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Is ATP a key player in conditioning neurons to support axonal regeneration?

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Neural Regeneration Research 2018年第12期13卷 2077-2079页

作者： xuenong bo Centre for Neuroscience and Trauma Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London

Neurons in the central nervous system （CNS） of adult mammals have a weak intrinsic regenerative capacity, which is one contributing factor to the failure of axonal regeneration. Finding the means to elevate the regenerative capacity of axotomised neurons is one requirement for successful regeneration. Forty-five years ago, it was reported that crushing of the sciatic nerves of adult mice two weeks before cutting the nerves accelerated the regrowth of their axons （McQuarrie and Grafstein, 1973）. The nerve injury two weeks before triggered the regeneration machinery in the injured neurons, leading to faster axonal regrowth after a subsequent lesion. Later it was found that a lesion to a peripheral nerve also strongly enhanced the regeneration of the central branches of the appropriate primary sensory neurons （Richardson and Issa, 1984）. This phenomenon is termed preconditioning lesion （or conditioning lesion if the central branches of the sensory neurons are injured after a concomitant in- jury to their peripheral branches）.

关键词： NERVE-CELL boDY ELECTRICAL-STIMULATION SENSORY AXONS RATS INJURY INFLAMMATION OUTGROWTH

The potential of gene therapies for spinal cord injury repair:a systematic review and meta-analysis of pre-clinical studies

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Neural Regeneration Research 2023年第2期18卷 299-305页

作者： Catriona J.Cunningham Mindaugas Viskontas Krzysztof Janowicz Yasmin Sani Malin EHåkansson Anastasia Heidari Wenlong Huang xuenong bo Institute of Medical Sciences School of MedicineMedical Sciences&NutritionUniversity of AberdeenAberdeenUK Centre for Neuroscience Surgery and TraumaBlizard InstituteBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK

Currently,there is no cure for traumatic spinal co rd injury but one therapeutic approach showing promise is gene *** this systematic review and meta-analysis,we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of *** this metaanalysis,registe red at PROSPERO(Registration ID:CRD42020185008),we identified relevant controlled in vivo studies published in English by searching the PubMed,Web of Science,and Embase *** restrictions of the year of publication were applied and the last literature search was conducted on August 3,*** then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator.A total of 71 studies met our inclusion crite ria and were included in the systematic *** results showed that overall,gene therapies were associated with improvements in locomotor score(standardized mean difference[SMD]:2.07,95%confidence interval[CI]:1.68-2.47,Tau^(2)=2.13,I^(2)=83.6%)and axonal regrowth(SMD:2.78,95%CI:1.92-3.65,Tau^(2)=4.13,I^(2)=85.5%).There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication *** used a modified CAMARADES(Collaborative Approach to M eta-Analysis and Review of Animal Data in Experimental Studies)checklist to assess the risk of bias,finding that the median score was 4(IQR:3-5).In particula r,reports of allocation concealment and sample size calculations were *** conclusion,gene therapies are showing promise as therapies for spinal co rd injury repair,but there is no consensus on which gene or genes should be targeted.

关键词： animal models gene delivery meta-analysis regenerative medicine spinal cord injury systematic review viral vectors

Acaricidal effect of the antimicrobial metabolite xenocoumacin 1 on spider mite control

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Journal of Integrative Agriculture 2024年第3期23卷 948-959页

作者： Jiaxing Wei Hong Yan Jie Ren Guangyue Li bo Zhang xuenong Xu Institute of Plant Protection Chinese Academy of Agricultural SciencesBeijing 100193China State Key Laboratory for Biology of Plant Diseases and Insect Pests Beijing 100193China Key Laboratory of Natural Enemies Insects Ministry of Agriculture and Rural AffairsBeijing 100193China

The two-spotted spider mite,Tetranychus urticae Koch,is one of the most harmful pests in many agroecosystems *** effectively manage this pest,there is an urgent need to develop novel bio-active acaricides that support integrated pest management strategies targeting *** this study,we explored the acaricidal effects of xenocoumacin 1 (Xcn1) on *** and its predator Neoseiulus californicus using the highly puri?ed ***1 was extracted and purified from the cell-free supernatant of the Xenorhabdus nematophila CB6 mutant constructed by the easy promoter activated compound identi?cation (easyPACId) *** the concentration of Xcn1 exceeded 100μg mL~(–1),the survival rate of spider mite adults declined to below 40%and the fecundity was decreased by 80%at six days *** concentrations of 25 and 50μg mL~(–1),Xcn1 signi?cantly impeded spider mite development by inhibiting the ***,neither concentration had any adverse effects on the survival or reproduction of the predatory mite *** results from laboratory and semi-?eld experiments consistently demonstrated the effectiveness of the antimicrobial metabolite Xcn1 in controlling pest mites at both the molecular and physiological *** study offers a promising possibility that combines the compatible biocontrol agents of Xcn1 and predatory mites for integrated pest mite control.

关键词： pest management predatory mite Xcn1 morphology developmental inhibition transcriptome

both host and diet shape bacterial communities of predatory mites

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Insect Science 2024年第2期31卷 551-561页

作者： Hong Yan Endong Wang Guo-Shu Wei bo Zhang xuenong Xu Institute of Plant Protection Chinese Academy of Agricultural SciencesBejingChina College of Plant Protection Hebei Agricultural UniversityBaodingHebei ProvinceChina Key Laboratory of Natural Enemies Insects Ministry of Agriculture and Rural AffairsBeijingChina

Microbial communities,derived from food,ambient,and inner,can affect host ecological adaption and *** with most phytophagous arthropods,predators may have more opportunities to develop specific microbiota depending on the level of prey *** explore how diet sources affect host microbial communities and vary across predator species,we considered 3 types of predators from Phytoseiidae(Acari:Mesostigmata):polyphagous(Amblyseius orientalis Ehara,Neoseiulus barkeri Hughes,and Amblyseius swirski Athias-Henrio),oligophagous(Neoseiulus californicus McGregor),and monophagous(Phytoseiulus persimilis Athias-Henriot)predatory *** polyphagous species were fed on 2 types of diets,natural prey and alternative *** using 16S rRNA sequencing,we found that diet was the main source of microbiota in predatory mites,while there was no clear pattern affected by prey *** 3 polyphagous predators,host species had a larger impact than prey on microbial *** *** or *** which showed consistency in their microbiota,prey switching significantly affectedβ-diversity of bacterial composition in ***,with 56%of the microbial *** short,our results confirmed the substantial influence of diet on host microbial construction in predatory species,and highlighted species differences in shaping the microbiota which are not necessarily related to prey specialization.

关键词： diet switching feeding habits host-microbial interactions invertebrate microbiota 16S rRNA

The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate(Epac)for central nervous system trauma

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Neural Regeneration Research 2021年第3期16卷 460-469页

作者： Alba Guijarro-Belmar Dominik Mateusz Domanski xuenong bo Derryck Shewan Wenlong Huang Institute of Medical Sciences School of MedicineMedical Sciences&NutritionUniversity of AberdeenAberdeenUK Center for Neuroscience Surgery and TraumaQueen Mary University of LondonLondonUK Sainsbury Wellcome Centre University College LondonLondonUK

Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor *** to the spinal cord leads to a series of detrimental events including ischaemia,haemorrhage and neuroinflammation,which over time result in further neural tissue ***,at chronic stages of traumatic spinal cord injury,the formation of a glial scar,cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal *** is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous *** intracellular signalling molecule,cyclic adenosine 3′,5′-monophosphate(cAMP),is known to play many important roles in the central nervous system,and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal ***,therapies directly targeting cAMP have not found their way into the clinic,as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects.A downstream effector of cAMP,exchange protein directly activated by cAMP 2(Epac2),is mainly expressed in the adult central nervous system,and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and ***,using ex vivo modelling of traumatic spinal cord injury,Epac2 activation was found to profoundly modulate the post-lesion environment,such as decreasing the activation of astrocytes and *** data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord ***,targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair,and future work is needed to fully establish its therapeutic potential.

关键词： astrocytes axonal regeneration cAMP central nervous system regeneration Epac glial scar microglia neuroinflammation neurons spinal cord spinal cord injury traumatic spinal cord injury

大鼠原代背根神经元和雪旺细胞在随机及有序排列聚甲基丙烯酸甲酯电纺纳米纤维上共培养的形态学

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吉林大学学报（医学版） 2016年第1期42卷 1-6,I0001页

作者：夏海坚 CHEN Qiao bo xuenong 孙晓川钟东夏永智重庆医科大学附属第一医院神经外科重庆400016 英国萨塞克斯大学生命科学院英国布莱顿BN19QJ 英国伦敦大学皇后玛丽学院Blizard研究所英国伦敦E12AT

目的:探讨聚甲基丙烯酸甲酯(PMMA)电纺纳米纤维支架的拓扑线索对于大鼠原代背根神经元(DRGn)培养及其与雪旺细胞(SCs)共培养的影响。方法:构建具有随机分布和轴向有序排列拓扑结构的PMMA电纺纳米纤维,分别为随机和有序PMMA电纺纳米纤维... 详细信息

目的:探讨聚甲基丙烯酸甲酯(PMMA)电纺纳米纤维支架的拓扑线索对于大鼠原代背根神经元(DRGn)培养及其与雪旺细胞(SCs)共培养的影响。方法:构建具有随机分布和轴向有序排列拓扑结构的PMMA电纺纳米纤维,分别为随机和有序PMMA电纺纳米纤维组,以PMMA薄膜作为对照组;分离纯化大鼠原代DRGn和SCs,与上述各组PMMA电纺纳米纤维共培养;利用慢病毒技术转染荧光蛋白基因作为显色方法,观察PMMA电纺纳米纤维的拓扑线索对于DRGn神经突生长的影响,在共培养实验通过荧光图像的快速傅立叶转换(FFT)及半高全宽值(FWHM)的计算,定量分析电纺纤维对DRGn神经突和SCs细胞突起的接触引导作用。结果:大鼠原代DRGn和SCs均能够顺利在PMMA材料上贴壁并生长;与PMMA薄膜组比较,随机和有序PMMA电纺纳米纤维组DRGn平均神经突数量及神经突长度差异无统计学意义(P>0.05);共培养实验中,电纺纤维的拓扑线索对于DRGn神经突和SCs细胞突起的生长均具有明显的接触引导作用,与PMMA薄膜组和随机PMMA电纺纳米纤维组比较,有序PMMA电纺纳米纤维组DRGn和SCs的FWHM值均明显降低(P<0.01),有序PMMA电纺纳米纤维能够在空间上促成DRGn神经突和SCs细胞突起建立共定位。结论:有序PMMA电纺纳米纤维具有作为脊髓损伤(SCI)后植入性支架材料的潜力,其拓扑线索有可能加速SCs的轴突髓鞘化过程。

关键词：纳米纤维细胞支架背根神经元雪旺细胞接触引导

Induced expression of polysialic acid on transplanted Schwann cells and in injured rat spinal cord promotes axon regeneration and functional recovery

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Induced expression of polysialic acid on transplanted Schwan...

2013年贵州省神经外科年会

作者： Fangyou Gao Yi Zhang Dongsheng Wu Jasmeen Mehta Juan Luo John V.Priestley Habib Ellamushi Peter M Richardson John Yeh xuenong bo Centre for Neuroscience and Trauma Queen Mary School of Medicine and DentistryUniversity of London4 Newark StreetLondonUK Department of Neurosurgery Guizhou Provincial People's Hospital Department of Neurosurgery Royal London HospitalLondonUK

Background Providing cellular support and modifying the glial scar around the lesion are two key strategies for promoting axonal regeneration after spinal cord *** cells(SCs) are an important source of cells for neural repair;however,naive SCs have poor integration with spinal cord *** previous studies showed that over-expressing polysialic acid(PSA) on SCs by transducing them with polysialyltransferase(PST) facilitates their integration and migration in spinal *** also showed that lentiviral vector(LV) mediated PSA expression in injured spinal cord modifies the glial scar and promotes the growth of ascending sensory *** and Methods To study the PST/SCs transplantation combined with direct LV/PST injection in spinal cords after dorsal column transection to find if the combined treatments could lead to faster and profounder motor functional recovery compared with animals receiving combined GFP/SCs transplantation with control LV/GFP *** Morphological study showed significantly more injured corticospinal axons growing close to the lesion/transplant borders and into the caudal spinal cord in the PST group than in the GFP ***,there was a significant increase in serotonergic axonal sprouting around the lesion/transplants in the PST *** also found over-expressing PSA around the lesion site did not cause allodynia and hyperalgesia in our injury *** These results demonstrate the promising therapeutic benefit of over-expressing PSA in transplanted SCs and spinal cord in promoting axonal growth and restoring motor function.

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P2X_3受体在感觉神经节的表达

中国组织化学与细胞化学杂志 2001年第2期10卷 121-123页

作者：向正华蔡文琴 xuenong bo Geoffrey Burnstock 第二军医大学组织胚胎学教研室上海200433 第三军医大学组织胚胎学教研室 400038 英国伦敦大学学院解剖与发育生物学系

用免疫组织化学与原位杂交研究 P2 X3受体在背根神经节、三叉神经节和结状神经节的分布。结果显示 :1.原位杂交 :在三种感觉神经节中 ,95 %左右的神经节细胞为 P2 X3m RNA阳性 ,中、小型神经节细胞的杂交信号一般要比大型的神经节细胞... 详细信息

用免疫组织化学与原位杂交研究 P2 X3受体在背根神经节、三叉神经节和结状神经节的分布。结果显示 :1.原位杂交 :在三种感觉神经节中 ,95 %左右的神经节细胞为 P2 X3m RNA阳性 ,中、小型神经节细胞的杂交信号一般要比大型的神经节细胞强一些。 2 .免疫组织化学 :免疫组织化学结果与原位杂交结果基本一致。此外 ,在各神经节内 ,均显示出许多P2 X3免疫阳性神经纤维 ,在足掌表皮也显示许多 P2 X3免疫反应阳性纤维。结果提示 :P2 X3不仅参与机体的痛觉的形成 ,还可能参与其它感觉。

关键词：原位杂交免疫组织化学大鼠 P2X3受体感觉神经节表达

Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice

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Signal Transduction and Targeted Therapy 2021年第1期6卷 131-143页

作者： Xuekun Fu bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu Sixiong Lin Sheng Chen Yumei Lai xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao School of Medicine Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Researchand Shenzhen Key Laboratory of Cell MicroenvironmentSouthern University of Science and Technology1088 Xue Yuan Road518055 ShenzhenGuangdongChina Law Sau Fai Institute for Advancing Translational Medicine in bone and Joint Diseases School of Chinese MedicineHong Kong Baptist University999077 Hong KongSARChina Department of Biology Southern University of Science and Technology518055 ShenzhenChina School of Biomedical Sciences University of Hong Kong21 Sassoon RoadHong KongChina Department of Spine Surgery Orthopedic Research InstituteThe First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and Traumatology510080 GuangzhouChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and Technology430022 WuhanChina Department of Orthopedic Surgery Rush University Medical CenterChicagoIL 60612USA State Key Laboratory of Military Stomatology National Clinical Research Center for Oral DiseasesShanxi International Joint Research Center for Oral DiseasesDepartment of Oral Anatomy and Physiology and TMDSchool of Stomatologythe Fourth Military Medical University145 Changle West RoadXi’anChina Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences518055 ShenzhenChina

In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely *** we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult ***-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by ***,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic ***,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in ***,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory ***,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized ***,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis.

关键词： homeostasis Kindlin skeletal