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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

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 injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The 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

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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

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Bone block from lateral window-correcting vertical and horizontal bone deficiency in maxilla posterior site:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2109-2115页

作者： Yu-Lan Wang Wen-Jun Shao Min Wang 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 430079Hubei ProvinceChina Department of oral Implantology School and Hospital of StomatologyWuhan UniversityWuhan 430079Hubei ProvinceChina

BACKGROUND Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm.However,managing cases becomes more challenging when a maxillary sinus pseudocyst is present or when there is insufficient bone width.In this case,we utilized the bone window prepared during the lateral window sinus lift as a shell for horizontal bone augmentation.This allowed for simultaneous horizontal and vertical bone augmentation immediately after the removal of the maxillary sinus pseudocyst.CASE SUMMARY A 28-year-old female presented to our clinic with the chief complaint of missing upper left posterior teeth.Intraoral examination showed a horizontal deficiency of the alveolar ridge contour.The height of the alveolar bone was approximately 3.6 mm on cone beam computed tomography(CBCT).And a typical well-defined'dome-shaped'lesion in maxillary sinus was observed on CBCT imaging.The lateral bony window was prepared using a piezo-ultrasonic device,then the bony window was fixed to the buccal side of the 26 alveolar ridge using a titanium screw with a length of 10 mm and a diameter of 1.5 mm.The space between the bony window and the alveolar ridge was filled with Bio-Oss,covered with a Bio-Gide collagen membrane,and subsequently sutured.Nine months later,the patient’s bone width increased from 4.8 to 10.5 mm,and the bone height increased from 3.6 to 15.6 mm.Subsequently,a Straumann^(■)4.1 mm×10 mm implant was placed.The final all-ceramic crown restoration was completed four months later,and both clinical and radiographic examinations showed that the implant was successful,and the patient was satisfied with the results.CONCLUSION The bone block harvested from the lateral window sinus lift can be used for simultaneous horizontal bone augmentation acting as a shell for good two-dimensional bone augmentation.

关键词： Sinus lift Lateral window Dental implant Horizontal bone augmentation Case report

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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 tumor.Such 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 ability.To 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 nanomedicine.All these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were included.With 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

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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

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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 response.These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine.While many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular aspects.Recent 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 conditions.This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation.To achieve this goal,we dissect the intricacies of autophagy and its mechanisms.Subsequently,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic trajectories.Furthermore,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic milieu.The 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

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Bioinspired mineral-in-shell nanoarchitectonics:functional empowerment of mineral precursors for guiding intradentinal mineralization

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Nano Research 2024年第5期17卷 4338-4349页

作者： Xiaoran Zheng Yang Liu Mingjing Li Yuyan Li Wanshan Gao Rongmin Qiu Jiaqi Xing Jiaojiao Yang Yantao Chen Xinyuan Xu Mingming Ding Jun Luo Jianshu Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China College of Stomatology Hospital of Stomatology Guangxi Medical UniversityGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and ReconstructionGuangxi Clinical Research Center for Craniofacial DeformityGuangxi Key Laboratory of Oral and Maxillofacial Surgery Disease TreatmentGuangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious DiseasesNanning 530021China State key laboratory of oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Shenzhen key laboratory of Environmental Chemistry and Ecological Remediation College of Chemistry and Environmental EngineeringShenzhen UniversityShenzhen 518060China Med-X Center for Material Sichuan UniversityChengdu 610041China

Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes.In this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization pathways.Our nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)nanoshell.The bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external stimuli.Theoretical simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral formation.Overall,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.

关键词： mineral-in-shell nanohybrids self-assembly biomineralization dentinal tubule occlusion dental hypersensitivity

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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 impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-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 sevoflurane.Mechanistic 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 proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways invo

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

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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 progression.By analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-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 cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,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 development.These 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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Strain engineering of Pt-based electrocatalysts for oxygen reaction reduction

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Frontiers in Energy 2024年第2期18卷 241-262页

作者： Zeyu WANG Yanru LIU Shun CHEN Yun ZHENG Xiaogang FU Yan ZHANG 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 Institute of New Energy Materials and Engineering School of Materials Science and EngineeringFuzhou UniversityFuzhou 350108China key laboratory of Marine Chemistry Theory and Technology(Ministry of Education) College of Chemistry and Chemical EngineeringOcean University of ChinaQingdao 266100China

Proton exchange membrane fuel cells(PEMFCs)are playing irreplaceable roles in the construction of the future sustainable energy system.However,the insufficient performance of platinum(Pt)-based electrocatalysts for oxygen reduction reaction(ORR)hinders the overall efficiency of PEMFCs.Engineering the surface strain of catalysts is considered an effective way to tune their electronic structures and therefore optimize catalytic behavior.In this paper,insights into strain engineering for improving Pt-based catalysts toward ORR are elaborated in detail.First,recent advances in understanding the strain effects on ORR catalysts are comprehensively discussed.Then,strain engineering methodologies for adjusting Ptbased catalysts are comprehensively discussed.Finally,further information on the various challenges and potential prospects for strain modulation of Pt-based catalysts is provided.

关键词： strain engineering Pt-based catalysts oxygen reduction reaction(ORR) catalytic performance proton exchange membrane fuel cells(PEMFCs)

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