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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

International Journal of oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He Department of oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina Department of oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina Department of oral Pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,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 *** 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 *** 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 *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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A folic acid-decorated nanoparticles loaded JQ1 for oral squamous cell carcinoma therapy

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Chinese Chemical Letters 2024年第3期35卷 332-336页

作者： Dequan Zeng Zhongkai Ma Xin Zan Ting Luo Xiang Wang Xiang Gao Xianghui Fu School of health Management Xihua UniversityChengdu 610039China State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesWest China College of StomatologySichuan UniversityChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Breast disease center Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality *** poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC *** that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these ***,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor *** then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type *** conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.

关键词： Folic acid Nanoparticles JQ1 oral squamous cell carcinoma Macrophages

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Epidemiological analysis of the clinicopathologic characteristics,treatment,and prognosis of 2648 jaw cysts in West China

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Chinese Medical Journal 2024年第9期137卷 1124-1126页

作者： Hui Li Zuoqiang Liu Linli Jiang Jiangyu Liang Lei Liu Department of oral and Maxillofacial Surgery State Key Laboratory of Oral Disease&National Center for Stomatology&National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China Department of Biomaterials Sciences and Prosthodontics School of DentistryUniversity of MichiganAnn ArborMIUnited States

To the Editor:The jaw cyst is one of the most common benign tumors in the oral and maxillofacial region.[1]To date,several studies have reported on jaw cysts in general populations from Italy,Brazil,Greece,and the United States in accordance with the 4th World health Organization(WHO)classication of head and neck tumors.[2]However,there are no clinicopathological studies of odontogenic and non-odontogenic cysts in a large Chinese population in relation to the latest WHO classi***,few epidemiological studies have analyzed treatment plans and the possible postoperative complications of jaw ***,this study aimed to perform a detailed and extended epidemiological analysis of jaw cysts in a large population in West China.

关键词： clinic treatment pathologic

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Magnesium promotes vascularization and osseointegration in diabetic states

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International Journal of oral Science 2024年第1期16卷 122-133页

作者： Linfeng Liu Feiyu Wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian Wang Hanwen Li Quan Yuan Shiwen Zhang State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral *** has been proved to promote bone healing under normal ***,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic *** generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased *** then developed Mg-coating implants with hydrothermal *** implants successfully improved the vascularization and osseointegration in diabetic ***,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under ***,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

关键词： healing diabetic impaired

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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Bioinspired mineral-in-shell nanoarchitectonics:Functional empowerment of mineral precursors for guiding intradentinal mineralization

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Nano Research 2024年第5期17卷 4338-4349页

作者： Xiaoran Zheng Yang Liu Mingjing Li Yuyan Li Wanshan Gao Rongmin Qiu Jiaqi Xing Jiaojiao Yang Yantao Chen Xinyuan Xu Mingming Ding Jun Luo Jianshu Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China College of Stomatology Hospital of Stomatology Guangxi Medical UniversityGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and ReconstructionGuangxi Clinical Research Center for Craniofacial DeformityGuangxi Key Laboratory of Oral and Maxillofacial Surgery Disease TreatmentGuangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious DiseasesNanning 530021China State Key Laboratory of oral diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Shenzhen Key Laboratory of Environmental Chemistry and Ecological Remediation College of Chemistry and Environmental EngineeringShenzhen UniversityShenzhen 518060China Med-X center for Material Sichuan UniversityChengdu 610041China

Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization *** this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization *** nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)*** bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external *** simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral ***,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.

关键词： mineral-in-shell nanohybrids self-assembly biomineralization dentinal tubule occlusion dental hypersensitivity

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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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Emerging roles of exosomes in oral diseases progression

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International Journal of oral Science 2024年第1期16卷 36-51页

作者： Jiayi Wang Junjun Jing Chenchen Zhou Yi Fan State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.

关键词： diseases diagnosis salivary

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Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

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International Journal of oral Science 2024年第2期16卷 306-321页

作者： Jiayi Wu Feifei Li Peng Yu Changhao Yu Chuyi Han Yitian Wang Fanyuan Yu Ling Ye State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal *** extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances *** knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic *** to date,the absence of promising therapeutic biomaterials/scaffolds *** reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of *** address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial *** data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony ***,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were *** study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

关键词： injuries healing suture

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Omics for deciphering oral microecology

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International Journal of oral Science 2024年第2期16卷 197-207页

作者： Yongwang Lin Xiaoyue Liang Zhengyi Li Tao Gong Biao Ren Yuqing Li Xian Peng State Key Laboratory of oral diseases&National center for Stomatology&National Clinical Research center for oral diseases West China Hospital of StomatologySichuan UniversityChengduChina

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic *** technological innovations are propelling the characterization and manipulation of oral ***-throughput sequencing enables comprehensive taxonomic and functional profiling of oral *** long-read platforms improve genome assembly from complex ***-cell genomics provides insights into uncultured *** imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing *** techniques link phylogenetic identity with *** spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for *** facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput *** integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and ***,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic *** convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

关键词： insight holds oral

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