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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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Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls

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World Journal of Pediatrics 2024年第6期20卷 581-589页

作者： Cornelia Wiechers Julian Sowula Karen Kreutzer Christoph E.Schwarz Christina Weismann Michael Krimmel Christian F.Poets Bernd Koos department of Neonatology Tuebingen University HospitalCalwerstrasse 772076 TuebingenGermany Center for Cleft Lip Palate and Craniofacial MalformationsTuebingen University HospitalTuebingenGermany department of Orthodontics Tuebingen University HospitalTuebingenGermany department of oral and Maxillofacial surgery Tuebingen University HospitalTuebingenGermany

Background Various conservative and surgical approaches exist to treat Robin sequence(RS),but their effects on facial profile and mandibular catch-up growth are unclear.A functional treatment concept,used in our centre for 25 years,includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding *** We performed a prospective study to objectively describe facial profiles in infants with RS treated with the above *** with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov *** with RS received 3D-photographs during clinically indicated *** controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 *** digitally measured jaw index(JI),defined as alveolar overjet(O)x maxillary arch(U)/mandibular arch(L),and the soft tissue reference points A’-point,Nasion’,B’-point angle(ANB’),describing the relative position of maxilla to mandible,were *** mixed models were used to examine time trajectories in JI and ANB’.Results A total of 2073D images,obtained in 19 infants with RS and 32 controls,were *** and ANB’decreased over time in both groups[for JI−0.18(95%CI−0.25 to−0.10);for ANB’:−0.40°per month[(95%CI−0.48 to−0.32)]]but remained lower in controls[for JI−2.5(95%CI−3.2 to−1.8);for ANB’-1.7°(95%CI−2.4 to−1.0)].Also,the ANB’model showed a significant effect of the interaction term diagnosis x *** Based on longitudinal 3D images,we describe changes in objective parameters of facial profile in infants with and without RS during the first year of *** findings indicate catch-up growth in infants treated for RS.

关键词： Infant Mandibular catch-up growth Pre-epiglottic Baton Plate Robin sequence Three-dimensional photography

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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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Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

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Oncology Research 2024年第3期32卷 585-596页

作者： GANG LIU LEI SHI BIN WANG ZEHUI WU HAIYUAN ZHAO TIANYU ZHAO LIANGHUI SHI department of Gastrointestinal surgery First ffiliated Hospital of Wannan Medical CollegeWuhu241001China Chongqing Key Laboratory of oral Diseases and Biomedical Sciences Stomatological Hospital of Chongqing Medical UniversityChongqing401147China

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed ***,the mechanism by which it promotes colon cancer remains *** vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 *** proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle *** sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling ***-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene *** effects of tumorigenesis were evaluated in BALB/c nude mice by tumor *** data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M ***-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell *** qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene ***116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude *** study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

关键词： lncRNA KCNQ1OT1 Colon cancer HCT116 cells Tumorigenesis

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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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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

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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

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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

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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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