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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 *** 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 *** 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 *** 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 *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** 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)

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1166-1179页

作者： Sebastián Díaz-López Jerónimo jiménez-Castro Carlos Enrique Robles-Barraza Carlos Ayala-de Miguel Manuel Chaves-Conde Medical Oncology Department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic *** are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each *** non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade *** changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is *** review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available *** would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology Diagnosis

Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： Laura García-Mendívil maría Pérez-Zabalza Antoni Oliver-Gelabert josémaría Vallejo-Gil Javier Fañanás-Mastral Manuel Vázquez-Sancho Javier AndréBellido-Morales Alexánder Sebastián Vaca-Núñez Carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental Medicine and Biology of Cuyo(IMBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic Lydia jiménez-Díaz Juan D.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative Medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

Grouping tree species to estimate basal area increment in temperate multispecies forests in Durango,Mexico

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Forest Ecosystems 2024年第1期11卷 1-13页

作者： Jaime Roberto Padilla-martínez Carola Paul Kai Husmann jose Javier Corral-Rivas Klaus von Gadow Department of Forest Economics and Sustainable Land-use Planning Faculty of Forest Sciences and Forest EcologyUniversity of GottingenBüsgenweg 137077GottingenGermany Facultad de Ciencias Forestales Universidad Juarez del Estado de DurangoRío Papaloapan y Boulevard Durango S/N34120DurangoMexico Faculty of Forestry and Forest Ecology Georg-August-UniversitatBüsgenweg 537077GottingenGermany Department of Forestry and Wood Science Faculty of AgriSciencesStellenbosch UniversityStellenbosch Private Bag X1Stellenbosch7602South Africa

Multispecies forests have received increased scientific attention,driven by the hypothesis that biodiversity improves ecological ***,a greater species diversity presents challenges for forest management and *** study aims to develop basal area growth models for tree species *** analysis is based on a dataset of 423 permanent plots(2,500 m^(2))located in temperate forests in Durango,***,we define tree species cohorts based on individual and neighborhood-based variables using a combination of principal component and cluster ***,we estimate the basal area increment of each cohort through the generalized additive model to describe the effect of tree size,competition,stand density and site *** principal component and cluster analyses assign a total of 37 tree species to eight cohorts that differed primarily with regard to the distribution of tree size and vertical position within the *** generalized additive models provide satisfactory estimates of tree growth for the species cohorts,explaining between 19 and 53 percent of the total variation of basal area increment,and highlight the following results:i)most cohorts show a"rise-and-fall"effect of tree size on tree growth;ii)surprisingly,the competition index"basal area of larger trees"had showed a positive effect in four of the eight cohorts;iii)stand density had a negative effect on basal area increment,though the effect was minor in medium-and high-density stands,and iv)basal area growth was positively correlated with site quality except for an oak *** developed species cohorts and growth models provide insight into their particular ecological features and growth patterns that may support the development of sustainable management strategies for temperate multispecies forests.

关键词： Temperate multispecies forests Cluster analysis Basal area increment Generalized additive models

A Transfer Function Design for Medical Volume Data Using a Knowledge Database Based on Deep Image and Primitive Intensity Profile Features Retrieval

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Journal of Computer Science & Technology 2024年第2期39卷 320-335页

作者： Younhyun Jung jim Kong 盛斌 Jinman Kim School of Computing Gachon UniversitySeongnam 13120Korea School of Computer Science The University of SydneySydney 2006Australia Department of Computer Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Direct volume rendering(DVR)is a technique that emphasizes structures of interest(SOIs)within a volume visually,while simultaneously depicting adjacent regional information,e.g.,the spatial location of a structure concerning its *** DVR,transfer function(TF)plays a key role by enabling accurate identification of SOIs interactively as well as ensuring appropriate visibility of *** generation typically involves non-intuitive trial-and-error optimization of rendering parameters,which is time-consuming and *** at mitigating this manual process have led to approaches that make use of a knowledge database consisting of pre-designed TFs by domain *** these approaches,a user navigates the knowledge database to find the most suitable pre-designed TF for their input volume to visualize the *** these approaches potentially reduce the workload to generate the TFs,they,however,require manual TF navigation of the knowledge database,as well as the likely fine tuning of the selected TF to suit the *** this work,we propose a TF design approach,CBR-TF,where we introduce a new content-based retrieval(CBR)method to automatically navigate the knowledge *** of pre-designed TFs,our knowledge database contains volumes with SOI *** an input volume,our CBR-TF approach retrieves relevant volumes(with SOI labels)from the knowledge database;the retrieved labels are then used to generate and optimize TFs of the *** approach largely reduces manual TF navigation and fine *** our CBR-TF approach,we introduce a novel volumetric image feature which includes both a local primitive intensity profile along the SOIs and regional spatial semantics available from the co-planar images to the *** the regional spatial semantics,we adopt a convolutional neural network to obtain high-level image feature *** the intensity profile,we extend the dynamic time warping technique to address subtle alignment

关键词： data retrieval direct volume rendering ray analysis transfer function

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： maría Norte-Muñoz maría Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega mar Pérez joséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz maría Teresa Moreno-Flores 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 SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

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World Journal of Methodology 2024年第2期14卷 107-126页

作者： Jacobo Trébol Ana Carabias-Orgaz maría Carmen Esteban-Velasco Asunción García-Plaza Juan Ignacio gonzález-Munoz Ana Belén Sánchez-Casado Felipe Carlos Parreno-Manchado marta Eguía-Larrea josé Antonio Alcázar-Montero Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain Cirugía Universidad de SalamancaSalamanca 37007SalamancaSpain Oftalmología Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle march to the end of June *** population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable *** our centre,we managed patients previously and newly diagnosed with *** established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected *** also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new *** To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related *** We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent *** analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual *** From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 g

关键词： COVID-19 SARS-CoV-2 Colon cancer Rectal cancer Breast cancer Liver cancer Pancreatic cancer Gastric cancer Oesophageal cancer Surgery