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

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

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FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han Department of trauma and orthopedics Peking University People’s HospitalBeijingChina National center for trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina trauma Medicine center Peking University People’s HospitalBeijingChina Department of orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

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Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第2期20卷 483-484页

作者： Yun Li Junfang Wu Department of Anesthesiology&Shock Trauma and Anesthesiology Research(STAR)CenterUniversity of Maryland School of MedicineBaltimoreMDUSA

traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability *** in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth *** survival changes have led neurotrauma researchers to examine how SCI interacts with brain *** health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.

关键词： alterations inflammation injury

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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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

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The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang Anke Baranowsky Johannes Keller Department of trauma and orthopedic surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis

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Distal femoral extension and shortening osteotomy as a part of multilevel surgery in children with cerebral palsy

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World Journal of Pediatrics 2017年第4期13卷 353-359页

作者： Matthias C.M.Klotz Klemens Hirsch Daniel Heitzmann Michael W.Maier Sebastien Hagmann Thomas Dreher Department of orthopedic and trauma surgery Heidelberg University ClinicsHeidelbergGermany

Background:There are several reports describing an increase in anterior pelvic tilt after hamstring lengthening in children with cerebral palsy (CP).Distal femoral extension and shortening osteotomy (DFESO) is an alternative treatment for correction of flexed knee gait,but investigations analyzing outcome and influence on adjacent joint are few in the *** purpose of this study was to analyze the influence of DFESO on knee and pelvis in children with ***,it was of interest if an additional patellar tendon advancement (PA) influences ***:In this retrospective study,31 limbs of 22 children (GMFCS Ⅰ-Ⅲ;mean age:12.1±3.1 years),who received DFESO were included and kinematic parameters (knee,pelvis) measured by 3-D-gait analysis were compared before and at least 1 year after surgery (mean follow-up period:15.6 months).Results:After surgery,during stance phase minimum knee flexion improved significantly by 20.5° (P<0.001) and mean anterior pelvic tilt increased by 4.0 degrees (P=0.045).In 16 limbs,the postoperative increase in maximum anterior pelvic tilt was more than 5°.Limbs who received an additional PA showed the biggest increase in anterior pelvic ***:DFESO is an effective method for correction of flexed knee gait in children with ***,the results of this study indicate that DFESO may lead to an increase in anterior pelvic tilt,which may lead to a recurrence of flexed knee *** this context,PA seemed to aggravate the effect on the pelvis.

关键词： cerebral palsy femoral extension osteotomy motion analysis

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Stem cells sources for intervertebral disc regeneration

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World Journal of Stem Cells 2016年第5期8卷 185-201页

作者： Gianluca Vadalà Fabrizio Russo Luca Ambrosio Mattia Loppini Vincenzo Denaro Department of orthopedic and trauma surgery University Campus Bio-Medico of Rome

Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible ***, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

关键词： Stem cells Intervertebral disc degeneration Spine Tissue engineering Cell therapy

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trauma-induced“Macklin effect”with pneumothorax and large pneumomediastinum,disguised by allergy

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Frontiers of Medicine 2013年第3期7卷 386-388页

作者： Salomone Di Saverio Kenji Kawamukai Andrea Biscardi Silvia Villani Luca Zucchini Gregorio Tugnoli Departments of Emergency and surgery Emergency Surgery and Trauma Surgery UnitTrauma CenterMaggiore Hospital-Bologna Local Health DistrictBolognaItaly Department of Thoracic surgery Trauma CenterMaggiore HospitalBolognaItaly Accident and Emergency Trauma CenterMaggiore HospitalBolognaItaly

A 56-year-old man presented spontaneously to the Emergency Department complaining of facial and neck oedema after assumption of nonsteroidal anti-inflammatory drugs(NSAIDS).The triage nurse assigned the patient to Accident&Emergency(A&E)doctor as probable allergic reaction to *** X-ray(CXR),ordered after 24 hours,revealed a huge subcutaneous chest and neck emphysema without clearly visible *** chest CT scan showed a small left pneumothorax and a large amount of air in the *** patient was conservatively treated since he was eupnoeic and hemodynamically *** pathophysiology of pneumomediastinum was first described by Macklin in *** Macklin effect involves alveolar ruptures with air dissection along bronchovascular sheaths to the *** this case the patient did not report in his history a recent blunt thoracic trauma and the initial suspicion of an allergic reaction has prevented physicians to immediately achieve the correct diagnosis.

关键词： thoracic trauma differential diagnosis critical care pneumothorax pneumomediastinum CT scan pitfalls lung and airways physiology

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MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells

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World Journal of Stem Cells 2023年第10期15卷 979-988页

作者： Jia-Jia Lu Xiao-Jian Shi Qiang Fu Yong-Chuan Li Lei Zhu Nan Lu Department of orthopedic trauma surgery Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200001China Department of orthopedic trauma surgery Shanghai Changzheng HospitalShanghai 200001China Department of orthopedic trauma Haimen People’s Hospital of Jiangsu ProvinceNantong 226100Jiangsu ProvinceChina

BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain *** To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of *** In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were *** expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic *** Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in *** differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these ***,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic ***2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic *** Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

关键词： Periosteal stem cell Osteogenic differentiation RUNX family transcription factor 2 MiroRNA-584-5p

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