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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-gonzález Elena gonzález-Rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez María Fernanda gonzález ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

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World Journal of Clinical Oncology 2021年第3期12卷 115-143页

作者： Felipe Couñago Carolina de la Pinta Susana gonzalo Castalia Fernández Piedad Almendros Patricia Calvo Begoña Taboada Antonio Gómez-Caamaño JoséLuis López Guerra Marisa Chust JoséAntonio gonzálezFerreira anaálvarez gonzález Francesc Casas Department of Radiation Oncology Hospital Universitario Quirónsalud MadridHospital La LuzUniversidad Europea de MadridMadrid 28223MadridSpain Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Radiation Oncology Hospital Universitario La PrincesaMadrid 28006Spain Department of Radiation Oncology GenesisCare MadridMadrid 28043Spain Department of Radiation Oncology Hospital General UniversitarioValencia 46014Spain Department of Radiation Oncology Hospital Clínico Universitario Santiago de CompostelaSantiago de Compostela 15706Spain Department of Radiation Oncology Hospital Universitario Virgen del RocíoSevilla 41013Spain Department of Radiation Oncology Fundación Instituto Valenciano de OncologíaValencia 46009Spain Department of Radiation Oncology GenesisCare-SpainSevilla 41092Spain Department of Radiation Oncology HGU Gregorio MarañónMadrid 28007Spain Department of Radiation Oncology Thoracic UnitHospital ClinicBarcelona 08036Spain

Small cell lung cancer(SCLC)accounts for approximately 20%of all lung *** main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to *** cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic *** 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of *** guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and ***,we discuss the main indications for reirradiation in local recurrence.

关键词： Small cell lung cancer Chemotherapy Hyperfractionated radiation therapy Prophylactic brain irradiation Brain metastases Reirradiation

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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： ana Milena Silva Olaya Fernanda Martins Almeida ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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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

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Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen gonzález‑Fernández Miguel A.García‑Álvarez Alberto Cuesta Department of Cell Biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-*** crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six *** the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been ***,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human *** of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or *** leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most ***,in vivo nodavirus infection resulted in alterations on the transcription of il17 *** nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead *** data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

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Yetter–Drinfeld Modules over Weak Braided Hopf Monoids and Center Categories

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Acta Mathematica Sinica,English Series 2014年第4期30卷 567-590页

作者： Jos Nicanor ALONSO lvarez Ramón gonzlez RODRIGUEZ Carlos SONEIRA CALVO Departamento de Matemticas Universidad de VigoCampus Universitario Lagoas-Marcosende Departamento de Matema'tica Aplicada II Universidad de VigoCampus Universitario Lagoas-Marcosende Departamento de Pedagoxía e Didctica Universidade da CoruaCampus Universitario de Elvia

In this paper, we introduce several centralizer constructions in a monoidal context and establish a monoidal equivalence with the category of Yetter-Drinfeld modules over a weak braided Hopf monoid. We apply the gener... 详细信息

关键词： Weak (braided) Hopf monoid Yetter-Drinfeld module center

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Tongluo Jiedu as an adjuvant therapy for oral cancer

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World Journal of Clinical Cases 2025年第5期13卷 52-57页

作者： Sarah Monserrat LomelíMartínez Melissa Martínez Nieto ana Esther Mercado gonzález Department of Medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810Mexico Department of Well-being and Sustainable Development Centro Universitario del NorteUniversidad de GuadalajaraColotlan 46200Mexico Independent Researcher Guadalajara 44340Mexico Antiguo Hospital Civil de Guadalajara“Fray Antonio Alcalde” Universidad de GuadalajaraGuadalajara 44280Mexico

Oral cancer is one of the malignant neoplasms that present major global health *** is the sixth most prevalent type of cancer in the world,with a high incidence and mortality *** letter is a review of the study by Yin et al which was published in the World Journal of Clinical Cases(2024).The study evaluated the effect of Tongluo Jiedu as an adjuvant treatment for oral *** the years,there has been a continuous search for effective and less invasive treatments for oral *** article emphasizes and discusses various therapeutic options currently available,and it highlights that early intervention and multidisciplinary management are crucial for improving *** Chinese medicine,particularly Tongluo Jiedu,presents potential complementary approach to co-nventional oral cancer *** research on Tongluo Jiedu should be focused on validation of its efficacy and safety through large,well-designed clinical trials,as well as better understanding of the molecular mechanisms in-volved,and optimization of therapeutic ***,continuous education of health professionals is key to the effective and safe integration of this traditional medicine into clinical *** research is essential for optimization of therapeutic strategies and for addressing the challenges presented by this neoplasm.

关键词： Oral cancer Tongluo Jiedu Traditional Chinese medicine Chinese herbal medicine Herbal drugs Dentistry

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Impact of Shaft Stiffness on Inertial Response of Fixed Speed Wind Turbines

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电力系统自动化 2012年第8期36卷 191-197页

作者： Francisco gonzlez-LONGATT Faculty of Engineering and Computing Coventry UniversityCoventry CV1 5FBUnited Kingdom

Future power system faces several challenges,one of them is the high penetration level of intermittent wind power generation,providing small or even no inertial response and being not contributing to the frequency *** effect of shaft stiffness on inertial response of fixed speed wind turbines is *** different drive-train models based on the multi-body system are *** small-signal analysis demonstrates no significant differences between models in terms of electro-mechanical eigen-values for increasing shaft *** natural resonance frequency of drive-train torsion modes shows slightly different values between damped and undamped models,but no significant differences are found in the number-mass ***-domain simulations show the changes in the active power contribution of a wind farm based on a fixed speed wind turbine during the system frequency *** changes in the kinetic energy during the dynamic process are calculated and their contribution to the inertia constant is small and *** largest contribution of the kinetic energy is provided at the beginning of the system frequency disturbance to reduce the rate of the frequency change,it is positive for the frequency stability.

关键词：风力发电机刚度模型惯性风力涡轮机频率稳定性轴定速传动系统

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Crossed Products over Weak Hopf Algebras Related to Cleft Extensions and Cohomology

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Chinese Annals of Mathematics,Series B 2014年第2期35卷 161-190页

作者： José Nicanor Alonso álvarez José Manuel Fernández VILABOA Ramón gonzález RODRíGUEZ Departamento de Matemáticas Universidad de VigoCampus Universitario Lagoas-Marcosende Departamento de álxebra Universidad de Santiago de Compostela Departamento de Matemática Aplicada II Universidad de VigoCampus Universitario Lagoas-Marcosende

The authors present the general theory of cleft extensions for a cocommutative weak Hopf algebra H. For a right H-comodule algebra, they obtain a bijective corre- spondence between the isomorphisms classes of H-cleft extensions AH → A, where AH is the subalgebra of coinvariants, and the equivalence classes of crossed systems for H over AH. Finally, they establish a bijection between the set of equivalence classes of crossed systems with a fixed weak H-module algebra structure and the second cohomology group H2φZ（AH）（H, Z（AH））, where Z（AH） is the center of AH.

关键词： Monoidal category Weak Hopf algebra Cleft extension Weak crossedproduct Sweedler cohomology for weak Hopf algebras

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