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Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

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neural Regeneration Research 2024年第2期19卷 434-439页

作者： Chenxi Zhao Tiangang Zhou Ming Li Jie Liu Xiaoqing Zhao Yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng department of Orthopedics Tianjin Medical University General HospitalTianjinChina International Science and Technology Cooperation Base of spinal cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Orthopedic Research Center of Shandong University Cheeloo College of MedicineDepartment of OrthopedicsQilu Hospital of Shandong UniversityJinanShandong ProvinceChina

Argatroban is a synthetic thrombin inhibitor approved by *** and Drug Administration for the treatment of ***,whether it plays a role in the repair of spinal cord injury is *** this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive *** results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal *** sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar *** blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal *** also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal *** together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

关键词： argatroban astrogliosis JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury thrombin vimentin

Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine?Autophagy regulation also works

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Chinese Chemical Letters 2024年第6期35卷 474-479页

作者： Yuanyi Zhou Ke Ma Jinfeng Liu Zirun Zheng Bo Hu Yu Meng Zhizhong Li Mingshan Zhu Postdoctoral Innovation Practice Base The First and Fifth Affiliated Hospital of Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People’s Hospital)Heyuan 517465China School of Environment Jinan UniversityGuangzhou 511443China department of Nephrology The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China

Exploring the therapeutic effect of single atom catalysts beyond reactive oxygen species(ROS)modulation would boost the prosperity of nanomedicine in cancer *** as a vital therapy target offers new options for the control of renal cell carcinoma(RCC)***,Fe single atom-decorated graphene oxide(Fe_(1)-GO)nanosheet is developed to be a feasible autophagy inducer in RCC *** the well-dispersed O-Fe_(1)-O active sites,Fe_(1)-GO kills ACHN cells effectively but maintains acceptable cytotoxicity to the normal podocyte and HK2 ***-depth analyses ascribe the inhibition of ACHN cells to the upregulated autophagy instead of the commonly known catalytic ROS *** in vivo therapeutic effect of Fe_(1)-GO nanomedicine is also validated by the RCC-bearing BALB/c mice model,realizing an 89% reduction of tumor weight and good *** work provides new insights into the design of autophagy regulators as well as potential therapeutic strategies for RCC treatment.

关键词： Fe single atom Autophagy Renal cell carcinoma Graphene oxide Cancer therapy

MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery

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Science China Chemistry 2024年第4期67卷 1216-1223页

作者： Qinyi Cao Yifan Zhang Yanping Tang Changjin Wu Jizhuang Wang Dan Li College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of functional Supramolecular Coordination Materials and Applications Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of spine and spinal cord reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan 517000China JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research College of PharmacyJinan UniversityGuangzhou 510632China department of Chemistry The University of Hong KongHong KongChina

Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile ***,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise *** fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug ***,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted *** approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during *** select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive *** design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under *** the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental *** to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in *** investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.

关键词： magnetic microrobot swarm MOF nanoparticles magnetic propulsion pH-responsive drug release targeted drug delivery

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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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neural Regeneration Research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of spinal cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic Research Center of Shandong University&Advanced Medical Research Institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived *** effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in *** results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft *** CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve ***,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

Dual-directional regulation of spinal cord injury and the gut microbiota

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neural Regeneration Research 2024年第3期19卷 548-556页

作者： Yinjie Cui Jingyi Liu Xiao Lei Shuwen Liu Haixia Chen Zhijian Wei Hongru Li Yuan Yang Chenguang Zheng Zhongzheng Li Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina School of Medical Technology Tianjin University of Traditional Chinese MedicineTianjinChina Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjinChina International Cooperation and Exchange Office Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina International Cooperation Base of spinal cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut *** spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains *** studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut *** in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord *** review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord *** research identified three key ***,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord ***,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut ***,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous *** microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut *** targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

关键词： chemokines cytokines gut microbiota NLRP3 spinal cord injury Toll-like receptor ligand tryptophan

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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neural Regeneration Research 2024年第5期19卷 1126-1132页

作者： Hengxing Zhou Yongfu Lou Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng department of Orthopedics The Second HospitalCheeloo College of MedicineShandong UniversityShandongChina department of Orthopedics Shandong University Center for OrthopedicsQilu HospitalCheeloo College of MedicineShandong UniversityShandongChina department of Orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal CordTianjinChina Faculty of Medicine and Health The Back Pain Research TeamSydney Musculoskeletal HealthThe Kolling InstituteUniversity of SydneySydneyNSWAustralia department of spine Surgery Honghui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina department of Burns and Plastic Surgery The Fourth Medical Center of Chinese PLA General HospitalBeijingChina Faculty of Medicine and Health School of Health SciencesUniversity of SydneyNSWAustralia Sydney spine Institute BurwoodSydneyNSWAustralia Laboratory of Epidemiology Tianjin Neurological InstituteDepartment of NeurologyTianjin Medical University General Hospital&Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina department of Orthopedics Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina department of spinal Surgery The Third Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina department of Orthopedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of spine Surgery Zhengzhou Orthopedics HospitalZhengzhouHenan ProvinceChina department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengduSichuan ProvinceChina department of Orthopedics Xinqiao HospitalArmy Medical UniversityChongqingChina department of Orthopedics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina department of spinal Surgery Shengj

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even *** has the largest population of patients with traumatic spinal cord *** studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been *** the best of our knowledge,no national-level study of treatment status and economic burden has been *** retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national *** included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of *** epidemiological and clinical features,treatment status,and total and daily costs were *** in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression *** percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent *** 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 *** total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 ho

关键词： China clinical features costs epidemiology methylprednisolone sodium succinate methylprednisolone retrospective study traumatic spinal cord injury treatment

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang department of spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

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neural Regeneration Research 2024年第9期19卷 2050-2056页

作者： Xigong Li Jing Fu Ming Guan Haifei Shi Wenming Pan Xianfeng Lou department of Orthopedics The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang ProvinceChina department of Stomatology Xixi HospitalHangzhouZhejiang ProvinceChina department of Orthopedics and Spine Surgerythe Affiliated Hospital of Xuzhou Medical Schoolthe Second People’s Hospital of ChangshuChangshuJiangsu ProvinceChina

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive *** res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and *** addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and *** r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of *** findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling *** findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

关键词： apoptosis autophagy Biochanin A heme oxygenase 1 inflammation Nrf2 protein nuclear factor kappa-B oxidative stress spinal cord injury Toll-like receptor 4

Resident immune responses to spinal cord injury:role of astrocytes and microglia

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neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission