This study examined the subacute oral toxicity of Dendropanax morbiferus H.Lév leaves hot-water extracts (DMWE) using male and female Spargue-Dawley rats. Rats were orally administered the DMWE at dose levels of 0, 250, 500, 1,000, and 2,000 mg/kg body weight (BW) for four weeks. For experimental period, clinical signs and the number of deaths were examined, and feed intake and BW of all experimental animals were measured once a week for four weeks. At the end of the experiment, blood samples were collected from all rats, and all animals were euthanized and autopsies were performed to collect major organs. No dead animals were found during the experimental period. In addition, no differences were found between control and DMWE-treated groups in feed intakes, BW changes, organ weights, clinical signs, hematological parameters, and serum biochemical parameters. The results of this study provided evidence that oral administration of DMWE at the dose of 2,000 mg/kg BW is safe in rats and may not exert severe toxic effects.

In this study, the acute toxicity of Dendropanax morbiferus H.Lév leaf hot-water extracts (DMWE) was examined in male and female ICR mice. Mice were orally administered the DMWE at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no significant differences in change of BW between control and all DMWE treated-groups. In hematological and blood biochemical analysis, none of the parameters were affected by the DMWE. Similarly, there were no significant effects on markers for liver and kidney functions in all DMWE treated-groups. Since there were no adverse effects of the DMWE in single oral toxicity tests, even at the highest doses, it was concluded that the lethal dose 50 (LD50) of DMWE is estimated at > 2,000 mg/kg BW.

Oral squamous cell carcinoma (OSCC), which accounts for approximately 90% of oral cancers, has a high rate of local recurrence and a poor prognosis despite improvements in treatment. Exosomes released from OSCC cells promote cell proliferation and metastasis. Although it is clear that the biogenesis of exosomes is mediated by the endosomal sorting complex required for transport (ESCRT) machinery, the gene expression pattern of ESCRT, depending on the cell type, remains elusive. The exosomal release from the human OSCC cell lines, HSC-3 and HSC-4, and their corresponding gefitinib-resistant sub-cell lines, HSC-3/GR and HSC-4/GR, was assessed by western blot and flow cytometry. The levels of ESCRT machinery proteins, including Hrs, Tsg101, and Alix, and whole-cell ubiquitination were evaluated by western blot. We observed that the basal level of exosomal release was higher in HSC-3/GR and HSC-4/GR cells than in HSC-3 and HSC-4 cells, respectively. Long-term gefitinib exposure of each cell line and its corresponding gefitinib-resistant sub-cell line differentially induced the expression of the ESCRT machinery. Furthermore, whole-cell ubiquitination and autophagic flux were shown to be increased in gefitinib-treated HSC-3 and HSC-4 cells. Our data indicate that the expression patterns of the ESCRT machinery genes are differentially regulated by the characteristics of cells, such as intracellular energy metabolism. Therefore, the expression patterns of the ESCRT machinery should be considered as a key factor to improve the treatment strategy for OSCC.

This study compared Korean adult learners’ English speech in dialogic and monologic tasks, measuring 57 college students’ oral proficiency in terms of holistic and analytic grades. The statistical analyses were focused on two questions: 1) how much do the holistic grades of oral proficiency and analytic grades of the four linguistic features function differently across the tasks? and 2) which linguistic feature has the strongest correlation with the holistic grades of English oral proficiency? The study found significant differences between the two tasks in five aspects (English oral proficiency, topic development, fluency, range, and accuracy). It also showed that a monologic task resulted in lower achievements in those five aspects. In the comparison of the correlations with English proficiency, the range reached the top in both tasks, followed by topic development. The study provides some helpful information regarding which types of speech tasks and linguistic features of EFL oral proficiency are more desirable for targeting in teaching and assessment.

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer and is associated with high recurrence, poor treatment, and low survival rates. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates the response to hypoxia, a major factor in the tumor microenvironment that affects tumor development and progression in various cancer types. However, microRNA (miRNA) sequence analysis revealed that only a few miRNAs targeting HIF-1α had been discovered. In the present study, we investigated HIF-1α expression in OSCC and the effect of HIF-1α-targeting miRNAs on the progression and metastatic potential of OSCC. We analyzed public databases to explore which miRNAs target HIF-1α expression. In addition, the expression of proteins involved in the cell cycle, proliferation, and apoptosis in HSC-2 cells was analyzed after miRNA-126 mimic treatment. Furthermore, to investigate the effect of miRNA-126 on the proliferation and invasion ability of OSCC cells, 5-ethynyl-2′-deoxyuridine and Transwell assays were performed. The activities of MMP-2 and MMP-9 were evaluated via gelatin zymography. Our results showed that miRNA-126, which targets HIF-1α, enhances OSCC cell proliferation by regulating the cell cycle and reinforces the cell mobility of OSCC via HIF-1α expression. These findings suggest that miRNA-126 may be a novel marker for OSCC treatment and the development of new tools for patients with OSCC.

Iron deficiency is known to be a common nutritional disorder in many countries, especially among children, women of childbearing age and pregnant women. SUNACTIVE Fe-P80 is a new type of iron supplement that applies nanotechnlateology for the purpose of overcoming the disadvantages of food supplements. This study was conducted to investigate the potential adverse effects of a 28-day repeated oral dose of SUNACTIVE Fe-P80 in rats. SUNACTIVE Fe-P80 was administered once daily by gavage to Sprague-Dawley rats for 28 days at doses of 0, 500, 1,000, and 2,000 mg/kg/day. Additional recovery groups from the control and highdose groups were observed for a 14-day recovery period. At the scheduled termination, the animals were sacrificed, their organs weighed, and blood samples collected. There were no treatment-related effects in the context of clinical signs, body weight, food intake, ophthalmoscopy, urinalysis, necropsy findings, organ weights, and hematologic, serum biochemical and histopathological parameters at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of SUNACTIVE Fe-P80 was ≥ 2,000 mg/kg/day in both the sexes, and no target organs were identified. Thus, the results suggest that SUNACTIVE Fe-P80 is relatively safe, as no treatment-related adverse effects were observed following a 28-day repeated oral dose experiment.

목적 : 본 연구는 구강운동촉진기술(Oral Motor Facilitation Technique; OMFT)이 뇌성마비의 섭식기능 증진에 미치는 효과를 확인하기 위한 목적으로 시행되었다. 연구방법 : 평균 연령 5.88 ± 1.98세(범위 3~10세) 연하장애를 동반한 21명의 뇌성마비를 대상으로 하 였다. 주 1회, 30분, 16주(16회) OMFT를 제공하였다. OMFT가 섭식기능에 미치는 효과 확인을 위해 먹기와 마시기 기능 분류 체계(Eating and Drinking Ability Classification System; EDACS)로 측정 하였다. OMFT를 개발한 연구자 1인이 평가를 포함한 전체 과정을 진행하였으며 아동의 섭식기능에 따 라 개별적인 접근이 적용되었다. OMFT 치료 전, 8주, 16주 총 3회 EDACS 평가를 통해 치료 기간별 치료 효과 차이를 프리드만 검정과 윌콕슨 부호 검정을 통해 검정 및 사후 검정을 진행하였다. 결과 : 16주의 OMFT 중재 후 뇌성마비 아동의 섭식기능(EDACS 단계)은 유의미하게 향상되었다. 16주 의 치료 기간이 8주에 비하여 섭식기능 향상에 효과적이었다. 반면 독립적인 먹기(EDACS 도움 단계) 는 변화가 없었다. 연령, Gross Motor Function Classification System(GMFCS) 단계, 뇌성마비 분류 등 요인별 사후검정 결과 EDACS 단계에서는 7~8세, GMFCS Ⅲ단계, 무정위형을 제외한 모든 변인에 서 치료 기간에 따라 유의미한 차이를 보였다. 그러나 EDACS 도움 단계에서의 유의미한 차이는 없었 다. 결론 : OMFT는 뇌성마비의 섭식기능 향상에 효과적인 구강운동치료법으로 확인되었다. 적정 기간의 OMFT 적용을 통해 임상에서 다양한 연령, 운동기능 상태, 병변 부위의 뇌성마비 아동의 섭식기능 향상 을 위한 종합적인 구강운동치료 활용하는데 도움이 될 것으로 기대된다.

Porphyromonas gingivalis, a major pathogen of chronic periodontitis, colonizes in subgingival crevice and affects surrounding oral tissues, especially in periodontitis patients. Oral cancer mainly occurs in old-aged persons, and are exposed to the P. gingivalis, released from periodontitis, one of the most common inflammatory disease of oral cavity. Thus oral cancer cells may be infected with P. gingivalis, and its biologic behavior are autologously and/or heterogeneously modulated by altering gene expression. Exosomes which are derived from cells contain not only coding genes but also non-coding RNAs such as long non-coding RNAs, miRNA, and piRNAs. Here, to investigate the effect of P. gingivalis on oral cancer cells and to gain insight into the crosstalk between inflammatory signal from tumor microenvironment and oral cancer, we observed miRNA profiles of exosomes from P. gingivalis–infected oral cancer cells. Upregulation of 6 miRNAs, miR-203-3p, miR-6516-3p, miR-483-5p, miR-1275, miR-8485, and miR-19a-3p, were observed whereas 14 miRNAs including let-7a-3p, miR-106a-5p were downregulated. In addition, KEGG pathway analysis using the upregulated- and downregulated- miRNAs showed association with cell adhesion molecules pathway and ECM-receptor interaction pathway, respectively. These findings suggest that P. gingivalis could modulate biologic behavior of oral cancer cells through changes of exosomal miRNAs.

A number of studies have been conducted to confirm the preventive effect of xylitol on dental caries as a whole or partial alternative to dietary sugars. This study reviewed the oral health effects of xylitol on the prevention mechanism of dental caries, the prevention of dental caries, the inhibition of mother-to-child transmission, and the oral health effects in the elderly based on existing studies on the oral health of xylitol. Carbohydrates and dietary sugars in food are fermented by acid-producing microorganisms in the mouth and produce dental plaque and acid, which cause dental caries. However, most dental decay-causing bacteria cannot produce acids by metabolizing xylitol. Xylitol, stored in cells as a non-metabolizable metabolite by Streptococcus mutans (S. mutans), affects bacterial glucose metabolism and inhibits bacterial growth. Xylitol consumption also reduces the amount of plaque and the population of S. mutans in both plaque and saliva. In addition, xylitol acts in the remineralization process. Xylitol has been confirmed to effectively prevent dental caries, inhibit mother-to-child transmission of MS, prevent dental caries, and increase salivary flow in the elderly. In conclusion, xylitol is an adequate sugar substitute for dental health, from infants to the elderly. For future studies, the researchers recommend reviewing the effects of xylitol on the oral and intestinal microbial environment and the side effects of excessive intake.

Background : Mucoepidermoid carcinoma (MEC) is the most common primary epithelial malignant salivary gland tumor in both adults and children. Histological grading of MEC is subjective, but plays an important role in predicting patient prognosis. Immunohistochemistry can accurately diagnose diseases and help with treatment and prognosis. The review of this paper was intended to be helpful in the differential diagnosis of mucinous epidermoid carcinoma. Methods : A PubMed search was carried out. Well-known biomarkers for mucoepidermoid carcinoma were searched in PubMed, and their differences with oral squamous cell carcinoma were compared. Results : When PubMed searched “oral mucoepidermoid carcinoma, biomarker”, a total of 241 papers were found, among which cytokeratin(22), Muc1(membrane-bound mucin1, 9), Muc4( membrane-bound mucin4, 6), Muc5ac (membrane-bound mucin5ac, 4), Muc5b (membrane-bound mucin5b, 3), p63 (15), PCNA (15), p53 (20), EGFR (Epidermal growth factor receptor, 21), c-erbB2 (HER2, 14), and pAKT (2) were searched and investigated. The biomarkers retrieved above were compared with those expressed in squamous cell carcinoma. Conclusion : Due to the above biomarkers, it is possible to classify mucoepidermoid carcinoma and differentiate it from other salivary gland tumors or oral squamous cell carcinoma.

Diabetic mellitus (DM) is a carbohydrate metabolic disorder that involves high blood sugar because insulin works abnormally. Type 2 diabetes accounts for most of them. However, diabetes treatments such as GLP-1 and DPP-4 inhibitors commonly caused side effects including gastrointestinal disorders. Grifola frondosa (G. frondosa) revealed various pharmacological effects in recent studies. It has a variety of anti-cancer polysaccharides through host-mediated mechanisms. D-fraction in G. frondosa has apoptotic effects, promoting myeloid cell proliferation and differentiation into granulocytes-macrophages. It has also been shown to reduce the survival rate of breast cancer cells. Though, no further study has been conducted on the specific effects of G. frondosa in the db/db mouse. Therefore, we would like to research the blood glucose improving effect of G. frondosa, a natural material, in type 2 diabetes model mouse, in this study. G. frondosa was administered to the disease model mouse (BKS.Cg-+Leprdb/+Leprdb/OlaHsd) for 8 weeks to monitor weight and blood glucose changes every week. And we evaluated anti-diabetes effects by checking biomarker changes shown through blood. Experiment did not show statistically significant weight differences, but control groups showed significantly higher weight gain than G. frondosa administered groups. We collected blood from the tail veins of the db/db mouse each week. As a result, the lowest blood sugar level was shown in the 500 mg/ kg group of G. frondosa. Glucose in the blood was examined with HBA1c, and 7.8% was shown in the 500 mg/kg administration group, lower than in other groups. These results suggest the potential improvements of diabetes in G. frondosa.

Leiomyosarcoma is malignant mesenchymal tumor of smooth muscle and commonly encountered in the gastrointestinal tract of dogs. However, primary canine leiomyosarcoma in oral cavity is rare due to lack of smooth muscle in the oral tissue. A 13-year-old, neutered male Poodle presented a hard and immobile mass on the left maxilla. Imprinting cytology from the mass as well as fine-needle aspirated cytology from the left scapular lymph node revealed predominant spindle cells met malignancy criteria of the tumors, including coarse chromatin, high N/C ratio, nuclear molding, macro/multi-nucleoli with cigar-shaped nucleus. Radiography of the skull showed lysis of the nasopalatine bone, and mineral radiopacity in the mass. Computed tomography showed soft tissue attenuating mass from the left incisor teeth to the left retrobulbar space with loss of nasopalatine bone and medial wall of orbit. The histopathological examination showed irregularly arranged malignant spindle-shaped cells with oval or elongated nuclei. The nucleolus is distinct and moderate cellular polymorphism is observed. Mitotic figures are occasionally observed. The tumor cells are positive to vimentin, desmin, α-smooth muscle actin when immunohistochemistry was performed, and in Masson’s trichrome stain, tumor cells are stained as red. Overall, histopathologic exam and immunohistochemistry confirmed canine oral leiomyosarcoma. Because of the poor prognosis, the owner did not consent further treatment.

Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro . However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca2+ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca2+ ([Ca2+]i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca2+]i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca2+ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca2+ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca2+]i mobilization, we identified modified expression levels of Ca2+ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca2+]i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.