The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the r...The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.展开更多
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial...Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.展开更多
Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor t...Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.展开更多
A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study de...A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study develops a poly(vinylidene fluoride-trifluoroethylene)(P(VDF-TrFE))membrane with a precisely controlled porous structure.Ultrasonic stimulation is applied to induce acoustic-mechanic-electric(AcME)conversion and regulate the membrane’s surface potential to modulate the in situ electrical microenvironment.When the ultrasound frequency aligns with the membrane’s inherent frequency,maximal electrical energy conversion occurs via the resonance effect,which generates the highest possible surface potential.The maximal AcME conversion is achieved by a 12μm pore-sized P(VDF-TrFE)membrane with a resonance frequency of 40 kHz,resulting in the highest surface potential of-65.56 mV.Finite element modeling indicates that the deformation and stress of porous membranes are higher than that of non-porous membranes under the stimulation of ultrasound,yielding the highest surface potential.In vitro experiments and sequencing analysis show that the honeycomb sandwich-structured P(VDF-TrFE)membrane under the stimulation of the resonance ultrasound promoted osteogenic differentiation of rBMSCs through the PI3K-Akt signaling pathway.When the porous membranes are implanted to cover cranial defects,the bone defect repair is significantly enhanced under the stimulation of ultrasound compared with the non-porous membranes.This study establishes a new strategy for efficient AcME conversion on piezoelectric membranes and offers new insights into the applications of ultrasound-responsive piezoelectric materials for bone defect repair.展开更多
Sterilization is the process of killing all microorganisms,while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores.Biomaterials involved in cell experime...Sterilization is the process of killing all microorganisms,while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores.Biomaterials involved in cell experiments,animal experiments,and clinical applications need to be in the aseptic state,but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection.Decellularized matrix(dECM)is the low immunogenicity material obtained by removing cells from tissues,which retains many inherent components in tissues such as proteins and proteoglycans.But there are few studies concerning the effects of sterilization or disinfection on dECM,and the systematic introduction of sterilization or disinfection for dECM is even less.Therefore,this review systematically introduces and analyzes the mechanism,advantages,disadvantages,and applications of various sterilization and disinfection methods,discusses the factors influencing the selection of sterilization and disinfection methods,summarizes the sterilization and disinfection methods for various common dECM,and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method,so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.展开更多
基金supported by the National Natural Science Foundation of China,No.81771351the National Key R&D Program of China,No.2017YFA0105802+1 种基金the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。
文摘The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.
基金funded by the National Natural Science Foundation of China(No.81500858 to Xinwen Zhang,No.81700977 to Xu Yan)Natural Science Foundation of Liaoning Province(China)(No.2022-MS-231 to Xinwen Zhang)+1 种基金the Science and Technology Planning Project of Shenyang(China)(No.22-321-33-26 to Dehao Shang)Grants-in-Aid for Scientific Research(Japan)(No.22K09927 to Zhou Wu).
文摘Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.
基金the National Key Research and Development Program of China(No.2022YFC2403203-3)Jilin Province Department of Finance(No.jcsz2023481-13)+2 种基金the National Natural Science Foundation of China(Nos.51972003 and 52271127)the Intergovernmental International Co-operation Project of Beijing Municipal Science and Technology Commission(No.Z221100002722004)the 2023 Management Research Project(No.YS040223).
文摘Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.
基金supported by the National Natural Science Foundation of China(Nos.82471029,U22A20314,and 81600905)the Peking University Medicine Fund of Fostering Young Scholars’Scentific&Technological Innovation supported by the Fundamental Research Funds for the Central Universities(No.BMU2018PY005)the National Key Research and Development Program of China(No.2018YFE0194400).
文摘A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study develops a poly(vinylidene fluoride-trifluoroethylene)(P(VDF-TrFE))membrane with a precisely controlled porous structure.Ultrasonic stimulation is applied to induce acoustic-mechanic-electric(AcME)conversion and regulate the membrane’s surface potential to modulate the in situ electrical microenvironment.When the ultrasound frequency aligns with the membrane’s inherent frequency,maximal electrical energy conversion occurs via the resonance effect,which generates the highest possible surface potential.The maximal AcME conversion is achieved by a 12μm pore-sized P(VDF-TrFE)membrane with a resonance frequency of 40 kHz,resulting in the highest surface potential of-65.56 mV.Finite element modeling indicates that the deformation and stress of porous membranes are higher than that of non-porous membranes under the stimulation of ultrasound,yielding the highest surface potential.In vitro experiments and sequencing analysis show that the honeycomb sandwich-structured P(VDF-TrFE)membrane under the stimulation of the resonance ultrasound promoted osteogenic differentiation of rBMSCs through the PI3K-Akt signaling pathway.When the porous membranes are implanted to cover cranial defects,the bone defect repair is significantly enhanced under the stimulation of ultrasound compared with the non-porous membranes.This study establishes a new strategy for efficient AcME conversion on piezoelectric membranes and offers new insights into the applications of ultrasound-responsive piezoelectric materials for bone defect repair.
基金This work was supported by the National Key R&D Program of China(No.2017YFA0105802)the Sichuan Science and Technology Program(No.2020YFH0008)the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science(2019JH3/30100022).
文摘Sterilization is the process of killing all microorganisms,while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores.Biomaterials involved in cell experiments,animal experiments,and clinical applications need to be in the aseptic state,but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection.Decellularized matrix(dECM)is the low immunogenicity material obtained by removing cells from tissues,which retains many inherent components in tissues such as proteins and proteoglycans.But there are few studies concerning the effects of sterilization or disinfection on dECM,and the systematic introduction of sterilization or disinfection for dECM is even less.Therefore,this review systematically introduces and analyzes the mechanism,advantages,disadvantages,and applications of various sterilization and disinfection methods,discusses the factors influencing the selection of sterilization and disinfection methods,summarizes the sterilization and disinfection methods for various common dECM,and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method,so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.
