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SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation

Signal Transduction and Targeted Therapy 2020年第1期5卷 2322-2331页

作者： Xavier Palomer MSilvia Román-Azcona javier pizarro-delgado Ana Planavila Francesc Villarroya Brenda Valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera Department of Pharmacology Toxicology and Therapeutic ChemistryIBUB(Institut de Biomedicina de la Universitat de Barcelona)Research Institute-Pediatric Research InstituteHospital Sant Joan de Déuand CIBER de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM)Faculty of Pharmacy and Food SciencesUniversity of BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Biomedicine IBUB and CIBER Fisiopatología de la Obesidad y Nutrición(CIBEROBN)Faculty of BiologyUniversity of BarcelonaBarcelonaSpain aBCNatal-Barcelona Center for Maternal–Fetal and Neonatal Medicine(Hospital Clínic and Hospital Sant Joan de Deu) Institut d’Investigacions Biomèdiques August Pi i SunyerUniversitat de Barcelonaand Center for Biomedical Research on Rare Diseases(CIBER-ER)BarcelonaSpain Genomic Programming of Betacells Laboratory Institut d’Investigacions August Pi i Sunyer(IDIBAPS)and CIBERDEMBarcelonaSpain Section of Epigenomics and Disease Department of Medicineand National Institute for Health Research(NIHR)Imperial Biomedical Research CentreImperial College LondonLondonUK Servicio de Cirugía Cardiovascular Hospital Universitario Marqués de ValdecillaDepartamento de Ciencias Médicas y QuirúrgicasFacultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)Centro de Investigación Biomédica en Red Cardiovascular(CIBERCV)Instituto de Salud Carlos IIISantanderSpain Departamento de Fisiología y Farmacología Facultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)SantanderSpain Department of Radiation Oncology Columbia UniversityNew YorkNYUSA

Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative *** of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac *** this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 ***3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of *** with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of ***,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its *** findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 *** fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.

关键词： SIRT3 inflammation cardiac

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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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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

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ON CONSERVATIVE APPROXIMATION BY LINEAR POLYNOMIAL OPERATORS AN EXTENSION OF THE BERNSTEIN'S OPERATOR

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Analysis in Theory and Applications 1995年第1期11卷 62-71页

作者： Francisco-javier Munoz-delgado Victoriano Ramirez-Gonzalez Paul Sablonniere Universidad de Jaen SpainUniversidad de Granada SpainInstitut National des Sciences Appliquees France

In this work we slwly linear polynomial operators preserving some consecutive i-convexities and leaving in-verant the polynomtals up to a certain degree. First we study the existence of an incompatibility between the conservation of cenain i-cotivexities and the invariance of a space of polynomials. Interpolation properties are obtained and a theorem by Berens and DcVore about the Bernstein's operator ts extended. Finally, from these results a genera'ized Bernstein's operator is obtained.

关键词： LPO ON CONSERVATIVE APPROXIMATION BY LINEAR POLYNOMIAL OPERATORS AN EXTENSION OF THE BERNSTEIN’S OPERATOR

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A virtual model of the retina based on histological data as a tool for evaluation of the visual fields

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Annals of Eye Science 2017年第1期2卷 113-126页

作者： Francisco-javier Carreras Ángel V.delgado José.L.García-Serrano Department of Surgery Medical School2Department of Applied PhysicsSchool of SciencesUniversity of GranadaGranadaSpain Hospital Clínico San Cecilio University of GranadaGranadaSpain School of Computer Science Department of Computer Science and Artificial IntelligenceUniversity of GranadaGranadaSpain

Background:To settle the fundamentals of a numerical procedure that relates retinal ganglion-cell density and threshold sensitivity in the visual *** sensitivity of a generated retina and visual pathways to virtual stimuli are simulated,and the conditions required to reproduce glaucoma-type defects both in the optic-nerve head(ONH)and visual fields are ***:A definition of selected structural elements of the optic pathways is a requisite to a translation of clinical knowledge to computer programs for visual field *** program is able to generate a database of normalized visual *** relationship between the number of extant receptive fields and threshold sensitivity is plotted for background sensitivity and corresponding automated perimetry.A solution in two planes to the 3D distribution of axons in the ONH is *** fields with induced damage in the optic disc are comparable in pattern and quantity to glaucomatous ***:The two-level simulation of the ONH facilitates the analysis of optic-cup/retinal *** can generate the virtual optic pathways tailored to the age and morphology of the patient’s eye,and it is possible to reproduce glaucomatous damage by“reverse engineering”*** virtual cortical model renders a quantitative relationship between visual defect and neural ***:A two-level computing of the retina/optic nerve facilitates the analysis of neuroretinal defects and can be incorporated to automatic perimeters to facilitate visual field analysis.

关键词： Computer modeling early optic pathways neuroretinal defects threshold sensitivity visual fields

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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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Nanoparticles embedded into glass matrices:glass nanocomposites

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Frontiers of Materials Science 2022年第3期16卷 1-81页

作者： javier FONSECA Department of Chemical Engineering Northeastern UniversityBoston 02115USA

Research on glass nanocomposites(GNCs)has been very active in the past *** have attracted—and still do—great interest in the fields of optoelectronics,photonics,sensing,electrochemistry,catalysis,biomedicine,and *** this review,the potential applications of GNCs in these fields are briefly described to show the reader the possibilities of these *** most important synthesis methods of GNCs(melt-quenching,sol-gel,ion implantation,ion-exchange,staining process,spark plasma sintering,radio frequency sputtering,spray pyrolysis,and chemical vapor deposition techniques)are extensively *** major aim of this review is to systematize our knowledge about the synthesis of GNCs and to explore the mechanisms of formation and growth of NPs within glass *** size-controlled preparation of NPs within glass matrices,which remains a challenge,is essential for advanced ***,a thorough understanding of GNC synthesis techniques is expected to facilitate the preparation of innovative GNCs.

关键词： glass nanocomposites melt-quenching sol-gel ion implantation ion-exchange

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Nonlinear criterion for strength mobilization in brittle failure of rock and its extension to the tunnel scale

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International Journal of Mining Science and Technology 2022年第4期32卷 685-705页

作者： Rodolfo Cabezas javier Vallejos Faculty of Engineering and Technology Universidad San SebastianSantiagoChile Advanced Mining Technology Center Universidad de ChileSantiagoChile Department of Mining Engineering Universidad de ChileSantiagoChile

As underground excavations are getting deeper and field stresses increase, the behavior of intact rock blocks plays an increasingly important role in understanding and estimating the overall rock mass strength. To model the brittle behavior of intact rock blocks, the stress–strain curve is usually idealized considering a linear strength mobilization approach(cohesion-weakening-friction-strengthening, CWFS),however, it is well recognized that rock presents a nonlinear behavior in terms of the confining *** study extends the strength mobilization in brittle failure of rock using nonlinear criteria. To determine the model parameters, a standard statistical method that uses the complete laboratory stress–strain curves of the intact rock is employed. Several hypotheses of linear and nonlinear models are statistically compared for different types of rock and confining stress levels. Results demonstrate that the best approach to model the brittle failure of rock is to consider a nonlinear strength envelope, such as the Hoek-Brown criterion assuming a residual uniaxial compressive strength different from zero and a mi parameter that increases, both with simultaneous mobilization. This model helps to recreate highconfining conditions and a more realistic transition between peak and post-peak strength. The obtained parameters are discussed and compared with literature values to verify the validity and to develop guidelines for the estimation of parameters, providing an objective mobilization criterion. Finally, the nonlinear model was applied to a finite element code and extended to a tunnel scale in the brittle rock under high-stress conditions. A reasonable fit between the simulations and the in-situ overbreak measurements was found.

关键词： Nonlinear strength Strength mobilization Brittle failure Intact rock Scaling

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See how atoms dance

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National Science Review 2020年第5期7卷 833-834页

作者： javier Aizpurua Center for Materials Physics (CSIC-UPV/EHU) DIPC

As for any other wave, classical light was often thought to be constrained by the diffraction limit. However, since the pioneering works in near-field microscopy,in which the evanescent components of light localized a... 详细信息

关键词： See how atoms dance

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Probabilistic Constructions of B_2[g] Sequences

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Acta Mathematica Sinica,English Series 2010年第7期26卷 1309-1314页

作者： javier CILLERUELO Instituto de Ciencias Matermáticas(CSIC-UAM-UCM) Department of Mathematics Universidad Autónoma de Madrid

We use the probabilistic method to prove that for any positive integer g there exists an infinite B2[g] sequence A = {ak} such that ak ≤ k^2＋1/g（log k）^1/g＋0（1） as k→∞. The exponent 2＋1/g improves the previo... 详细信息

关键词： Sidon sets B2 [g] sequences probabilistic method

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