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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

Drug-loading ZIF-8 for modification of microporous bone scaffold to promote vascularized bone regeneration

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Chinese Chemical Letters 2024年第6期35卷 358-364页

作者： Xin Zhang Junyu Chen Xiang Pei Linxin Yang Liang Wang Luona Chen Guangmei Yang Xibo Pei Qianbing Wan Jian Wang State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesChengdu 610041China department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengdu 610041China

Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue *** at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone *** osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable ***,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone *** processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these ***,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted *** conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.

关键词： Drug-loading nanoparticles Surface coating Microporous bone scaffold Vascularization bone regeneration

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

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

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

Synthesis and potential osteogenic applications of Wnt3a-loaded ZIF-8 nanoparticles

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Chinese Chemical Letters 2024年第3期35卷 399-405页

作者： Hengfei Wang Song Chen Zihan He Junyu Chen Zhou Zhu Qianbing Wan Jian Wang Xibo Pei State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesDepartment of ProsthodonticsWest China Hospital of StomatologySichuan UniversityChengdu 610041China Chongqing Key Laboratory of oral diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationStomatological Hospital of Chongqing Medical UniversityChongqing 400016China

The Wnt signaling pathway plays a critical role in bone homeostasis,and the related protein therapy strategies have been reported to have great potential in osseointegration;however,they face formidable challenges such as complex external environments and unavoidable protein *** this work,we report a novel approach combining the synthesis of metal–organic frameworks(MOFs)and protein encapsulation in a one-pot process based on zeolitic imidazolate framework-8(ZIF-8)and Wnt3a protein,with improved biomechanical behavior and enhanced protein biological *** combination was designed to enhance the Wnt3a protein function through the improved chemical stability provided by the ZIF-8 ***,the zinc ions contained in the ZIF-8 crystals induced bone homeostasis,further favoring the *** results showed that the Wnt3a protein-loaded ZIF-8 crystals served as efficient drug delivery vehicles to promote osteogenesis,preventing protein *** particular,Wnt3a-loaded ZIF-8 nanoparticles(Wnt3a@ZIF-8 NPs)had higher efficacy on bone marrow mesenchymal stem cells(BMSCs)than ZIF-8 NPs or Wnt3a proteins,contributing to the osteogenesis through ZIF-8 crystals and intracellular Wnt3a proteins released from Wnt3a@ZIF-8 ***,polymerase chain reaction(PCR)analysis showed that the osteogenic pathways were ***,the present one-pot process can open up new avenues to develop signaling protein-delivery systems for applications in protein therapy strategies.

关键词： Metal–organic frameworks Nanoparticle Drug release Osteogenesis Bone defects

Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering Research Center of oral Biomaterials Chengdu 610041China department of Head and Neck Oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment Side effect

An overview of autophagy in the differentiation of dental stem cells

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BIOCELL 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU LULU WANG LI-AN WU State Key Laboratory of oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.

关键词： Dental stem cells Cell differentiation Autophagy Mitophagy Autophagy regulation

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

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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