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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

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

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

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

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Chinese Chemical Letters 2024年第1期35卷 371-378页

作者： Ran Tian Xinyu Qiu Wenyun Mu Bolei Cai Zhongning Liu Shiyu Liu Xin Chen School of Chemical Engineering and Technology Department of Chemical EngineeringShaanxi Key Laboratory of Energy Chemical Process IntensificationXi'an Jiao Tong UniversityXi'an 710049China School of stomatology State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral DiseasesDepartment of Preventive DentistryThe Fourth Military Medical UniversityXi'an 710032China School of stomatology State Key Laboratory of Military StomatologyDepartment of Oral and Maxillofacial SurgeryThe Fourth Military Medical UniversityXi'an 710032China Department of Prosthodontics Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China School of stomatology State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringThe Fourth Military Medical UniversityXi'an 710032China

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer ***,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection *** hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed *** bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose ***,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

关键词： Smart hydrogel with self-adaptable size Breast cancer therapy Dual responsive cargoes release Selective tumor elimination On-demand adipose tissue regeneration Effective bacteria inhibition

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

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of Oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li 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 Orthopedic Surgery and Orthopedic research Institute West China HospitalSichuan UniversityChengduChina

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 ***, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

关键词： Sema3A formation overload

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

The evolution of robotics:research and application progress of dental implant robotic systems

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International Journal of Oral Science 2024年第2期16卷 173-185页

作者： Chen Liu Yuchen Liu Rui Xie Zhiwen Li Shizhu Bai Yimin Zhao state key laboratory of Oral&Maxillofacial Reconstruction and Regeneration Xi’anChina national clinical research Center for Oral Diseases Xi’anChina Shaanxi key laboratory of stomatology Xi’anChina Digital Center School of StomatologyThe Fourth Military Medical UniversityXi’anChina

The use of robots to augment human capabilities and assist in work has long been an *** has been developing since the 1960s when the first industrial robot was *** technology has advanced,robotic-assisted surgery has shown numerous advantages,including more precision,efficiency,minimal invasiveness,and safety than is possible with conventional techniques,which are research hotspots and cutting-edge *** article reviewed the history of medical robot development and seminal research papers about current research *** the autonomous dental implant robotic system as an example,the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.

关键词： robot robotic application

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 ***-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal *** proteins initiate inflammatory dysfunction,such as neurogenic heterotopic *** recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention ***,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two *** examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast *** relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in *** injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in *** 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