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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang henrik Biverstål Nicolas GBazan shuai Tan Nailin Li Makiko ohshima Marianne schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Neuroinflammation as a therapeutic target in huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani h.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. huntington's disease(hD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： huntington inflammation Medicine

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Glial response in the midcingulate cortex in huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani h.Palpagama Andrea Kwakowsky Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

huntington’s disease(hD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying hD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： huntington degeneration cortex

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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri h.Juárez Adalberto Merighi Department of Veterinary sciences University of TurinGrugliascoTOItaly Department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MsCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MsC *** increasing number of pre-clinical studies suggest that delivering in vivo an MsC-conditioned medium(i.e.,the medium collected from MsC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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high-spin states of ^(125)sb:Particle-core excitation coupling

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science China(Physics,Mechanics & Astronomy) 2003年第4期46卷 390-397页

作者：刘忠张玉虎马英君 Y.sasaki K.Yamada h.Oshima h.yokose M.Ishizuka T.Komatsubara K.Furuno Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Institute of Physics and Tandem Accelerator Center University of TsukubaIbaraki 305-0006Japan

Excited states of125sb have been studied using in-beam γ spectroscopy techniques via the124sn(7Li, α2n) reaction at a beam energy of 32 MeV. A high-spin level scheme including 21 new γ-transitions and 14 new excited states have been established. Three isomers have been identified at 1970, 2110 and 2471 keV and the ranges of their half-lives have been estimated from the delayed coincidence data. The level structure of125sb is discussed in terms of particle-core excitation coupling. With the help of empirical shell model calculations the three isomers are proposed to have three-quasiparticle πg7/2?v(h 11/2 s 1/2)5?, πg7/2?v(h 11/2 d 3/2)7? and πg7/2?v(h 11 2/2 )10 + configurations, respectively.

关键词： in-beam γ spectroscopy isomer particle-core coupling

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Free vibration and transient response of double curved beams connected by intermediate straight beams

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 37-62页

作者： R.A.JAFARI-TALOOKOLAEI h.GhANDVAR E.JUMAEV s.KhATIR T.CUONG-LE school of Mechanical Engineering Babol Noshirvani University of Technology Department of Mechanical Engineering Faculty of Engineering New Uzbekistan University University of Business and science Center for Engineering Application and Technology solutions Ho Chi Minh City Open University

This paper investigates the free vibration and transient response of interconnected structures including double curved beams and intermediate straight beams,which are all constructed from functionally graded porous(FGP) materials. The strain potential and kinetic energies of each beam along with the work done by the external force are calculated. Additionally, a higher-order beam element is introduced to derive stiffness and mass matrices, along with the force vector. The curved and straight beams are discretized, and their assembled stiffness, mass matrices, and force vectors, are *** conditions at the joints are used to derive the total matrices of the entire structure. subsequently, the natural frequencies and transient response of the system are determined. The accuracy of the mathematical model and the self-developed computer program is validated through the comparison of the obtained results with those of the existing literature and commercial software ANsYs, demonstrating excellent ***, a comprehensive study is conducted to investigate the effects of various parameters on the free vibration and transient response of the considered structure.

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A New high-spin Level scheme of ^128I

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Chinese Physics Letters 2010年第8期27卷 58-61页

作者：王海霞张玉虎丁兵周小红张宁涛柳敏良马英君 Y. sasakiz K. Yamada h. ohshima s. yokose M. Ishizuka T. Komatsubara K. Furuno Insititute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 Graduate school of the Chinese Academy of sciences Beijing 100049 Department of Physics Jilin University Changehun 130021 Institute of Physics and Tandem Accelerator Center University of Tsukuba Ibaraki 305-0006 Japan

high-spin states in the beam energies. A new and 72 γ transitions odd-odd nucleus ^128I are investigated via the ^124 sn（^7 Li,3n）^128 I reaction at 28 and 32 Me V level scheme of 12sI is established up to high-spin states at I^π = 16, including 48 levels The present level scheme is largely different from the one in a recent publication due to identification of several doublet and triplet γ transitions and their proper placements in the level scheme. The high-spin level structure exhibits no obvious collective properties and is possibly associated with two and multi-quasiparticle configurations.

关键词： ENERGY levels (Quantum mechanics) PhAsE transformations (Physics) NUCLEAR reactions PARTICLE beams QUAsIPARTICLEs (Physics)

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