慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象的尿代谢组研究

目的：探索慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿代谢差异指标,为中医舌象生物学物质基础微观辨证提供证据。方法：采用气相色谱／质谱联用（GC／MS ）技术方法获取慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿液样本代谢指纹谱,用无监督的学习模式进行多变量统计分析,观察不同组别的人群之间是否存在“自然”的分类结构。利用有监督的学习模式进行数据分类模型的建立和检验,寻找造成样本聚集和离散的主要差异变量。利用商业化的代谢物谱库以及标准品数据库,进行物质鉴定。结果：慢性乙型肝炎舌红苔黄和舌淡苔白者在有监督的学习模式下具有良好的分开趋势,慢乙肝不同舌象者较健康者的差异代谢物谱主要与能量代谢、氨基酸代谢、核苷酸代谢以及肠道菌群代谢相关。结论：舌象是机体变化的重要窗口,不同舌象的外在表观潜在体内的代谢差异。     

Bmi1 Drives Stem-Like Properties and is Associated with Migration,Invasion, and Poor Prognosis in Tongue Squamous Cell Carcinoma

Bmi1 (B-cell-specific Moloney murine leukemia virus insertion site 1) had been found to involve in self -renewal of stem cells and tumorigenesis in various malignancies. The purpose of this study is to evaluate the role of Bmi1 in the development of tongue squamous cell carcinoma (TSCC) and its functional effect on the migration and invasion of TSCC. Initially, immunohistochemistry revealed that Bmi1 overexpression was a common event in premalignant dysplasia, primary TSCC, and lymph node metastases and was associated with a poor prognosis. A significant correlation between Bmi1 and SOD2 (manganese superoxide dismutase) expression was observed. Side population (SP) cells were used as cancer stem-like cells and further assessed by sphere and colony formation assays, and the expression of stem cell markers. TSCC cells with higher migration and invasion ability (UM1 cell lines) showed a higher proportion of SP cells and Bmi1 expression than TSCC cells with lower migration and invasion ability (UM2 cell lines). Knockdown of Bmi1 in UM1 or SP cells inhibited migration and invasion and decreased the sphere and colony formation, and the expression of stem cell markers and SOD2. Direct binding of C-myc to the Bmi1 promoter was demonstrated by chromatin immunoprecipitation and luciferase assays. Moreover, C-myc knockdown in SP cells inhibited their migration and invasion and decreased the expression of Bmi1 and SOD2. Our results indicate that the deregulation of Bmi1 expression is a frequent event during the progression of TSCC and may have a prognostic value for patients with this disease. The Bmi1-mediated migration and invasion of TSCC is related to cancer stem-like cells and involves the C-myc-Bmi1-SOD2 pathway.     

Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development

Taste papillae are ectodermal specializations that serve to house and distribute the taste buds and their renewing cell populations in specific locations on the tongue. We previously showed that Sonic hedgehog (Shh) has a major role in regulating the number and spatial pattern of fungiform taste papillae on embryonic rat tongue, during a specific period of papilla formation from the prepapilla placode. Now we have immunolocalized the Shh protein and the Patched receptor protein (Ptc), and have tested potential roles for Shh in formation of the tongue, emergence of papilla placodes, development of papilla number and size, and maintenance of papillae after morphogenesis is advanced. Cultures of entire embryonic mandible or tongues from gestational days 12 to 18 [gestational or embryonic days (E)12-E18] were used, in which tongues and papillae develop with native spatial, temporal, and molecular characteristics. The Shh signaling pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking antibody. Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings, and are progressively restricted to papilla placodes and then to regions of developing papillae. Ptc encircles the dense Shh immunoproduct in papillae at various stages. When the Shh signal is disrupted in cultures of E12 mandible, tongue formation is completely prevented. At later stages of tongue culture initiation, Shh signal disruption alters development of tongue shape (E13) and results in a repatterned fungiform papilla distribution that does not respect normally papilla-free tongue regions (E13-E14). Only a few hours of Shh signal disruption can irreversibly alter number and location of fungiform papillae on anterior tongue and elicit papilla formation on the intermolar eminence. However, once papillae are well formed (E16-E18), Shh apparently does not have a clear role in papilla maintenance, nor does the tongue retain competency to add fungiform papillae in atypical locations. Our data not only provide evidence for inductive and morphogenetic roles for Shh in tongue and fungiform papilla formation, but also suggest that Shh functions to maintain the interpapilla space and papilla-free lingual regions. We propose a model for Shh function at high concentration to form and maintain papillae and, at low concentration, to activate between-papilla genes that maintain a papilla-free epithelium.     

Apparent decoupling of prey recognition ability with prey availability in an insular snake population

Numerous studies on the feeding behavior of snakes have reported the consistency of tongue-flick responses with their natural diets. For representatives of widely distributed, dietary generalist species from particular localities, we can expect that their tongue-flick responses to potential prey unavailable in their original habitats have been reduced whereas those to prey common in the habitats have been enhanced. To test this hypothesis, intraspecific variation in tongue-flick responses to prey chemicals was examined using ingestively naive snakes (Elaphe quadrivirgata) from dietarily different populations: populations from the main Japanese island, where the snakes' diet predominantly consists of sympatric frogs, and from Mikura-jima Island, where no frogs occur and the snakes thus chiefly prey on lizards. We presented chemical stimuli from six items including those from their natural and potential prey (fish, frog, lizard, mouse, water, and cologne) to newborn snakes. Significant effects of stimuli on the tongue-flick responses were detected. On the other hand, effects of population and interaction between stimuli and population were not significant, and individual comparisons revealed no significant interlocality differences in responses to either frog or lizard chemicals. Thus, our hypothesis was not supported. However, in the Mikura-jima sample, significantly fewer snakes responded to frog chemicals than in the main island sample. The significance of the inconsistency between prey recognition ability and prey availability in the Mikura-jima population are discussed. Received: October 17, 2000 / Accepted: December 14, 2000     

Denver Papillae Protocol for Objective Analysis of Fungiform Papillae

The goal of the Denver Papillae Protocol is to use a dichotomous key to define and prioritize the characteristics of fungiform papillae (FP) to ensure consistent scoring between scorers. This protocol builds off of a need that has arisen from the last two decades of taste research using FP as a proxy for taste pore density. FP density has historically been analyzed using Miller & Reedy’s 1990 characterizations of their morphology: round, stained lighter, large, and elevated. In this work, the authors forewarned that stricter definitions of FP morphology needed to be outlined. Despite this call to action, follow up literature has been scarce, with most studies continuing to cite Miller & Reedy’s original work. Consequently, FP density reports have been highly variable and, combined with small sample sizes, may contribute to the discrepant conclusions on the role of FP in taste sensitivity. The Genetics of Taste Lab explored this apparent inconsistency in counting and found that scorers were individually prioritizing the importance of these characteristics differently and had no guidance for when a papilla had some, but not all, of the reported qualities of FP. The result of this subjectivity is highly variable FP counts of the same tongue image. The Denver Papillae Protocol has been developed to remedy this consequence through use of a dichotomous key that further defines and prioritizes the importance of the characteristics put forth by Miller & Reedy. The proposed method could help create a standard way to quantify FP for researchers in the field of taste and nutritional studies.     

Graft union formation in artichoke grafting onto wild and cultivated cardoon: An anatomical study

In order to develop a non-chemical method such as grafting effective against well-known artichoke soil borne diseases, an anatomical study of union formation in artichoke grafted onto selected wild and cultivated cardoon rootstocks, both resistant to Verticillium wilt, was performed. The cardoon accessions Belgio (cultivated cardoon) and Sardo (wild cardoon) were selected as rootstocks for grafting combinations with the artichoke cv. Romolo. Grafting experiments were carried out in the autumn and spring. The anatomical investigation of grafting union formation was conducted by scanning electron microscopy (SEM) on the grafting portions at the 3rd, 6th, 10th, 12th day after grafting. For the autumn experiment only, SEM analysis was also performed at 30 d after grafting.     

Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16 transgenic mice

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common neoplasms in the world. During the past 2 decades, the role of high-risk human papilloma virus (HR-HPV) has been studied and the data supporting HPV as a one of the causative agents in the development and progression of a sub-set of head and neck squamous cell carcinomas (HNSCC) has accumulated. In order to investigate the role of HR-HPV oncogene expression in early epithelial alterations in vivo, we produced transgenic mice expressing HPV16 early region genes from the promoter of the bovine keratin 6 gene (Tg[bK6-E6/E7]). In this article, we demonstrate that E6/E7 transgene was abundantly expressed and cellular proliferation was increased in the middle tongue epithelia of transgenic mice, and that in the same region young (27 weeks old) Tg[bK6-E6/E7] mice spontaneously developed histological alterations, mainly focal epithelial hyperplasia (FEH).     

Trypanosoma congolense. II. Histopathologic findings in experimentally infected cattle

Heart, kidney, lung, liver, brain, spleen, lymph nodes, tongue, and diaphragm of 9 cattle experimentally infected with the Trans Mara I strain of Trypanosoma congolense, were examined histologically. A haemosiderosis, infiltrations in the kidney, changes in the vascular wall mainly of the arteries of the lung, scattered local perivascular, and meningeal infiltrations, and small juxtavascular glial nodules in the CNS were found.     

崇安草蜥舌的显微和超微结构

采用显微技术观察了崇安草蜥(Takydromus sylvaticus)舌的显微和超微结构.舌腹面黏膜光滑;背面黏膜粗糙,由丝状乳头和轮廓乳头组成.丝状乳头锥体形,数量较多,排列成行,分布于舌体背面两侧和侧翼的腹面.在舌的横切片上有3～7个轮廓乳头,其表面平整,周围有环形沟,舌腺开口于环形沟中.舌肌肉发达.超微结构显示,舌上皮细胞问具有紧密连接,舌乳头细胞表面具有丰富的微绒毛.舌腺为单管泡状腺,分泌管由单层柱状上皮构成.柱状上皮细胞有两种,一种为分泌细胞,一种为暗细胞.分泌细胞内有典型的分泌颗粒,可协助食物的吞咽.暗细胞内无分泌颗粒,是否与离子分泌以及渗透压调节有关,尚需进一步证实.     

TGF-β mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue-tissue interactions during tongue morphogenesis

Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that cranial neural crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2^flox/flox) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-β2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2^flox/flox mice. Thus, TGF-β induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development.