記述言語：英語   出版者・発行元：一般社団法人　日本毒性学会  

Cleft palate (CP) is one of the most common birth defects and is caused by a combination of genetic and/or environmental factors. Environmental factors such as pharmaceutical exposure in pregnant women are known to induce CP. Recently, microRNA (miRNA) was found to be affected by environmental factors. The aim of the present study was to investigate the involvement of miRNA against phenytoin (PHE)-induced inhibition of proliferation in human embryonic palatal mesenchymal (HEPM) cells. We demonstrated that PHE inhibited HEPM cell proliferation in a dose-dependent manner. We found that treatment with PHE downregulated cyclin-D1 and cyclin-E expressions in HEPM cells. Furthermore, PHE increased miR-4680-3p expression and decreased two downstream genes (ERBB2 and JADE1). Importantly, an miR-4680-3p-specific inhibitor restored HEPM cell proliferation and altered expression of ERBB2 and JADE1 in cells treated with PHE. These results suggest that PHE suppresses cell proliferation via modulation of miR-4680-3p expression.

DOI： 10.2131/jts.49.1

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記述言語：英語   出版者・発行元：International Journal of Oral and Maxillofacial Surgery  

The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1–2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.

DOI： 10.1016/j.ijom.2022.08.021

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記述言語：英語   出版者・発行元：バイオメディカルリサーチプレス  

A cleft lip, with or without a cleft palate, is a common birth defect caused by environmental factors or genetic mutations. Environmental factors, such as pharmaceutical exposure in pregnant women, are known to induce cleft lip, with or without cleft palate in the child. This study aimed to investigate the protective effect of Sasa veitchii extract (SE) on phenytoin-induced inhibition of cell proliferation in human lip mesenchymal cells (KD cells) and human embryonic palatal mes-enchymal cells (HEPM cells). We demonstrated that cell proliferation was inhibited by phenytoin in a dose-dependent manner in both KD and HEPM cells. Co-treatment with SE restored phenyto-in-induced toxicity in KD cells but did not protect HEPM cells against phenytoin-induced toxicity. Several microRNAs (miR-27b, miR-133b, miR-205, miR-497-5p, and miR-655-3p) is reported to associate with cell proliferation in KD cells. We measured the seven kinds of microRNAs (miR-27b-3p, miR-27b-5p, miR-133b, miR-205-3p, miR-205-5p, miR-497-5p, and miR-655-3p) and found that SE suppressed miR-27b-5p induced by phenytoin in KD cells. Furthermore, co-treat-ment with SE enhanced the expression of miR-27b-5p downstream genes (PAX9, RARA, and SUMO1). These results suggest that SE protects phenytoin-induced cell proliferation inhibition by modulating miR-27b-5p.

DOI： 10.2220/biomedres.44.73

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記述言語：英語   出版者・発行元：バイオメディカルリサーチプレス  

ヒト口唇間葉系細胞のKD細胞とヒト胚口蓋間充織細胞のHEPM細胞を用いて、フェニトイン誘発細胞増殖阻害に対するクマザサ抽出物(SE)の防護作用について検討した。その結果、KD細胞とHEPM細胞の増殖はフェニトインにより用量依存的に阻害された。また、KD細胞のフェニトイン誘発細胞増殖阻害はSEにより濃度依存的に抑制されたが、HEPM細胞のフェニトイン誘発細胞増殖阻害はSEにより抑制されなかった。次に、KD細胞で細胞増殖との関連性が報告されている7種類のマイクロRNA発現を調べたところ、フェニトインによりmiR-27b-5pとmiR-205-3pが上方制御され、フェニトイン誘発によるmiR-27b-5p発現は、SEにより抑制されることが確認された。他にも、miR-27b-5pの下流遺伝子であるPAX9遺伝子、RARA遺伝子およびSUMO1遺伝子の発現は、SEにより増加することも明らかにされた。以上より、SEはmiR-27b-5pを調節することにより、フェニトイン誘発による細胞増殖阻害からヒト口唇間葉細胞を防護することが示唆された。

記述言語：日本語   出版者・発行元：日本毒性学会  

<p><b><u>Background:</u></b> Cleft palate (CP) is the second most common birth defect in humans worldwide. Previous studies have identified gene mutations, chromosomal abnormalities, and teratogens in CP. In addition to genetic mutations, genetic background (e.g. ethnicity, population of origin, and gender), substantially influences CP prevalence. Maternal age, smoking, alcohol consumption, obesity, and micronutrient deficiencies are known, or strongly suspected, experimental risk factors for CP. Therefore, the etiology of CP is complex, and its risk factors are still being elucidated. Folic acid is known to decrease the risk of CP. Although dietary intake of folic acid is first choice to prevent CP, searching the alternative method is also important for the patients such as folic acid metabolism anomaly. In the present study, we examined the protective effects of Sasa vetichii extract (SE) in all trans-retinoic acid (atRA)-induced cell proliferation inhibition in human embryonic palatal mesenchymal cells (HEPM cells). </p><p><b><u>Results and Discussion</u></b>: We demonstrated that atRA induced cell proliferation inhibition in a dose dependent manner in HEPM cells. We found that SE did not affect cell proliferation. Co-treatment with SE restored atRA-induced toxicity. Furthermore, we found that atRA-induced miR-4680-3p and co-treatment with SE downregulated miR-4680-3p. Additionally, downstream gene (ERBB2 and JADE1) of miR-4680-3p was potentiated by co-treatment with SE. These results suggested that SE protected atRA-induced cell proliferation inhibition by modulating miR-4680-3p</p>

DOI： 10.14869/toxpt.50.1.0_p2-114

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記述言語：英語   出版者・発行元：Spandidos Publications  

DOI： 10.3892/etm.2022.11600

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/etm.2022.11600.

記述言語：英語   出版者・発行元：Pathology Research and Practice  

We recently demonstrated that Semaphorin 3 A (Sema3A), the expression of which is negatively regulated by Wnt/β-catenin signaling, promotes odontogenic epithelial cell proliferation, suggesting the involvement of Sema3A in tooth germ development. Salivary glands have a similar developmental process to tooth germ development, in which reciprocal interactions between the oral epithelium and adjacent mesenchyme proceeds via stimulation with several growth factors; however, the role of Sema3A in the development of salivary glands is unknown. There may thus be a common mechanism between epithelial morphogenesis and pathogenesis; however, the role of Sema3A in salivary gland tumors is also unclear. The current study investigated the involvement of Sema3A in submandibular gland (SMG) development and its expression in adenoid cystic carcinoma (ACC) specimens. Quantitative RT-PCR and immunohistochemical analyses revealed that Sema3A was expressed both in epithelium and in mesenchyme in the initial developmental stages of SMG and their expressions were decreased during the developmental processes. Loss-of-function experiments using an inhibitor revealed that Sema3A was required for AKT activation-mediated cellular growth and formation of cleft and bud in SMG rudiment culture. In addition, Wnt/β-catenin signaling decreased the Sema3A expression in the rudiment culture. ACC arising from salivary glands frequently exhibits malignant potential. Immunohistochemical analyses of tissue specimens obtained from 10 ACC patients showed that Sema3A was hardly observed in non-tumor regions but was strongly expressed in tumor lesions, especially in myoepithelial neoplastic cells, at high frequencies where phosphorylated AKT expression was frequently detected. These results suggest that the Sema3A-AKT axis promotes cell growth, thereby contributing to morphogenesis and pathogenesis, at least in ACC, of salivary glands.

DOI： 10.1016/j.prp.2022.153991

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ol.2018.9115.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00432-017-2398-2