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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémar.ínez-Hernández Alejandro mar.ín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández ana Esther Moreno-mar.ínez mar.Cuadrado-Tejedor ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmar.s can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Grasslands Response to Livestock Grazing Intensity in the Austral Pampas(Argentina):Testing the Intermediate Disturbance Hypothesis

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Phyton-International Journal of Experimental Botany 2024年第8期93卷 2037-2050页

作者： ana Elena de Villalobos mar.a Andrea Long Grupo de Investigación en Ecosistemas de Pastizal(GIEP) CERZOSCONICETBahía Blanca8000Argentina Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del SurBahía Blanca8000Argentina

Livestock grazing has a significant impact on natural grasslands,with approximately one-third of the world’s land area dedicated to this *** 20%of global grasslands are highly degraded due to overgrazing,affecting their productivity and conservation *** practices are required to ensure sustainable livestock production that supports *** Intermediate Disturbance Hypothesis(IDH)suggests that environments with moderate levels of disturbance exhibit a higher species *** grazing can reduce the dominance of certain species,thereby enhancing plant ***,concerns arise regarding the increase of exotic and unpalatable species under moderate grazing levels,complicating grassland conservation *** impact of livestock grazing on the functional structure of grasslands depends on factors such as grazing intensity,livestock species,and environmental *** in grazing intensity may increase specific and functional diversity under moderate grazing,potentially masking the presence of invasive exotic *** the Austral Pampas(Pampean phytogeographic province,Buenos Aires,Argentina),grasslands face various pressures from domestic livestock grazing that endanger their integrity if not properly ***,our study aims to investigate potential differences in species richness and diversity,functional diversity,exotic plant abundance,and the number and distribution of plant functional groups across varying grazing *** IDH is utilized as a tool to regulate livestock pressure for grassland *** and functional diversity indices were used to assess the impact of grazing on grassland *** grazing increased species and functional diversity,while intensively grazed or ungrazed areas showed reduced *** presence influenced the balance between native and exotic plants,with ungrazed areas having higher native plant abundance and grazed areas exhibiti

关键词： Natural grasslands grazing effects disturbance specific and functional diversity

The immune system:uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares mar.Cuadrado-Tejedor ana García-Osta Juan JoséLasarte Immunology and Immunotherapy Program Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Pathology Anatomy and Physiology DepartmentSchool of MedicineUniversity of NavarraIDISNAPamplonaSpain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth *** perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological *** addition to the direct effects of sense-induced mediators in the brain.

关键词： prompt system transmitting

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana M.López-Estévez Y.Zhang mar.a Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia mar.a J.Vicent Defang Ouyang Dolores Torres mar.a José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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 mar.a Fernanda González ana mar.a 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)

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

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World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura mar.ina Grizzuti Abel Heredia Isabel Comino ana Florencia Costa Roberto Puebla mar.a Paz Temprano Sonia Isabel Niveloni Gabriel de Diego mar.a E Oregui Edgardo Gustavo Smecuol Mauricio C de mar.i Elena F Verdú Carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant *** To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual *** This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term *** a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or *** endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of *** samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and *** Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol ***,628/640(98.1%)stool samples were *** was undetectable(0.32μg/g)to potentially cause mucosal *** GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in ***-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP *** with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific *** This exploratory study conducted in a real-life setting revealed high adherence to the *** AN-PEP treatment did not significantly reduce the overall GIP stool ***,given the observation of a significantly lower prevale

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

Adding vortexing to the Maki technique provides no benefit for the diagnosis of catheter colonization or catheter-related bacteremia

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World Journal of Critical Care Medicine 2024年第1期13卷 58-64页

作者： Leonardo Lorente mar.a Lecuona Fernandez Adriana González-Mesa Judith Oliveras-Roura Cristina Rosado Pablo Cabrera Emma Casal Alejandro Jiménez mar.a Luisa Mora ana Madueño Intensive Care Unit Hospital Universitario de CanariasLa Laguna 38320Spain Microbiology and Infection Control Service Hospital Universitario de CanariasLa Laguna 38320Spain Research Unit Hospital Universitario de CanariasLa Laguna 38320Spain

BACKGROUND A previous study compared vortexing and Maki techniques for the diagnosis of catheter-related bloodstream infection(CRBSI),and concluded that vortexing was not superior to Maki *** To determine whether the combined use of vortexing and Maki techniques provides profitability versus the Maki technique for the diagnosis of catheter tip colonization(CTC)and *** Observational and prospective study carried out in an Intensive Care *** with suspected catheter-related infection(CRI)and with one central venous catheter for at least 7 days were *** area under the curve(AUC)of the Maki technique,the vortexing technique and the combination of both techniques for the diagnosis of CTC and CRBSI were *** We included 136 episodes of suspected *** found 21 cases of CTC of which 10 were also CRBSI *** the 21 CTC episodes,18(85.7%)were diagnosed by Maki technique and vortexing technique,3(14.3%)only by the technique of Maki,and none only by technique of *** the 10 CRBSI episodes,9(90.0%)were diagnosed by the techniques of Maki and vortexing,1(10.0%)was diagnosed only by the technique of Maki,and none only by the technique of *** no found differences in the comparison of AUC between the technique of Maki and the combination of Maki and vortexing techniques for the diagnosis of CTC(P=0.99)and CRBSI(P=0.99).CONCLUSION The novel finding of our study was that the combined use of vortexing and Maki techniques did not provide profitability to the technique of Maki alone to CRBSI diagnosis of.

关键词： Vortexing Maki Bloodstream infection Colonization

Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros ana mar.a Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús mar.ínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute， Icahn School of Medicine at Mount Sinai Department de Nutrició， Ciències de l'Alimentació I Gastronomia， XIA， Facultat de Farmàcia i Ciències de l'alimentació， Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB)， Universitat de Barcelona Department of Internal Medicine， Hospital Clínic， Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)， University of Barcelona Consorcio CIBER， M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn)， Instituto de Salud Carlos III (ISCIII) Mediterranean Diet Foundation 5. Foundation for Science， Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico San Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in ***: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health ***: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend <0.001)， and the highest quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend <0.001) and TG (β=-3.22， 95%CI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%CI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， espe

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-mar.inez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva ana M.Gomez-Lahoz Jorge Monserrat mar.Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primar. injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this ***(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a *** initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and *** the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are ***,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities