International Journal of Oral Science最新文献_第2页

Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis. 放线菌全身感染导致巨噬细胞中的 Caspase-11 介导的炎性体激活会加重关节炎。

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-08-15 DOI: 10.1038/s41368-024-00315-x

Tokuju Okano, Hiroshi Ashida, Noriko Komatsu, Masayuki Tsukasaki, Tamako Iida, Marie Iwasawa, Yuto Takahashi, Yasuo Takeuchi, Takanori Iwata, Miwa Sasai, Masahiro Yamamoto, Hiroshi Takayanagi, Toshihiko Suzuki

{"title":"Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis.","authors":"Tokuju Okano, Hiroshi Ashida, Noriko Komatsu, Masayuki Tsukasaki, Tamako Iida, Marie Iwasawa, Yuto Takahashi, Yasuo Takeuchi, Takanori Iwata, Miwa Sasai, Masahiro Yamamoto, Hiroshi Takayanagi, Toshihiko Suzuki","doi":"10.1038/s41368-024-00315-x","DOIUrl":"10.1038/s41368-024-00315-x","url":null,"abstract":"Clinical studies have shown that Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans. This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A. actinomycetemcomitans.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"54"},"PeriodicalIF":10.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects. 牙龈卟啉单胞菌中的 Gingipain 通过直接蛋白水解作用降解胰岛素受体，从而导致胰岛素抵抗。

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-08-01 DOI: 10.1038/s41368-024-00313-z

Fen Liu, Bofeng Zhu, Ying An, Zhifei Zhou, Peiying Xiong, Xuan Li, Yang Mi, Tongqiang He, Faming Chen, Buling Wu

{"title":"Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects.","authors":"Fen Liu, Bofeng Zhu, Ying An, Zhifei Zhou, Peiying Xiong, Xuan Li, Yang Mi, Tongqiang He, Faming Chen, Buling Wu","doi":"10.1038/s41368-024-00313-z","DOIUrl":"10.1038/s41368-024-00313-z","url":null,"abstract":"Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR-insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"53"},"PeriodicalIF":10.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-08-01 DOI: 10.1038/s41368-024-00319-7

Yunfan Zhang, Jiale Yan, Yuning Zhang, Hao Liu, Bing Han, Weiran Li

{"title":"Age-related alveolar bone maladaptation in adult orthodontics: finding new ways out.","authors":"Yunfan Zhang, Jiale Yan, Yuning Zhang, Hao Liu, Bing Han, Weiran Li","doi":"10.1038/s41368-024-00319-7","DOIUrl":"10.1038/s41368-024-00319-7","url":null,"abstract":"Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"52"},"PeriodicalIF":10.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models 在头颈外科手术中评估新开发的口腔颌面外科机器人平台（KD-SR-01）：猪模型临床前试验

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-07-10 DOI: 10.1038/s41368-024-00318-8

Zhongkai Ma, Zhiyong Guo, Zhangfan Ding, Chang Cao, Jialu He, Heyi Tang, Yufei Hua, Jiawei Hong, Qiang Shen, Grace Paka Lubamba, Xiaoyi Wang, Zheng Yang, Guiquan Zhu, Chunjie Li

{"title":"Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models","authors":"Zhongkai Ma, Zhiyong Guo, Zhangfan Ding, Chang Cao, Jialu He, Heyi Tang, Yufei Hua, Jiawei Hong, Qiang Shen, Grace Paka Lubamba, Xiaoyi Wang, Zheng Yang, Guiquan Zhu, Chunjie Li","doi":"10.1038/s41368-024-00318-8","DOIUrl":"https://doi.org/10.1038/s41368-024-00318-8","url":null,"abstract":"Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"302 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic high-density lipoprotein (sHDL): a bioinspired nanotherapeutics for managing periapical bone inflammation 合成高密度脂蛋白（sHDL）：一种用于控制根尖周骨炎的生物启发纳米疗法

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-07-02 DOI: 10.1038/s41368-024-00316-w

Renan Dal-Fabbro, Minzhi Yu, Ling Mei, Hajime Sasaki, Anna Schwendeman, Marco C. Bottino

{"title":"Synthetic high-density lipoprotein (sHDL): a bioinspired nanotherapeutics for managing periapical bone inflammation","authors":"Renan Dal-Fabbro, Minzhi Yu, Ling Mei, Hajime Sasaki, Anna Schwendeman, Marco C. Bottino","doi":"10.1038/s41368-024-00316-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00316-w","url":null,"abstract":"Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (i.e., dental pulp tissue), resulting in inflammation and apical bone resorption affecting 50% of the worldwide population, with more than 15 million root canals performed annually in the United States. Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago, such as calcium hydroxide, zinc oxide–eugenol, or even formalin products. Here, we present, for the first time, a nanotherapeutics based on using synthetic high-density lipoprotein (sHDL) as an innovative and safe strategy to manage dental bone inflammation. sHDL application in concentrations ranging from 25 µg to 100 µg/mL decreases nuclear factor Kappa B (NF-κB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500 µg/mL concentration markedly decreases in vitro osteoclastogenesis (P < 0.001), and inhibits IL-1α (P = 0.027), TNF-α (P = 0.004), and IL-6 (P < 0.001) production in an inflammatory state. Notably, sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation, mainly by downregulating at least 3-fold the pro-inflammatory genes, such as Il1b, Il1a, Il6, Ptgs2, and Tnf. In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 ± 0.05) mm3 and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm3 (P = 0.012 3) and (2 443 ± 931) cells (P = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"62 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression. 作者更正：FUT8 介导的 SEMA7A N-糖基化异常促进头颈部鳞状细胞癌的进展。

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-07-02 DOI: 10.1038/s41368-024-00307-x

Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He

引用次数: 0

Stabilization of EREG via STT3B-mediated N-glycosylation is critical for PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma. 通过 STT3B 介导的 N-糖基化稳定 EREG 是头颈部鳞状细胞癌中 PDL1 上调和免疫逃避的关键。

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-07-01 DOI: 10.1038/s41368-024-00311-1

Shengming Xu, Haifeng Wang, Yu Zhu, Yong Han, Liu Liu, Xiangkai Zhang, Jingzhou Hu, Wuchang Zhang, Shengzhong Duan, Jiong Deng, Zhiyuan Zhang, Shuli Liu

{"title":"Stabilization of EREG via STT3B-mediated N-glycosylation is critical for PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma.","authors":"Shengming Xu, Haifeng Wang, Yu Zhu, Yong Han, Liu Liu, Xiangkai Zhang, Jingzhou Hu, Wuchang Zhang, Shengzhong Duan, Jiong Deng, Zhiyuan Zhang, Shuli Liu","doi":"10.1038/s41368-024-00311-1","DOIUrl":"10.1038/s41368-024-00311-1","url":null,"abstract":"Dysregulated Epiregulin (EREG) can activate epidermal growth factor receptor (EGFR) and promote tumor progression in head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underlying EREG dysregulation remain largely unknown. Here, we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues. Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway. Of note, we found that N-glycosylation of EREG was essential for its stability, membrane location, biological function, and upregulation of its downstream target PDL1 in HNSCC. EREG was glycosylated at N47 via STT3B glycosyltransferases, whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG. Consistently, knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells. Moreover, treatment of HNSCC cells with NGI-1, an inhibitor of STT3B, blocked STT3B-mediated glycosylation of EREG, leading to its degradation and suppression of PDL1. Finally, combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo. Taken together, STT3B-mediated N-glycosylation is essential for stabilization of EREG, which mediates PDL1 upregulation and immune evasion in HNSCC.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"47"},"PeriodicalIF":10.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis. 源自上皮细胞的外泌体 miR-17-5p 参与了上皮细胞与成纤维细胞的异常串扰，并诱发了口腔黏膜下纤维化的发展。

IF 10.8 1区医学

International Journal of Oral Science Pub Date : 2024-06-20 DOI: 10.1038/s41368-024-00302-2

Changqing Xie, Liang Zhong, Hui Feng, Rifu Wang, Yuxin Shi, Yonglin Lv, Yanjia Hu, Jing Li, Desheng Xiao, Shuang Liu, Qianming Chen, Yongguang Tao

{"title":"Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis.","authors":"Changqing Xie, Liang Zhong, Hui Feng, Rifu Wang, Yuxin Shi, Yonglin Lv, Yanjia Hu, Jing Li, Desheng Xiao, Shuang Liu, Qianming Chen, Yongguang Tao","doi":"10.1038/s41368-024-00302-2","DOIUrl":"10.1038/s41368-024-00302-2","url":null,"abstract":"Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"16 1","pages":"48"},"PeriodicalIF":10.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nociceptive adenosine A2A receptor on trigeminal nerves orchestrates CGRP release to regulate the progression of oral squamous cell carcinoma 三叉神经上的痛觉腺苷 A2A 受体协调 CGRP 的释放以调节口腔鳞状细胞癌的进展

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-06-18 DOI: 10.1038/s41368-024-00308-w

Lanxin Jiang, Ying Zhou, Shijie Tang, Dan Yang, Yixin Zhang, Jiuge Zhang, Fan Yang, Tong Zhou, Xiaoqiang Xia, Qianming Chen, Lu Jiang, Yuchen Jiang, Xiaodong Feng

{"title":"Nociceptive adenosine A2A receptor on trigeminal nerves orchestrates CGRP release to regulate the progression of oral squamous cell carcinoma","authors":"Lanxin Jiang, Ying Zhou, Shijie Tang, Dan Yang, Yixin Zhang, Jiuge Zhang, Fan Yang, Tong Zhou, Xiaoqiang Xia, Qianming Chen, Lu Jiang, Yuchen Jiang, Xiaodong Feng","doi":"10.1038/s41368-024-00308-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00308-w","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor (A2AR) on trigeminal ganglia. Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"71 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expert consensus on endodontic therapy for patients with systemic conditions 关于对患有全身性疾病的患者进行牙髓治疗的专家共识

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-06-17 DOI: 10.1038/s41368-024-00312-0

Xin Xu, Xin Zheng, Fei Lin, Qing Yu, Benxiang Hou, Zhi Chen, Xi Wei, Lihong Qiu, Chen Wenxia, Jiyao Li, Lili Chen, Zuomin Wang, Hongkun Wu, Zhiyue Lu, Jizhi Zhao, Yuhong Liang, Jin Zhao, Yihuai Pan, Shuang Pan, Xiaoyan Wang, Deqin Yang, Yanfang Ren, Lin Yue, Xuedong Zhou

引用次数: 0