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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

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： ana Milena Silva Olaya Fernanda Martins Almeida ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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)

Creeping fat and gut microbiota in Crohn’s disease

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World Journal of Gastroenterology 2025年第1期31卷 16-23页

作者： ana EV Quaglio Daniéla O Magro Marcello Imbrizi Ellen CS De Oliveira Luiz C Di Stasi Ligia Y Sassaki Verum Ingredients Botucatu Technology ParkBotucatu 18605-525São PauloBrazil Department of Surgery Faculty of Medical SciencesState University of CampinasCampinas 13083-970São PauloBrazil Department of Gastroenterology Faculty of Medical SciencesUniversity of CampinasCampinas 13083-970São PauloBrazil Department of Internal Medicine Medical SchoolSão Paulo State UniversityBotucatu 18618-686São PauloBrazil Department of Biophysics and Pharmacology Institute of BiosciencesSão Paulo State UniversityBotucatu 18618-689São PauloBrazil

In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental *** microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of ***,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and *** bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD *** creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to *** gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing ***,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.

关键词： Creeping fat Mesenteric adipose tissue Gut microbiota Crohn’s disease Inflammatory bowel disease

Effect of Zn binding to phytate and humic substances on its uptake by wheat(Triticum durum L.)as affected by carbonates and Fe oxides

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Pedosphere 2022年第6期32卷 823-832页

作者： ana M.garcÍA-LÓPEZ Ramiro RECENA Antonio DELGADO Department of Agronomy ETSIAUniversity of SevilleSeville 41013(Spain)

Although complexation with soil organic matter may improve zinc(Zn)bioavailability to plants,the effect of Zn sorbent surface on the use of complexed Zn by plants remains *** objective of this research was to elucidate how Zn complexation with humic substances(HS)and phytate affects the uptake of Zn by wheat plants depending on the main sorbent surface in growth media,i.e.,carbonates and Fe *** this end,two pot experiments were performed,one using Fe oxide-coated siliceous as the siliceous growth medium sand and the other using a mixture of calcareous sand and siliceous sand as the calcareous growth *** experiment involved three Zn sources,Zn-HS complex,Zn phytate,and ZnSO_(4).All sources were applied with surface irrigation at two Zn rates(0.25 and 2 mg kg^(-1) growth medium).The Zn-HS complex significantly increased Zn uptake by plants in both media,relative to the other two Zn sources,but no significant difference was observed between Zn phytate and ZnSO_(4).In the calcareous medium,Zn-HS complex and Zn phytate resulted in significantly higher dry biomass yields of wheat than ZnSO_(4).In the siliceous medium,spike and shoot dry biomass yields with Zn-HS complex at the low rate and Zn phytate at both rates were not significantly different from those with ZnSO_(4) at the high *** harvest,approximately 50%of the Zn applied as Zn-HS complex remained extractable by diethylenetriaminepentaacetic acid(DTPA),while this proportion was less than 20%for the other Zn ***,Zn-HS complex and Zn phytate are sources of available Zn for plants,and they are more effective than ZnSO_(4) in increasing plant growth,particularly when carbonates are the main Zn sorbent surface.

关键词： calcareous growth medium micronutrient organic matter organic phosphorus Zn availability Zn deficiency Zn sorbent surface Zn source

Stem cell therapy for faecal incontinence: Current state and future perspectives

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World Journal of Stem Cells 2018年第7期10卷 82-105页

作者： Jacobo Trébol ana Carabias-Orgaz Mariano garcía-Arranz Damián garcía-Olmo General and Digestive Tract Surgery Department Salamanca University Healthcare Centre anaesthesiology Department Complejo Asistencial de ávila New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez Díaz General and Digestive Tract Surgery Department Quiron-Salud Hospitals Surgery Department Universidad AutónomaMadrid

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

关键词： Faecal incontinence anal sphincter Cell implantation Tissue engineering Cell therapy Stem cells

Further the liquid biopsy:Gathering pieces of the puzzle of genometastasis theory

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World Journal of Clinical Oncology 2017年第5期8卷 378-388页

作者： ana garcía-Casas Dolores C garcía-Olmo Damián garcía-Olmo Universidad Complutense de Madrid Centre de Recerca Experimental Biomèdica Aplicada(CREBA) IRBLLEIDA Department of Surgery Universidad Autónoma de MadridInstituto de Investigación SanitariaFundación Jiménez Díaz

Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism,not yet fully *** is almost beyond doubt is that circulatory system is crucial for cancer *** this system,much attention has been recently paid to liquid *** technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic,prognostic and follow-up of *** CTCs tend to be scarce in serum and plasma from cancer patient,abundant circulating nucleic acids can be detected in the same *** fact,together with the genetic origin of cancer,stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis,a recently discovered phenomenon called *** innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory *** is more,many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of *** this review,we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this *** objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

关键词： Genometastasis Cancer metastasis Circulating Nucleic acids:Circulating tumor cells Liquid biopsy Exosomes Virtosomes

Type XIX collagen: a promising biomarker from the basement membranes

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Neural Regeneration Research 2020年第6期15卷 988-995页

作者： ana C.Calvo Laura Moreno Leticia Moreno Janne M.Toivonen Raquel Manzano Nora Molina Miriam de la Torre Tresa López Francisco J.Miana-Mena María J.Munoz Pilar Zaragoza Pilar Larrodé Alberto garcía-Redondo Rosario osta Laboratory of Genetics and Biochemistry(LAGENBIO) University of ZaragozaFaculty of Veterinary SciencesInstituto de Investigación Sanitaria de Aragón(IIS)IA2CIBERNEDZaragozaSpain Hospital Clínico Universitario Lozano Blesa ZaragozaSpain Neurology Department ALS UnitCIBERER U-723Health Research InstituteMadridSpain

Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological *** XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this *** collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different *** molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to *** most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of *** physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in ***,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic *** XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis *** novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

关键词： anti-tumor and anti-angiogenic properties C1 domain COL19A1 gene and protein levels compensatory effect FACIT collagens hippocampal interneurons matricryptins multiplexins NC1 domain regenerative response skeletal muscle type XIX collagen

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

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World Journal of Gastroenterology 2019年第38期25卷 5883-5896页

作者： ana Isabel Gil-garcía Antonio Madejón Irene Francisco-Recuero ana López-López Emiliana Villafranca Miriam Romero Araceli garcía Antonio Olveira Rocío Mena Juan Ramón Larrubia Javier garcía-Samaniego Hepatology Unit Hospital Universitario La PazMadrid 28046Spain Centro de Investigación Biomédica en Red Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación del Hospital Universitario la Paz Madrid 28046Spain Biochemistry Department Faculty of MedicineUniversidad Autónoma de MadridMadrid 28029Spain Instituto de Genética Médica y Molecular Hospital Universitario La PazMadrid 28046Spain Translational Hepatology Unit Hospital General Universitario de GuadalajaraGuadalajara 19002Castilla-La ManchaSpain

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health *** this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral *** To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey *** Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV *** High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E *** HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS *** HCC related variants were the major strains and persisted over time(up to 48 mo).Pa

关键词： Hepatitis B virus Hepatocellular carcinoma PreS deletions Hepatitis B virus treatment Grey zone