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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco garcía-garcía Victoria moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

Dominance of transposable element‑related satDNAs results in great complexity of“satDNA library”and invokes the extension towards“repetitive DNA library”

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Marine Life Science & Technology 2024年第2期6卷 236-251页

作者： Monika Tunjić‑Cvitanić Daniel garcía‑Souto Juan J.Pasantes EvaŠatović‑Vukšić Division of Molecular Biology Ruđer BoškovićInstitute10000 ZagrebCroatia Genomes and Disease Centre for Research in Molecular Medicine and Chronic Diseases(CIMUS)Universidade de Santiago de Compostela15706 Santiago de CompostelaSpain Department of Zoology Genetics and Physical AnthropologyUniversidade de Santiago de Compostela15706 Santiago de CompostelaSpain Centro de investigación Mariña Dpto de BioquímicaXenética e InmunoloxíaUniversidade de Vigo36310 VigoSpain

Research on bivalves is fast-growing,including genome-wide analyses and genome sequencing.Several characteristics qualify oysters as a valuable model to explore repetitive DNA sequences and their genome organization.Here we char-acterize the satellitomes of five species in the family Ostreidae(Crassostrea angulata,C.virginica,C.hongkongensis,C.ariakensis,Ostrea edulis),revealing a substantial number of satellite DNAs(satDNAs)per genome(ranging between 33 and 61)and peculiarities in the composition of their satellitomes.Numerous satDNAs were either associated to or derived from transposable elements,displaying a scarcity of transposable element-unrelated satDNAs in these genomes.Due to the non-conventional satellitome constitution and dominance of Helitron-associated satDNAs,comparative satellitomics demanded more in-depth analyses than standardly employed.Comparative analyses(including C.gigas,the first bivalve species with a defined satellitome)revealed that 13 satDNAs occur in all six oyster genomes,with Cg170/Hindiii satDNA being the most abundant in all of them.Evaluating the“satDNA library model”highlighted the necessity to adjust this term when studying tandem repeat evolution in organisms with such satellitomes.When repetitive sequences with potential variation in the organizational form and repeat-type affiliation are examined across related species,the introduction of the terms“TE library”and“repetitive DNA library”becomes essential.

关键词： Satellitome Comparative satellitomics Helitron Bivalves “Dark matter of the genome”

Quality assessment of the Topo-iberia CGPS stations and data quality's effects on postfit ionosphere-free phase residuals

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Geodesy and Geodynamics 2024年第2期15卷 189-199页

作者： Juan A.garcía-Armenteros Center for Advanced Studies in Earth Sciences Energy and Environment(CEACTEMA)University of Jaén23071 JaenSpain

This paper analyzed GPS data from the Topo-iberia network spanning almost 12 years(2008-2020).The data quality information for all 26 Topo-iberia stations is provided for the first time,complementing the Spanish Geological Survey’s storage work.Data analyses based on quality indicators obtained using TEQC have been carried out.The guidelines and data quality information from the iGS stations have been considered as the quality references,with the stations ALJi,EPCU,and TiOU standing out as the worst stations,while on the contrary,FUEN,PALM,PiLA,and TRiA meet the quality requirements to become an iGS station.The relationship between the GPS data quality and their GAMiT-and Gipsy X-derived postfit ionosphere-free phase residuals has also been investigated,and the results reveal an inversely proportional relationship.it has been found that the stations showing an increase in elevation of the horizon line,also show an increase in cycle slips and multipath,are among the poorest quality stations,and among those with the highest postfit RMS of phase residuals.Moreover,the evolution of the vegetation around the antenna should be considered as it could cause a progressive loss of quality,which is not complying with the iGS standards.The quality assessment shows that the Topo-iberia stations are appropriate for geodetic purposes,but permanent monitoring would be necessary to avoid the least possible loss of data and quality.in addition,a method to characterize the GNSS data quality is proposed.

关键词： GPS dataquality's effects iGS quality standard Postfit LC phase residual Qualityassessment Topo-iberia CGPS network

Myelin histology:a key tool in nervous system research

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Neural Regeneration Research 2024年第2期19卷 277-281页

作者： Óscar Darío garcía-garcía Víctor Carriel Jesús Chato-Astrain Department of Histology Tissue Engineering GroupUniversity of Granada&Instituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain

The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.in this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.

关键词： fluorescence microscopy histology light microscopy lipid histochemistry metallographic techniques myelin histochemistry myelin immunohistochemistry myelin structure&composition myelin ultrastructural evaluation tissue fixation&processing

Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan JoséPérez-moreno instituto de Biomedicina de Sevilla(iBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower limbs.Pat ients can also experience peripheral neuropathy,cognitive impairment,and other neurological symptoms.To date,more than 80 genes have been implicated in HSP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSP.

关键词： reticulum endoplasmic

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther moreno-Martínez Mar Cuadrado-Tejedor Ana garcía-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David garcía-Bernal Diego garcía-Ayuso Manuel Vidal-Sanz Marta Agudo-Barriuso Grupo de investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

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Neural Regeneration Research 2024年第1期19卷 55-61页

作者： Paula lzquierdo-Altarejos Victoria moreno-Manzano Vicente Felipo Laboratory of Neurobiology Centro Investigación Príncipe FelipeValenciaSpain Neuronal and Tissue Regeneration Laboratory Centro Investigación Príncipe FelipeValenciaSpain

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive molecules.Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation.The cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological situations.Extracellular vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative diseases.Extracellular vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the brain.This contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative diseases.The mechanisms involved are beginning to be unde rstood.For example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal rats.identifying the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early detection.in contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor function.These extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target organs.Extracellular vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and hepatic encephalopathy.Extracellular vesicles f

关键词： extracellular vesicles inflammation cognitive function mesenchymal stem cells neurodegenerative diseases neuroinflammation therapy transforming growth factor-β

Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

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World Journal of Gastroenterology 2024年第18期30卷 2485-2487页

作者： David Aguirre-Villarreal ignacio garcía-Juárez Department of Gastroenterology and Liver Transplant Unit Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,t... 详细信息

关键词： Cirrhosis Acute variceal bleeding Antibiotic prophylaxis Endoscopic band ligation Spontaneous bacterial peritonitis