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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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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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Chlorogenic acid supported strontium polyphenol networks ensemble microneedle patch to promote diabetic wound healing

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Chinese Chemical Letters 2024年第8期35卷 491-497页

作者： Peizhe Li Qiaoling Liu Mengyu Pei Yuci Gan Yan Gong Chuchen Gong Pei Wang Mingsong Wang Xiansong Wang Da-Peng Yang Bo Liang Guangyu Ji Research Institute of Plastic Surgery Weifang Medical UniversityWeifang 261000China The Second Affiliated Hospital of Fujian medical University Quanzhou 362000China Department of Thoracic surgery Shanghai Key Laboratory of Tissue EngineeringShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China The Third Affiliated Hospital of Xinxiang medical University Institutes of Health Central PlainClinical Medical Center of Tissue Engineering and RegenerationXinxiang Medical UniversityXinxiang 453003China School of Rehabilitation Science and engineering University of Health and Rehabilitation SciencesQingdao 266024China

Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)*** this,we introduced a strontium polyphenol network microneedle patch(SrC-MPNs@MN-PP)for percutaneous drug *** patch,formulated with polymer poly(γ-glutamic acid)(γ-PGA)and epsilon-poly-l-lysine(ε-PLL),incorporates strontium polyphenol networks(SrC-MPNs).The release of chlorogenic acid(CGA)from SrC-MPNs not only neutralizes ROS,but strontium ions also foster ***,SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.

关键词： Chlorogenic acid Strontium Microneedle patch Strontium polyphenol network Exudate absorption Diabetic wound healing

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An aptamer-driven DNA nanodevice for improved delivery of synthetic immunostimulants

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Nano Research 2024年第10期17卷 9078-9083页

作者： Dejie Lu Zhenghan Di Lele Li Jian Zhao Li Zheng Guangxi engineering center in Biomedical Materials for tissue and Organ regeneration Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and ApplicationGuangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Efficient delivery of therapeutics to immune cells remains a formidable challenge for cancer *** this work,we demonstrate that an aptamer-driven DNA nanodevice,constructed through linkage of a synthetic immunostimulant(Toll-like receptor 9 agonist:CpG motif)to an aptamer,could significantly enhance the immunostimulatory activity by facilitating the uptake and retention of therapeutics in *** administration of the DNA nanodevice results in efficient tumor growth inhibition in both breast cancer and melanoma mouse *** studies suggest that the DNA nanodevice leads to reeducation of tumor-associated macrophages and ultimately to reversing the tumor immune *** strategy for aptamer-mediated and vehicle-free delivery of immunostimulatory oligonucleotides provides a potential platform for cancer immunotherapy.

关键词： aptamer immunostimulatory oligonucleotides DNA nanodevice tumor-associated macrophages cancer therapy

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Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel

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Regenerative Biomaterials 2024年第3期3卷 56-67页

作者： Ming Ke Wenhui Xu Yansha Hao Feiyang Zheng Guanyuan Yang Yonghong Fan Fangfang Wang Zhiqiang Nie Chuhong Zhu Department of Anatomy Third Military Medical UniversityChongqing 400038China State Key Laboratory of Trauma Burn and Combined InjuryChongqing 400038China Department of Plastic and Aesthetic Surgery Southwest HospitalThird Military Medical UniversityChongqing 400038China engineering Research center of tissue and Organ regeneration and Manufacturing Ministry of EducationChongqing 400038China

engineering myocardium has shown great clinal potential for repairing permanent myocardial ***,the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical *** prepared a mixed gel containing fibrin(5 mg/ml)and collagen I(0.2 mg/ml)and verified that human umbilical vein endothelial cells(HUVECs)and human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)could fom microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of ***-CMs and HUVECs in the mixed gel formed self-organized cell clusters,which were then cultured in different media using a three-phase *** successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of *** tissue exhibited autonomous beats that occured at a frequency similar to a normal human heart *** internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in *** summary,we propose a simple method for constructing vascularized engineered myocardial tissue,through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation *** constructed tissue has potential value for clinical use after preliminary evaluation.

关键词： engineered myocardium vascularized hiPSC-CM HUVEC fibrin

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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

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In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration

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Military medical Research 2024年第1期11卷 152-155页

作者： Enhe Jirigala Bin Yao Zhao Li Yi-Jie Zhang Chao Zhang Li-Ting Liang Fan-Liang Zhang Xing-Yu Yuan Xian-Lan Duan Wei Song Meng-De Zhang Yi Kong Xiao-Bing Fu Sha Huang Research center for tissue Repair and regeneration Medical Innovation Research DepartmentChinese PLA General Hospital and PLA Medical CollegeBeijing 100048China Institute of Basic medical Research Inner Mongolia Medical UniversityHohhot 010110China Academy of medical engineering and Translational Medicine Tianjin UniversityTianjin 300072China School of Medicine Nankai UniversityTianjin 300071China

Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical ***,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).

关键词： Sweat gland GelMA In situ niche Cell differentiation tissue incorporation Vascularization

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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural regeneration Research 2025年第09期 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin University Key Laboratory for Disaster Medicine Technology Henan medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical University clinical medical center of tissue engineering and regeneration Xinxiang Medical University Institutes of Health Central Plain Xinxiang Medical University School of Public Health Xinxiang Medical University

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-β deposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely "turn off" the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular

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Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing

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Regenerative Biomaterials 2024年第3期3卷 43-55页

作者： Mindong Du Shuhan Liu Nihan Lan Ruiming Liang Shengde Liang Maoqiang Lan Disen Feng Li Zheng Qingjun Wei Ke Ma Department of Orthopaedics Trauma and Hand Surgery The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530521China Guangxi engineering center in Biomedical Materials for tissue and Organ regeneration The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medicar UniversityNanning530021China Guangxi Collaborative Innovation center for Biomedicine The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Department of Plastic&Cosmetic Surgery.The First Affliated Hospital of Guangxi medical University Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning530021China

The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound *** scavenging,which regulates the ROS microenvironment,is essential for wound *** this study,we used novel electrospun PCL/gelatin/arbutin(PCL/G/A)nanofibrous membranes as wound dressings,with PCL/gelatin(PCL/G)as the backbone,and plantderived arbutin(hydroquinone-β-D-glucopyranoside,ARB)as an effective antioxidant that scavenges ROos and inhibits bacterial infection in *** loading of ARB increased the mechanical strength of the nanofibres,with a water vapour transmission rate of more than 2500g/(m^(2)×24h),and the water contact angle decreased,indicating that hydrophilicity and air permeability were significantly *** release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable *** experiments showed that the PCL/G/A nanofibre membranes were biocompatible,and DPPH and ABTS+radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant *** addition,haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in *** vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and *** conclusion,we successfully prepared a multifunctional wound dressing,PCL/G/A,for skin wound healing and investigated its potential role in wound healing,which is beneficial for the clinical translational application of phytomedicines.

关键词： arbutin nanofiber membranes wound dressing reactive oxygen species

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Expert consensus on the diagnosis and therapy of endo-periodontal lesions

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International Journal of Oral Science 2024年第3期16卷 381-389页

作者： Bin Chen Yanan Zhu Minkui Lin Yangheng Zhang Yanfen Li Xiangying Ouyang Song Ge Jiang Lin Yaping Pan Yan Xu Yi Ding Shaohua Ge Faming Chen Zhongchen Song Shaoyun Jiang Jiang Sun Lijun Luo Junqi Ling Zhi Chen Lin Yue Xuedong Zhou Fuhua Yan Department of Periodontology Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina Department of Endodontics Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina clinical Research center for Oral tissue Deficiency Diseases of Fujian Province&Fujian Key Laboratory of Oral Diseases&Fujian Provincial engineering Research center of Oral Biomaterial School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Periodontology 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 DevicesBeijingChina School and Hospital of Stomatology Zunyi Medical UniversityZunyiChina Department of Stomatology Beijing TongRen HospitalCapital Medical UniversityBeijingChina Department of Periodontics School and Hospital of StomatologyChina Medical UniversityShenyangChina Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityJiangsu Key Laboratory of Oral DiseasesNanjing Medical UniversityNanjingChina State Key Laboratory of Oral Diseases&National center for Stomatology&National clinical Research center for Oral Diseases&Department of Periodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Periodontology School and Hospital of StomatologyShandong 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 Diseases JinanJinanChina State Key Laboratory of Oral&Maxillofacial Reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesDepartment of periodontologySchool of StomatologyThe Fou

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing *** etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical ***,EPLaffected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal *** compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

关键词： diagnosis periodontal lesions

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