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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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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 maría 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

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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

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola Mavillard Javier Perez-Florido Francisco M.ortuño Amador Valladares Miren L.Álvarez-Villegas Gema Roldán Rosario Carmona Manuel Soriano Santiago Susarte Pilar Fuentes Daniel López-López ana maría nuñez-negril.o Alejandra Carvajal Yolanda Morgado Daniel Arteaga Rosa Ufano Pablo Mir Juan F.Gamella Joaquín Dopazo Carmen Paradas Macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de Medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del Movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de Medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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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 Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández ana Esther Moreno-martínez 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 hallmarks 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

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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 maría Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia maría J.Vicent Defang ouyang Dolores Torres maría 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

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A review on the scale-up of high-shear wet granulation processes and the impact of process parameters

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Particuology 2024年第9期92卷 180-195页

作者： ana Rita Alves marta Filipe Simões Sérgio Simões João Gomes University of Coimbra CERESDepartment of Chemical EngineeringFaculty of Sciences and TechnologyRua Sílvio Lima3030-790CoimbraPortugal Bluepharma-Indústria Farmacêutica São Martinho do BispoCoimbra3045-016Portugal Faculty of Pharmacy University of CoimbraAzinhaga de Santa Comba3000-548CoimbraPortugal

Wet granulation is one of the most important agglomeration processes,and high-shear granulation(HSG)one of the most employed technologies in the pharmaceutical *** most critical process parameters of HSG are discussed in this *** main concern in scaling up the wet granulation process is the differences between scales,which prevent the particles from having the same experience across all *** scale-up of wet granulation processes is commonly divided into two categories:engineering and attribute-based *** engineering-based scale-up approach is a strategy based on dimensional analysis and an attribute-based supported on the principles of“equifinality”,where process variables are adjusted to obtain equivalent granule *** work presents the effect of different HSG process parameters on the scale-up,as well as the use of process analytical tools(PAT)and modelling *** aim is to review applied scale-up approaches in HSG and discuss benefits and *** is proven why the scale-up for oral solid pharmaceutical products is still considered a hot topic and a very challenging task for development and engineering teams.

关键词： High-shear wetgranulation Parametric-based Attribute-based Physics-based modelling Impeller design Scale-up

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Taurine: a promising nutraceutic in the prevention of retinal degeneration

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Neural Regeneration Research 2024年第3期19卷 606-610页

作者： Diego García-Ayuso Johnny Di Pierdomenico ana martínez-Vacas Manuel Vidal-Sanz Serge Picaud maría PVillegas-Pérez 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 SaludMurciaEspaña Sorbonne Université INSERMCNRSInstitut de la VisionParisFrance

Taurine is considered a non-essential amino acid because it is synthesized by most ***,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain *** may be especially important for the *** concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion *** plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective *** has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory *** review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

关键词： amino acid anti-inflammatory antioxidant gamma-aminobutyric acid nutraceutical photoreceptor degeneration retina retinitis pigmentosa taurine

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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 martina Grizzuti Abel Heredia Isabel Comino ana Florencia Costa Roberto Puebla maría Paz Temprano Sonia Isabel Niveloni Gabriel de Diego maría E oregui Edgardo Gustavo Smecuol Mauricio C de marzi 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(of samples,and no differences between treatment arms were *** 0.5%of samples had GIP concentrations sufficiently high(>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(Pot 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

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Testicular prostheses-impact on quality of life and sexual function

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Asian Journal of Andrology 2024年第2期26卷 160-164页

作者： ana Sofia Araujo Sara anacleto Ricardo Rodrigues Catarina Tinoco Andreia Cardoso Carlos oliveira Ricardo Leao Department of Urology Braga's HospitalBraga 4710Portugal Faculty of Medicine Coimbra UniversityCoimbra 3000Portugal

orchiectomy is the recommended treatment for many testicular ***,testicular prosthesis placement is not always performed for different *** this study,we aimed to evaluate patients'opinions and the impact on sexual function and quality of *** retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology,Braga's Hospital(Braga,Portugal),where testicular implants were always available and the decision to undergo the procedure was made fully independent of *** completed four questionnaires that assessed demographic data,satisfaction,self-esteem,and sexual *** the 96 patients who underwent orchidectomy,59 replied to the questionnaires,and of these patients,86.4%decided to undergo silicone-based testicular prostheses *** remaining 13.6%refused the implant based on concerns about complications(37.5%),because they felt that it was unnecessary(37.5%),or because it was not offered by the doctor(25.0%).overall,96.1%of these patients were satisfied with the implant;however,25.5%classified it as"too firm".No statistically significant differences were found in sexual function(all P>0.05).However,it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses(74.0%vs 50.0%),and none of them reported severe erectile dysfunction(0 vs 16.7%).Regarding self-esteem,both patients with and without prostheses present very similar average scores with no statistically significant *** present study highlights the highest level of satisfaction among patients who received testicular *** prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.

关键词： orchiectomy patient satisfaction quality of life sexual dysfunction sexual health testicular prostheses

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