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The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial tissue engineering

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Journal of Bionic engineering 2024年第2期21卷 924-937页

作者： Sharareh Ghaziof Shahrokh Shojaei Mehdi Mehdikhani Mohammad Khodaei Milad Jafari Nodoushan Department of Biomedical engineering Central Tehran BranchIslamic Azad UniversityTehran***Iran stem cells Research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran Department of Biomedical engineering Faculty of EngineeringUniversity of IsfahanIsfahan***Iran Materials engineering Group Golpayegan College of EngineeringIsfahan University of TechnologyGolpayegan87717-67498Iran Hard tissue engineering Research Center Tissue Engineering and Regenerative Medicine InstituteCentral Tehran BranchIslamic Azad UniversityTehran***Iran

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of *** this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the ***,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were *** microstructural observation of the scaffolds reported interconnected pores with 150–300µm in *** 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D *** release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th *** addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved *** findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

关键词： Polycaprolactone Gold nanoparticles Drug delivery systems Spironolactone Cell behavior Myoblasts

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IRE1α regulates the PTHrP-IHH feedback loop to orchestrate chondrocyte hypertrophy and cartilage mineralization

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Genes & Diseases 2024年第1期11卷 464-478页

作者： Mengtian Fan Nana Geng Xingyue Li Danyang Yin Yuyou Yang Rong Jiang Cheng Chen Naibo Feng Li Liang Xiaoli Li Fengtao Luo Huabing Qi Qiaoyan Tan Yangli Xie Fengjin Guo laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China laboratory of stem cells and tissue engineering School of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Department of Orthopedics The 1st Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Wound Repair and Rehabilitation Medicine State Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is *** inositol-requiring enzyme 1a/X-box-binding protein-1 spliced(IRE1α/XBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage ***,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains ***,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone ***1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth *** deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and ***1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage ***,ER stress cannot be activated normally in ERN1-deficient *** conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER ***1 may have a potential role as a new target for cartilage growth and maturation.

关键词： Cartilage development ER stress ERN1 IHH PTHrP/PTH1R

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CRISPR,CAR-T,and NK:Current applications and future perspectives

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Genes & Diseases 2024年第4期11卷 246-257页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Amir Ali Hamidieh Saman Hosseinkhani Department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom branch***Iran National Institute of Genetic engineering and Biotechnology(NIGEB) Tehran 14965/161Iran Department of stem cells technology and tissue Regeneration Faculty of Interdisciplinary Science and TechnologiesTarbiat Modares UniversityTehran 15614Iran Pediatric Cell Therapy and Gene Therapy Research Center GeneCell&Tissue Research InstituteTehran University of Medical SciencesTehran ***Iran Department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 15614Iran

Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer *** this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy *** the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been *** killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity *** on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the *** methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer *** improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor *** achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed inthis review.

关键词： Cancer CAR T-cell CRISPR Gene editing Immunotherapy NK cell

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Wireless electrical stimulation generated by piezoelectric nanomaterial promotes the dental pulp regeneration via regulating mitochondrial Ca^(2+)/PKA signaling pathway

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Journal of Materials Science & Technology 2024年第1期168卷 24-34页

作者： Jianmao Zheng Jiyuan Zuo Cairong Xiao Qining Guo Xiaobin Fu Chengyun Ning Peng Yu Guangdong Provincial Key laboratory of Stomatology Hospital of StomatologySun Yat-Sen UniversityGuangzhou 510080China School of Materials Science and engineering National Engineering Research Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510641China

The induction of dental pulp stem cells(DPSCs)into odontogenic differentiation is a cutting-edge method of dental pulp regeneration ***,it remains a challenge to develop biomaterials and ther-apies that can induce odontogenic ***,we propose a wireless electrical stimulation strat-egy to induce DPSCs odontogenic differentiation via K_(0.5)Na_(0.5)NbO_(3)piezoelectric nanoparticles(KNN)and polarized KNN(PKNN),which can be endocytosed by *** vitro,several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN,and the increase was more obvious in the PKNN *** wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter(MCU),increased the production of adenosine triphos-phate(ATP),and induced odontogenic differentiation through the activation of the cAMP-PKA signaling *** vivo,dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN,which was more clinically friendly compared with the wired device,and the induction was more obvious in the PKNN group consistent with in vitro *** conclusion,this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.

关键词： Piezoelectric nanoparticles Dental pulp stem cells Odontogenic differentiation

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Mesenchymal stem cell-derived exosomes: Versatile nanomaterials for skin wound treatment

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Nano Research 2024年第4期17卷 2836-2856页

作者： Yuzhen Xiao Hexi Li Junhui Zhang Songyun Yang Chunsen Zhang Yizhou Huang Xin Tang Huiqi Xie Department of Orthopedic Surgery and Orthopedic Research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610041China Sports Medicine Center West China HospitalSichuan UniversityChengdu 610041China

Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine ***,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive *** the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound *** hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their *** to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin *** further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive ***,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.

关键词： exosomes mesenchymal stem cells diabetic wounds burn wounds scar wound healing

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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Skeletal stem cells in bone development,homeostasis,and disease

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Protein & Cell 2024年第8期15卷 559-574页

作者： Guixin Yuan Xixi Lin Ying Liu Matthew B.Greenblatt Ren Xu The First Affliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal stem Cell State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361005China Xiamen Key laboratory of Regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue RegenerationOrgan Transplantation InstituteSchool of MedicineXiamen UniversityXiamen 361102China Department of Pathology and laboratory Medicine Weill Cormell Medical CollegeNew YorkNY 10065USA Research Division Hospital for Special SurgeryNew YorkNY10065USA

tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem *** studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and *** investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time ***,recent studies have shed light on the characteristics of ssCs in both physiological and pathological *** review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

关键词： skeletal stem cells bone development endochondral ossification intramembranous ossification lineage tracing

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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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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of Dayton Premedical Program University of Dayton Center for tissue Regeneration and engineering at Dayton (TREND) University of Dayton The Integrative Science and engineering Center University of Dayton Center for Genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells

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Regenerative Biomaterials 2024年第2期3卷 76-87页

作者： Tao Lu Long Yang Zhuoyang Li Yin Liu Shun'en Xu Chuan Ye Department of Orthopaedics The Affliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Orthopaedics The First People's Hospital of GuiyangGuiyang 550004China Center for tissue engineering and stem Cell Research Guizhou Medical UniversityGuiyang 550004China Department of Otolaryngology Head and Neck Surgery Xinqiao HospitalArmy Medical University(Third Military Medical University)Chongqing 400037China Department of Dental implant Stomatological Hospital of GuiyangGuiyang 550000China

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic *** scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were *** subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction *** fabricated P34HB ultrafine fiber slow-release *** ization *** distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active *** vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular *** Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on ***,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 *** findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.

关键词： bone tissue engineering cell electrospinning in vivo induction immediate implantation biomaterials

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