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RNA sequencing screening of differentially expressed genes after spinal cord injury

Neural Regeneration Research 2019年第9期14卷 1583-1593页

作者： Yi Li Ying Chen Xiang Li Jian Wu Jing-Ying Pan Ri-Xin Cai Ri-Yun Yang Xiao-Dong Wang School of Biology&Basic Medical Sciences Soochow UniversitySuzhouJiangsu ProvinceChina Department of Histology and Embryology Medical CollegeNantong UniversityNantongJiangsu ProvinceChina Jiangsu key laboratory of Neuroregeneration Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina

In the search for a therapeutic schedule for spinal cord injury,it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury ***,ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord *** emergence of second-generation sequencing technology(RNA sequencing)has provided a better *** this study,RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic *** numbers of genes that changed significantly were 944,1362 and 1421 at 1,4 and 7 days after spinal cord injury *** gene ontology analysis and temporal expression analysis of the differentially expressed genes,C5ar1,Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot *** mRNA expression trends of C5ar1,Socs3 and CCL6 genes were consistent with the RNA sequencing *** verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury.C5ar1 was mainly expressed in neurons and ***,the gene Itgb2,which may be related to C5ar1,was found by Chilibot database and literature *** histochemical results showed that the expression of Itgb2 was highly consistent with that of ***2 was expressed in *** sequencing technology can screen differentially expressed genes at different time points after spinal cord *** analysis and verification,genes strongly associated with spinal cord injury can be *** can provide experimental data for further determining the molecular mechanism of spinal cord injury,and also provide possible targets for the treatment of spinal cord *** study was approved

关键词： nerve regeneration spinal cord injury RNA sequencing C5ar1 Itgb2 Socs3 CCL6 astrocytes rats neural regeneration

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Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome

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Neural Regeneration Research 2019年第5期14卷 896-902页

作者： Ying Tang Hong-Liang Liu Ling-Xia Min Hao-Shi Yuan Lei Guo Peng-Bo Han Yu-Xin Lu Jian-Feng Zhong Dong-Lin Wang key laboratory of Biorheological Science and Technology Ministry of Education (Chongqing University) Chongqing University Cancer Hospital Department of Rehabilitation Southwest Hospital Third Military Medical University Department of Spine Surgery Second Affiliated Hospital of Xi'an Medical University Department of Orthopedics Chinese PLA Beijing Army General Hospital

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.

关键词： nerve regeneration spinal cord injury tau injury severity outcome cerebrospinal fluid serum biomarker Basso,Beattie,and Bresnahan locomotor rating scale neural regeneration

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Identification of four differentially expressed genes associated with acute and chronic spinal cord injury based on bioinformatics data

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Neural Regeneration Research 2021年第5期16卷 865-870页

作者： Su-Ping Niu Ya-Jun Zhang Na Han Xiao-Feng Yin Dian-Ying Zhang Yu-Hui Kou key laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Office of Academic Research Peking University People’s HospitalBeijingChina

Complex pathological changes occur during the development of spinal cord injury(SCI),and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic *** study was designed to explore differentially expressed genes(DEGs)associated with the acute and chronic stages of SCI using bioinformatics *** expression profiles(GSE45006,GSE93249,and GSE45550)were downloaded from the Gene Expression Omnibus ***-associated DEGs from rat samples were identified,and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were *** addition,a protein-protein interaction network was *** 66 DEGs were identified in GSE45550 between 3–14 days after SCI,whereas 2418 DEGs were identified in GSE450061–56 days after ***,1263,195,and 75 overlapping DEGs were identified between these two expression profiles,3,7/8,and 14 days after SCI,***,16 overlapping DEGs were obtained in GSE450061–14 days after SCI,including Pank1,Hn1,Tmem150c,Rgd1309676,Lpl,Mdh1,Nnt,Loc100912219,Large1,Baiap2,Slc24a2,Fundc2,Mrps14,Slc16a7,Obfc1,and ***,3882 overlapping DEGs were identified in GSE932491–6 months after SCI,including 3316 protein-coding genes and 567 long non-coding RNA genes.A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping *** significant functions of these 1135 genes were correlated with the response to the immune effector process,the innate immune response,and cytokine ***,the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways,osteoclast differentiation,the nuclear factor-κB signaling pathway,and the chemokine signaling ***,an analysis of the overlapping DEGs associated with both acute and chronic SCI,assessed using the expressio

关键词： bioinformatics differential expression factor gene immune response injury pathways protein spinal cord

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Association of variants in the KIF1A gene with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2022年第1期11卷 235-247页

作者： Panlin Liao Yanchun Yuan Zhen Liu Xiaorong Hou Wanzhen Li Jin Wen Kexuan Zhang Bin Jiao Lu Shen Hong Jiang Jifeng Guo Beisha Tang Zhuohua Zhang Zhonghua Hu Junling Wang Hunan key laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangsha 410008China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Diseases Xiangya HospitalCentral South UniversityChangsha 410008China key laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha 410008China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha 410008China Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangsha 410008China Hunan key laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangsha 410008China.

Background:Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal *** in many other neurodegenerative disorders,the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal ***,sen-sory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2(HSAN2)and spastic paraplegia 30(SPG30)share several causative genes with ALS,as well as having common clinical ***1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors(SVPs)and dense core vesicles and has been reported as a causative gene for HSAN2 and ***:Here,we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ***:We identified rare damage variants(RDVs)in the KIF1A gene associated with ALS and delineated the clini-cal characteristics of ALS patients with KIF1A ***,these patients tended to exhibit sensory ***,the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A *** examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A,VAMP2,and *** of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A ***:Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS,indicating KIF1A as an important player in the oligogenic scenario of ALS.

关键词： Amyotrophic lateral sclerosis KIF1A Axonal transport Presynaptic vesicle precursors

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Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population:a retrospective genotype-phenotype analysis of 105 patients

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World Journal of Pediatrics 2023年第7期19卷 674-686页

作者： Wei Wang Si-Hao Gao Min Weil Lin-Qing Zhong Wei Liu Shan Jian Juan Xiao Cai-Hui Zhang Jian-Guo Zhang Xiao-Feng Zeng Wei-Bo Xia Zheng-Qing Qiu Hong-Mei Song Department of Pediatrics Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.1 ShuaifuyuanDongchengBeijing 100730China Department of Radiology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Orthopedic Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Rheumatology and Clinical Immunology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID) Ministry of Science and TechnologyBeijing 100730China State key laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital(PUMCH)Beijing 100730China key laboratory of Rheumatology and Clinical Immunology Ministry of EducationBeijing 100730China Department of Endocrinology National Health Commission Key Laboratory of EndocrinologyPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Background Progressive pseudorheumatoid dysplasia(PPRD)is a rare genetic disease with autosomal recessive *** was a lack of genotype-phenotype correlation data from the Chinese *** study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD *** Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College ***-cal records were collected from the electronic medical record system and patient-held portable health *** Chinese PPRD cases were gathered from both international and Chinese local *** collected demographic infor-mation,genetic variants,clinical manifestations,and imaging characteristics for further *** We included 105 Chinese PPRD patients in the current ***-three variants,including nine novels and five hotspot variants,were identified,with 26/33(79%)variants exclusively seen in the Chinese *** PPRD patients share a phenotype similar to that in international *** involvement may progress with age(R2=0.2541).Long bone shortening and severe deformities occur in three patients with biallelic null variants,of which at least one vari-ant is located in exon *** hotspot variants,c.624dupA(p.C209Mfs*21)were associated with later onset and more involved *** joints were more likely to be affected in patients carrying c.624dupA(p.C209Mfs*21)and c.866dupA(p.S209Efs*13).Shoulder joints are more likely to be involved in patients with biallelic null variants(P=0.027).Conclusions Chinese PPRD patients share a unique mutation *** the five hotspot variants,c.624dupA is associated with later onset of disease,more extensive joint involvement,and a tendency to affect elbow *** null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

关键词： CCN6 Genetics Mutations Progressive pseudorheumatoid dysplasia WISP3

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Bioinspired MXene-Based User-Interactive Electronic Skin for Digital and Visual Dual-Channel Sensing

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Nano-Micro Letters 2022年第7期14卷 228-245页

作者： Wentao Cao Zheng Wang Xiaohao Liu Zhi Zhou Yue Zhang Shisheng He Daxiang Cui Feng Chen Department of Orthopedic School of MedicineSpinal Pain Research InstituteShanghai Tenth People’s HospitalTongji UniversityShanghai 200072People’s Republic of China National Engineering Research Center for Nanotechnology Shanghai 200241People’s Republic of China Institute of Micro-Nano Science and Technology School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China

User-interactive electronic skin(e-skin) that could convert mechanical stimuli into distinguishable outputs displays tremendous potential for wearable devices and health care applications. However, the existing devices have the disadvantages such as complex integration procedure and lack of the intuitive signal display function. Here, we present a bioinspired user-interactive e-skin, which is simple in structure and can synchronously achieve digital electrical response and optical visualization upon external mechanical stimulus. The e-skin comprises a conductive layer with a carbon nanotubes/cellulose nanofibers/MXene nanohybrid network featuring remarkable electromechanical behaviors, and a stretchable elastomer layer, which is composed of silicone rubber and thermochromic pigments. Furthermore, the conductive nanohybrid network with outstanding Joule heating performance can generate controllable thermal energy under voltage input and then achieve the dynamic coloration of silicone-based elastomer. Especially, such an innovative fusion strategy of digital data and visual images enables the e-skin to monitor human activities with evermore intuition and accuracy. The simple design philosophy and reliable operation of the demonstrated e-skin are expected to provide an ideal platform for next-generation flexible electronics.

关键词： MXene Electronic skin Electromechanical behavior Joule heating Visualization

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Effects of dexmedetomidine on excitatory synaptic transmission in rat spinal dorsal horn

Effects of dexmedetomidine on excitatory synaptic transmissi...

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中国神经科学学会第十届全国学术会议

作者： Yan Zhang Zhi-Qi Zhao Yu-Qiu Zhang Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University Cell Electrophysiology laboratory Wannan Medical College

Objective To investigate cellular mechanisms underlying the analgesic effects of dexmedetomidine,a selective α2-adrenergic receptor agonist,at spinal *** The whole-cell patch clamp recording and field potential recording were performed on the superficial dorsal horn（SDH,laminae HI） of spinal cord slices with attached dorsal root from juvenile（2-3 weeks） *** synaptic transmission（eEPSCs） and long-term potentiation（LTP）of C-fiber evoked field potentials（fEPSPs） were recorded from SDH neurons by stimulating dorsal root（DR） and Lissauer’s tract（LT） *** We found that eEPSC were rapidly and dose-dependently reduced by bath application of *** amplitude and frequency of spontaneous EPSC（sEPSC）,exogenous N-methyl-D-aspartate（NMDA）-induced currents and α-amino-3-hydroxy-5-methyl-4-isoxazolepropri-anate（AMPA）-induced currents were all ***,slices pretreated with dexmedetomidine showed failed LTP induction compared with control *** These data suggest that dexmedetomidine possibly inhibits excitatory synaptic transmission in rat spinal dorsal horn through pre-synaptic and post-synaptic mechanisms.

关键词： AMPA receptor NMDA receptor LTP dexmedetomidine spinal cord

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Modulation of morphine antinoceptive tolerance in bone cancer pain rats by P2X7 purinoceptor

Modulation of morphine antinoceptive tolerance in bone cance...

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中国神经科学学会第十届全国学术会议

作者： Hui LI Zhi-Qi ZHAO Yu-Qiu ZHANG Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University

Bone cancer pain is the most severe chronic pain,and morphine is the most effective ***,long-term morphine therapy produces morphine antinociceptive *** far,studies on morphine tolerance are mostly carried out in normal animals,despite that the clinical morphine antinociceptive tolerance occurs only in patients with chronic ***,chronic pathological pain is quite different from normal physiological pain in *** it is more meaningful to study the mechanisms of morphine tolerance in chronic pain animal *** plays an important role in the development of both chronic pain and morphine *** the firsr time,we investigate the role of P2X7 purinoceptor-mediated the activation of spinal microghal p38/MAPK signaling pathway proinflammatory cytokines（***-lβ and IL-18） and astrocytic products（e.g.D-Serine） release,and hypersensitivity of spinal dorsal horn neurons in morphine tolerance in a rat model of bone cancer *** data showed that the chronic morphine treatment for10 days resulted in a significant loss of analgesic potency in both mechanical and thermal nociceptive tests in rats suffered from bone cancer *** expression levels of P2X7R,Ibal-1,IL-18 and IL-lβ in the spinal dorsal horn were remarkably increased,both in bone cancer rats and chronic morphine treated na（i|¨）ve ***,in chronic morphine treated bone cancer rats,spinal Ibal-1 and IL-18 levels were much lower than bone cancer rats without chronic morphine treatment and naive rats chronic with morphine *** results suggest that in chronic pathological pain status,the mechanism of morphine tolerance is more complicated.

关键词： bone cancer pain morphine tolerance P2X7R

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Shared genetic architecture highlights the bidirectional association between major depressive disorder and fracture risk

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General Psychiatry 2024年第3期37卷 352-363页

作者： Pianpian Zhao Zhimin Ying Chengda Yuan Haisheng Zhang Ao Dong Jianguo Tao Xiangjiao Yi Mengyuan Yang Wen Jin Weiliang Tian David Karasik Geng Tian Houfeng Zheng The Affiliated Hangzhou First People’s Hospital School of MedicineWestlake UniversityHangzhouZhejiangChina Westlake laboratory of Life Sciences and Biomedicine HangzhouZhejiangChina Diseases&Population(DaP)Geninfo Lab School of Life SciencesWestlake UniversityHangzhouZhejiangChina Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzhouZhejiangChina Department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Dermatology Hangzhou Hospital of Traditional Chinese MedicineHangzhouZhejiangChina Department of Global Statistics Eli Lilly and CompanyBranchburgNew JerseyUSA Azrieli Faculty of Medicine Bar-Ilan UniversitySafedIsrael Binzhou Medical University YantaiShandongChina

Background There is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms,while more studies demonstrate that depression negatively affects bone density and increases fracture *** To explore the relationship between major depressive disorder(MDD)and fracture *** We conducted a nested case-control analysis(32670 patients with fracture and 397017 individuals without fracture)and a matched cohort analysis(16496 patients with MDD and 435492 individuals without MDD)in the same prospective UK Biobank data ***,we investigated the shared genetic architecture between MDD and fracture with linkage disequilibrium score regression and the MiXeR statistical *** used the conditional/conjunctional false discovery rate approach to identify the specific shared *** calculated the weighted genetic risk score for individuals in the UK Biobank and logistic regression was used to confirm the association observed in the prospective *** We found that MDD was associated with a 14%increase in fracture risk(hazard ratio(HR)1.14,95%CI 1.14 to 1.15,pdata suggested a genetic overlap between MDD and ***,we identified four shared genomic loci,with the top signal(rs7554101)near *** protein encoded by SGIP1 is involved in cannabinoid receptor type 1 *** found that genetically predicted MDD was associated with a higher risk of fracture and vice *** addition,we found that the higher expression level of SGIP1 in the spinal cord and muscle was associated with an increased risk of fracture and *** The genetic pleiotropy between MDD and fracture highlights the bidirectional association observed in the epidemiological *** shared ge

关键词： fracture matched osteoporosis

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spinal inflammatory and anti-inflammatory factors in bone cancer pain in rodents

Spinal inflammatory and anti-inflammatory factors in bone ca...

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中国神经科学学会第十届全国学术会议

作者： Wen-Li MI Shan HU Jrng ZHAO Qian LI Ping HAN Zhi-Fu WANG Qi-Liang MAO-YING Gen-Cheng WU Yan-Qing WANG Department of Integrative Medicine and Neurobiology State Key Laboratory of Medical NeurobiologyInstitutes of Brain ScienceFudan University

Objective Cancer pain,especially bone cancer pain,affects the life quality of cancer patients,and current treatments for this pain are *** neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain(CIBP).The present study was designed to investigate the role of neuroinflammatory and anti-inflammatory actors in bone cancer pain(BCIP) in rats and *** The mechanical allodynia was tested by von Frey hairs in rats or mice inoculated with Walker 256mammary gland carcinoma cells or 4T-1 cells *** approaches as well as Western Blotting and fluorescent immunohistochemistry staining were applied to assess the roles played by spinal neuroinflammation in bone cancer ***(1) *** mice inoculated with carcinoma cells showed mechanical allodynia,heat hyperalgesia and a reduction in limb *** the mRNA and the protein levels of IL-33 and relative cytokines(IL-1β,IL-6,TNF-α) were significantly increased in the spinal cord after the inoculation of carcinoma *** administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected ***2 mice showed a significant amelioration of mechanical allodynia and heat hyperalgesia compared to wild-type ***,concentrations of spinal IL-1β,IL-6 and TNF-α in the cancer-bearing ST2 mice had no significant *** data further suggested that IL-33/ST2 signaling played a vital role in cancer pain.(2) Anti-inflammatory ***(LXs),endogenous lipoxygenase-derived eicosanoids,represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving *** injection with the same dose(0.3 nmol) of lipoxin A4(LXA4),lipoxin B4(LXB4) or aspirin-triggered-15-epi-lipoxin A4(ATL) could alleviate the mechanical allodynia in C

关键词： cancer-induced bone pain allodynia proinflammatory cytokines interleukin-33 ST2 lipoxins,aspirin-triggered-15-epi-lipoxinA4 spinal cord

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