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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo Yunfeng Lin State Key Laboratory of oral Diseases&National center for Stomatology&National Clinical Research center for oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China department of oral and maxillofacial surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research center of oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment *** patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal *** address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of *** synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with *** in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone *** findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

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Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai State Key Laboratory of oral&maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State Key Laboratory of oral&maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of oral&maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang center for Life and medical Sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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

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

FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

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International Journal of oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He department of oral maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina department of oral surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina department of oral Pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren department of oral and maxillofacial-Head and Neck Oncology 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 Stomatology&Shanghai Research Institute of StomatologyShanghaiChina department of oral and maxillofacial surgery Zhongshan HospitalFudan UniversityShanghaiChina School and Hospital of Stomatology Kunming Medical UniversityKunmingChina center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central Hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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

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

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