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Neural Regeneration research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu department of orthopedic surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina department of orthopedic surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina department of orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of orthopedic surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of orthopedic surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu department of Spinal surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and research Center Peking University People’s HospitalBeijingChina department of orthopedic surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun department of orthopedic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina department of orthopedic surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design

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Bioactive Materials 2024年第10期40卷 1-18页

作者： Juehan Wang Yulin Jiang Ce Zhu Zheng Liu Lin Qi Hong Ding Jing Wang Yong Huang Yubao Li Yueming Song Ganjun Feng Li Zhang Limin Liu Analytical&Testing Center Department of Orthopedic Surgery and Orthopedic Research InstituteWest China HospitalSichuan UniversityChengdu610065China

Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)*** of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP ***,re-energizing the mitochondria damaged in the inflammatory milieu to restore their function,is equally ***,we proposed an interesting concept of mitochondrion-engine equipped with coolant,which enables first to“cool-down”the inflammatory environment,next to restore the MMP,finally to allow cells to regain normal energy metabolism through materials *** such,we developed a multifunctional composite composed of a reactive oxygen species(ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane(TPU)*** TPU scaffold was coated with conductive polypyrrole(PPy)to electrophoretically deposit L-arginine,which could upregulate the Mammalian target of rapamycin(mTOR)pathway,thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD *** the ROS-responsive hydrogel acting as the“mito-engine coolant”could scavenge the excessive ROS to create a favorable environment for IVD cells *** by in vitro and in vivo evaluations,the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative *** and histological assessments in vivo revealed the efficacy of this system in IVD *** unique bioinspired design integrated biomaterial science with mitochondrial biology,presents a promising paradigm for IDD treatment.

关键词： Mitochondrial dysfunction Intervertebral disc degeneration L-arginine ROS scavenging Polyurethan scaffold

Chylothorax following posterior low lumbar fusion surgery:A case report

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World Journal of Clinical Cases 2021年第22期9卷 6522-6530页

作者： Xian-Ming Huang Ming Luo Li-Yu Ran Xuan-He You Di-Wei Wu Shi-Shu Huang Quan Gong department of orthopedic surgery and orthopedic research institute West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery;however,it is one of the rare complications in orthopedic *** case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion *** etiology,diagnosis,and treatment were analyzed and *** SUMMARY A 50-year-old woman was admitted with repeated back and leg *** was diagnosed with L4 degenerative spondylolisthesis,L4/L5 and L5/S1 intervertebral disc herniation and L5 instability,and underwent successful posterior L4-S1 instrumentation and fusion ***,thoracic effusion was identified 2 d after *** thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative *** patient was discharged after 12-d persisting drainage,3-d total parenteral nutrition and fasting,and other supportive *** recurring symptoms were observed within 12 mo *** Differential diagnosis is crucial for unusual thoracic *** diagnosis and treatment of chylothorax are *** intraoperative protection to relieve high thoracic pressure caused by the prone position is important.

关键词： Chylothorax Conservative managements Diagnosis Posterior lumbar surgery Complication Case report

Skeletal interoception in osteoarthritis

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Bone research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu department of Joint surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China department of orthopedic surgery and orthopedic research institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners hospitals Pediatric research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Multidimensionally Nano‑topologized Polycaprolactone Fibrous Membrane Anchored with Bimetallic Peroxide Nanodots for Microenvironment‑Switched Treatment on Infected Diabetic Wounds

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Advanced Fiber Materials 2024年第6期6卷 1777-1797页

作者： Lin Qi Yong Huang Zheng Liu Jiangshan Liu Jing Wang Huilun Xu Hao Yang Limin Liu Ganjun Feng Shuyu Zhang Yubao Li Li Zhang Analytical and Testing Center Sichuan UniversityChengdu 610065China department of orthopedic surgery and orthopedic research institute&west china hospital Sichuan UniversityChengdu 610065China west china School of Basic Medical Science and Forensic Medicine Sichuan UniversityChengdu 610065China

Delayed healing of diabetic wounds poses a major challenge to human health due to severe vascular dysfunction,sustained inflammation,and vulnerability to microbial ***,we constructed multidimensionally nano-topologized elec-trospun polycaprolactone(PCL)fibrous membranes with shish-kebab nanoarrays on each fiber through self-induced crys-tallization,on which the CuO2-MgO2 bimetallic peroxide nanodots(BPNs)were anchored by polydopamine(PDA)as the bridging *** activated by the acidic microenvironment(typically infected diabetic wound),BPNs on fibers reacted immediately to release Cu2+and Mg2+ions together with hydrogen peroxide(H2O2)molecules,which were then transferred into·OH radicals through Fenton-type reactions catalyzed by Cu2+for instant bacteria *** the same time,the released Cu2+and Mg2+ions were retained to improve the angiogenesis and suppress the inflammation infiltration,thus remodeling the wound ***,the one-dimensional(1D)-constructed nano shish-kebabs and PDA coating on fibers provided additional topological activation for cell adhesion and directed migration along the aligned fiber *** the meticulous design,the resultant membranes markedly accelerated the infected wound healing in the diabetic rat *** study pioneers a unique design to develop a nanocomposite fibrous membrane that combines multidimensional topologies with chemodynamic therapy(CDT),for efficiently combating infected diabetic wounds.

关键词： Electrospinning Polycaprolactone Multidimensional topology Metal peroxides Diabetic wound