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Mitochondrial components transferred by MSC-derived exosomes promoted bone regeneration under high salt microenvironment via DRP1/Wnt signaling

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Nano Research 2024年第9期17卷 8301-8315页

作者： Yiming Wang Shuai Lin Liujing Chen Mingzhao Li Zilu Zhu Zimeng Zhuang Meilian Cai Han Zhang Chenyang Xing Weiran Li Ruili Yang department of orthodontics School and Hospital of StomatologyPeking UniversityBeijing 100081China National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China Beijing Key Laboratory of Digital stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China

Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ***,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone *** this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and ***,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in ***,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling ***,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem *** study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.

关键词： high salt dynamin-related protein 1 mitochondrial injury exosomes bone regeneration

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Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

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World Journal of Stem Cells 2024年第3期16卷 267-286页

作者： Tong Wu Fu Zheng Hong-Yi Tang Hua-Zhi Li Xin-Yu Cui Shuai Ding Duo Liu Cui-Ying Li Jiu-Hui Jiang Rui-Li Yang department of orthodontics Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China department of Central Laboratory Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root ***-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture *** is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still *** To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying *** A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue *** vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red *** expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via *** The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),*** could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by ***,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by ***,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA ***,LIPUS increased alveolar

关键词： Low-intensity pulsed ultrasound Bone resorption Osteogenesis Cytoskeleton-Lamin A/C-Yes-associated protein axis Bone marrow mesenchymal stem cells Orthodontic tooth movement

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Expert consensus on pediatric orthodontic therapies of malocclusions in children

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International Journal of Oral Science 2024年第2期16卷 186-196页

作者： 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 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 State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&department of orthodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&Key Laboratory of Oral Biomedicine Ministry of Education&Hubei Key Laboratory of stomatology&department of orthodontics&Center for Dentofacial Development and Sleep Medicine School and Hospital of StomatologyWuhan UniversityWuhanChina Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences&Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Stomatological Hospital of Chongqing Medical UniversityChongqing Medical University&College of StomatologyChongqing Medical UniversityChongqingChina department of orthodontics Hospital of StomatologyJilin UniversityChangchunChina department of Orthodontic&Oral Biomedical Engineering Laboratory Shanghai Stomatological HospitalFudan UniversityShanghaiChina department of orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina department of orthodontics School and Hospital of StomatologyCollege of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue

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 *** its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these *** 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 *** 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 *** 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 *** consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early *** 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.

关键词： permanent stated children

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More than just aligning the teeth:Clear aligners with multifunctional prowess

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Nano Research 2024年第8期17卷 7665-7674页

作者： Yang Chen Lei-Ming Cao Nian-Nian Zhong Zi-Zhan Li Lin-Lin Bu Fang-Yi Huo Hong He 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 430079China department of Oral and Maxillofacial-Head Neck Oncology School and Hospital of StomatologyWuhan UniversityWuhan 430079China department of Zhuankou Clinical Branches School and Hospital of StomatologyWuhan UniversityWuhan 430000China department of orthodontics School and Hospital of StomatologyWuhan UniversityWuhan 430079China

With the increasing demand for beauty and health,clear aligners(CAs)have been widely applied among patients with ***,patients treated with CAs also face some potential complications,such as demineralization,dental caries,and periodontal *** addition,some patients have additional needs to improve their quality of life,such as bleaching *** order to prevent or solve these problems,the modification of CAs is a promising method because their extensive long-term contact with tooth surfaces makes them ideal devices for implementing adjuvant medical *** this review,we discuss various advanced CAs with medical functions based on the clinical needs of *** far as we know,the additional functions of CAs mainly include antibacterial,remineralization,whitening,and accelerating tooth *** functions are achieved by two major pathways,the combination of CAs with drugs/biomaterials and increasing the capacity or affinity of *** addition,we discuss the current limitations of in vitro experiments which are designed to explore the effectiveness and properties of novel CAs,and the challenges of bringing a multifunctional appliance from proposal to clinical *** the end of this review,we provide insights into the broader prospects for the improvement of CAs.

关键词： advanced clear aligners medical device modification drug delivery system personalized medicine

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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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The essential roles of m^(6)A modification in osteogenesis and common bone diseases

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Genes & Diseases 2024年第1期11卷 335-345页

作者： Yuxi Gu Yidan Song Yihua Pan Jun Liu State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases Department of OrthodonticsWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China

N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding *** affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional *** play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,*** diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health *** processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA *** a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and *** recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related *** this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional *** also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.

关键词： Bone diseases m^(6)A modification Osteogenesis Regulatory role Stem cells

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Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

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World Journal of Stem Cells 2024年第5期16卷 560-574页

作者： Meng-Hao Lyu Ce Bian Yi-Ping Dou Kang Gao Jun-Ji Xu Pan Ma department of Periodontics School of StomatologyCapital Medical UniversityBeijing 100050China department of orthodontics School of StomatologyCapital Medical UniversityBeijing 100050China department of Dental Implantology School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical UniversityBeijing 100050China

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be *** the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair *** To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory *** IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory *** this study,we investigated its impact on the proliferation,migration,and osteogenesis of *** expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated ***,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 *** IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of ***,STAT3 signaling plays a crucial role in the process by which IL-10 influences ***,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of *** Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of *** IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

关键词： Macrophages Interleukin-10 Bone marrow mesenchymal stem cells Signal transducer and activator of transcription 3 Inflammatory response

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Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair

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Nano Research 2024年第3期17卷 2154-2163页

作者： Yunfei Zhao Xiaohao Liu Zhi Zhou Chaobo Feng Nan Luo Jiajun Yan Shuo Tan Yang Lu Feng Chen Bing-Qiang Lu Shisheng He department of Orthopedic Spinal Pain Research InstituteShanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China department of Preventive Dentistry 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 StomatologyShanghai Research Institute of StomatologyShanghai 200011China

Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue *** current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low *** typically results in inefficient mineralization and weak control over biomineral ***,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic *** approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and *** resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy *** shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory *** study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.

关键词： biomineralization organic solvent bacterial cellulose(BC) hard tissue repair

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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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Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+T cell infiltration in mice

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International Journal of Oral Science 2024年第2期16卷 359-369页

作者： 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 department of Endodontics Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghaiChina Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina Hongqiao International institute of Medicine Shanghai Tongren Hospital/Faculty of Basic MedicineKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghaiChina department of orthodontics Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghaiChina department of Periodontology Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghaiChina stomatology Hospital School of StomatologyZhejiang University School of MedicineHangzhouChina

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the *** 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 ***,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 *** 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 IFNγneutralizing *** study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

关键词： hypertension prevention interferon

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