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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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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

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subcutaneous implantable defibrillator: state-of-the art 2013

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World Journal of Cardiology 2013年第9期5卷 347-354页

作者： Finn Akerstrm Miguel A Arias Marta Pachón al.erto puchol.jesús jiménez-l.pezl Cardiac Arrhythmia and Electrophysiology Unit Department of CardiologyHospital Virgen de la Salud

The subcutaneous implantable cardioverter-defibrillator(s-ICD)has recently been approved for commercial use in Europe,New Zealand and the United *** is comprised of a pulse generator,placed subcutaneously in a left lateral position,and a parasternal subcutaneous lead-electrode with two sensing electrodes separated by a shocking *** an entirely subcutaneous system it avoids important periprocedural and long-term complications associated with transvenous implantable cardioverter-defibrillator(TV-ICD)systems as well as the need for fluoroscopy during implant *** candidates include pediatric patients with congenital heart disease that limits intracavitary lead placements,those with obstructed venous access,chronic indwelling catheters or high infection risk,as well as young patients with electrical heart disease(e.g.,Brugada syndrome,long QT syndrome,and hypertrophic cardiomyopathy).Nevertheless,given the absence of intracavitary leads,the s-ICD is unable to offer pacing(apart from shortterm post-shock pacing).It is therefore not suitable in patients with an indication for antibradycardia pacing or cardiac resynchronization therapy,or with a history of repetitive monomorphic ventricular tachycardia that would benefit from antitachycardia *** data from initial clinical studies and post-commercialization"real-life"case series,including over 700 patients,have so far been promising and shown that the s-ICD successfully converts induced and spontaneous ventricular tachycardia/ventricular fibrillation episodes with associated complication and inappropriate shock rates similar to that of ***,by using far-field electrograms better tachyarrhythmia discrimination when compared to TV-ICDs has been *** results from ongoing clinical studies will determine the s-ICD system’s long-term performance,and better define suitable patient profiles.

关键词： Implantable cardioverter-defibrillator subcutaneous sudden death Ventricular tachycardia Ventricular fibrillation

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status and prospects for symmetric organic redox flow batteries

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Journal of Energy Chemistry 2025年第1期100卷 125-143页

作者： Md al Raihan C.Adam Dyker Department of Chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

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A DYNAMICs APPROACH TO THE COMPUTATION OF EIGENVECTORs OF MATRICEs

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Journal of Computational Mathematics 2005年第6期23卷 657-672页

作者： s. jiménez l. Vézquez Colaborador honorifico Dept. Matemátiea AplicadaUniversidad Complutense de Madrid 28040 Madrid Spain Dept. Matemdtica Aplicada Facultad de Informática Universidad Complutense de Madrid 28040 Madrid Spain Centro de Astrobiologla CSIC/INTA 28850 Torrejón de Ardoz Madrid Spain

We construct a family of dynamical systems whose evolution converges to the eigenvectors of a general square matrix, not necessarily symmetric. We analyze the convergence of those systems and perform numerical tests. ... 详细信息

关键词： smallest real eigenvalue Iterative method

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Visual function,performance,and processing of basketball players *** individuals

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Journal of sport and Health science 2020年第6期9卷 587-594页

作者： jesús Vera Raimundo jiménez David Cárdenas Beatriz Redondo José Antonio García Department of Optics Faculty of ScienceUniversity of GranadaGranada 18071Spain Department of Physical Education and sport Faculty of Sport ScienceUniversity of GranadaGranada 18071Spain sport and Health University Mixed Institute University of GranadaGranada 18071Spain

Background:Athletes tend to have better visuo-motor performance than do sedentary ***,several basic visual-function and perceptual parameters remain unexplored to *** this study,we investigated whether differences exist in visual function,performance,and processing between basketball players and individuals without a sport-involvement ***:A total of 33 healthy men with no visual impairment or pathology were divided into 2 groups,depending on the involvement in sport(semi-professional basketball players and sedentary individuals).We tested their baseline heart-rate variability in the resting position apart from subjective questionnaires to determine their physical fitness level,and we checked their visual function,performance,and processing through an extended battery of optometric ***:The 2 groups differed in resting heart-rate variability parameters(pssimilarities in regular time practising sports per *** basketball players showed a closer breakpoint and recovery nearpoint of convergence,a higher fusional-vergence rate,better discriminability halos,and better eye-hand coordination(all p valueslusion:These results show evidence that athletes,basketball players in this case,exhibit better performance in several visual abilities in comparison to a group of individuals without sporting backgrounds,suggesting an improvement due to the systematic involvement of those skills during basketball practice.

关键词： Exercise Fitness level Health Heart rate variability Visual skills Team sport

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Control of tendon cell fate in the embryonic limb: A molecular perspective

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BIOCEll 2023年第3期47卷 465-471页

作者： jessICA CRIsTINA MARÍN-llERA CARlOs AMAURY jimÉnez-CÁRDENAs jesÚs CHIMal-MONROY Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de México Ciudad UniversitariaApartado Postal 70228MéxicoDF 04510México

The molecular cascade underlying tendon formation starts when progenitor cells begin to express the scleraxis(scx)*** knockout mice develop some but not all tendons,suggesting that additional factors are necessary for tendon commitment,maintenance,and *** transcription factors,such as Mohawk(Mkx)or early growth response(Egr),maintain scx expression and extracellular matrix formation during *** inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of *** the commitment of tenogenic lineage occurs,transforming growth factor-beta(TGFβ)induces the scx gene expression,becoming involved in the maintenance of tendon cell *** this point of view,we discussed two phases of the tenogenic process during limb development:dependent and independent of mechanical ***,we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons.

关键词： Tendon differentiation Tenocyte scleraxis Mohawk Early growth response Tendon development WNT TGFβ

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lipschitz algebras and Peripherally-multiplicative Maps

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Acta Mathematica sinica,English series 2008年第8期24卷 1233-1242页

作者： A.jim■nez-VARGAs Moisés VIllEGAs-VallECIllOs Departamento de■lgebray Análisis Matemático Universidad de Almería04071AlmeríaSpain

let X be a compact metric space and let lip（X） be the Banach algebra of all scalar- valued lipschitz functions on X, endowed with a natural norm. For each f ∈ lip（X）, σπ（f） denotes the peripheral spectrum of f. We state that any map Φ from lip（X） onto lip（Y） which preserves multiplicatively the peripheral spectrum： σπ（Φ（f）Φ（g）） = σπ（fg）, A↓f, g ∈ lip（X） is a weighted composition operator of the form Φ（f） = τ· （f °φ） for all f ∈ lip（X）, where τ ： Y → {-1, 1} is a lipschitz function and φ ： Y→ X is a lipschitz homeomorphism. As a consequence of this result, any multiplicatively spectrum-preserving surjective map between lip（X）-algebras is of the form above.

关键词： lipschitz algebra peripherally-multiplicative map spectrum-preserving map peaking function peripheral spectrum

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Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

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World Journal of Gastroenterology 2016年第29期22卷 6573-6581页

作者： Miguel jiménez-Pérez Rocío González-Grande Pilar Espana Contreras Isabel Pinazo Martínez jesús de la Cruz lombardo Raúl Olmedo Martín UGC de Aparato Digestivo Unidad de Hepatologia-Trasplante Hepatico Hospital Universitario Regional de Malaga 29010 Malaga Spain liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario 29010 Malaga Spain

The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

关键词： Direct-acting antivirals Resistance Treatment Hepatitis C virus

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Effects of P301l-TAU on post-translational modifications of microtubules in human iPsC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301l)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301l-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301l-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301l-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301l mutation showed increased TAU phosphorylation at the AT8,but not the p-ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301l-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301l-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301l-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301l pR5 mice TAU tauopathy tubulin code

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