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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu key laboratory of molecular medicine Nanjing UniversityNanjingJiangsu ProvinceChina State key laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu Jia Rui Mao Xiang Cao Yun Xu Department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State key laboratory of Pharmaceutical Biotechnology and Institute of Translational medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu key laboratory for molecular medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina Nanjing Neurology Medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of laboratory medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of laboratory medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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Preparation of ^(99m)Tc-PQQE and preliminary biological evaluation for the NMDA receptor

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nuclear Science and Techniques 2013年第3期24卷 31-38页

作者： ZHOU Xingqin KONG Yanyan ZOU Meifen ZHANG Jiankang CAO Guoxian key laboratory of nuclear medicine Ministry of HealthJiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear Medicine

The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.

关键词： NMDA受体生物学评价 N-甲基-D-天冬氨酸受体制备吡咯喹啉醌停留时间生物学特性放射性物质

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Advances in ethnopharmacology,phytochemistry and pharmacology of Erigerontis Herba and its Chinese medicine prescriptions

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Traditional medicine Research 2025年第1期10卷 44-61页

作者： Yang Zhou Yuan-Yan Huang Ding-Yue Shang Ying Chen Meng Tian Cheng-Yu Jin Xin Lu Bing-Chun Yan Han-Qing Pang Institute of Translational medicine School of MedicineYangzhou UniversityYangzhou 225009China jiangsu key laboratory of Integrated Traditional Chinese and Western medicine for Prevention and Treatment of Senile Diseases Yangzhou UniversityYangzhou 225009China School of medicine Nanjing University of Chinese MedicineNanjing 210023China State key laboratory for Chemistry and molecular Engineering of Medicinal Resources Guangxi Normal UniversityGuiling 541004China.

Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away *** has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and *** review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of *** information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic *** is a member of Compositae family and is mainly grown in southern *** Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving *** now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other *** extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative ***,the major active compound of EH,has been used as a quality *** no obvious toxicity of EH has been *** to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine *** several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain *** fully exploi

关键词： Erigeron breviscapus traditional applications ethnopharmacology phytochemistry pharmacology

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Synthesis and Crystal Structure of 2-(2-Ethyl-1H-imidazol-1-yl)-1-hydroxy- ethane-1,1-diyldiphosphonic Acid (EIHDP)

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Chinese Journal of Structural Chemistry 2011年第11期30卷 1635-1639页

作者：王洪勇邹霈谢敏浩何拥军吴军刘娅灵吴昊 key laboratory of nuclear medicine Ministry of Health Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine

The crystal structure of the title compound （C7H14N2O7P2, Mr = 300.14） was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic, space group P1 with a = 8.258（3）, b = 8.886（3）, c = 9.275（3） A, a = 96.669（3）, β = 115,706（3）, γ= 104.467（3）°, V= 573.8（3） A^3, Z = 2, Dc = 1.737 g/cm^3, 2（MoKa） = 0.71073, F（000） = 720,μ（MoKa） = 0.41 mm^-1 R = 0.030 and wR = 0.078. A total of 1970 unique reflections were collected, of which 1742 with I 〉 2σ（I） were observed. EIDHP has a structure similar to zoledronic acid （ZL）. ZL is a potent bone antiresorptive bisphosphonate drug having significant activity against several parasitic protozoa. EIHDP has inner-salt character, consisting of a negatively charged PO3 group and a positively charged N（1） atom. The crystal structure is stabilized by interrnolecular hydrogen bonds of O-H…O and N-H…O.

关键词： crystal structure EIDHP bisphosphonate synthesis

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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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Semi-automated synthesis,validation and microPET imaging of ^(18)F-FP-DTBZ as a vesicular monoamine transporter ligand

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nuclear Science and Techniques 2012年第1期23卷 40-46页

作者： CHEN Zhengping LIU Chunyi LI xiaomin TANG Jie TAN Cheng HUANG Hongbo YU Huixin LUO Shineng key laboratory of nuclear medicine Ministry of HealthJiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear MedicineWuxi 214063China

This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by a semi-automated procedure in a 21-35% yield without decay correction and with a radiochemical purity of >98%.Bioistribution in rats exhibited a favorable brain uptakes of the ligand (0.31±0.04 ID% at 60min post injection,n=8).The highest radioactivity located in VMAT2 enriched striatal *** target-to-nontarget ratio (striatum/cerebellum,ST/CB) was 4.81±*** studies implied that striatum uptake could be blocked by DTBZ (a VMAT2 inhibitor) but could not by CFT (a dopamine transporter inhibitor).MicroPET imaging with 18F-FP-DTBZ in normal rats gave high quality images in which high radioactivity were observed in the striatal ***-and-activity curves revealed good retention in the target (striatum) and rapid clearance in the background (cerebellum),which resulted in a maximum ST/CB ratio of 5.08±0.81 (n=3) in *** contrast,the 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18F-FP-DTBZ concentration on the unlesioned side (unlesioned-ST/CB=5.21±0.38,n=3) than the lesioned (lesioned-ST/CB=2.34±0.51).The results validated that 18F-FP-DTBZ is a favorable PET ligand binding to VMAT2.

关键词：半自动化转运蛋白成像质量合成验证单胺囊泡放射化学纯度

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Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

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World Journal of Gastrointestinal Oncology 2016年第2期8卷 165-172页

作者： yu-ping xu min yang key laboratory of nuclear medicine ministry of healthjiangsu key laboratory of molecular nuclear medicinejiangsu institute of nuclear medicineWuxi 214063Jiangsu ProvinceChina

Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.

关键词： Pancreatic cancer Diagnosis Therapy Radiopharmaceuticals Positron emission tomography

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Melanin-based nanoparticles in biomedical applications:From molecular imaging to treatment of diseases

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Chinese Chemical Letters 2019年第3期30卷 533-540页

作者： Xinyu Wang Jie Sheng Min Yang key laboratory of nuclear medicine Ministry of Health Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine The First Clinical Medical College Nanjing Medical University

Melanin nanoparticles(MNPs) is a kind of natural nanomaterial, not only retain the inherent characteristics of melanin(metal ion chelation, photothermal conversion property, etc.) but also can exhibit more excellent properties, such as high dispersion stability, good biocompatibility and biodegradability. Furthermore, these performances can be enhanced to target the specific sites and treat diseases by the surface modification or combination with functional substance. All these advantages of MNPs made it an ideal platform for developing biomedical applications. In this paper, the MNPs preparation methods were summarized first. Biomedical applications of MNPs were also reviewed,including molecular imaging(magnetic resonance, positron emission tomography, and photoacoustic imaging) and treatment of diseases(drug delivery, photothermal therapy, antioxidant therapy, and iron overload therapy). Further development and prospects of MNPs for practice in biology or medicine were also discussed.

关键词： Melanin Nanoparticles Imaging Drug delivery Biomedical application

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