Journal of Oral Biosciences最新文献_第7页

Oral microbiome profiles of gingivitis and periodontitis by next-generation sequencing among a group of hospital patients in Korea: A cross-sectional study 通过新一代测序分析韩国一组医院患者牙龈炎和牙周炎的口腔微生物组概况：一项横断面研究

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-11-23 DOI: 10.1016/j.job.2024.100591

Yeon-Hee Lee , Hae Jeong Park , Su-Jin Jeong , Q-Schick Auh , Junho Jung , Gi-Ja Lee , Seungil Shin , Ji-Youn Hong

Objectives

The oral microbiome plays an important role in the development and progression of periodontal disease. The purpose of this study was to compare microbial profiles of oral cavities in good health, with gingivitis, and in a state of periodontitis, and to identify novel pathogens involved in periodontal diseases.

Methods

One hundred and two participants, including 33 healthy controls, 41 patients with gingivitis, and 28 patients with periodontitis, were included in this cross-sectional study. Salivary oral microbiomes were investigated using 16S rRNA metagenomic sequencing, and the microbial profiles of each group were compared using age- and sex-adjusted general linear models.

Results

The abundance of amplicon sequence variants and Chao1 diversity were significantly elevated in the gingivitis and periodontitis groups relative to healthy controls (p = 0.046). Based on linear discriminant analysis (LDA) scores (>2), Tenericutes, Mollicutes, Mycoplasmatales, Mycoplasmataceae, Mycoplasma, Bacteroidaceae, and Phocaeicola were significantly enriched in the gingivitis group, and Synergistetes, Synergistia, Synergistales, Synergistaceae, Fretibacterium, Sinanaerobacter, and Filifactor were enriched in the periodontitis group. The relative abundances of Fretibacterium fastidiosum, Sinanaerobacter chloroacetimidivorans, and Filifactor alocis (q = 0.008, all bacteria) were highest in the periodontitis group and lowest in the control group. The relative abundance of Treponema denticola was significantly elevated in the periodontitis group compared to the other two groups (q = 0.024).

Conclusions

Oral microbiomes differed between groups. T. denticola, F. fastidiosum, S. chloroacetimidivorans and F. alocis were significantly more abundant in the periodontitis group than in the control group. Additionally, the abundance of T. denticola and F. fastidiosum in the periodontitis group was significantly different from that in the gingivitis group.

目的：口腔微生物组在牙周病的发生和发展中起着重要作用。本研究的目的是比较健康口腔、牙龈炎口腔和牙周炎口腔的微生物特征，并确定与牙周疾病有关的新型病原体：这项横断面研究的参与者有 112 人，包括 33 名健康对照者、41 名牙龈炎患者和 28 名牙周炎患者。采用 16S rRNA 元基因组测序法对唾液口腔微生物组进行了调查，并采用年龄和性别调整后的一般线性模型对各组的微生物谱进行了比较：结果：与健康对照组相比，牙龈炎组和牙周炎组的扩增子序列变异丰度和 Chao1 多样性明显升高（p = 0.046）。根据线性判别分析（LDA）得分（>2），龈炎组明显富集了Tenericutes、Mollicutes、Mycoplasmatales、Mycoplasmataceae、Mycoplasma、Bacteroidaceae和Phocaeicola，牙周炎组富集了Synergistetes、Synergistia、Synergistales、Synergistaceae、Fretibacterium、Sinanaerobacter和Filifactor。牙周炎组中快断杆菌（Fretibacterium fastidiosum）、氯乙酰亚氨基单胞菌（Sinanaerobacter chloroacetimidivorans）和丝状杆菌（Filifactor alocis）（q = 0.008，所有细菌）的相对丰度最高，而对照组最低。与其他两组相比，牙周炎组中牙髓震颤素的相对丰度显著升高（q = 0.024）：结论：不同组的口腔微生物组存在差异。牙周炎组中的牙周脓杆菌、F. fastidiosum、S. chloroacetimidivorans 和 F. alocis 的数量明显多于对照组。此外，牙周炎组中牙髓炎杆菌和F. fastidiosum的数量也与牙龈炎组明显不同。

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引用次数: 0

Anti-fungal effects of slightly acidic electrolyzed water on Candida species 微酸性电解水对念珠菌的抗真菌作用

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-11-07 DOI: 10.1016/j.job.2024.10.005

Chia-Hsin Wu , Yoshino Kaneyasu , Kanako Yano , Hideo Shigeishi , Honami Kitasaki , Tomoko Maehara , Yoshie Niitani , Toshinobu Takemoto , Yuichi Mine , Mi Nguyen-Tra Le , Miki Kawada-Matsuo , Hitoshi Komatsuzawa , Kouji Ohta

Objectives

Slightly acidic electrolyzed water (SAEW) is produced by electrolyzing 2–6% diluted hydrochloric acid in a membrane-less chamber, resulting in 5.0–6.5 pH, and can be applied to various foods as a disinfectant. Although SAEW has shown to have bactericidal activity, the details of its anti-fungal effects towards Candida species remain unknown. Therefore, we examined the fungicidal effects of SAEW on Candida spp. and biofilms on acrylic resins.

Methods

The fungicidal effects of SAEW on Candida spp. at different reaction times and total numbers of colonies in culture plates were examined. Subsequently, SAEW was added to Candida spp. biofilms formed on polystyrene plates, and adenosine triphosphate (ATP) in SAEW was measured to examine its fungicidal effects towards Candida spp. biofilms. The fungicidal effect of SAEW on Candida spp. biofilms was determined by counting the number of colonies on the acrylic resin after adding SAEW.

Results

SAEW completely killing activity within 1 min with the tested Candida spp. C. albicans and C. glabrata ATP were increased 5 min after adding SAEW compared with the controls, suggesting the removal of biofilm. Of the C. albicans on acrylic resin, >99.9%were killed by SAEW compared to their levels in deionized distilled water (DW) (76.2 × 10²/mL and 43.3 × 10²/mL, respectively). Similarly, 93.1% of C. glabrata were killed by SAEW compared to DW (159.3x102/mL).

Conclusions

SAEW may be useful in preventing oral candidiasis as part of oral care.

目的：微酸性电解水（SAEW）是通过在无膜室中电解 2-6% 的稀盐酸而产生的，pH 值为 5.0-6.5，可用作各种食品的消毒剂。虽然 SAEW 具有杀菌活性，但其对念珠菌的抗真菌效果尚不清楚。因此，我们研究了 SAEW 对念珠菌属和丙烯酸树脂上的生物膜的杀菌效果：方法：研究 SAEW 在不同反应时间下对念珠菌属的杀菌效果以及培养皿中的菌落总数。随后，在聚苯乙烯板上形成的念珠菌生物膜中加入 SAEW，测定 SAEW 中的三磷酸腺苷（ATP），以考察其对念珠菌生物膜的杀菌效果。加入 SAEW 后，通过计数丙烯酸树脂上的菌落数量来确定 SAEW 对念珠菌属生物膜的杀菌效果：结果：SAEW 在 1 分钟内完全杀死了被测试的念珠菌属。与对照组相比，加入 SAEW 5 分钟后，白色念珠菌和光滑念珠菌的 ATP 增加，表明生物膜已被清除。与它们在去离子水（DW）中的含量（分别为 76.2x102/mL 和 43.3x102/mL）相比，SAEW 杀死了丙烯酸树脂上 99.9% 以上的白僵菌。同样，与去离子水（159.3x102/mL）相比，SAEW杀死了93.1%的水虱：结论：作为口腔护理的一部分，SAEW 可用于预防口腔念珠菌病。

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引用次数: 0

Development of a new antibody drug to treat congenital tooth agenesis 开发治疗先天性牙齿缺失的新型抗体药物。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-10-09 DOI: 10.1016/j.job.2024.10.002

K. Takahashi , H. Kiso , E. Mihara , J. Takagi , Y. Tokita , A. Murashima-Suginami

Background

This study aimed to develop a therapeutic agent promoting teeth regeneration from autologous tissues for congenital tooth agenesis, specifically for hypodontia (≤5 missing congenital teeth, 10% prevalence) and oligodontia (≥6 missing congenital teeth, 0.1% prevalence).

Highlight

We studied mice genetically deficient in the USAG-1 protein, an antagonist of BMP/Wnt which forms excessive teeth. We identified USAG-1 as a target molecule for increasing the number of teeth. Crossing USAG-1-deficient mice with a congenital tooth agenesis model restored tooth formation. We produced anti-USAG-1 neutralizing antibodies as potential therapeutic agents for the treatment of congenital tooth agenesis. Mice anti-USAG-1 neutralizing antibodies can potentially rescue the developmentally arrested tooth germ programmed to a certain tooth type. A humanized anti-USAG-1 antibody was developed as the final candidate.

Conclusion

Targeting USAG-1 shows promise for treating missing congenital tooth. Anti-USAG-1 neutralizing antibodies have been developed and will progress towards clinical trials, which may regenerate missing congenital teeth in conditions, such as hypodontia and oligodontia. The protocol framework for a phase 1 study has been finalized, and preparation for future studies is underway.

研究背景本研究旨在开发一种促进自体组织牙齿再生的治疗剂，用于治疗先天性牙齿缺失，特别是牙列不齐（先天性牙齿缺失≤5颗，发病率为10%）和少牙症（先天性牙齿缺失≥6颗，发病率为0.1%）：我们研究了基因缺失 USAG-1 蛋白的小鼠，它是 BMP/Wnt 的拮抗剂，会形成过多的牙齿。我们发现 USAG-1 是增加牙齿数量的目标分子。将 USAG-1 缺失小鼠与先天性牙齿缺失模型杂交，可恢复牙齿的形成。我们制备了抗 USAG-1 中和抗体，作为治疗先天性牙齿缺失的潜在药物。小鼠抗USAG-1中和抗体有可能挽救发育停滞的牙胚，使其形成某种牙型。结论：靶向USAG-1有望用于治疗先天性牙齿缺失：结论：以 USAG-1 为靶点有望治疗先天性牙齿缺失。抗USAG-1中和抗体已经开发出来，并将进入临床试验阶段，这可能会使缺失的先天性牙齿再生，如牙列不齐和少牙症。第一阶段研究的方案框架已经确定，未来研究的准备工作正在进行中。

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引用次数: 0

Herbal medicine Ninjinyoeito inhibits RANKL-induced osteoclast differentiation and bone resorption activity by regulating NF-κB and MAPK pathway 中药 Ninjinyoeito 通过调节 NF-kB 和 MAPK 通路，抑制 RANKL 诱导的破骨细胞分化和骨吸收活性。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-10-02 DOI: 10.1016/j.job.2024.09.007

Kaung Htike , Kunihiro Yoshida , Takanori Eguchi , Katsuki Takebe , Xueming Li , Yaxin Qu , Eiko Sakai , Takayuki Tsukuba , Kuniaki Okamoto

Objectives

Osteoporosis is a systemic bone metabolism disorder characterized by decreased bone mass and strength. Osteoclasts (OCs) are giant multinucleated cells that regulate bone homeostasis by degrading bone matrix. Excessive OC differentiation and activity can lead to serious bone metabolic disorders including osteoporosis. Current treatments, including antiresorptive drugs, exert considerable adverse effects, including jaw osteonecrosis. Herbal medicines, such as Ninjinyoeito (NYT), may also offer efficacy, but with fewer adverse effects. In this study, we investigated NYT's effects on osteoclastogenesis.

Methods

Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were performed to examine NYT's effects on OC differentiation and function. OC-related gene expression at mRNA and protein levels was investigated to confirm NYT's inhibitory action against osteoclastogenesis. We also demonstrated involvement of signaling pathways mediated by IκBα and mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38] and showed nuclear translocation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and nuclear factor kappa B (NF-κB) p65 during osteoclastogenesis.

Results

TRAP staining and bone resorption assays confirmed that NYT significantly inhibited OC differentiation and function. Western blot and RT-PCR results showed that NYT ameliorated osteoclastogenesis by suppressing mRNA and protein level expression of OC-related genes. Moreover, blots and immunocytochemistry (ICC) data clarified that NYT abrogates signaling pathways mediated by IκBα and MAPK (ERK, JNK, p38), and demonstrated nuclear translocation of NFATc1 and NF-κB p65 during OC differentiation.

Conclusions

These findings suggest NYT is an alternative therapeutic candidate for treating osteoporosis.

目的：骨质疏松症是一种全身性骨代谢疾病，以骨量和骨强度下降为特征。破骨细胞（OC）是一种巨大的多核细胞，通过降解骨基质来调节骨平衡。过度的 OC 分化和活动可导致严重的骨代谢紊乱，包括骨质疏松症。目前的治疗方法，包括抗骨质吸收药物，会产生相当大的不良影响，包括颌骨骨坏死。中药，如九节鞭（NYT），也可能具有疗效，但不良反应较少。在这项研究中，我们调查了NYT对破骨细胞生成的影响：方法：采用耐酒石酸磷酸酶（TRAP）染色法和骨吸收测定法研究 NYT 对 OC 分化和功能的影响。研究了OC相关基因在mRNA和蛋白质水平上的表达，以证实NYT对破骨细胞生成的抑制作用。我们还证明了IκBα和丝裂原活化蛋白激酶（MAPK）[细胞外信号调节激酶（ERK）、c-Jun N-末端激酶（JNK）和p38]介导的信号通路的参与，并显示了在破骨细胞生成过程中活化T细胞胞浆核因子1（NFATc1）和核因子卡巴B（NF-κB）p65的核转位：结果：TRAP染色和骨吸收试验证实，NYT能显著抑制OC的分化和功能。Western印迹和RT-PCR结果显示，NYT通过抑制OC相关基因的mRNA和蛋白水平表达，改善了破骨细胞的生成。此外，印迹和免疫细胞化学（ICC）数据表明，NYT抑制了由IκBα和MAPK（ERK、JNK、p38）介导的信号通路，并证明了在OC分化过程中NFATc1和NF-κB p65的核转位：这些研究结果表明，NYT是治疗骨质疏松症的另一种候选疗法。

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引用次数: 0

Potassium nitrate suppresses hyperactivities of Vc neurons of the model with dentin hypersensitivity 硝酸钾可抑制牙本质过敏模型 Vc 神经元的过度活动。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-19 DOI: 10.1016/j.job.2024.09.005

Shiori Sugawara , Koichi Iwata , Toshiki Takamizawa , Masashi Miyazaki , Masayuki Kobayashi

Objective

Potassium nitrate (KNO₃) suppresses nociception induced by dental hypersensitivity (HYS). We aimed to examine the effects of KNO₃ on the neural activity of the trigeminal spinal subnucleus caudalis (Vc) in HYS model rats.

Methods

KNO₃ or vehicle was applied to the exposed dentin of HYS rats for 3 days. c-Fos expression and neuronal activity in the Vc after acetone treatment for cold stimulation were examined to evaluate the effects of KNO₃ application on dentin.

Results

The number of c-Fos-immunoreactive cells in the Vc was lower in the group that received KNO₃ (KNO₃ group) than in the group that received vehicle (control group). Spike firing of Vc neurons in response to cold stimulation of the dentin was recorded before and after KNO₃ application to the cavity, and the increased neural activity was effectively suppressed by KNO₃ application. Scanning electron microscopy revealed that the dentin tubules were not occluded by deposits in any of the groups.

Conclusions

KNO₃-induced suppression of Vc neuronal activity does not involve physical occlusion of the dentin tubules but likely involves suppression of Aδ or C-fiber activities in the tooth pulp, resulting in the suppression of Vc neuronal activities.

目的硝酸钾（KNO3）能抑制牙科超敏反应（HYS）引起的痛觉。我们旨在研究 KNO3 对 HYS 模型大鼠三叉神经脊髓尾下核（Vc）神经活动的影响：方法：在 HYS 大鼠暴露的牙本质上涂抹 KNO3 或载体 3 天，检测丙酮处理冷刺激后 Vc 中 c-Fos 的表达和神经元活性，以评估涂抹 KNO3 对牙本质的影响：结果：接受 KNO3 治疗组（KNO3 组）的 Vc 中 c-Fos 免疫反应细胞数量低于接受药物治疗组（对照组）。在龋洞中施用 KNO3 之前和之后，记录了 Vc 神经元对牙本质冷刺激的尖峰点燃反应，施用 KNO3 有效地抑制了神经活动的增加。扫描电子显微镜显示，各组的牙本质小管均未被沉积物堵塞：结论：KNO3 诱导的 Vc 神经元活动抑制并不涉及牙本质小管的物理闭塞，而可能涉及牙髓中 Aδ 或 C 纤维活动的抑制，从而导致 Vc 神经元活动的抑制。

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引用次数: 0

Comparison of rhythmic jaw muscle activities induced by electrical stimulations of the corticobulbar tract during rapid eye movement sleep with those during wakefulness and non-rapid eye movement sleep in freely moving Guinea pigs 自由活动的豚鼠在快速眼动睡眠时与清醒和非快速眼动睡眠时通过电刺激皮质束诱发的下颌肌肉节律性活动的比较。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-18 DOI: 10.1016/j.job.2024.09.004

Makoto Higashiyama , Yuji Masuda , Ayano Katagiri , Hiroki Toyoda , Masaharu Yamada , Atsushi Yoshida , Takafumi Kato

Objective

Rhythmic jaw muscle activities (RJMAs) occur during rapid eye movement (REM) sleep in humans and animals even though motoneurons are inhibited. The present study compared the characteristics of jaw muscle activities induced by electrical microstimulations of the corticobulbar tract (CT) during REM sleep with those during wakefulness and non-REM sleep.

Methods

Eleven guinea pigs were surgically prepared for polygraphic recordings with the implantation of a stimulating electrode. Long- and short-train repetitive electrical microstimulations were applied to the CT under freely moving conditions. The response rate, latency, burst amplitude, and cycle length in the digastric muscle were calculated and cortical and cardiac activities were quantified.

Results

Long-train microstimulations induced RJMAs in the digastric muscle followed by masseter muscle activity during wakefulness and non-REM sleep and only induced rhythmic digastric muscle activity during REM sleep. The response rate of RJMAs and the burst amplitude of digastric muscles were significantly lower during REM sleep than during wakefulness and non-REM sleep. However, response latency did not significantly differ between REM sleep and wakefulness. Transient cortical and cardiac changes were associated with RJMAs induced during non-REM sleep, but not during REM sleep. Short-train microstimulations induced a short-latency digastric response, the amplitude of which was significantly lower during REM sleep than during non-REM sleep and wakefulness.

Conclusions

These results suggest that the masticatory CPG was activated by electrical CT stimulations independently of the motoneuron inhibitory system during REM sleep.

目的：人类和动物在快速眼动睡眠（REM）期间会出现有节奏的下颌肌肉活动（RJMA），即使运动神经元受到抑制。本研究比较了快速眼动睡眠期与清醒和非快速眼动睡眠期皮质束（CT）电微刺激诱发的下颌肌肉活动的特征：方法：对 11 只豚鼠进行手术准备，植入一个刺激电极以进行多图记录。在自由移动的条件下，对 CT 进行长程和短程重复微电刺激。结果：结果：在清醒状态和非快速眼动睡眠状态下，长程微刺激可诱发掘胸肌的 RJMAs，随后是咀嚼肌活动，而在快速眼动睡眠状态下仅诱发有节律的掘胸肌活动。在快速动眼期睡眠中，RJMA 的反应率和指阔肌的爆发振幅明显低于清醒和非快速动眼期睡眠。然而，快速动眼期睡眠和清醒时的反应潜伏期并无明显差异。短暂的皮层和心脏变化与非快速动眼期睡眠时诱导的 RJMAs 有关，但与快速动眼期睡眠时无关。短程微刺激诱发了短时咀嚼反应，其振幅在快速动眼期睡眠中明显低于非快速动眼期睡眠和清醒时：这些结果表明，在快速动眼睡眠期间，咀嚼CPG是由CT电刺激激活的，与运动神经元抑制系统无关。

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引用次数: 0

Antihypertensive agent losartan promotes tongue squamous cell carcinoma cell proliferation via EGFR/ERK1/2/cyclin D1 signaling axis 降压药洛沙坦通过表皮生长因子受体/ERK1/2/环素D1信号轴促进舌鳞状细胞癌细胞增殖

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-07 DOI: 10.1016/j.job.2024.09.003

Luo-Yun Wu , Bor-Chyuan Su , Hsin-Hsien Yu , Chih-Cheng Cheng , Chia-Chi Tsai , Pei-Ling Hsu , Chu-Wan Lee

Objective

To study the effects of losartan, an angiotensin II receptor blocker, in the SCC4 and SCC25 human tongue squamous cell carcinoma cell lines.

Methods

Cell proliferation was measured by MTS/PMS activity and trypan blue exclusion assays. The levels of the cell proliferation marker, cyclin D1, were analyzed by western blotting. Apoptosis was assessed by caspase-3 activation and Annexin V-FITC/propidium iodide double staining. Activation of epidermal growth factor receptor (EGFR) and ERK1/2 was validated by western blotting.

Results

Moderate concentrations of losartan enhanced the proliferation of SCC4 and SCC25 cells. However, high losartan concentrations induced apoptosis in SCC4 cells. Losartan activated the EGFR/ERK1/2/cyclin D1 signaling axis, which in turn promoted cell proliferation. Afatinib (EGFR inhibitor) and U0126 (ERK1/2 inhibitor) abolished losartan-induced cell proliferation. In contrast, UC2288 (p21 inhibitor) enhanced it.

Conclusions

Losartan exhibited dual effects on tongue squamous cell carcinoma cells. Moderate losartan concentrations facilitated cell proliferation, whereas high concentrations induced cytotoxicity in tongue carcinoma cells.

目的研究血管紧张素 II 受体阻滞剂洛沙坦对 SCC4 和 SCC25 人舌鳞癌细胞系的影响：方法：细胞增殖通过 MTS/PMS 活性和胰蓝排除试验进行测定。细胞增殖标记物细胞周期蛋白 D1 的水平通过 Western 印迹法进行分析。细胞凋亡通过 caspase-3 活化和 Annexin V-FITC/ 碘化丙啶双染色进行评估。表皮生长因子受体（EGFR）和ERK1/2的活化通过Western印迹进行验证：结果：中等浓度的洛沙坦能增强 SCC4 和 SCC25 细胞的增殖。然而，高浓度的洛沙坦可诱导 SCC4 细胞凋亡。洛沙坦激活了表皮生长因子受体/ERK1/2/环素D1信号轴，进而促进了细胞增殖。阿法替尼（表皮生长因子受体抑制剂）和 U0126（ERK1/2 抑制剂）抑制了洛沙坦诱导的细胞增殖。与此相反，UC2288（p21 抑制剂）却能促进细胞增殖：结论：洛沙坦对舌鳞癌细胞具有双重作用。结论：洛沙坦对舌鳞癌细胞具有双重作用，适度浓度的洛沙坦可促进细胞增殖，而高浓度的洛沙坦可诱导舌癌细胞产生细胞毒性。

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引用次数: 0

Productions of Th2 cytokines, IL-4 and IL-10, were enhanced via the function of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells treated with caffeic acid phenethyl ester 经咖啡酸苯乙酯处理的抗 CD3 抗体刺激的小鼠脾细胞通过 IL-2 的功能增强了 Th2 细胞因子（IL-4 和 IL-10）的产生。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-04 DOI: 10.1016/j.job.2024.09.001

Moe Takahashi , Masako Mizuno-Kamiya , Shifa Rahman , Hanemi Tsuruta , Kumiko Ikeno , Harumi Kawaki , Genjiro Nakamura , Yasunori Muramatsu , Toru Nikaido , Hisakazu Fujita , Nobuo Kondoh

Objectives

Interleukin (IL)-2 production by mouse spleen cells stimulated with an anti-CD3 antibody is significantly enhanced by caffeic acid phenethyl ester (CAPE), a major constituent of Chinese propolis (CP). In this study, we evaluated the functional significance of IL-2 in CAPE-treated activated spleen cells.

Methods

Mouse spleen cells were stimulated with an anti-CD3 monoclonal antibody in the presence of CAPE. Cytokine production was examined using an enzyme-linked immunosorbent assay (ELISA). Messenger RNA expression was examined via reverse transcription quantitative polymerase chain reaction (RT-PCR). IL-2 function was assessed using IL-2 and a neutralizing antibody. Spleen cell subsets were identified and characterized using flow cytometry.

Results

CAPE treatment of anti-CD3 antibody-stimulated spleen cells reduced IFN-γ production, then enhanced IL-2 production, followed by enhancement of IL-4 and IL-10 production. The Th2 cytokine production enhancing effects of CAPE were completely abolished by addition of an anti-IL-2 neutralizing antibody. In the absence of CAPE, exogenously added IL-2 could enhance IL-4 production to a lesser degree, but did not stimulate IL-10 production, in stimulated spleen cells. Interestingly, CAPE significantly reduced the proportions of CD4⁺ and CD8⁺ cells, and increased those of CD4⁻CD8⁻ cells among anti-CD3 stimulated spleen cells, in the presence or absence of anti-IL-2 neutralizing antibody treatment.

Conclusion

CAPE reduced IFN-γ production, then enhanced IL-4 and IL-10 production via the activity of specifically elevated IL-2 in stimulated spleen cells. CAPE exerted these effects in a CD4⁻ CD8⁻ cell specific manner.

目的用抗CD3抗体刺激小鼠脾脏细胞产生的白细胞介素（IL）-2在中国蜂胶（CP）的主要成分咖啡酸苯乙酯（CAPE）的作用下明显增强。本研究评估了经 CAPE 处理的活化脾细胞中 IL-2 的功能意义：方法：在 CAPE 存在的情况下，用抗 CD3 单克隆抗体刺激小鼠脾脏细胞。使用酶联免疫吸附试验（ELISA）检测细胞因子的产生。通过逆转录定量聚合酶链反应（RT-PCR）检测信使 RNA 水平的表达。使用 IL-2 和中和抗体评估 IL-2 功能。使用流式细胞术鉴定和描述脾脏细胞亚群：结果：CAPE 处理抗 CD3 抗体刺激的脾细胞可减少 IFN-γ 的产生，然后增强 IL-2 的产生，接着增强 IL-4 和 IL-10 的产生。加入抗 IL-2 中和抗体后，CAPE 增强 Th2 细胞因子产生的作用完全消失。在没有CAPE的情况下，外源添加的IL-2能在较小程度上促进受刺激脾细胞中IL-4的产生，但不能刺激IL-10的产生。有趣的是，无论有无抗IL-2中和抗体处理，CAPE都能显著降低抗CD3刺激的脾细胞中CD4+和CD8+细胞的比例，并增加CD4-CD8-细胞的比例：结论：CAPE可减少IFN-γ的产生，然后通过特异性升高的IL-2活性增强受刺激脾细胞中IL-4和IL-10的产生。CAPE 以 CD4- CD8- 细胞特异性的方式发挥这些作用。

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引用次数: 0

STAT3 interactome predicts presence of proteins that regulate immune system in oral squamous cell carcinoma STAT3相互作用组预测了口腔鳞状细胞癌中调节免疫系统的蛋白质的存在。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-03 DOI: 10.1016/j.job.2024.09.002

Rajdeep Chakraborty , Pallavi Khodlan , Aidan Tay , Fei Liu

Objectives

Signal transducer and activator of transcription 3 (STAT3) is one of the key proliferation mechanism–related proteins that helps in oral squamous cell carcinoma (OSCC) progression. Immune evasion by STAT3 is mediated by the JAK2/STAT3/PDL1 signaling axis. Based on previous findings, we hypothesized that STAT3-binding partners participate in the inhibition of anti-tumor activity in OSCC.

Methods

A 3D cancer-immune co-culture model was constructed using oral cancer cell lines SCC4, SCC9, SCC25, and CAL27 and normal oral cell line OKF6. The cells were co-cultured with natural killer (NK-92) and Jurkat cells. The target protein STAT3 was chosen based on SWATH data, and co-immunoprecipitation (Co-IP)-based proteomics was conducted. The Co-IP LC-MS/MS output was analysed to determine the protein interaction network, gene ontology, pathway analysis, and protein cluster annotation.

Results

STAT3 in oral cancer cell lines interacts with the epidermal growth factor receptor (EGFR) and other proteins that participate in proliferation and immune mechanisms. Proteome analysis showed that some STAT3-binding proteins found in this study are known immune system regulators.

Conclusion

Overall, STAT3 interactive proteins regulate the immune system in oral squamous cell carcinoma cells.

目的：信号转导和转录激活因子 3（STAT3）是与增殖机制相关的关键蛋白之一，有助于口腔鳞状细胞癌（OSCC）的进展。STAT3 的免疫逃避是由 JAK2/STAT3/PDL1 信号轴介导的。基于之前的研究结果，我们假设 STAT3 结合伙伴参与了 OSCC 抗肿瘤活性的抑制：方法：我们利用口腔癌细胞系 SCC4、SCC9、SCC25 和 CAL27 以及正常口腔细胞系 OKF6 构建了三维癌症-免疫共培养模型。细胞与自然杀伤细胞（NK-92）和Jurkat细胞共培养。根据 SWATH 数据选择了目标蛋白 STAT3，并进行了基于共免疫沉淀（Co-IP）的蛋白质组学研究。对共沉淀 LC-MS/MS 产物进行分析，以确定蛋白质相互作用网络、基因本体、通路分析和蛋白质集群注释：结果：口腔癌细胞系中的 STAT3 与表皮生长因子受体（EGFR）及其他参与增殖和免疫机制的蛋白质相互作用。蛋白质组分析表明，本研究发现的一些 STAT3 结合蛋白是已知的免疫系统调节因子：总之，STAT3 交互蛋白可调节口腔鳞状细胞癌细胞的免疫系统。

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引用次数: 0

Y-27632 enables long-term expansion of mouse submandibular gland epithelial cells via inactivation of TGF-β1/CTGF/p38 and ROCK2/JNK signaling pathway Y-27632 通过抑制 TGF-β1/CTGF/p38 和 ROCK2/JNK 信号通路，实现小鼠下颌下腺上皮细胞的长期扩增。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-09-01 DOI: 10.1016/j.job.2024.08.005

Kichul Kim , Naeun Oh , Hyewon Kim , Sangho Roh

Objectives

This study aimed to investigate the effects of Y-27632 on the long-term maintainence of mouse submandibular epithelial cells (SG-Epis) in vitro and to elucidate the underlying mechanisms.

Methods

The role of the Rho-associated kinase (ROCK) inhibitor Y-27632 in maintaining SG-Epis and its underlying mechanisms were evaluated by examining the in vitro expansion of mouse SG-Epis. Changes in key cellular characteristics, such as proliferation, long-term expansion, and mRNA and protein expression, were assessed in the presence or absence of Y-27632.

Results

Treatment with Y-27632 significantly enhanced the proliferative potential of SG-Epis, preserving Krt8 and Krt14 expression over 17 passages. In the absence of Y-27632, SG-Epis lost their epithelial morphology. However, Y-27632 treatment maintained the epithelial morphology and downregulated mRNA levels of Tgf-β1, Ctgf, and Rock2. Treatment with TGF-β1 indicated that TGF-β/CTGF/p38 signaling is responsible for the maintenance of SG-Epis, while RNA interference studies revealed that ROCK2/c-Jun N-terminal kinase (JNK) signaling is also crucial for SG-Epis proliferation and maintenance.

Conclusions

The TGF-β1/CTGF/p38 and ROCK2/JNK signaling pathways are responsible for SG-Epis proliferation, and Y-27632 treatment effectively inactivates these pathways, enabling long-term in vitro maintenance of SG-Epis. The culture method utilizing Y-27632 provides an effective approach for the in vitro expansion of SG-Epis.

研究目的本研究旨在探讨Y-27632对小鼠颌下腺上皮细胞（SG-Epis）体外长期维持的影响，并阐明其潜在机制：方法：通过研究小鼠SG-Epis的体外扩增，评估了Rho相关激酶（ROCK）抑制剂Y-27632在维持SG-Epis中的作用及其内在机制。在有无Y-27632存在的情况下，对增殖、长期扩增、mRNA和蛋白质表达等关键细胞特征的变化进行了评估：结果：用Y-27632处理可显著增强SG-Epis的增殖潜力，并在17次传代中保持Krt8和Krt14的表达。在没有 Y-27632 的情况下，SG-Epis 会失去上皮形态。然而，Y-27632 处理可维持上皮形态，并下调 Tgf-β1、Ctgf 和 Rock2 的 mRNA 水平。用TGF-β1处理表明，TGF-β/CTGF/p38信号转导是维持SG-Epis的原因，而RNA干扰研究表明，ROCK2/c-Jun N-末端激酶（JNK）信号转导对SG-Epis的增殖和维持也至关重要：结论：TGF-β1/CTGF/p38和ROCK2/JNK信号通路是SG-Epis增殖的原因，Y-27632能有效地使这些通路失活，从而实现SG-Epis的体外长期维持。利用 Y-27632 的培养方法为 SG-Epis 的体外扩增提供了一种有效的方法。

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引用次数: 0