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Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

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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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

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Bone Research 2024年第1期12卷 137-152页

作者： Weicheng Lu Jianfei Yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai Jiao department of stomatology Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina State Key Laboratory of Oral and maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina The Dental College of Georgia Augusta UniversityAugustaGAUSA

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关键词： neurogenic ossification pathogenesis

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Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of Oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren department of Oral and maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina department of Oral and maxillofacial surgery Zhongshan HospitalFudan UniversityShanghaiChina School and Hospital of stomatology Kunming Medical UniversityKunmingChina Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central Hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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DLX3(Q178R)mutation delays osteogenic differentiation via H19/miR-29c-3p/KDM5B axis in TDO-iPSCs-derived MSCs

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Genes & Diseases 2024年第4期11卷 49-52页

作者： Liying Dong Na Zhao Dongmei Wang Meng Wang Yixin Zhang Liangjie Sun Chong Ding Yixiang Wang Zeyun Ma Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China department of Oral and maxillofacial surgery Peking University School and Hospital of StomatologyBeijing 100081China National Engineering Laboratory for Digital and Material Technology of stomatology Peking University School and Hospital of StomatologyBeijing 100081China Beijing Key Laboratory of Digital stomatology Peking University School and Hospital of StomatologyBeijing 100081China The Second Clinical Division Peking University School and Hospital of StomatologyBeijing 100081China department of VIP Service Peking University School and Hospital of StomatologyBeijing 100081China department of Restorative Dentistry and Biomaterials Sciences Harvard School of Dental MedicineBostonMA 02115USA department of Prosthodontics Fudan UniversityShanghai 200001China Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological HospitalFudan UniversityShanghai 200001China

Tricho-dento-osseous(TDO)syndrome is a rare autosomal dominant disease resulting from distal-less homeobox 3(DLX3)mutation.1,2 Accumulative bone density in alveolar bone is a clinically favorable phenotype for TDO patients.However,the limited number of bone marrow mesenchymal stem cells(BMSCs)in TDO patients restricts their application.

关键词： patients clinically alveolar

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Assessment of Two Years of Free Surgical Treatment of Cleft Lip, Palate and Alveolar (CLPA) in the maxillofacial surgery and stomatology department of the Hospital University of Treichville-Abidjan

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Open Journal of stomatology 2023年第8期13卷 223-232页

作者： Anoumon Marguerite Reine Evelyne Anzouan-Kacou Romaric Evrard Assi Yapo Jean Francois Regis Koffi Behibro Beatrice Tehoua Ettien Franck-Olivier Manoussa Seguy Emmanuel Kouadio Konan department of stomatology and maxillofacial surgery Treichville University Hospital Abidjan C&ocircte d’Ivoire department of surgery and Specialties Faculty of Medical Sciences Felix Houphouet-Boigny University Abidjan C&ocircte d’Ivoire

Introduction: Cleft lip, palate and alveolar (CLPA) are congenital malformations of the face due to a defect in the fusion of embryonic buds during the first weeks of embryogenesis. These malformations affect the upper lip, the alveolar bone and the palate. The incidence in Africa ranges from 1/2000 to 1/500 births. Their multidisciplinary management is long and costly. Thus, the help provided by humanitarian organisations during free care campaigns is welcome. Materials and Methods: This is a retrospective descriptive study conducted from August 2014 to July 2016 in the maxillofacial surgery and stomatology department of the Treichville University Hospital in Abidjan, Côte d’Ivoire. The objective was to describe the epidemiological, clinical and therapeutic aspects of CLPA during a humanitarian campaign for free care. Results: 51 cases of CLPA were operated on. Males were involved in 54.9% of the cases, i.e. a sex ratio of 1.2. The average age of the patients at the time of the operation was 3.44 years with extremes of 3 months and 52 years. Patients with low socioeconomic status represented 84.3% of the cases. Cleft lips (31.4%) and cleft palates (33.33%) predominated. For cleft lips, unilateral forms were the most frequent (73.5%) and the left side was most often affected (59.2%). The most common surgical techniques used were MILLARD cheiloplasty for cleft lips (79.36%) and Dorrance pushback for cleft palates (78.05%). The postoperative course was simple in the majority of cases (80.47%). Patients and/or parents were satisfied with the postoperative results in over 90% of cases. Discussion: Cleft lip and palate are common. Their management by humanitarian missions through mass campaigns allows us to receive a large number of patients affected by this pathology who are treated with a high satisfaction rate. Conclusion: The characteristics of cleft lip and palate in this study are in many respects identical to those described in the literature, but with some differences specific to Africa, notably the absence of

关键词： Cleft Lip and Palate Free Care Humanitarian surgery

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Treatment and Sequelae of Panfacial Fractures in the maxillofacial surgery and stomatology department of the Hospital University of Treichville-Abidjan (Cote d’Ivoire)

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Open Journal of stomatology 2023年第12期13卷 433-441页

作者： Romaric Evrard Assi Yapo Anoumon Marguerite Reine Evelyne Anzouan-Kacou Beatrice Tehoua Ettien Jean Francois Regis Koffi Behibro Franck-Olivier Manoussa Seguy Emmanuel Kouadio Konan department of stomatology and maxillofacial surgery Treichville University Hospital Abidjan C&ocircte d’Ivoire department of surgery and Specialties Faculty of Medical Sciences Felix Houphouet-Boigny University Abidjan C&ocircte d’Ivoire

Introduction: The treatment of panfacial fractures is complex and constitutes a challenge for the maxillofacial surgeon, who, despite therapeutic progress, frequently suffers functional and aesthetic sequelae. This study aimed to describe the treatment and evaluate the functional and aesthetic sequelae of panfacial fractures in the stomatology and maxillofacial surgery department of the Treichville University Hospital. Materials and Methods: We conducted a retrospective study over a 6 years in the stomatology and maxillofacial surgery department of Treichville University Hospital. Forty-two patients with panfacial fractures were included in the study. Results: Forty-two patients were registered. The average time to osteosynthesis was 12.4 days. Nasotracheal intubation was used most often (88%), and in the majority of cases, mixed osteosynthesis combining a screwed plate and steel wire was performed (64.29%). The “Bottom-up and Outside-in” surgical sequence was the most commonly used (64.29%). All patients had at least one functional and/or cosmetic sequela after treatment. Functional sequelae were dominated by occlusal problems and aesthetic sequelae by nasal deformities. Discussion: Panfacial fractures are characterised by their complexity, presenting maxillo-facial surgeons with a therapeutic and evolutionary challenge. The quality of the initial, often multidisciplinary, management of panfacial fractures is an essential factor in both functional and aesthetic prognosis. Conclusion: The treatment of panfacial fractures, even if well managed, is sometimes a source of sequelae, requiring often complex secondary management.

关键词： Aesthetic Sequelae Functional Sequelae Management Panfacial Fracture Treatment

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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo Yunfeng Lin State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China department of Oral and maxillofacial surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of Oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

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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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Bone block from lateral window-correcting vertical and horizontal bone deficiency in maxilla posterior site:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2109-2115页

作者： Yu-Lan Wang Wen-Jun Shao Min Wang State Key Laboratory of Oral and maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool and Hospital of StomatologyWuhan UniversityWuhan 430079Hubei ProvinceChina department of Oral Implantology School and Hospital of StomatologyWuhan UniversityWuhan 430079Hubei ProvinceChina

BACKGROUND Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm.However,managing cases becomes more challenging when a maxillary sinus pseudocyst is present or when there is insufficient bone width.In this case,we utilized the bone window prepared during the lateral window sinus lift as a shell for horizontal bone augmentation.This allowed for simultaneous horizontal and vertical bone augmentation immediately after the removal of the maxillary sinus pseudocyst.CASE SUMMARY A 28-year-old female presented to our clinic with the chief complaint of missing upper left posterior teeth.Intraoral examination showed a horizontal deficiency of the alveolar ridge contour.The height of the alveolar bone was approximately 3.6 mm on cone beam computed tomography(CBCT).And a typical well-defined'dome-shaped'lesion in maxillary sinus was observed on CBCT imaging.The lateral bony window was prepared using a piezo-ultrasonic device,then the bony window was fixed to the buccal side of the 26 alveolar ridge using a titanium screw with a length of 10 mm and a diameter of 1.5 mm.The space between the bony window and the alveolar ridge was filled with Bio-Oss,covered with a Bio-Gide collagen membrane,and subsequently sutured.Nine months later,the patient’s bone width increased from 4.8 to 10.5 mm,and the bone height increased from 3.6 to 15.6 mm.Subsequently,a Straumann^(■)4.1 mm×10 mm implant was placed.The final all-ceramic crown restoration was completed four months later,and both clinical and radiographic examinations showed that the implant was successful,and the patient was satisfied with the results.CONCLUSION The bone block harvested from the lateral window sinus lift can be used for simultaneous horizontal bone augmentation acting as a shell for good two-dimensional bone augmentation.

关键词： Sinus lift Lateral window Dental implant Horizontal bone augmentation Case report

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CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of Oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou Xinjia Cai Fengyang Jing Xuefen Li Jianyun Zhang Heyu Zhang Tiejun Li department of Oral Pathology 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 Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

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