Histatins,wound healing,and cell migration

Wounds in the oral mucosa heal faster and more efficiently than those in the skin, although the mechanisms underlying these differences are not completely clear. In the last 10 years, a group of salivary peptides, the histatins, has gained attention on behalf of their ability to improve several phases of the wound‐healing process. In addition to their roles as anti‐microbial agents and in enamel maintenance, histatins elicit other biological effects, namely by promoting the migration of different cell types contained in the oral mucosa and in non‐oral tissues. Histatins, and specifically histatin‐1, promote cell adhesion and migration in oral keratinocytes, gingival and dermal fibroblasts, non‐oral epithelial cells, and endothelial cells. This is particularly relevant, as histatin‐1 promotes the re‐epithelialization phase and the angiogenic responses by increasing epithelial and endothelial cell migration. Although the molecular mechanisms associated with histatin‐dependent cell migration remain poorly understood, recent studies have pointed to the control of signaling endosomes and the balance of small GTPases. This review aimed to update the literature on the effects of histatins in cell migration, with a focus on wound healing. We will also discuss the consequences that this increasing field will have in disease and therapy design.     

周期性张应变对人牙周膜细胞迁移的影响

目的 探讨周期性张应变对人牙周膜细胞(human periodontal ligament cells,hPDLC)迁移的影响及其相关机制,为进一步了解机械力对hPDLC功能的影响提供资料.方法 应用FX-4000T细胞应变加载系统,对体外培养的hPDLC施加周期性张应变,牵张幅度分别为10%和20%,加载时间为6 h和24 h,频率均为0.1 Hz,以未加载的静态细胞作为对照组,应用划痕法观察hPDLC的迁移,蛋白质印迹法检测hPDLC的基质金属蛋白酶9(matrix metalloproteinases-9,MMP-9)的表达变化;用细胞外信号调节蛋白激酶(extracellular signal-regulated kinase,ERK)的特异性抑制剂PD98059预处理hPDLC后,在0.1 Hz、10%幅度条件下,加载6 h,检测细胞p-ERK1/2和MMP-9表达的变化.用细胞迁移划痕法观察加载10%和20%幅度张应变,观察24 h后PD98059和MMP家族的抑制剂强力霉素(doxycycline,DOX)对hPDLC迁移的影响.结果 细胞迁移划痕实验结果显示,牵张幅度和加载时间均可显著促进细胞迁移.与静态组相比,施加牵张幅度分别为10%和20%的张应变6 h后,hPDLC迁移变化不明显,但加载24 h后,10%和20%幅度的张应变均显著促进了hPDLC迁移(P<0.05),细胞迁移率分别为(45 ±8)%和(66±14)%,且20%比10%幅度牵张对细胞迁移的促进作用更显著(P<0.05).蛋白印迹法结果显示,周期性张应变促进了hPDLC的MMP-9表达.牵张幅度对细胞MMP-9的表达有显著影响(P<0.05),但加载时间对细胞MMP-9的表达无显著影响.ERK1/2的抑制剂PD98059不仅可以明显抑制张应变诱导的p-ERK1/2活化,而且可通过ERK信号通路明显抑制张应变诱导的细胞MMP-9表达.细胞迁移划痕实验还证实,加载幅度分别10%和20%的张应变24 h后,抑制剂PD98059和DOX均能有效抑制周期性张应变诱导的hPDLC迁移.结论 周期性张应变可通过激活hPDLC的ERK信号通路,促进细胞的MMP-9表达,从而诱导体外培养的hPDLC迁移.     

Salivary trefoil factor 3 enhances migration of oral keratinocytes

Trefoil factor 3 (TFF3) is a member of the mammalian TFF family. Trefoil factors are secreted onto mucosal surfaces of the entire body and exert different effects according to tissue location. Trefoil factors may enhance mucosal healing by modulating motogenic activity, inhibiting apoptosis, and promoting angiogenesis. Trefoil factor 3 is secreted from the submandibular gland and is present in whole saliva. The aim of this study was to assess the migratory and proliferative effects of TFF3 on primary oral human keratinocytes and oral cancer cell lines. The addition of TFF3 increased the migration of both normal oral keratinocytes and the cancer cell line D12, as evaluated by a two-dimensional scratch assay. By contrast, no increase in proliferation or energy metabolism was observed after stimulation with TFF3. Trefoil factor 3-enhanced migration was found to be driven partly by the extracellular signal-related kinase (Erk1/2) pathway, as shown by addition of the mitogen-activated protein kinase (MAPK) inhibitor PD 98059. Previous functional studies on trefoil peptides have all been based on cells from monolayered epithelium like the intestinal mucosa; this is the first report to show that normal and cancerous keratinocytes from stratified epithelium respond to TFF stimuli. Taken together, salivary TFF3 is likely to contribute to oral wound healing.     

Effects of HB-EGF and epiregulin on wound healing of gingival cells in vitro

Oral Diseases (2011) 17 , 785–793 Objective: Gingival wound healing is important to periodontal disease and surgery. This in vitro study was conducted to assess the manner in which heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and epiregulin cooperatively participate in the wound‐healing process in the gingival epithelial and fibroblast cells of the oral mucosa. Material and Methods: Gingival epithelium and fibroblast were separated from gingival tissue biopsies and prepared to primary cultures. The changes in the mRNA expression were evaluated via real‐time PCR. The effects on cell proliferation, migration, and repopulation were evaluated in vitro. Results: The different regulation of expressions of HB‐EGF, epiregulin, and epidermal growth factor receptors was observed over time and with different gingival cell types. HB‐EGF exerted a cell migration‐inducing effect on both epithelial and fibroblast cells, whereas epiregulin did not. Both growth factors functioned as mitogens for epithelial cell proliferation, but not for fibroblast proliferation. HB‐EGF strongly promoted epithelial cell repopulation and mildly promoted fibroblast repopulation, whereas epiregulin promoted only fibroblast repopulation. Conclusion: These results indicated that both growth factors might function importantly in the wound‐healing process of human gingival tissue via the different regulation of the expression, cell migration, proliferation, and repopulation.     

Nicotine modulates gelatinase B (MMP‐9) and epilysin (MMP‐28) expression in reconstituted human oral epithelium

J Oral Pathol Med (2011) 40 : 33–36 Oral epithelial keratinocytes express nicotinic cholinergic receptors which activation modulates keratinocytes differentiation and migration through different metabolic pathways. Matrix metalloproteinases (MMPs) are Zn‐dependent enzyme involved in cell migration. Among them, gelatinase B (MMP‐9) and epilysin (MMP‐28) are two MMPs expressed by human keratinocytes during both wound healing and proliferation. Their expression has been investigated in a reconstituted human oral epithelium (HOE) exposed to nicotine (Nic, 1–50 μM) for 72 h both in the absence and presence of the nicotinic antagonist mecamylamine (Mec), H7, a PKC inhibitor and PD98059, a MAPK inhibitor (PD). At the end of treatment, MMP‐28 expression has been analyzed in epithelium sections using an anti‐MMP‐28 antibody, whereas MMP‐9 presence and activity has been measured in cell‐conditioned medium analyzed by gelatine zymography. The expression of MMP‐9 was reduced by Nic in a dose‐dependent fashion and this effect was antagonized by Mec, H7 and PD. On the other hand, Nic increased the expression of MMP‐28, and this effect was blocked both by H7 and PD, whereas Mec even enforced it. Nic effects on MMP‐9 and MMP‐28 expression by oral keratinocytes were not previously reported and these data suggest MMPs expression mediated by PKC and MAPK as a possible target for Nic toxicity in oral epithelium.     

Upregulation of heme oxygenase-1 in oral epithelial dysplasias

The expression of heme oxygenase-1 (HO-1), stress-related enzyme, is induced in leukaemia and some cancer tissues, but relatively little is known about the differential pattern of HO-1 expression and proliferation in premalignant lesions of the epithelial oral mucosa. The purpose of this study was to evaluate whether HO-1 expression and proliferation were increased in preneoplastic lesions compared to normal and oral cancer tissues. Immunohistochemical staining was used to examine the expression patterns of HO-1 and proliferating cell nuclear antigen (PCNA) in a series of normal mucosa and mild-to-severe cases of oral epithelial dysplasia (OED) and oral squamous cell carcinoma. Both HO-1 and PCNA are expressed in the basal cells of normal oral mucosa. In patients with OED and carcinoma in situ, immunostaining for PCNA and HO-1 was more intense, and gradually extended into the superficial layers of the mucosa. HO-1 and PCNA expression was correlated with the degree of epithelial dysplasia. Oral squamous cell carcinoma also showed elevated expression of HO-1, but this level was not higher than in severe OED or carcinoma in situ. These results suggest that the up-regulation of HO-1 in premalignant oral lesions is part of an early cytoprotection mechanism against carcinogenesis in the oral mucosa.     

Hypoxia inducible factor‐1α expression in areca quid chewing‐associated oral squamous cell carcinomas

Oral Diseases (2010) 16 , 696–701 Objectives: Hypoxia inducible factor (HIF)‐1α gene expression is mainly induced by tissue hypoxia. Overexpression of HIF‐1α has been demonstrated in a variety of cancers. The aim of this study was to compare HIF‐1α expression in normal human oral epithelium and areca quid chewing‐associated oral squamous cell carcinoma (OSCC) and further to explore the potential mechanisms that may lead to induce HIF‐1α expression. Methods: Twenty‐five OSCC from areca quid chewing‐associated OSCC and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N‐acetyl‐l ‐cysteine (NAC), AP‐1 inhibitor curcumin, extracellular signal‐regulated protein kinase inhibitor PD98059, and protein kinase C inhibitor staurosporine were added to find the possible regulatory mechanisms. Results: Hypoxia inducible factor‐1α expression was significantly higher in OSCC specimens than normal specimen (P < 0.05). Arecoline was found to elevate HIF‐1α expression in a dose‐ and time‐dependent manner (P < 0.05). The addition of NAC, curcumin, PD98059, and staurosporine markedly inhibited the arecoline‐induced HIF‐1α expression (P < 0.05). Conclusions: Hypoxia inducible factor‐1α expression is significantly upregulated in areca quid chewing‐associated OSCC and HIF‐1α expression induced by arecoline is downregulated by NAC, curcumin, PD98059, and staurosporine.     

Whole cigarette smoke promotes human gingival epithelial cell apoptosis and inhibits cell repair processes

Semlali A, Chakir J, Goulet J‐P, Chmielewski W, Rouabhia M. Whole cigarette smoke promotes human gingival epithelial cell apoptosis and inhibits cell repair processes. J Periodont Res 2011; 46: 533–541.
©2011 John Wiley & Sons A/S Background and Objective: Smoking cigarettes increases the risk of developing various types of human diseases, including cancers and periodontitis. As gingival epithelial cells are known to play an active role in innate immunity via the secretion of a wide variety of mediators, and as these cells are the first ones exposed to environmental stimuli such as cigarette smoke, we sought to investigate the effects of whole cigarette smoke on normal human gingival epithelial cells and tissue. Material and Methods: Human gingival epithelial cells were extracted from healthy nonsmokers and used either as a monolayer or as an engineered human oral mucosa to investigate the effect of whole cigarette smoke on cell growth, apoptosis and wound repair/migration. Results: Our findings show that when gingival epithelial cells were exposed once to whole cigarette smoke, this resulted in a significant inhibition of cell growth through an apoptotic pathway, as confirmed by an increase of Bax and a decrease of Bcl‐xL and caspase‐3 activity. Cigarette smoke also inhibited epithelial cell migration. These effects may explain the disorganization of the engineered human oral mucosa tissue when exposed to whole cigarette smoke. Conclusion: Exposure to whole cigarette smoke markedly inhibits epithelial cell growth through an apoptosis/necrosis pathway that involves Bax and Bcl‐xL proteins and caspase‐3 activity. Cigarette smoke also disrupts epithelial cell migration, which may negatively affect periodontal wound healing.     

Tumor Necrosis Factor‐α and Interleukin (IL)‐1β, IL‐6, and IL‐8 Impair In Vitro Migration and Induce Apoptosis of Gingival Fibroblasts and Epithelial Cells,Delaying Wound Healing

Background: Multiple factors affect oral mucosal healing, such as the persistence of an inflammatory reaction. The present study evaluates effects of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β, IL‐6, and IL‐8 on epithelial cells (ECs) and human gingival fibroblasts (GFs) in vitro. Methods: GFs and ECs were seeded in 96‐well plates (1 × 10⁴ cells/well) in plain culture medium (Dulbecco’s modified Eagle’s medium [DMEM]) containing 1% antibiotic/antimycotic solution and 10% fetal bovine serum, and incubated for 24 hours. Both cell lines were exposed for 24 hours to the following cytokines: 1) TNF‐α (100 ng/mL); 2) IL‐1β (1 ng/mL); 3) IL‐6 (10 ng/mL); and 4) IL‐8 (10 ng/mL). All cytokines were diluted in serum‐free DMEM. Control cultures were exposed only to serum‐free DMEM. Effects of exposure to inflammatory cytokines were determined by means of: 1) apoptosis (anexin V); 2) cell migration (wound healing assay); 3) inflammatory cytokine synthesis (enzyme‐linked immunosorbent assay). Data were analyzed by Kruskal–Wallis and Mann–Whitney U tests (α = 0.05). Results: Increased apoptosis rates were noted when cells were exposed to inflammatory cytokines, except ECs exposed to IL‐1β. Cell migration was negatively affected by all inflammatory cytokines for both cell lines. ECs and GFs exposed to IL‐6 and IL‐8 significantly increased synthesis of TNF‐α and IL‐1β. Conclusions: Demonstrated results indicate negative effects of tested inflammatory cytokines on ECs and GFs, inducing apoptosis and impairing cell migration. These results can justify delayed oral mucosa healing in the presence of inflammatory reaction.     

正常人唾液中透明质酸含量的研究

目的 检测非刺激和刺激情况下,正常人全唾液和纯肋腺液中透明质酸的含量,以探讨正常人唾液中透明质酸的含量和了解唾液中透明质酸在伤口愈合中的作用。方法 采用酶联免疫吸附试验法（ELISA）,对20名健康成人唾液进行测定。结果 透明质酸的含量依次为：非刺激下全唾液（369.89mg/ml）,刺激下全唾液（158.61ng/m）,非刺激下腮腺液（95.80ng/m）,刺激下腮腺液（79.20ng/ml）。结论 ①唾液中含有透明质酸;②宵同类型的唾液透明质酸的含量有较大差异;③透明质酸在唾液中的高浓度可能有助于唾液的伤口愈合、口腔粘膜的保护和润滑作用。     

Behavior of HO-1-N-1, buccal mucosa carcinoma derived cells,on [Ca2+]i responses to stimulants

Buccal mucosa carcinoma-derived cell line, HO-1-N-1, epithelial-like cells, was obtained in order to investigate the characteristics of oral cancer cells and examine the [Ca2+]i responses to stimulants, such as bradykinin (BK), histamine (HIST), thapsigargin (TG), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha ). Intracellular Ca2+ influx was observed by all stimulants that enhanced the [Ca2+]i response. However, intracellular Ca2+ release was not observed in response to growth factors. The [Ca2+]i response of BK (100 nM) was inhibited by 10 micro M of the BKB2 antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-BK, and HIST (1 mM) was completely inhibited by 100 nM of the H1 antagonist, (+)-chlorpheniramine, in the presence and absence of extracellular Ca2+ (1.5 mM).     

Saliva and wound healing

The oral mucosa is frequently exposed to mechanical forces, which may result in tissue damage. Saliva contributes to the repair of the oral mucosa in several ways. In the first place, it creates a humid environment to improve the function of inflammatory cells. During the last few years, it has been shown that saliva also contains a large number of proteins with a role in wound healing. Saliva contains growth factors, especially Epidermal Growth FACTOR, which promotes the proliferation of epithelial cells. Trefoil factor 3 and histatin promote the process of wound closure. The importance of Secretory Leucocyte Protease Inhibitor is demonstrated by the fact that in the absence of this salivary protein, oral wound healing is considerably delayed. Understanding these salivary proteins opens the way for the development of new wound healing medications.     

TEAD4与口腔鳞癌预后和细胞迁移侵袭的研究

目的:研究TEA转录因子4(TEAD4)在口腔鳞癌(OSCC)组织中的表达与临床病理参数、预后的关系。方法:免疫组化检测79例原发性OSCC标本和21例口腔正常上皮黏膜中TEAD4的表达水平,分析其与临床病理参数之间的关系。使用小干扰RNA(siRNA)转染沉默Cal27细胞内源性TEAD4,通过Western blot、qRT-PCR、划痕试验、Transwell侵袭等实验探究TEAD4沉默对OSCC细胞系Cal27迁移、侵袭的影响。结果:免疫组化结果显示TEAD4在OSCC组织中表达明显高于正常口腔黏膜(P<0.05)。TEAD4高表达与患者颈淋巴结转移、临床分期和患者总体生存率相关(P<0.05)。TEAD4沉默后Cal27细胞侵袭、迁移能力明显减弱。结论:TEAD4高表达与OSCC恶性表型及预后有关,参与OSCC细胞迁移、侵袭表型的调控。     

Glycosylation pattern and cell attachment-inhibiting property of human salivary mucins

BACKGROUND: Whole human saliva (WHS) and its high molecular weight mucin constituent (Muc) inhibit fibroblast attachment and might influence periodontal and peri-implant wound healing. The aim of this work was to study the potential role of glycosylation of Muc in fibroblast attachment-inhibiting property and to examine in vitro the effect of WHS and Muc on epithelial cell attachment. METHODS: Muc was isolated from WHS by CsCl density gradient ultracentrifugation; covalently immobilized on polystyrene; and subjected to enzymic digestion by N-glycanase, O-glycanase, and sialidase, or chemical desulfation and periodate treatment. Wells of tissue culture microtiter plates were incubated with WHS, Muc, or buffer as control; suspensions of normal human oral keratinocytes, spontaneously immortalized human keratinocytes, or human gingival fibroblasts were applied; and cell attachment determined using methylene blue assay. RESULTS: While enzymic cleavage of N-linked carbohydrates showed no effect, selective removal of O-linked residues and sialic acid as well as desulfation and periodate oxidation resulted in statistically significant reduction of cell attachment-inhibiting property of immobilized Muc. Significantly lower numbers of attached cells of each cell type were found in wells pretreated with WHS or Muc. CONCLUSIONS: Inhibition of cell attachment may be mediated by the carbohydrate residues suggesting specific interactions between the salivary constituent and the cell surface. Exposure of root and implant surfaces to saliva during early wound healing events might influence healing by inhibiting surface colonization by oral keratinocytes and fibroblasts, and enhancing wound repair in the form of long junctional epithelium rather than regeneration.     

表皮生长因子在牙齿萌出通道形成中的作用研究

目的:研究表皮生长因子(EGF)在牙齿萌出过程中,是否参与软、硬组织通道的形成。方法:①免疫组化法检测表皮生长因子及其受体在出生后13、15 d以及成年小鼠下颌第一磨牙萌出部位口腔黏膜的表达变化;②原代培养Wistar大鼠牙囊细胞,选择生长良好的第3代细胞,MTT法筛选EGF作用于牙囊细胞的较佳效应浓度。将第3代牙囊细胞以1×105/孔接种到培养皿中,加入最佳浓度的EGF孵育0.5、1、3、6 h后,Trizol一步法分别提取总RNA,采用反转录聚合酶链反应(RT-PCR)检测同一浓度的EGF作用不同时间后,牙囊细胞MCP-1 mRNA的表达变化。结果:①牙萌出时,EGF在萌出牙齿冠方黏膜的上皮层呈弱阳性表达,表皮生长因子受体(EGFR)在口腔上皮全层呈强阳性表达。而牙萌出后,EGF的表达集中于口腔黏膜的固有层,EGFR的表达集中于上皮基底层;②在EGF浓度为5～10 ng/mL时,对牙囊细胞的增殖具有明显促进作用(P<0.05),其中10 ng/mL促进作用最强。牙囊细胞与10 ng/mL的EGF共同孵育0.5、1、3、6 h均能明显促进牙囊细胞MCP-1 mRNA的表达(P<0.05),其中3 h时促进作用最强,以后逐渐恢复,但仍比对照组高(P<0.05)。结论:EGF及其受体可能促进萌出牙齿冠方实性上皮团的形成;适当浓度的EGF能显著增加牙囊细胞的增殖活性,并上调牙囊细胞中MCP-1 mRNA的表达。     

Adrenergic signaling in human oral keratinocytes and wound repair

Catecholamines are present in saliva, but their influence on oral epithelium is not understood. Because psychological stress increases salivary catecholamines and impairs oral mucosal wound healing, we sought to determine if epithelial adrenergic signaling could link these two findings. We found that cultured human oral keratinocytes (HOK) express the α(2B)- and β(2)-adrenergic receptors (ARs). Exposure of HOK to either epinephrine or the β-AR agonist, isoproterenol, reduced migratory speed and decreased in vitro scratch wound healing. Incubation with the β-AR antagonist timolol reversed the catecholamine-induced effects, indicating that the observed response is mediated by β-AR. Epinephrine treatment decreased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38; these decreases were also reversed with timolol. Cultured HOK express enzymes of the epinephrine synthetic pathway, and generate epinephrine. These findings demonstrate that stress-induced elevations of salivary catecholamines signal through MAPK pathways, and result in impaired oral keratinocyte migration required for healing.     

Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells

J Oral Pathol Med (2010) 40 : 390–396 Background: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression. Methods: Thirty‐two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N‐acetyl‐l ‐cysteine (NAC), extracellular signal‐regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002, cyclooxygenase‐2 inhibitor NS‐398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms. Results: HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P < 0.05). No significant difference in HSP47 expression was observed with respect to age, sex, T category, stage, and differentiation (P > 0.05). The lower HSP47 expression was associated with lymph node metastasis (P = 0.015). Arecoline was found to elevate HSP47 expression in a dose‐ and time‐dependent manner (P < 0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline‐induced HSP47 expression (P < 0.05). Conclusion: Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing‐associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline‐induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A.     

ADAR1对口腔鳞癌细胞生物学特征的影响

检测RNA编辑酶1（ ADAR1）在口腔鳞癌细胞中的表达,探讨其对口腔鳞癌细胞生物学行为特征的影响及作用机制。方法：利用实时定量RT?PCR、Western Blot检测ADAR1在口腔鳞癌细胞中的表达;化学合成siRNA（ si?ADAR1）转染细胞,观察其迁移和侵袭能力;检测ADAR1敲减后口腔鳞癌细胞中上皮间质转化指标（ Vimentin、E?cadherin）、干性指标（ Sox2、Oct4）以及 onco?microRNAs （ miR?21?3p、miR?18a?3p、miR?210?3p、miR?155?5p、miR?181a?3p、miR?19a?3p ）表达水平。结果：ADAR1在口腔鳞癌细胞中高表达;ADAR1敲减后的口腔鳞癌细胞迁移和侵袭能力下降（P＜0．05）,上皮间质转化指标 E?cadherin低表达、Vimentin高表达,干性指标（ Sox2、Oct4）及口腔鳞癌相关onco?MicroRNAs低表达。结论：ADAR1与口腔鳞癌细胞的生物学行为密切相关,推测 ADAR1可能通过促进口腔鳞癌相关 onco?microRNAs成熟影响口腔鳞癌细胞的生物学行为。     

Estimates,from salivary analyses,of the turnover time of the oral mucosal epithelium in humans and the number of bacteria in an edentulous mouth

The objectives were to obtain rough estimates of the number of bacteria in an edentulous mouth and the mean turnover time of the oral mucosa and the conditions under which the salivary phase in the mouth might act as a bacterial continuous culture system. The premise was that at steady state in vivo, the rates of loss of bacteria and epithelial cells in saliva must be equal to their rates of proliferation. Drooled saliva was collected from 17 subjects and the number of epithelial cells per millilitre was determined in a Coulter Counter. The numbers of adherent bacteria per epithelial cell were counted on cells stained with Toluidine Blue. For 10 subjects, salivary bacterial counts were obtained after saliva had been diluted in Reduced Transport Fluid and grown anaerobically on Blood Agar for 5 days. From the known surface areas of the oral mucosa and individual epithelial cells and the rate of loss of epithelial cells into saliva, the surface layer of epithelial cells was calculated to be replaced every 2.7h. From the calculated number of epithelial cells lining the oral mucosa, the number of bacteria per epithelial cell, and the rate of swallowing of the bacteria in saliva, the number of bacteria in an edentulous mouth was calculated to be about 1.58 x 10(9) and the mean time between bacterial cell divisions to be 1.38h. Given a residual volume of 0.8ml and a maximal bacterial division rate of 3h(-1), the salivary phase in the mouth could act as a continuous culture system for certain fast-growing bacteria only if the maximum flow rate were <0.04ml/min.     

SOX2通过PI3K/AKT通路调控口腔鳞癌细胞迁徙的机制研究

目的:研究过表达SOX2通过PI3K/AKT通路促进口腔鳞癌(oral squamous cell carcinoma,OSCC)细胞迁移及上皮间质转化(epithelial mesenchymal transition,EMT)的作用及机制.方法:收集OSCC组织及正常口腔黏膜组织,培养OSCC细胞株Tca83、SC...