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Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after spinal cord injury

Research 2024年第1期2023卷 17-32页

作者： Bolin Zheng Yijing He Shuai Yin Xu Zhu Qing Zhao Huiyi Yang Zhaojie wang Rongrong Zhu Liming Cheng key laboratory of spine and spinal cord injury repair and regeneration Ministry of EducationDepartment of OrthopedicsTongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research School of Life Science and TechnologyTongji UniversityShanghai 200092China Clinical Center for Brain and spinal cord Research Tongji UniversityShanghai 200092China

spinal cord injury triggers complex pathological cascades,resulting in destructive tissue damage and incomplete tissue *** formation is generally considered a barrier for regeneration in the central nervous ***,the intrinsic mechanism of scar formation after spinal cord injury has not been fully ***,we report that excess cholesterol accumulates in phagocytes and is inefficiently removed from spinal cord lesions in young adult ***,we observed that excessive cholesterol also accumulates in injured peripheral nerves but is subsequently removed by reverse ***,preventing reverse cholesterol transport leads to macrophage accumulation and fibrosis in injured peripheral ***,the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids and can heal without excess cholesterol *** found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation,persistent macrophage activation,and *** internalization suppresses macrophage apoptosis mediated by CD5L expression,indicating that myelin-derived cholesterol plays a critical role in impaired wound *** together,our data suggest that the central nervous system lacks an efficient approach for cholesterol clearance,resulting in excessive accumulation of myelin-derived cholesterol,thereby inducing scar formation after injury.

关键词： healing spinal impaired

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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

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Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 682-688页

作者：吴治文 WANG Zihao CAI Zepeng QU Liting 于涛 College of Chemistry and Materials Science 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

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different *** this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis *** the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of *** the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this *** the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the *** dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement *** work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

关键词： bone repair self-reinforce chemoresponsive hydrogen bond

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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

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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China key laboratory of spine and spinal cord injury repair and regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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Effect of SARS-CoV-2 infection in early pregnancy on placental development

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Science China(Life Sciences) 2024年第3期67卷 622-625页

作者： Shanru Yi Liping Wang Mengting Wang Wei Hong Ben Xu Xiaoying He Mengtian Yang Zhiping Wu Beiying Wang Guang Yang Shijun Shen Xinyu Cui Ruixue Wang Kai Wang Hong Wang Xiaocui Li Shaorong Gao Cizhong Jiang Jiayu Chen Clinical and Translation Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China key laboratory of spine and spinal cord injury repair and regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Shanghai key laboratory of Maternal Fetal Medicine Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ... 详细信息

关键词： pregnancy fetal Effect

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Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 93-106页

作者： Wenju Liu Chuan Chen Yawei Gao Xinyu Cui Yuhan Zhang Liang Gu Yuanlin He Jing Li Shaorong Gao Rui Gao Cizhong Jiang key laboratory of spine and spinal cord injury repair and regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Department of Epidemiology and Biostatistics Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing 210029China

The development and maturation of follicles is a sophisticated and multistage *** dynamic gene expression of oocytes and their surrounding somatic cells and the dialogs between these cells are critical to this *** this study,we accurately classified the oocyte and follicle development into nine stages and profiled the gene expression of mouse oocytes and their surrounding granulosa cells and cumulus *** clustering of the transcriptomes showed the trajectories of two distinct development courses of oocytes and their surrounding somatic *** expression changes precipitously increased at Type 4 stage and drastically dropped afterward within both oocytes and granulosa ***,the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage,most of which persistently passed on to the later ***,cell communications within and between oocytes and granulosa cells became active from Type 4 stage *** dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional ***2/3,TGFBR2/3,INHBA/B,and ACVR1/1B/2B of TGF-βsignaling pathway functioned in the follicle *** signaling pathway regulated the development of granulosa ***,many maternally DNA methylation-or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during ***,Type 4 stage is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells,and the cell dialogs become active to assure follicle *** findings shed new insights on the transcriptome dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.

关键词： Folliculogenesis Oocyte Granulosa cell Transcriptome Cell dialog

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Neutrophil extracellular traps mediate neuro-immunothrombosis

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Neural regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China key laboratory of spine and spinal cord injury repair and regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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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

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