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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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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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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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Rheological and tribological approaches as a tool for the development of sustainable lubricating greases based on nano-montmorillonite and castor oil

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Friction 2021年第2期9卷 415-428页

作者： Jose Enrique marTÍN-ALFONSO maría Jose marTÍN-ALFONSO Concepción VALENCIA maría Teresa CUBERES Department of Chemical Engineering and Materials Science Campus de“El Carmen”University of HuelvaChemical Product and Process Technology Research Center(Pro2TecS)Huelva 21071Spain Department of Applied Mechanics and Project Engineering University of Castilla-La ManchaAlmadén 13400Spain

This study investigates the development of novel montmorillonite/castor oil blends to formulate sustainable lubricating greases to promote the replacement of petrochemicals industry-derived materials by substances obtained from renewable ***,the effect of the thickener concentration on the rheological,chemical,thermal,tribological properties,and atomic force microscopy(AFM)microstructure of these systems were *** results showed that the C20A nanoclay content could be used to modulate the viscosity values,the linear viscoelastic functions,and tribological properties of these montmorillonite *** general,these gel-like dispersions exhibited remarkable lubricant properties;the samples showed values of the friction coefficient and wear scars similar or lower than those obtained with model bentonite grease.

关键词： lubricating greases nanoclay vegetable oil rheology tribology

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Immunogenicity and mechanisms impairing the response to vaccines in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第40期21卷 11273-11281页

作者： Alicia C marín Javier P Gisbert maría Chaparro Gastro- enterology Unit Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria PrincesaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas28021 MadridSpain

Inflammatory bowel disease(IBD) is an immunological disorder that is usually treated with immunosuppressive therapy,potentially leading to increases in vulnerability to infections. Although many infections can be pre-vented by vaccination,vaccination coverage in these patients in clinical practice is insufficient. Therefore,the seroprotection condition should be verified,even for routine vaccines,such as hepatitis B or pneu-mococcus. Response to vaccines in IBD patients is thought to be impaired due to the immunological alterations generated by the disease and to the immunomodulatory treatments. The immunogenicity of hepatitis B,influenza,and pneumococcal vaccines is impaired in IBD patients,whereas the response to papillomavirus vaccine seems similar to that observed in the healthy population. On the other hand,data on the immunogenicity of tetanus vaccine in IBD patients are conflicting. Studies assessing the response to measles-mumps-rubella,varicella,and herpes zoster vaccines in IBD patients are scarce. The cellular and molecular mechanisms responsible for the impairment of the response to vaccination in IBD patients are poorly understood. Studies aiming to assess the response to vaccines in IBD patients and to identify the mechanisms involved in their immunogenicity are warranted. A better understanding of the immune response,specifically to vaccines,in patients with immune-mediated diseases(such as IBD),is crucial when developing vaccines that trigger more potent immunologic responses.

关键词： Crohn’s disease Inflammatory bowel disease Tumor n

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Weighted Inequalities for Fractional Type Operators with Some Homogeneous kernels

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Acta Mathematica Sinica,English Series 2013年第3期29卷 449-460页

作者： maría Silvina RIVEROS marta URCIUOLO FaMAF-UNC CIEM-CONICET Ciudad Universitaria

In this paper, we study integral operators of the formappropriate weighted BMO and weak type estimates for certain weights satisfying the above inequality. We also give a Coifman type estimate for these operators.

关键词： Fractional operators Calderon-Zygmund operators BMO Muckenhoupt weights

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Umbilical cord as a mesenchymal stem cell source for treating joint pathologies

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World Journal of Orthopedics 2011年第6期2卷 43-50页

作者： maría Carmen Arufe Alexandre De la Fuente Isaac Fuentes Francisco Javier De Toro Francisco Javier Blanco Department of Medicine Area of Anatomy and Human EmbryologyCampus Oza s/nFac.of Health ScienceUniversity of A Coruna15006 A CorunaSpain Osteoarticular and Aging Research lab Cellular Therapy UnitINIBIC-CH Universitario A Coruna15006 A CorunaSpain Rheumatology Division INIBIC-CH Universitario A Coruna15006 A CorunaSpain Cathedra Bioiberica Universidad de A Coruna15006 A CorunaSpain CIBER-BBN-Instituto de Salud Carlos III 15006 A CorunaSpain Centro de Investigacion Biomedica Hospital Universitario A CorunaC/Xubias 8415006 A CorunaSpain

Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of ***,the regeneration of articular cartilage is a continuing challenge for biomedical *** of the most promising therapeutic approaches is cellbased tissue engineering,which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured *** use of healthy chondrocytes has been found to have limitations.A promising alternative cell population is mesenchymal stem cells(MSCs),known to possess excellent proliferation potential and proven capability for differentiation into ***“immunosuppressive”property of human MSCs makes them an important candidate for allogeneic cell *** use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting *** allogeneic cell-based approach would enable MSCs to be isolated from any donor,expanded and cryopreserved in allogeneic MSC banks,providing a readily available source of progenitors for cell replacement *** possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology *** objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.

关键词： Human Mesenchymal stem cell Umbilical cord Cartilage degeneration

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Brain and spinal cord trauma:what we know about the therapeutic potential of insulin growth factor 1 gene therapy

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Neural Regeneration Research 2023年第2期18卷 253-257页

作者： maría Jose Bellini Florencia labombarda lab de Bioquímica del Envejecimiento INIBIOLP-CONICETFacultad de Ciencias MedicinaUniversidad Nacional de La PlataLa PlataArgentina laboratory of Neuroendocrine Biochemistry IBYME-CONICETBuenos AiresArgentina Department of Human Biochemistry Faculty of MedicineUniversidad de Buenos AiresBuenos AiresArgentina

Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive *** group also has contributed significantly to the study of cognitive impairments in a rat model of spinal co rd *** findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes,drugs of abuse,and combined *** are related to changes in brain structures involved in cognition and emotion,such as the *** spinal cord injury decreases neurogenesis,enhances glial reactivity leading to hippocampal neuroinflammation,and trigge rs cognitive *** brain distal abnormalities are recently called te rtiary *** that there is no treatment for Tertiary Damage,insulin growth factor 1 gene therapy emerges as a good *** growth factor 1 gene thera py recove rs neurogenesis and induces the polarization from pro-inflammato ry towards anti-inflammatory microglial phenotypes,which represents a potential strategy to treat the neuroinflammation that supports te rtiary *** growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is *** growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.

关键词： cognitive impairments gene therapy hippocampus insulin growth factor 1 microglial cells neurodegeneration neurogenesis neuroinflammation spinal cord injury traumatic brain injury

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Site Characterization Index for Continuous Power Quality Monitoring Based on Higher-order Statistics

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Journal of Modern Power Systems and Clean Energy 2022年第1期10卷 222-231页

作者： Olivia Florencias-Oliveros Juan-José González-de-la-Rosa Jose-maría Sierra-Fernández Agustín Agüera-Pérez Manuel-Jesús Espinosa-Gavira José-Carlos Palomares-Salas Department of Automation Engineering ElectronicsArchitecture and Computers NetworksResearch Group TIC168Higher Polytechnic SchoolUniversity of CádizAlgeciras 11202Spain

The high penetration of distributed generation(DG)has set up a challenge for energy management and consequently for the monitoring and assessment of power quality(PQ).Besides,there are new types of disturbances owing to the uncontrolled connections of non-linear *** stochastic behaviour triggers the need for new holistic indicators which also deal with big data of PQ in terms of compression and scalability so as to extract the useful information regarding different network states and the prevailing PQ disturbances for future risk assessment and energy management *** and continuous monitoring would guarantee the report to claim for damages and to assess the risk of PQ *** this context,we propose a measurement method that postulates the use of two-dimensional(2D)diagrams based on higher-order statistics(HOSs)and a previous voltage quality index that assesses the voltage supply waveform in a continous monitoring *** suitable for both PQ and reliability applications,the results conclude that the inclusion of HOS measurements in the industrial metrological reports helps characterize the deviations of the voltage supply waveform,extracting the individual customers’pattern fingerprint,and compressing the data from both time and spatial *** method allows a continuous and robust performance needed in the SG ***,the method can be used by an average consumer as a probabilistic method to assess the risk of PQ deviations in site characterization.

关键词： Continuous statistical monitoring big data data compression higher-order statistics(HOSs) power quality(PQ)

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Proteomics for discovery of candidate colorectal cancer biomarkers

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World Journal of Gastroenterology 2014年第14期20卷 3804-3824页

作者： Paula lvarez-Chaver Olalla Otero-Estévez maría Páez de la Cadena Francisco J Rodríguez-Berrocal Vicenta S martínez-Zorzano Unidad de Proteómica Servicio de Determinación EstructuralProteómica y GenómicaCentro de Apoyo Científico y Tecnológico a la InvestigaciónUniversidad de VigoCampus As Lagoas-Marcosende área de Bioquímica y Biología Molecular Departamento de BioquímicaGenética e InmunologíaFacultad de BiologíaUniversidad de VigoCampus As Lagoas-Marcosende

Colorectal cancer(CRC)is the second most common cause of cancer-related deaths in Europe and other Western countries,mainly due to the lack of wellvalidated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early *** it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes,much less is known at the proteome ***,in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis,prognosis and as therapeutic targets for this malignancy,as well as to elucidate the molecular mechanisms of colorectal *** important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single *** review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods,quantitative mass spectrometry-based techniques or protein ***,we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue,serum and faeces,besides cell lines and murine models,discussing their advantages and disadvantages,and summarize the most frequently identified candidate CRC markers.

关键词： Colorectal cancer Serum Tissue Proteins Biomarkers Proteomics Protein identification Mass spectrometry

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