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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

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

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International Journal of oral Science 2024年第1期16卷 163-172页

作者： Xiao Yang Hui Zhao rui Li Yang Chen Zhi Xu Zhengjun Shang state key laboratory of oral&maxillofacial reconstruction and regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of oral and maxillofacial-Head and Neck Oncology School of Stomatology–Hospital of StomatologyWuhan UniversityWuhanChina Department of Stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

关键词： angiogenesis elevated endogenous

Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

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Chinese Journal of Chemistry 2024年第10期42卷 1175-1189页

作者： Guo-Feng Luo Wei-Hai Chen Xian-Zheng Zhang state key laboratory of oral&maxillofacial reconstruction and regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei KeyLaboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanHubei 430079China key laboratoryof Biomedical Polymers of Ministry of Education&Departmentof Chemistry Wuhan UniversityWuhanHubei 430072China

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of *** barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration *** achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing *** these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were *** the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

关键词： Nanomedicine Tumor stroma Deep penetration Enhanced drug perfusion Cancer therapy Drug carriers Biomaterials Nanotechnology

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

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

More than just aligning the teeth:Clear aligners with multifunctional prowess

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Nano research 2024年第8期17卷 7665-7674页

作者： Yang Chen Lei-Ming Cao Nian-Nian Zhong Zi-Zhan Li Lin-Lin Bu Fang-Yi Huo Hong He state key laboratory of oral and maxillofacial reconstruction and regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool and Hospital of StomatologyWuhan UniversityWuhan 430079China Department of oral and maxillofacial-Head Neck Oncology School and Hospital of StomatologyWuhan UniversityWuhan 430079China Department of Zhuankou Clinical Branches School and Hospital of StomatologyWuhan UniversityWuhan 430000China Department of Orthodontics School and Hospital of StomatologyWuhan UniversityWuhan 430079China

With the increasing demand for beauty and health,clear aligners(CAs)have been widely applied among patients with ***,patients treated with CAs also face some potential complications,such as demineralization,dental caries,and periodontal *** addition,some patients have additional needs to improve their quality of life,such as bleaching *** order to prevent or solve these problems,the modification of CAs is a promising method because their extensive long-term contact with tooth surfaces makes them ideal devices for implementing adjuvant medical *** this review,we discuss various advanced CAs with medical functions based on the clinical needs of *** far as we know,the additional functions of CAs mainly include antibacterial,remineralization,whitening,and accelerating tooth *** functions are achieved by two major pathways,the combination of CAs with drugs/biomaterials and increasing the capacity or affinity of *** addition,we discuss the current limitations of in vitro experiments which are designed to explore the effectiveness and properties of novel CAs,and the challenges of bringing a multifunctional appliance from proposal to clinical *** the end of this review,we provide insights into the broader prospects for the improvement of CAs.

关键词： advanced clear aligners medical device modification drug delivery system personalized medicine

recent advances in morphology control of platinum catalysts toward oxygen reduction reaction

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Frontiers in Energy 2024年第3期18卷 330-355页

作者： Shun CHEN Yanru LIU Xiaogang FU Wanglei WANG state key laboratory of Solidification Processing Atomic Control and Catalysis Engineering LaboratorySchool of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China state key laboratory of oral and maxillofacial reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Dental MaterialsSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China

Exploring advanced platinum (Pt)-based electrocatalysts is vital for the widespread implementation of proton exchange membrane fuel cells (PEMFCs). Morphology control represents an effective strategy to optimize the behavior of Pt catalysts. In this work, an attempt is made to comprehensively review the effect of morphology control on the catalytic behavior of catalysts in the oxygen reduction reaction (Orr). First, the fundamental physicochemical changes behind morphology control, including exposing more active sites, generating appropriate lattice strains, and forming different crystalline surfaces, are highlighted. Then, recently developed strategies for tuning the morphologies of electrocatalysts, including core-shell structures, hollow structures, nanocages, nanowires, and nanosheets, are comprehensively summarized. Finally, an outlook on the future development of morphology control of Pt catalysts is presented, including rational design strategies, advanced in situ characterization techniques, novel artificial intelligence, and mechanical learning. This work is intended to provide valuable insights into designing the morphology and technological innovation of efficient redox electrocatalysts in fuel cells.

关键词： morphology platinum catalysts electrocatalysis Orr PEMFC

Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

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International Journal of oral Science 2024年第2期16卷 280-292页

作者： Ziming Wang Hao Zeng Can Wang Jiaolong Wang Jing Zhang Shuyuan Qu Yue Han Liu Yang Yueqi Ni Wenan Peng Huan Liu Hua Tang Qin Zhao Yufeng Zhang 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 UniversityWuhanChina School of Stomatology Nanchang UniversityNanchangChina Institute of Infection and Immunity Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanChina Medical research Institute School of MedicineWuhan UniversityWuhanChina

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth *** the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone ***301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone ***,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain *** this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)*** first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b−macrophages via high-throughput rNA ***,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)*** single-cell rNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in *** following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis ***,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in ***,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages *** a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

关键词： period upstream eventually

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological research 2024年第3期45卷 663-678页

作者： Li-rong Liang Bing Liu Shu-Hui Cao You-Yi Zhao Tian Zeng Mei-Ting Zhai Ze Fan Dan-Yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang state key laboratory of oral&maxillofacial reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China Department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive ***,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive ***,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly *** this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal *** neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral *** indicated that ADNP was significantly down-regulated following developmental exposure to *** adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine ***,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane ***-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by *** analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic *** of Wnt signaling was restored in the davunetide-treated ***,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general *** study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity