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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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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier ramos laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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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

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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)

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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： rafael Franco Claudia garrigós Toni Capó Joan Serrano-marín rafael Rivas-Santisteban Jaume lillo Molecular Neurobiology laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression g proteincoupled receptors glia neurons

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Duplication of the Inferior Vena Cava, Azygos Continuation and Retro Aortic Renal Vein: Fortuitous Discovery

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Forensic Medicine and Anatomy Research 2021年第3期9卷 31-40页

作者： géraud léra akpo.ndeye bigué mar Soukeyna Abouabdillah Nfaly Badji Hamidou Deme Youssoupha Kasse Ibrahima Niang Mamadou lamine gueye marcel Mbarga Ibrahima Faye Abdoulaye Dione Diop Assane Ndiaye Sokhna Ba Diop El Hadji Niang Service de radiologie Imagerie Médicale de l’h&#244pital Ariste Le Dantec Dakar Sénégal laboratoire d’Anatomie UFR des Sciences de la Santé Université Iba Der Thiam de Thiès Thiès Sénégal Service de radiologie Imagerie Médicale de l’h&#244pital Fann Dakar Sénégal Service de radiologie Imagerie Médicale de l’h&#244pital Dalal Jam Dakar Sénégal laboratoire d’Anatomie UFR des Sciences de la Santé Université Assane SECK de Ziguinchor Ziguinchor Sénégal

We present a rare case associating inferior vena cava’s (IVC) complex variations. Anatomical, embryological and clinical aspects are discussed. Duplication’s discovery was fortuitous during an abdominal ultrasound and was confirmed by the CT scan. The latter also highlighted azygos continuation, retro aortic renal vein and an iliac venous anomaly. These variants are important to know in order to be able to differentiate them from lymphadenopathy, para-vertebral masses, and aortic pathologies. It is necessary to report them before any retroperitoneal surgery or interventional vascular procedure.

关键词： Duplication IVC Continuation Azygos Tomodensitometry

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Incidental Finding of a Fenestrated Vertebrobasilar Junction Aneurysm

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Forensic Medicine and Anatomy Research 2022年第2期10卷 44-49页

作者： Youssoupha Kassé géraud léra akpo Ibrahima Niang Khadidiatou Diouf Ka Rokhaya Diagne Ndèye bigué mar Khaoulah Talhaoui Aminata Mbaye Papa Malick Dibor Diouf Mame Coumba Fall Sokhna BaDiop radiology and Medical Imaging Department of FANN Hospital Dakar Senegal Neurology Department of FANN Hospital Dakar Senegal Anatomy laboratory of Health Sciences Department of Iba Der Thiam University Thies Senegal

Basilar artery fenestration is a rare anatomical variation resulting from the failed fusion of the two vertebral arteries during embryonic life. In order of frequency, it is the second most common location of vascular fenestrations after the anterior communicating artery. Vertebrobasilar junction aneurysms are uncommon but often associated with basilar artery fenestration. We report the case of a fenestrated vertebrobasilar junction saccular aneurysm in a 57-year-old woman. The diagnosis was incidentally made on CT angiography which found the anatomical variant and the aneurysm. The radiological features illustrating this association are detailed here and a brief discussion of its pathogenesis and management was made. Vertebrobasilar junction aneurysms are rare and their presence should suggest an associated basilar fenestration.

关键词： Basilar Artery Fenestration Vertebrobasilar Aneurysm CT Brain Angiography

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radio-Anatomical Study of Anterior Variants of the Polygon of Willis

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Open Journal of radiology 2023年第4期13卷 185-194页

作者： Diop Aboulaye Dione mar ndeye bigué Diouf Joseph Coumba Ndofféne Diop Sokhna Ba Medical Imaging Service Fann Hospital Dakar Senegal laboratory of Anatomy/UMRED Iba Der Thiam University Thiès Senegal

The anterior system of the polygon of Willis plays an anastomotic role between the carotid territories and communicates with the posterior system. It ensures adequate cerebral blood flow in the event of internal occlusion. Its ability to redistribute blood flow depends on its morphology, the presence and size of the vessels that constitute it and their variants, knowledge of which is essential. The morphology of the carotid system is not constant and a number of variants are well recognized with greater hemodynamic importance. In this context, we undertook this work which aims to seek the anatomical variants of the anterior part of the PW;to determine the diameters of the vessels of the latter and to correlate these results with epidemiological data. We carried out a retrospective, descriptive and analytical study over a period of 4 months at Fann University Hospital, targeting patients who had undergone brain MRI with a 3D TOF sequence whatever the indication. Patients with lesions of cerebrovascular pathologies such as ischemia, hemorrhage, aneurysm, arteriovenous malformations or presenting a limited analysis examination due to the presence of kinetic or other artifact, were not included. Demographic data and anatomical variants were studied as well as the measurements of any continuous arterial segment greater than 0.8 mm in diameter. Those less than 0.8 mm in diameter were considered hypoplastic. The C3 segment of the internal carotid arteries, the A1 segment of the anterior cerebral arteries, the anterior communicating artery, constituted our main measurement sites. The sex ratio was 1.06, the mean age of the patients was 43 years ± 17.9 with extremes of 11 and 85 years. The anterior configuration of the polygon was complete in 57.5% representing 50% of men and 65.5% of women, in 56% of subjects under 40 years old and 58% in subjects over 40 years old. We noted a predominance of type a in 47% of patients followed by type g found in 35% of patients. The morphol

关键词： Polygon of Willis Anamicals Variants Vascular Diseases

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Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

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World Journal of Clinical Oncology 2025年第1期16卷 5-9页

作者： Macarena Teja maría I garrido Abrahams Ocanto Felipe Counago Department of radiation Oncology GenesisCare-San Francisco de Asís University HospitalMadrid 28002Spain Department of radiation Oncology GenesisCare-Vithas La Milagrosa University HospitalMadrid 28010Spain National Director GenesisCare SpainMadrid 28043Spain Department of Medicine School of MedicineHealth and SportEuropean University of MadridMadrid 28670Spain

Pancreatic cancer is usually associated with a poor *** is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are *** et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NlR),platelet-to-lymphocyte ratio(PlR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NlR,and PlR and a hospital discharge of less than 15 *** a univariable analysis,PNI,SII,NlR and PlR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall *** meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their ***,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant *** are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

关键词： Inflammatory biomarkers Nutritional biomarkers Pancreatic cancer Prognosis Surgical complications

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Dendritic nanoarchitecture imparts ZSM-5 zeolite with enhanced adsorption and catalytic performance in energy applications

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Journal of Energy Chemistry 2023年第5期80卷 77-88,I0003页

作者： maría del mar Alonso-Doncel Cristina Ochoa-Hernández gema gómez-Pozuelo Adriana Oliveira Joségonzález-Aguilar ángel Peral raúl Sanz David P.Serrano Thermochemical Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Heterogeneous Catalysis Max-Planck-Institut für KohlenforschungKaiser-Wilhem-Platz14540Muheim an der RuhGermay Department of Chemical and Environmental Technology Rey Juan Carlos UniversityC/Tulipan s/nE28933MostolesMadridSpain High Temperature Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Chemical Energy and Mechanical TechnologyRey Juan Carlos UniversityC/Tulipan s/n28933MostolesMadridSpain

The development of zeolites possessing dendritic features represents a great opportunity for the design of novel materials with applications in a large variety of fields and,in particular,in the energy sector to afford its transition towards a low carbon *** the current work,ZSM-5 zeolite showing a dendritic3D nanoarchitecture has been synthesized by the functionalization of protozeolitic nanounits with an amphiphilic organosilane,which provokes the branched aggregative growth of zeolite *** ZSM-5 exhibits outstanding accessibility arising from a highly interconnected network of radially-oriented mesopores(3-10 nm)and large cavities(20-80 nm),which add to the zeolitic micropores,thus showing a well-defined trimodal pore size *** singular features provide dendritic ZSM-5 with sharply enhanced performance in comparison with nano-and hierarchical reference materials when tested in a number of energy related applications,such as VOCs(toluene)adsorption(improved capacity),plastics(low-density polyethylene)catalytic cracking(boosted activity)and hydrogen production by methane catalytic decomposition(higher activity and deactivation resistance).

关键词： Dendritic ZSM-5 VOCs adsorption Plastics cracking Methane decomposition Hydrogen production

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