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METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs

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International Journal of Oral Science 2024年第3期16卷 528-538页

作者： Yizhou Jin Xiao Han Yuejun Wang Zhipeng Fan Beijing Key Laboratory of tooth regeneration and Function Reconstruction Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina research Unit of tooth development and regeneration Chinese Academy of Medical SciencesBeijingChina

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic ***,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic *** knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion ***,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ***,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin ***98059(a selective ERK inhibitor)blocks the corin-mediated promotion *** regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion ***,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation *** conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK *** hope this brings new insights into future clinical treatments for BRONJ.

关键词： impaired cor mediated

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PRX1-positive mesenchymal stem cells drive molar morphogenesis

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International Journal of Oral Science 2024年第2期16卷 293-305页

作者： Xiaoqiao Xu Xuyan Gong Lei Zhang Han Zhang Yao Sun Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghaiChina

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be *** merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1^(+)cells within *** PRX1^(+)cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell *** into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1^(+)cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling *** loss of Wnt5a exhibits a defect phenotype similar to that of *** addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth *** findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

关键词： Wnt5a mesenchymal inhibited

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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

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Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren Tianmeng Sun Paul T.Sharpe Hongchen Sun Zhengwen An Department of Oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK Department of Oral Pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular *** contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and *** can be traced to their cells of origin and exhibit a similar ***,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent *** stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell *** mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously ***,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell *** EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample ***,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular ***,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic *** highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical *** aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles Oral tissue MSC Therapeutic application Tissue regeneration

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Flexible wearable sensors:An emerging platform for monitoring of bacterial infection in skin wounds

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Engineered regeneration 2024年第2期5卷 186-198页

作者： Hao Meng Weicheng Zhong Kui Ma Jianlong Su Liqian Ma Yaying Hao Yufeng Jiang Xi Liu Xiaobing Fu Cuiping Zhang research Center for Tissue Repair and regeneration Affiliated to the Medical Innovation research Department PLA General Hospital and PLA Medical CollegeBeijing 100048PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine Beijing 100048PR China Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048PR China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Department of Tissue regeneration and Wound Repair PLA General HospitalBeijingPR China

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic ***,achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerat-ing the healing ***,flexible wearable sensors have garnered significant attention,especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive *** provide more precise and continuous monitoring data,making them as emerging tools for clinical *** this review,we first discuss the species and community distribution of different types of bacteria in chronic ***,we introduce currently developed techniques for detecting bacteria at wound ***-lowing that,we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound *** believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

关键词： Flexible wearable sensors Chronic wounds Bacterial infections Real-time detection

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Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo Guangdong Key Laboratory of Non-human Primate research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical *** the population ages,NDs are imposing a huge burden on public health systems and affected *** models are important tools for preclinical investigations to understand disease pathogenesis and test potential *** numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation *** World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to *** is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience ***,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel *** review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

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Large animal models for Huntington's disease research

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Zoological research 2024年第2期45卷 275-283页

作者： Bofeng Han Weien Liang Xiao-Jiang Li Shihua Li Sen Yan Zhuchi Tu Guangdong-Hongkong-Macao CNS regeneration Institute of Jinan University Key Laboratory of CNS Regeneration(Jinan University)-Ministry of EducationGuangdong Key Laboratory of Non-Human Primate ResearchGuangzhouGuangdong 510632China Department of Pathophysiology School of MedicineJinan UniversityGuangzhouGuangdong 510632China

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no ***,the development of appropriate disease models is critical to thoroughly investigate disease *** genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT *** HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain *** models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic *** to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD *** models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment *** have explored the advantages of utilizing large animal models,particularly pigs,in previous *** then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of *** the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic *** also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and *** objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

关键词： Huntington's disease Large animal models Sheep Non-human primates Transgenic pigs

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Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK

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International Journal of Oral Science 2024年第3期16卷 471-485页

作者： Dexuan Zhuang Shuangshuang Wang Huiting Deng Yuxin Shi Chang Liu Xue Leng Qun Zhang Fuxiang Bai Bin Zheng Jing Guo Xunwei Wu School and Hospital of Stomatology Cheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration&Shandong Provincial Clinical Research Center for Oral DiseasesJinanChina Engineering Laboratory for Biomaterials and Tissue regeneration Ningbo Stomatology HospitalSavaid Stomatology SchoolHangzhou Medical CollegeNingboChina Cedars-Sinai Cancer Institute Department of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesCAUSA

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new *** has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC *** found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in ***-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC ***,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC ***,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of *** summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell *** study supports the potential clinical utility of phenformin for OSCC treatment in the future.

关键词： drugs treatment AMPK DDI

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A noval iron-capturing nanocomposites against biofilms for disrupting bacterial nutritional balance

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Science China Chemistry 2024年第6期67卷 1760-1761页

作者： Jinying Lin Qihang Ding Yao Sun Department of Oral Implantology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool of StomatologyJilin UniversityChangchun130021China Department of Chemistry Korea UniversitySeoul02841Korea National Key Laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan430079China

Currently,the escalating crisis of bacterial infections and antibiotic resistance poses a significant global public health challenge[1-3].This situation has driven the search for novel antimicrobial ***,a crucial micr... 详细信息

关键词： metabolism resistance balance

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Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural regeneration research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad Center of regeneration Medicine and Stem Cell research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during *** cells are generated in an organized fashion during *** early stages of brain development,neural stem cells(NSC... 详细信息

关键词： cortex cerebral development

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A Comprehensive Overview of the Neural Mechanisms of Light Therapy

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Neuroscience Bulletin 2024年第3期40卷 350-362页

作者： Xiaodan Huang Qian Tao Chaoran Ren Guangdong-Hongkong-Macao Institute of CNS regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhou 510632China Psychology Department School of MedicineJinan UniversityGuangzhou 510632China

Light is a powerful environmental factor influencing diverse brain *** evidence supports the beneficial effect of light therapy on several diseases,including depression,cognitive dysfunction,chronic pain,and sleep ***,the precise mechanisms underlying the effects of light therapy are still not well *** this review,we critically evaluate current clinical evidence showing the beneficial effects of light therapy on *** addition,we introduce the research progress regarding the neural circuit mechanisms underlying the modulatory effects of light on brain functions,including mood,memory,pain perception,sleep,circadian rhythm,brain development,and metabolism.

关键词： Light therapy Neural circuit Mood Cognition Pain Sleep development Metabolism

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