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

Nano research 2024年第6期17卷 5424-5434页

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

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

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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Emerging roles of exosomes in oral diseases progression

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

作者： Jiayi Wang Junjun Jing Chenchen Zhou Yi Fan State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&West China Hospital of stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

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

关键词： diseases diagnosis salivary

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Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

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

作者： Jiayi Wu Feifei Li Peng Yu Changhao Yu Chuyi Han Yitian Wang Fanyuan Yu Ling Ye State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&West China Hospital of stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

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

关键词： injuries healing suture

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Magnesium promotes vascularization and osseointegration in diabetic states

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

作者： Linfeng Liu Feiyu Wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian Wang Hanwen Li Quan Yuan Shiwen Zhang State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&West China Hospital of stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

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

关键词： healing diabetic impaired

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Omics for deciphering oral microecology

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

作者： Yongwang Lin Xiaoyue Liang Zhengyi Li Tao Gong Biao Ren Yuqing Li Xian Peng State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina

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

关键词： insight holds oral

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Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

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Journal of Pharmaceutical Analysis 2024年第4期14卷 619-621页

作者： Xuefeng Zhang Hao Xu Tong Zhou Xiaodong Feng Qianming Chen State Key Laboratory of Oral Diseases National Center of StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China

Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.

关键词： SOX2 therapeutic squamous

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3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

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Journal of Magnesium and Alloys 2024年第3期12卷 966-979页

作者： Xiao Zhao Siyi Wang Feilong Wang Yuan Zhu Ranli Gu Fan Yang Yongxiang Xu Dandan Xia Yunsong Liu Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China national center of stomatology National Engineering Laboratory for Digital and Material Technology of StomatologyNational Clinical Research Center for Oral DiseasesBeijing Key Laboratory of Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing 100081China Department of Dental Materials Peking University School and Hospital of StomatologyBeijing 100081China

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its *** this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these *** used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling *** explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL *** 5 and 10 wt%Mg-1Ca/PCL composites were found to have good ***,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure *** vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and *** tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone *** results indicated that the Wnt/β-catenin pathway was involved in the osteogenic ***,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical *** of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone ***,there remain many limitations in the materials and manufacturing methods used to fabricate *** study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation ***,the fused deposition modeling method allows precise control of the macroscopic morphology and microsc

关键词： 3D printing Bone tissue engineering Magnesium Osteogenic Polycaprolactone Scaffold.

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A Wnt10a-Notch signaling axis controls Hertwig’s epithelial root sheath cell behaviors during root furcation patterning

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International Journal of Oral Science 2024年第3期16卷 425-435页

作者： Kai Sun Miao Yu Jiayu Wang Hu Zhao Haochen Liu Hailan Feng Yang Liu Dong Han Department of Prosthodontics 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 DevicesBeijingChina Chinese Institute for Brain research BeijingChina

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root ***,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains *** this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to *** assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and *** staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)***-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)***,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially *** together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

关键词： Wnt10a Notch impaired

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

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

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China national Engineering research center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of Oral Diseases&national center for stomatology&national clinical research center for Oral Diseases&Department of Oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

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

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

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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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