International Journal of Oral Science最新文献

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Age-related alveolar bone maladaptation in adult orthodontics: finding new ways out. 成人正畸中与年龄相关的牙槽骨适应不良:寻找新出路。
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":"<p><p>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.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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":"<p>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 (<i>P</i> = 0.126), better intraoperative bleeding control (<i>P</i> = 0.001), and a significant reduction in cognitive workload (<i>P</i> &lt; 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.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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":"<p>Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (<i>i.e</i>., 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 (<i>P</i> &lt; 0.001), and inhibits IL-1α (<i>P</i> = 0.027), TNF-α (<i>P</i> = 0.004), and IL-6 (<i>P</i> &lt; 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 <i>Il1b</i>, <i>Il1a</i>, <i>Il6</i>, <i>Ptgs2</i>, and <i>Tnf</i>. In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 ± 0.05) mm<sup>3</sup> and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm<sup>3</sup> (<i>P</i> = 0.012 3) and (2 443 ± 931) cells (<i>P</i> = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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
{"title":"Author Correction: FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.","authors":"Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He","doi":"10.1038/s41368-024-00307-x","DOIUrl":"10.1038/s41368-024-00307-x","url":null,"abstract":"","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":10.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491854","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
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":"<p><p>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.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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":"<p><p>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.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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":"<p>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 A<sub>2A</sub> receptor (A<sub>2A</sub>R) on trigeminal ganglia. Antagonism of trigeminal A<sub>2A</sub>R with a selective A<sub>2A</sub>R inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A<sub>2A</sub>R 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 A<sub>2A</sub>R. Therefore, we established trigeminal A<sub>2A</sub>R-mediated CGRP release as a promising druggable circuit in OSCC treatment.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"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
{"title":"Expert consensus on endodontic therapy for patients with systemic conditions","authors":"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","doi":"10.1038/s41368-024-00312-0","DOIUrl":"https://doi.org/10.1038/s41368-024-00312-0","url":null,"abstract":"<p>The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333554","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
Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC 单细胞和大容量转录组的整合分析揭示了丝氨酸-甘氨酸-一碳代谢的异质性与 HNSCC 的不同预后和治疗脆弱性的关系
IF 14.9 1区 医学
International Journal of Oral Science Pub Date : 2024-06-17 DOI: 10.1038/s41368-024-00310-2
Lixuan Wang, Rongchun Yang, Yue Kong, Jing Zhou, Yingyao Chen, Rui Li, Chuwen Chen, Xinran Tang, Xiaobing Chen, Juan Xia, Xijuan Chen, Bin Cheng, Xianyue Ren
{"title":"Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC","authors":"Lixuan Wang, Rongchun Yang, Yue Kong, Jing Zhou, Yingyao Chen, Rui Li, Chuwen Chen, Xinran Tang, Xiaobing Chen, Juan Xia, Xijuan Chen, Bin Cheng, Xianyue Ren","doi":"10.1038/s41368-024-00310-2","DOIUrl":"https://doi.org/10.1038/s41368-024-00310-2","url":null,"abstract":"<p>Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine–glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8<sup>+</sup> T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333670","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
A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis 对人类牙龈缝隙液的多平台分析揭示了牙周炎临床进展过程中的一种相关调控细胞死亡机制--铁突变
IF 14.9 1区 医学
International Journal of Oral Science Pub Date : 2024-05-27 DOI: 10.1038/s41368-024-00306-y
Alfredo Torres, M. Angélica Michea, Ákos Végvári, Marion Arce, Valentina Pérez, Marcela Alcota, Alicia Morales, Rolando Vernal, Mauricio Budini, Roman A. Zubarev, Fermín E. González
{"title":"A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis","authors":"Alfredo Torres, M. Angélica Michea, Ákos Végvári, Marion Arce, Valentina Pérez, Marcela Alcota, Alicia Morales, Rolando Vernal, Mauricio Budini, Roman A. Zubarev, Fermín E. González","doi":"10.1038/s41368-024-00306-y","DOIUrl":"https://doi.org/10.1038/s41368-024-00306-y","url":null,"abstract":"<p>Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156717","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}
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