Pub Date : 2024-04-16DOI: 10.1038/s41368-024-00292-1
Kang Li, Caihua Zhang, Ruoxing Zhou, Maosheng Cheng, Rongsong Ling, Gan Xiong, Jieyi Ma, Yan Zhu, Shuang Chen, Jie Chen, Demeng Chen, Liang Peng
Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.
{"title":"Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification","authors":"Kang Li, Caihua Zhang, Ruoxing Zhou, Maosheng Cheng, Rongsong Ling, Gan Xiong, Jieyi Ma, Yan Zhu, Shuang Chen, Jie Chen, Demeng Chen, Liang Peng","doi":"10.1038/s41368-024-00292-1","DOIUrl":"https://doi.org/10.1038/s41368-024-00292-1","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556671","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}
Pub Date : 2024-04-16DOI: 10.1038/s41368-024-00290-3
Cai Qi, Qiang Sun, Dexuan Xiao, Mei Zhang, Shaojingya Gao, Bin Guo, Yunfeng Lin
Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.
{"title":"Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing","authors":"Cai Qi, Qiang Sun, Dexuan Xiao, Mei Zhang, Shaojingya Gao, Bin Guo, Yunfeng Lin","doi":"10.1038/s41368-024-00290-3","DOIUrl":"https://doi.org/10.1038/s41368-024-00290-3","url":null,"abstract":"<p>Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556875","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}
Pub Date : 2024-04-16DOI: 10.1038/s41368-024-00293-0
Yawen Cheng, Yuan Zhu, Yaoshan Liu, Xuenan Liu, Yanan Ding, Deli Li, Xiao Zhang, Yunsong Liu
Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.
{"title":"Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake","authors":"Yawen Cheng, Yuan Zhu, Yaoshan Liu, Xuenan Liu, Yanan Ding, Deli Li, Xiao Zhang, Yunsong Liu","doi":"10.1038/s41368-024-00293-0","DOIUrl":"https://doi.org/10.1038/s41368-024-00293-0","url":null,"abstract":"<p>Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556704","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}
Pub Date : 2024-04-16DOI: 10.1038/s41368-024-00299-8
Chenchen Zhou, Peipei Duan, Hong He, Jinlin Song, Min Hu, Yuehua Liu, Yan Liu, Jie Guo, Fang Jin, Yang Cao, Lingyong Jiang, Qingsong Ye, Min Zhu, Beizhan Jiang, Wenhua Ruan, Xiao Yuan, Huang Li, Rui Zou, Yulou Tian, Li Gao, Rui Shu, Jianwei Chen, Renkai Liu, Shujuan Zou, Xiaobing Li
Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.
{"title":"Expert consensus on pediatric orthodontic therapies of malocclusions in children","authors":"Chenchen Zhou, Peipei Duan, Hong He, Jinlin Song, Min Hu, Yuehua Liu, Yan Liu, Jie Guo, Fang Jin, Yang Cao, Lingyong Jiang, Qingsong Ye, Min Zhu, Beizhan Jiang, Wenhua Ruan, Xiao Yuan, Huang Li, Rui Zou, Yulou Tian, Li Gao, Rui Shu, Jianwei Chen, Renkai Liu, Shujuan Zou, Xiaobing Li","doi":"10.1038/s41368-024-00299-8","DOIUrl":"https://doi.org/10.1038/s41368-024-00299-8","url":null,"abstract":"<p>Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556885","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}
The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.
{"title":"The evolution of robotics: research and application progress of dental implant robotic systems","authors":"Chen Liu, Yuchen Liu, Rui Xie, Zhiwen Li, Shizhu Bai, Yimin Zhao","doi":"10.1038/s41368-024-00296-x","DOIUrl":"https://doi.org/10.1038/s41368-024-00296-x","url":null,"abstract":"<p>The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140534275","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}
Pub Date : 2024-03-28DOI: 10.1038/s41368-024-00291-2
Xiaoqian Meng, Linjuan Du, Shuo Xu, Lujun Zhou, Boyan Chen, Yulin Li, Chumao Chen, Huilin Ye, Jun Zhang, Guocai Tian, Xuebing Bai, Ting Dong, Wenzhen Lin, Mengjun Sun, Kecong Zhou, Yan Liu, Wuchang Zhang, Shengzhong Duan
Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.
{"title":"Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice","authors":"Xiaoqian Meng, Linjuan Du, Shuo Xu, Lujun Zhou, Boyan Chen, Yulin Li, Chumao Chen, Huilin Ye, Jun Zhang, Guocai Tian, Xuebing Bai, Ting Dong, Wenzhen Lin, Mengjun Sun, Kecong Zhou, Yan Liu, Wuchang Zhang, Shengzhong Duan","doi":"10.1038/s41368-024-00291-2","DOIUrl":"https://doi.org/10.1038/s41368-024-00291-2","url":null,"abstract":"<p>Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ<sup>+</sup>) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified <i>Prevotella zoogleoformans</i> as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140310669","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}
Pub Date : 2024-03-28DOI: 10.1038/s41368-024-00289-w
Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He
SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.
{"title":"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/s41368-024-00289-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00289-w","url":null,"abstract":"<p>SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8<sup>+</sup> T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140310588","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}
Pub Date : 2024-03-13DOI: 10.1038/s41368-024-00288-x
Kai Sun, Miao Yu, Jiayu Wang, Hu Zhao, Haochen Liu, Hailan Feng, Yang Liu, Dong Han
Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.
{"title":"A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.","authors":"Kai Sun, Miao Yu, Jiayu Wang, Hu Zhao, Haochen Liu, Hailan Feng, Yang Liu, Dong Han","doi":"10.1038/s41368-024-00288-x","DOIUrl":"10.1038/s41368-024-00288-x","url":null,"abstract":"<p><p>Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a<sup>fl/fl</sup> mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10a<sup>fl/fl</sup> mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a<sup>fl/fl</sup> mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a<sup>fl/fl</sup> mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10a<sup>fl/fl</sup> molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119485","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}
Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.
{"title":"Promising dawn in tumor microenvironment therapy: engineering oral bacteria.","authors":"Zifei Wang, Wansu Sun, Ruixue Hua, Yuanyin Wang, Yang Li, Hengguo Zhang","doi":"10.1038/s41368-024-00282-3","DOIUrl":"10.1038/s41368-024-00282-3","url":null,"abstract":"<p><p>Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110226","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}
Pub Date : 2024-03-01DOI: 10.1038/s41368-024-00285-0
Dingming Huang, Xiaoyan Wang, Jingping Liang, Junqi Ling, Zhuan Bian, Qing Yu, Benxiang Hou, Xinmei Chen, Jiyao Li, Ling Ye, Lei Cheng, Xin Xu, Tao Hu, Hongkun Wu, Bin Guo, Qin Su, Zhi Chen, Lihong Qiu, Wenxia Chen, Xi Wei, Zhengwei Huang, Jinhua Yu, Zhengmei Lin, Qi Zhang, Deqin Yang, Jin Zhao, Shuang Pan, Jian Yang, Jiayuan Wu, Yihuai Pan, Xiaoli Xie, Shuli Deng, Xiaojing Huang, Lan Zhang, Lin Yue, Xuedong Zhou
Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.
{"title":"Expert consensus on difficulty assessment of endodontic therapy","authors":"Dingming Huang, Xiaoyan Wang, Jingping Liang, Junqi Ling, Zhuan Bian, Qing Yu, Benxiang Hou, Xinmei Chen, Jiyao Li, Ling Ye, Lei Cheng, Xin Xu, Tao Hu, Hongkun Wu, Bin Guo, Qin Su, Zhi Chen, Lihong Qiu, Wenxia Chen, Xi Wei, Zhengwei Huang, Jinhua Yu, Zhengmei Lin, Qi Zhang, Deqin Yang, Jin Zhao, Shuang Pan, Jian Yang, Jiayuan Wu, Yihuai Pan, Xiaoli Xie, Shuli Deng, Xiaojing Huang, Lan Zhang, Lin Yue, Xuedong Zhou","doi":"10.1038/s41368-024-00285-0","DOIUrl":"https://doi.org/10.1038/s41368-024-00285-0","url":null,"abstract":"<p>Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001044","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}