involves several distinct steps and multiple gene products. The organism must first navigate within the oral fluids in order to reach the hard or soft tissues of the mouth. Retention and growth of bacteria on these surfaces is facilitated by a repertoire of adhesins including fimbriae, hemagglutinins and proteinases. Once established subgingivally, P. gingivalis cells participate in intercellular communication networks with other oral prokaryotic cells and with eukaryotic cells. The establishment of these multiple interactive interfaces can lead to biofilm formation, invasion of root dentin and internalization within gingival epithelial cells. The resulting bacterial and host cellular locations, products and fate contribute to the success of P. gingivalis in colonizing the periodontal region.     

口腔癌细胞诱导的淋巴管内皮细胞基因表达谱的变化

目的探讨在口腔癌细胞影响下淋巴管内皮细胞分子表型的变化。方法利用体外共培养模型,将淋巴管内皮细胞与口腔癌细胞进行共培养,模拟肿瘤中淋巴管内皮细胞的变化。应用Affymetrix U133 Plus 2.0基因芯片对肿瘤组织中淋巴管内皮细胞（TLEC）与淋巴管内皮细胞（LEC）基因表达的差异进行了检测和比较。并对功能相似的表达差异基因进行分类。结果差异基因表达谱共发现了677个基因表达差异在1倍以上,其中在TLEC中表达上调的基因有384条,下调的基因有293条。这些基因与细胞黏附、凋亡、运动、发育及血管生成有关。同时这些基因还参与细胞的信号传导、免疫应答、细胞代谢等过程。结论LEC与TLEC在分子水平是有差别的。以此为基础,可以针对淋巴管内皮细胞进行靶向阻断,达到治疗口腔癌淋巴道转移的目的。     

Laser ionization mass spectrometry in oral squamous cell carcinoma

Biomarker research in oral squamous cell carcinoma (OSCC) aims for screening/early diagnosis and in predicting its recurrence, metastasis and overall prognosis. This article reviews the current molecular perspectives and diagnosis of oral cancer with proteomics using matrix‐assisted laser desorption ionization (MALDI) and surface‐enhanced laser desorption ionization (SELDI) mass spectrometry (MS). This method shows higher sensitivity, accuracy, reproducibility and ability to handle complex tissues and biological fluid samples. However, the data interpretation tools of contemporary mass spectrometry still warrant further improvement. Based on the data available with laser‐based mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug targets. Majority of these biomarkers are involved in cell homeostasis and are either physiologic responders or enzymes. Therefore, proteins directly related to tumorigenesis have more diagnostic value. Salivary secretory markers are another group that offers a favourable and easy strategy for non‐invasive screening and early diagnosis in oral cancer. Key molecular inter‐related pathways in oral carcinogenesis are also intensely researched with software analysis to facilitate targeted drug therapeutics. The review suggested the need for incorporating ‘multiple MS or tandem approaches’ and focusing on a ‘group of biomarkers’ instead of single protein entities, for making early diagnosis and treatment for oral cancer a reality.     

非编码RNA与口腔颌面-头颈部癌研究

微小RNA(MicroRNA,miRNA)是非编码RNA(ncRNAs)中研究最广泛的一类,它们通过转录后调控基因的沉默,而达到调控基因从mRNA到蛋白的转录翻译。研究预测,miRNAs调控超过60%编码蛋白的转录,它们的功能涉及调控细胞增殖、分化和凋亡等生理过程,还涉及癌症的发生和发展。通过对口腔颌面部癌ncRNAs异常表达和作用的研究,有望促进分子诊断和治疗技术的发展。基于ncRNAs的定量检测和表达调控技术的应用,ncRNAs分子的生物学功能得以鉴定和明确。当然,ncRNAs的靶基因以及miRNAs与癌症关系的研究,还仅处在研究的初级阶段,对于ncRNAs的病理作用范围、作用机制的深入研究和进一步阐明,是未来研究的主要方向。