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Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation

Journal of Geriatric Cardiology 2023年第9期20卷 684-692页

作者： Pablo Domínguez-Erquicia Sergio Raposeiras-Roubín Emad Abu-Assi andrea Lizancos-Castro Jose A Parada-Barcia andrégonzález-garcía Ana Ledo-Piñeiro Vanesa Noriega-Caro Carla Iglesias-Otero andrésÍñiguez-Romo Department of Cardiology University HospitalÁlvaro CunqueiroVigoSpain Health Research Institute Galicia Sur VigoSpain

BACKGROUND The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well *** goal of this study was to evaluate the predictive value of HASBLED,ORBIT and ATRIA for major bleeding(MB)and intracranial hemorrhage(ICH)in patients≥75 years with atrial fibrillation and oral anticoagulation(OAC).METHODS A retrospective unicenter study including patients≥75 years with atrial fibrillation(AF)and OAC.A total of 7613 patients≥75 years with AF and OAC included between 2014 and 2018(registry:NCT04364516).We analyzed the discriminative value of HASBLED,ATRIA and ORBIT scores for bleeding endpoints(major bleeding as primary endpoint and intracerebral hemorrhage as secondary).Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major *** discrimination was assessed using Harrell’s *** was assessed with goodness-of-fit test proposed by Gronnesby and *** During a mean follow up of 4.0 years(IQR:2.4–5.7 years),729 patients developed MB(2.61 per 100 patients/year)and 243 patients developed ICH(0.85 per 100 patients/year).Three scores showed a low discrimination for major bleeding,being ORBIT the best(HASBLED C statistic=0.557;ATRIA C statistic=0.568;ORBIT C statistic=0.595)and also a low discrimination for ICH(HASBLED C statistic=0.509;ATRIA C statistic=0.522;ORBIT C statistic=0.526).Among the variables that are part of the scores and other baseline characteristics,after multivariable adjustment only sex(male),dementia,prior admission for bleeding,anemia and liver disease were found as a predictors of *** In older patients under oral anticoagulation with atrial fibrillation,the risk scores HASBLED,ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial ***,other better alternatives should be evaluated for this purpose.

关键词： patients bleeding fibrillation

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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-gonzález Elena gonzález-Rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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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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Peptidomic analysis of whey protein hydrolysates and prediction of their antioxidant peptides

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Food Science and Human Wellness 2022年第2期11卷 349-355页

作者： Jesus Morales garcía Chibuike C.Udenigwe Jorge Duitama andrés Fernando gonzález Barrios Grupo de Diseño de Productos y Procesos(GDPP) Department of Chemical and Food EngineeringUniversidad de los AndesBogotá111711Colombia School of Nutrition Sciences University of OttawaOttawaOntarioK1N 6N5Canada Systems and Computing Engineering Department Universidad de Los AndesBogotá111711Colombia

Enzymatic hydrolysis of proteins is a breakdown process of peptide bond in proteins,releasing some peptides with potential biological *** studies on enzymatic hydrolysis of whey proteins have not identified the complete peptide profiles after *** this study,we reconstructed a profile of peptides from whey hydrolysates with two enzymes and different processing *** also developed an ensemble machine learning predictor to classify peptides obtained from whey hydrolysis.A total of 2572 peptides were identified over three process conditions with two enzymes in duplicate.499 peptides were classified and chosen as potential antioxidant peptides from whey *** peptides classified as antioxidants in the hydrolysates had a proportion of 13.1%-24.5%regarding all peptides *** results facilitate the selection of promising peptides involved in the antioxidant properties during the enzymatic hydrolysis of whey proteins,aiding the discovery of novel antioxidant peptides.

关键词： Whey hydrolysate Antioxidant peptide Peptidomics Prediction

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Gut-liver axis in sepsis-associated liver injury:Epidemiology,challenges and clinical practice

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World Journal of Gastroenterology 2025年第1期31卷 163-166页

作者： Fabiana andréa Moura Aryana Isabelle de Almeida Neves Siqueira College of Nutrition Federal University of AlagoasMaceio 57072-970AlagoasBrazil College of Medicine Federal University of AlagoasMaceio 57072-970AlagoasBrazil

Although the liver has a remarkable regenerative capacity,sepsis-associated liver injury(SLI)is a complication often seen in intensive care *** to its role in immune and inflammatory regulation,the liver is particularly vulnerable during severe *** the global prevalence,causes,and management of SLI is essential to improve outcomes and reduce healthcare *** paper aims to explore these factors,with an emphasis on identifying effective strategies for clinical *** et al’s bibliometric analysis of 787 publications(745 original articles and 42 reviews,mostly in animal models)from 2000 to 2023 highlights the growing interest in SLI,focusing on oxidative stress,gut microbiota,and inflammatory *** components such as nuclear factor-kappa B and the NOD-like receptor thermal protein domain associated protein 3 inflammasome pathway,along with their links to gut microbiota imbalance and oxidative stress,are crucial for understanding SLI *** gut-liver axis,particularly the role of intestinal permeability and bacterial translocation in liver inflammation,is *** this context,bacterial translocation is especially relevant for critically ill patients,as it can exacerbate liver *** findings underscore the need for integrated care in intensive care units,prioritizing gut health and careful antibiotic use to prevent *** extensive research,there remains a lack of clinical trials to validate therapeutic *** abundance of experimental studies highlights potential therapeutic targets,stressing the need for high-quality randomized clinical trials to translate these findings into clinical practice.

关键词： Dysbiosis Oxidative stress Inflammation Microbiota Sepsis-associated liver injury

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Anthropomorphism Indexes of the Kinematic Chain for Artificial Hands

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Journal of Bionic Engineering 2020年第3期17卷 501-511页

作者： Immaculada Llop-Harillo Antonio Pérez-gonzález Javier andrés-Esperanza Grupo de Biomecdnicay Ergonomia Departamento de Ingenieria Mecdnicay Construccidny Universitat Jaume I(UJI)Castelldn 12071Spain

Anthropomorphic hands have received increasing research interest in the fields of robotics and *** it is not yet clear how to evaluate their *** in the kinematic chain is essential to achieve both functionality and cosmesis.A few previous works have addressed the definition of anthropomorphism indexes,although they have some limitations in its *** this study,three different anthropomorphism indexes have been defined to compare the kinematic chain of artificial hands with that of the human *** indexes are based on the comparison of:(I)the parameters of the kinematic chain(dimensions,type of joints,orientations and ranges of motion),(2)the reachable workspace,and(3)common grasping *** artificial hands with different degrees of anthropomorphism have been compared using the three Anthropomorphism Indexes of the Kinematic Chain(AIKC).The results show a high correlation between the first and third AIKC for the hands *** second AIKC presents much lower values than the other two,although they are higher for hands that combine abduction/adduction and flexion/extension movements in the kinematic chain of each *** indexes can be useful during the initial stage of designing artificial hands or evaluating their anthropomorphism.

关键词： anthropomorphism grasping indexes kinematics multifingered hands

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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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High CO_(2)permeation using a new Ce_(0.85)Gd_(0.15)O_(2-δ)-LaNiO_(3)composite ceramic–carbonate dual-phase membrane

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Journal of Environmental Sciences 2024年第6期140卷 219-229页

作者： Daniela gonzález-Varela JFrancisco Gómez-garcía Gustavo Tavizon Heriberto Pfeiffer Instituto de Investigaciones en Materiales Universidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico Departamento de Física y Química Teórica Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico 不详

This work shows the synthesis,characterization and evaluation of dense-ceramic membranes made of Ce_(0.85)Gd_(0.15)O_(2-δ)-LaNiO_(3)(CG-LN)composites,where the fluorite-perovskite ratio(CG:LN)was varied as follows:75:25,80:20 and 85:15 wt.%.Supports were initially characterized by XRD,SEM and electrical conductivity(using vacuum and oxygen atmospheres),to determine the composition,microstructural and ionic-electronic conductivity ***,supports were infiltrated with an eutectic carbonates mixture,producing the corresponding dense dual-phase membranes,in which CO_(2)permeation tests were ***,CO_(2)permeation experiments were performed from 900 to 700℃,in the presence and absence of oxygen(flowed in the sweep membrane side).Results showed that these composites possess high CO_(2)permeation properties,where the O_(2)addition significantly improves the ionic conduction on the sweep membrane ***,the GC80-LN20 composition presented the best results due to the following physicochemical characteristics:high electronic and ionic conductivity,appropriate porosity,interconnected porous channels,as well as thermal and chemical stabilities between the composite support and carbonate phases.

关键词： CO_(2)permeation Doped CeO_(2) LaNiO_(3) Impedance Ceramic carbonate membrane

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Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen gonzález‑Fernández Miguel A.garcía‑Álvarez Alberto Cuesta Department of Cell Biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-*** crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six *** the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been ***,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human *** of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or *** leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most ***,in vivo nodavirus infection resulted in alterations on the transcription of il17 *** nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead *** data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

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