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Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma

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International Journal of Oral Science 2024年第2期16卷 251-264页

作者： Gan Xiong Nan Xie Min Nie Rongsong Ling Bokai Yun Jiaxiang Xie Linlin Ren Yaqi Huang Wenjin Wang Chen Yi Ming Zhang Xiuyun Xu Caihua Zhang Bin Zou Leitao Zhang Xiqiang Liu Hongzhang Huang Demeng Chen Wei Cao Cheng Wang hospital of stomatology Sun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of stomatology Sun Yat-sen UniversityGuangzhouChina Guanghua School of stomatology Sun Yat-sen UniversityGuangzhouChina Department of Periodontics Affiliated Stomatology Hospital of Guangzhou Medical UniversityGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhouChina Institute for Advanced Study Shenzhen UniversityShenzhenChina Center for Translational Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhouChina Department of Oral and Maxillofacial Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Oral and Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina National Center for stomatology National Clinical Research Center for Oral diseasesShanghai Key Laboratory of StomatologyShanghaiChina

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence ***,the mechanisms governing tumor initiation and recurrence are poorly ***,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell *** results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)*** note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated *** EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived *** data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

关键词： inhibited cycling eliminated

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Regulating Blood Clot Fibrin Films to Manipulate Biomaterial-Mediated Foreign Body Responses

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Research 2024年第2期2023卷 565-581页

作者： Yang Zou Zhengjie Shan Zongpu Han Jieting Yang Yixiong Lin Zhuohong Gong Lv Xie Jieyun Xu Runlong Xie Zhuofan Chen Zetao Chen hospital of stomatology Guanghua School of StomatologySun Yat-sen University and Guangdong Research Center for Dental and Cranial Rehabilitation and Material EngineeringGuangzhou 510055China

The clinical efficacy of implanted biomaterials is often compromised by host immune recognition and subsequent foreign body responses(FBRs).During the implantation,biomaterials inevitably come into direct contact with the blood,absorbing blood protein and forming blood *** studies have been carried out to regulate protein adsorption,thus manipulating ***,the role of clot surface fibrin films formed by clotting shrinkage in host reactions and FBR is often *** of the principle of fibrin film formation being relevant to fibrinogen or clotting factor absorption,it is feasible to manipulate the fibrin film formation via tuning the absorption of fibrinogen and clotting *** biological hydroxyapatite reserved bone architecture and microporous structure,the smaller particle size may expose more microporous structures and adsorb more fibrinogen or clotting ***,we set up 3 sizes(small,<0.2 mm;medium,1 to 2 mm;large,3 to 4 mm)of biological hydroxyapatite(porcine bone-derived hydroxyapatite)with different microporous structures to investigate the absorption of blood protein,the formation of clot surface fibrin films,and the subsequent *** found that small group adsorbed more clotting factors because of more microporous structures and formed the thinnest and sparsest fibrin *** thinnest and sparsest fibrin films increased inflammation and profibrosis of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton-autophagy,leading to the stronger *** group adsorbed lesser clotting factors,forming the thickest and densest fibrin films,easing inflammation and profibrosis of macrophages,and finally mitigating ***,this study deepens the understanding of the role of fibrin films in host recognition and FBR and demonstrates the feasibility of a strategy to regulate FBR by modulating fibrin films via tuning the absorption of blood proteins.

关键词： Blood subsequent biomaterials

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Cdc42 deletion yielded enamel defects by disrupting mitochondria and producing reactive oxygen species in dental epithelium

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Genes & Diseases 2024年第5期11卷 335-349页

作者： Jinxuan Zheng Rongcheng Yu Yiqi Tang Sihui Su Sainan Wang Chenxi Liao Xuecong Li Jiabin Liao Dongsheng Yu Tingting Ai Wei Zhao Vicky Yau Chufeng Liu Liping Wu Yang Cao hospital of stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong 510055China Guangdong Provincial Key Laboratory of Oral Diseases GuangzhouGuangdong 510055China Department of Cariology and Endodontology 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 Oral and Maxillofacial Surgery University at BuffaloBuffaloNY 14214USA Department of Orthodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Developmental defects of enamel are common due to genetic and environmental factors before and after ***42,a Rho family small GTPase,regulates prenatal tooth development in ***,its role in postnatal tooth development,especially enamel formation,remains ***,we investigated Cdc42 functions in mouse enamel development and tooth repair after ***42 showed highly dynamic temporospatial patterns in the developing incisors,with robust expression in ameloblast and odontoblast ***,epithelium-specific Cdc42 deletion resulted in enamel defects in *** differentiation was inhibited,and hypomineralization of enamel was observed upon epithelial Cdc42 *** analysis showed that abnormal mitochondrial components,phosphotransferase activity,and ion channel regulator activity occurred in the Cdc42 mutant dental *** oxygen species accumulation was detected in the mutant mice,suggesting that abnormal oxidative stress occurred after Cdc42 ***,Cdc42 mutant mice showed delayed tooth repair and generated less calcified *** dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression,increased Atp5j2 levels,and reactive oxygen species overproduction in the mutant repair ***-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical *** Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth *** findings suggested that mitochondrial dysfunction,up-regulated oxidative stress,and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant ***,Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

关键词： Cdc42 Enamel defects Mitochondrial dysfunction Rho GTPase Tooth repair

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Wireless electrical stimulation generated by piezoelectric nanomaterial promotes the dental pulp regeneration via regulating mitochondrial Ca^(2+)/PKA signaling pathway

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Journal of Materials Science & Technology 2024年第1期168卷 24-34页

作者： Jianmao Zheng Jiyuan Zuo Cairong Xiao Qining Guo Xiaobin Fu Chengyun Ning Peng Yu Guangdong Provincial Key Laboratory of stomatology Hospital of StomatologySun Yat-Sen UniversityGuangzhou 510080China School of Materials Science and Engineering National Engineering Research Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510641China

The induction of dental pulp stem cells(DPSCs)into odontogenic differentiation is a cutting-edge method of dental pulp regeneration ***,it remains a challenge to develop biomaterials and ther-apies that can induce odontogenic ***,we propose a wireless electrical stimulation strat-egy to induce DPSCs odontogenic differentiation via K_(0.5)Na_(0.5)NbO_(3)piezoelectric nanoparticles(KNN)and polarized KNN(PKNN),which can be endocytosed by *** vitro,several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN,and the increase was more obvious in the PKNN *** wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter(MCU),increased the production of adenosine triphos-phate(ATP),and induced odontogenic differentiation through the activation of the cAMP-PKA signaling *** vivo,dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN,which was more clinically friendly compared with the wired device,and the induction was more obvious in the PKNN group consistent with in vitro *** conclusion,this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.

关键词： Piezoelectric nanoparticles Dental pulp stem cells Odontogenic differentiation

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Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&West China hospital of stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

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Expert consensus on difficulty assessment of endodontic therapy

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International Journal of Oral Science 2024年第1期16卷 15-25页

作者： 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 State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina The State Key Laboratory Breeding Base of Basic Science of stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Operative Dentistry&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Preventive Dentistry 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 Geriatric dentistry West China Hospital of Stomatology

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.

关键词： anatomy difficulty treatment

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Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

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Journal of Magnesium and Alloys 2024年第2期12卷 546-572页

作者： Khurram Munir Jixing Lin Xian Tong Arne Biesiekierski Yuncang Li Cuie Wen School of Engineering RMIT UniversityMelbourneVictoria 3001Australia School and hospital of stomatology Wenzhou Medical UniversityWenzhou 325027China

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone *** earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg *** study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot *** indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening *** extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant *** polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the ***,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and *** study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

关键词： Corrosion property In vitro cytotoxicity Magnesium alloys Mechanical property Rare earth elements

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Expert consensus on irrigation and intracanal medication in root canal therapy

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International Journal of Oral Science 2024年第1期16卷 26-35页

作者： Xiaoying Zou Xin Zheng Yuhong Liang Chengfei Zhang Bing Fan Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Zhi Chen Xi Wei Lihong Qiu Wenxia Chen Wenxi He Xin Xu Liuyan Meng Chen Zhang Liming Chen Shuli Deng Yayan Lei Xiaoli Xie Xiaoyan Wang Jinhua Yu Jin Zhao Song Shen Xuedong Zhou Lin Yue Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Center of stomatology Peking University HospitalBeijingChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&West China hospital of stomatology Sichuan UniversityChengduChina Department of Emergency Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Restorative Dental Sciences EndodonticsFaculty of DentistryThe University of Hong KongPok Fu LamHong Kong SARChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina State Key Laboratory of Oral&Maxillofacial Reconstruction and R

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.

关键词： treatment irrigation Expert

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WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

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Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

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International Journal of Oral Science 2024年第1期16卷 163-172页

作者： Xiao Yang Hui Zhao Rui Li Yang Chen Zhi Xu Zhengjun Shang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Oral and Maxillofacial-Head and Neck Oncology School of Stomatology–Hospital of StomatologyWuhan UniversityWuhanChina Department of stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

关键词： angiogenesis elevated endogenous

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