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Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways:Experimental and clinical evidence

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World Journal of Experimental Medicine 2024年第2期14卷 46-52页

作者： Raúl Lelio Sanz sebastián garcía menéndez Felipe Inserra Leon Ferder Walter Manucha Department of Pathology Facultad de Ciencias MédicasUniversidad Nacional de CuyoMendoza 5500Argentina Department of Pharmacology Instituto de Medicina y Biología Experimental de CuyoCentro Científico TecnológicoMendoza 5500Argentina Department of nephrology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina Department of Cardiology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina

Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and *** dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and *** II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS *** activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative *** of energy production by mitochondria is a common feature of all metabolic *** SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ***,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against *** cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these *** clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal ***2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen *** findings suggest that SGLT2i hold great potential for the treatment of ***,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.

关键词： Sodium-glucose cotransporter-2 inhibitors Cardiovascular diseases Sirtuins Oxidative stress Inflammation Mitochondrial dysfunction

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Dendritic spine degeneration:a primary mechanism in the aging process

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neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández Fernado garcía-Dolores Humberto nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(InCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto nacional de Medicina Genómica(InMEGEn) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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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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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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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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Using fused filament fabrication to improve the tribocorrosion behaviour of 17-4 PH SS in comparison to other metal forming techniques

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Friction 2024年第10期12卷 2325-2343页

作者： Cristina garcÍA-CABEZÓn Juan Alfonso nARAnJO Celia garcÍA-HERnÁndez Cristina BERGES Gemma HERRAnZ Fernando MARTÍn-PEDROSA Materials Engineering E.I.I.Universidad de ValladolidValladolid 47011Spain InEI-Escuela Técnica Superior de Ingeniería Industrial(ETSII) Universidad de Castilla La ManchaCastilla-La Mancha 13071Spain

Fused filament fabrication(FFF)is one of the additive manufacturing processes which has gained more interest because of its simplicity and *** technology is similar to the conventional metal injection moulding(MIM)process,consisting of the feedstock preparation of metal powder and polymer binders,followed by layer-by-layer 3D printing(FFF)or injection(MIM)to create green parts and,finally,debinding and ***,both technologies provide near-dense *** work presents an in-depth study of the processing method’s *** porosity,microstructure,hardness,corrosion,and tribocorrosion behaviour are compared for 17-4 PH SS samples processed from powder by additive manufacturing using FFF and MIM,as well as conventional powder metallurgy(PM)*** samples exhibited the highest macro and microhardness,while corrosion behaviour was similar for both MIM and FFF samples,but superior in comparison to conventional PM ***,the FFF-as fabricated samples displayed a significant improvement in tribocorrosion resistance that could be explained by the higher proportion of delta ferrite and retained austenite in their microstructure.

关键词： 17-4 PH SS fused filament fabrication(FFF) metal injection moulding(MIM) corrosion behaviour powder metallurgy(PM) tribocorrosion behaviour

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Influence of parameters on the microstructure of a duplex stainless steel joint welded by a GMAW welding process

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Progress in natural Science:Materials International 2022年第4期32卷 415-423页

作者： Sandra Chacón-Fernández Antonio Portolés garcía Gerardo Romaní Labanda Universidad Politécnica de Madrid Escuela Técnica Superior de Ingenieros Industriales UPM

Duplex stainless steels（DSSs） are widely used in industry for their desirable properties. Any fusion welding technique modifies the microstructure and, consequently, the properties of the material. This paper presents a parametric study of the variables that determine the energy contribution（current, voltage and welding speed） and the structural modifications produced during gas metal arc welding. The analysis comprises metallographic study,phase balance, dimensioning of the weld beads and tensile and hardness tests. The influence of the variables studied on the thermal cycles obtained（temperatures reached and cooling rate） was determined by using a finite element model. The results showed that, in addition to the indicated parameters, the parameter power transfer per volume（W/m3） and the geometry in the bead must be controlled due to their influence on the heat flow distribution and phase balance.

关键词： Welding Heat input GMAW Duplex stainless steels (DSS) Finite element model (FEM)

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EXTRACTInG BEHAVIOURAL MODELS FROM 2010FIFA WORLD CUP

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Journal of Systems Science & Complexity 2013年第1期26卷 43-61页

作者： menndez Héctor BELLO-ORGAZ Gema CAMACHO David Department of Computer Science Universidad Autnoma de Madrid

The FIFA World Cup^(TM) is the most profitable worldwide *** FIFA publishes global statistics of this competition which provide global data about the players and teams during the *** work is focused on the extraction of behavioural patterns for both,players and teams strategies,through the automated analysis of this *** knowledge and models extracted in this work could be applied to soccer leagues or even it could be oriented to sport ***,the main contribution is related to the study on several automatic knowledge extraction techniques,such as clustering methods,and how these techniques can be used to obtain useful behavioural models from a global statistics *** information provided by the clustering algorithms shows similar properties which have been combined to define the models,making the human interpretation of these statistics ***,the most successful teams strategies have been analysed and compared.

关键词： Behavioural patterns clustering FIFA World Cup football soccer web mining.

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Potential anti neuro-inflammatory effect of BioCen-128 in animal models of dementia

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Animal Models and Experimental Medicine 2022年第4期5卷 369-376页

作者： nashelly Esquivel Yenela garcía Roberto menéndez Teidy Egarcía Ana RMorales Claudio Rodríguez national Center for Bioproducts(BIOCEn) BejucalCuba Center for neurosciences(CnEURO) PlayaCuba Department of Pharmacology Institute of Marine Sciences(ICIMAR)HavanaCuba

Background:BioCen-128 is a new active pharmaceutical ingredient composed of a specific bovine thymic fraction of a polypeptide *** results of similar thymus extracts have been shown to be effective in delaying the processes associated with aging,immunosenescence and Alzheimer’s disease(AD),where the inflammation plays an important *** of the anti-i nflammatory potential of BioCen-128,the aim of this study was to evaluate the granuloma model induced by a cotton wool implantation and the model induced by intracerebroventricular(ICV)administration of streptozotocin(STZ).Method:The experiment was carried out using male OF-1mice weighing 20±2 ***:Mice administered BioCen-128 in via the IP route at 5,10 and 20 mg/kg of corporal weigh showed a decrease in the wet and dry weights of the granuloma,providing evidence of a systemic anti-i nflammatory *** the ICV model of STZ,the administration of BioCen-128 improved cognitive ***:These responses suggested an anti-neuroinflammatory effect explainable by the action of thymosinβ4 and thymosin alfa *** results suggested that BioCen-128 could be used in the prevention and treatment of some diseases,for example AD,where neuroinflammation is one of the biological events that take place.

关键词： BioCen-128 cotton pellet mice neuroinflammation

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