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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin yang Yu-Wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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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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Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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Neural Regeneration Research 2025年第11期20卷 3302-3316页

作者： Yali Chen Yiyong Wei jin Liu Tao Zhu Cheng Zhou Donghang Zhang Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Laboratory of Anesthesia and Critical Care Medicine National-Local Joint Engineering Research Center of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)ShenzhenGuangdong ProvinceChina Department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative *** cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous *** the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal ***,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal *** explore the conservation and divergence across species,we compared these findings with those from *** the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic *** the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,*** comparative results revealed substantial heterogeneity in all glial cell types between humans and ***,we detected sex differences in gene expression in human spinal cord glial ***,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in *** all microglial subtypes,all differentially expressed genes were located on the sex *** addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in ***,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for explo

关键词： astrocyte glial cell human microglia oligodendrocyte sex differentiation single-nucleus RNA sequencing spatial transcriptomics species variation spinal cord

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Hydrogels with Dynamically Controllable Mechanics and Biochemistry for 3D Cell Culture Platforms

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Chinese Journal of Polymer Science 2022年第1期40卷 38-46页

作者： Hai-yang Wu Lei yang Jiang-Shan Tu Jie Wang jin-Ge Li hong-Ying Lv Xiao-Niu yang State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China Polymer Composite Engineering Laboratory Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Huangpu Institute of Advanced Materials Changchun Institute of Applied ChemistryChinese Academy of SciencesGuangzhou 510530China

Many cell-matrix interaction studies have proved that dynamic changes in the extracellular matrix(ECM)are crucial to maintain cellular properties and ***,developing materials that can recapitulate the dynamic attributes of the ECM is highly desired for threedimensional(3 D)cell culture *** this end,we sought to develop a hydrogel system that would enable dynamic and reversible turning of its mechanical and biochemical properties,thus facilitating the control of cell culture to imitate the natural ***,a hydrogel with dynamic mechanics and a biochemistry based on an addition-fragmentation chain transfer(AFCT)reaction was ***-modified hyaluronic acid(HA)and allyl sulfide-modifiedε-poly-L-lysine(EPL)were synthesized to form hydrogels,which were non-swellable and *** reversible modulus of the hydrogel was first achieved through the AFCT reaction;the modulus can also be regulated stepwise by changing the dose of UVA *** patterning of fluorescent markers in the hydrogel was also ***,this dynamically controllable hydrogel has great potential as a 3 D cell culture platform for tissue engineering applications.

关键词： Hydrogel Addition-fragmentation chain transfer Dynamic mechanics Controllable biochemistry 3D cell culture platform

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A highly selective magnetic sensor with functionalized Fe/Fe_3O_4 nanoparticles for detection of Pb^(2+)

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Chinese Chemical Letters 2016年第6期27卷 891-895页

作者： Yan yang yang Zhang jin-Chao Shen hong yang Zhi-Guo Zhou Shi-Ping yang The Key Laboratory of Resource Chemistry of Ministry of Education Shanghai Key Laboratory of Rare Earth Functional Materials and Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors Shanghai Normal University

A magnetic sensor for detection of Pb^2＋ has been developed based on Fe/Fe3O4 nanoparticles modified by3-（3,4-dihydroxyphenyl）propionic acid（DHCA）. The carboxyl groups of DHCA have a strong affinity to coordination behavior of Pb^2＋ thus inducing the transformation of Fe/Fe3O4 nanoparticles from a dispersed to an aggregated state with a corresponding decrease, then increase in transverse relaxation time（T2） of the surrounding water protons. Upon addition of the different concentrations of Pb^2＋ to an aq. solution of DHCA functionalized Fe/Fe3O4 nanoparticles（DHCA-Fe/Fe3O4 NPs）（[Fe] = 90 mmol/L）, the change of T2 values display a good linear relationship with the concentration of Pb^2＋ from 40 μmol/L to 100 μmol/L and from 130 μmol/L to 200 μmol/L, respectively. Owing to the especially strong interaction between DHCA and Pb^2＋, DHCA-Fe/Fe3O4 NPs exhibited a high selectivity over other metal ions.

关键词： Magnetic sensor Fe/Fe3O4 nanoparticles Pb2+

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A de novo transcriptomic analysis to reveal functional genes in Apolygus lucorum

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Insect Science 2016年第1期23卷 2-14页

作者： De-Pan Cao yang Liu jin-jin Wei Jian-hong Li Gui-Rong Wang State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing Laboratory of Pesticide College of Plant Science & Technology Huazhong Agricultural University Wuhan China

The widespread planting of genetically engineered cotton producing the CrylAc toxin has led to significantly reduced pesticide applications since 1997. However, conse- quently, the number of green mirid bugs （GMB）, Apolygus lucorum （Meyer-Diir） has in- creased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera （Hiibner）, has become the major pest in the transgenic Bt cotton field and has influenced cotton yield. Disproportionately, only a few studies on GMB at molecular level have been re- ported. Libraries from both third instar nymphs and adults were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 uni- genes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes （42.01%） matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes （DEGs） strategy between the two developmental stages： nymph and adult. The results demonstrated that thousands of genes were significantly differentially ex- pressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding.

关键词： Apolygus lucorum digestion immunity metamorphosis transcriptome

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绿原酸对中性粒细胞功能及胞外诱捕网形成的影响及机制

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中国药理学通报 2025年第1期41卷 101-107页

作者：杨运刘娅王翠彭春红贵州中医药大学第二临床医学院贵州贵阳550025 七星关区中医妇幼集团医院贵州毕节551700 毕节市中医医院贵州毕节551700 贵州医科大学临床医学院贵州贵阳550025 贵州省人民医院呼吸与危重医学科贵州贵阳550002 国家卫健委肺脏免疫性疾病重点实验室贵州贵阳550002

目的探究绿原酸(chlorogenic acid,CGA)对中性粒细胞(neutrophil,NEU)功能及中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)形成的影响及机制。方法从小鼠骨髓中分离并纯化NEU;将NEU与CGA共培养,通过CCK-8法筛选共培养适合的干预浓度;检测NEU迁移能力、髓过氧化物酶(MPO)以及脱颗粒弹性蛋白酶(NE)、基质金属蛋白酶9(MMP-9)的水平观察CGA对NEU功能的影响;免疫荧光法观察NETs的主要结构组蛋白H3及DNA骨架,以及检测NEU释放的游离DNA(cf-DNA)含量,观察NETs的形成情况;检测NEU产生的活性氧(ROS)水平,以确定CGA是否影响NEU释放NETs过程中的ROS的生成。结果CGA在浓度为100、200、400μmol·L^(-1)时对NEU活性有明显抑制作用(P<0.01)。与空白组(Blank)相比,CGA(100、200、400μmol·L^(-1))干预后,细胞迁移能力及MPO、NE、MMP-9分泌量增加(P<0.05),组蛋白H3及DNA骨架、cf-DNA的释放量明显增加(P<0.01),细胞产生的ROS也明显增加(P<0.01),上述作用在一定范围内具有浓度依赖性。结论CGA能够增强NEU功能及促进NETs的形成,可能与促进细胞内ROS水平增加有关。

关键词：绿原酸中性粒细胞胞外诱捕网免疫抗菌活性氧

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Impact of proton pump inhibitors on clinical outcomes in patients after acute myocardial infarction: a propensity score analysis from China Acute Myocardial Infarction(CAMI) registry

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Journal of Geriatric Cardiology 2020年第11期17卷 659-665页

作者： Wen-Ce SHI Si-De GAO jin-Gang yang Xiao-Xue FAN Lin NI Shu-hong SU Mei YU hong-Mei yang Meng-Yue YU Yue-jin yang Department of Cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research and Biometrics Center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Xinxiang Central Hospital XinxiangHenan ProvinceChina Langfang People’s Hospital LangfangHebei ProvinceChina First Hospital of Qinhuangdao QinhuangdaoHebei ProvinceChina

Background Proton pump inhibitors(PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction(AMI) patients treated with dual antiplatelet therapy(DAPT). However, previous pharmacodynamic and clinical studies have reported controversial results on the interaction between PPI and the P2 Y12 inhibitor clopidogrel. We investigated the impact of PPIs use on in-hospital outcomes in AMI patients, aiming to provide a new insight on the value of PPIs. Methods A total of 23,380 consecutive AMI patients who received clopidogrel with or without PPIs in the China Acute Myocardial Infarction(CAMI) registry were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events(MACCE) defined as a composite of in-hospital cardiac death, re-infarction and stroke. Propensity score matching(PSM) was used to control potential baseline confounders. Multivariate logistic regression analysis was performed to evaluate the effect of PPIs use on MACCE and gastrointestinal bleeding(GIB). Results Among the whole AMI population, a large majority received DAPT and 67.5% were co-medicated with PPIs. PPIs use was associated with a decreased risk of MACCE(Before PSM OR: 0.857, 95% CI: 0.742-0.990, P = 0.0359;after PSM OR: 0.862, 95% CI: 0.768-0.949, P = 0.0245) after multivariate adjustment. Patients receiving PPIs also had a lower risk of cardiac death but a higher risk of complicating with stroke. When GIB occurred, an alleviating trend of GIB severity was observed in PPIs group. Conclusions Our study is the first nation-wide large-scale study to show evidence on PPIs use in AMI patients treated with DAPT. We found that PPIs in combination with clopidogrel was associated with decreased risk for MACCE in AMI patients, and it might have a trend to mitigate GIB severity. Therefore, PPIs could become an available choice for AMI patients during hospitalization.

关键词： Acute myocardial infarction Clopidogrel Drug interaction Propensity score

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Design and Synthesis of a Novel Peptidomimetic Inhibitor of Caspase-3

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Chemical Research in Chinese Universities 2006年第2期22卷 225-228页

作者： ZHANG jin-liang LIU Lin-hua GUO yang-hong yang jin-gang LI Wei Zhong Da-fang WANG Ji-dong College of Life Science Jilin University Changchun 130021 P. R. China

Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the intrinsic and extrinsic activation pathways. Therefore, caspase-3 is an attractive target for therapeutic intervention. For instance, inhibitors of caspase-3 have been described as promising cardioprotectants, neuroprotectants and antiarthritic agents. A novel peptidomimetic inhibitor of caspase-3, has been designed, which still has the properties of a reversible inhibitor, while the P1 site at the C-terminal remains, and only L-amino acid has been replaced by D-amino acid. Also presented here is the synthesis of the inhibitor and its inhibitory activity against caspase-3, which was tested by the fluorescent activity assay.

关键词： Caspase-3 Inhibitor Retro-inverso Peptidomimetie Synthesis

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Facile and efficient synthesis of quinoline-4-carboxylic acids under microwave irradiation

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Chinese Chemical Letters 2010年第1期21卷 35-38页

作者： Zhu, Hui yang, Ri Fang Yun, Liu hong Li, jin Beijing Inst Pharmacol & Toxicol Dept Med Chem Beijing 100850 Peoples R China

A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under m... 详细信息

关键词： Quinoline-4-carboxylic acids Pfitzinger reaction Microwave irradiation

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