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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)

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko Jeremic Lydia Jiménez-díaz Juan d.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： joséM.Izquierdo Centro de Biología Molecular Severo Ochoa(CBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan antonio López-Villodres Beatriz garcía-díaz departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma Bionand) MálagaSpain

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual ***,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action *** and not less important,OLs provide trophic support to neurons and ***,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

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

Abiotic and biotic drivers of struvite solubilization in contrasting soils

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Pedosphere 2023年第6期33卷 828-837页

作者： antonio RUIZ-NAVARRO Manuel dELGAdO-BAQUERIZO Concha CANO-díaz Carlos garcíA Felipe BASTIdA Centro de Edafologia y Biologia Aplicada del Segura Consejo Superior de Investigaciones Cientificas(CEBAS-CSIC)Department of Soil and Water ConservationEspinardoMurcia E-30100Spain ICL Specialty Fertilizers Iberia TotanaMurcia E-30850Spain Laboratorio de Biodiversidad y Funcionamiento Ecosistemico Instituto de Recursos Naturales y Agrobiologia de Sevilla(IRNAS)CSICAv.Reina Mercedes 10Sevilla E-41012Spain IRNAS-CSIC Unidad Asociada Universidad Pablo de OlavideUniversidad Pablo de Olavide(UPO)Sevilla 41013Spain Centre for Research and development in Agrifood Systems and Sustainability(CISAS) Instituto Politecnico de Viana do Castelo(IPVC)Rua Escola Industrial e Comercial Nun'Alvares 34Viana do Castelo 4900-347Portugal

Phosphorus(P) limitation in the coming decades calls for the utilization of alternative fertilizers in agriculture. Struvite is a promising P source, but its potential role as a fertilizer is dependent on different physical, chemical, and biological properties, which are very heterogeneous in soil, complicating the prediction of the best soil conditions for its application. Here, we evaluated the solubility of struvite in soil, its redistribution into P fractions, and its potential abiotic and biotic drivers in 62 globally distributed soils with contrasting properties through an incubation assay. We found that after 40 d, about 35% of struvite P was redistributed into soil fractions more accessible to plants and microbes. Phosphorus redistribution from struvite was driven by a complex suite of soil physical, chemical, and microbial properties as well as environmental factors that varied across soils. Soil texture played a critical role in determining the redistribution of P in struvite-amended soils in soluble(H2O extraction), labile(NaHCO3 extraction), and moderately labile(NaOH extraction) *** addition, the soil solution cation concentration was one of the most important drivers of available struvite-derived P fractions. The great importance of texture and cations in determining struvite-derived P fractions in soil was contrasted with the relatively minor role of pH. At the microbial level, the number of bacterial operational taxonomic units(OTUs) from the unfertilized soils that correlated with struvite-derived P fractions was higher than that of fungi. The number of OTUs that correlated with the struvite-derived soluble P fraction was dominated by fungi, whereas the number of OTUs that correlated with the struvite-derived labile P fraction was dominated by bacteria. Overall, this study provided a predictive framework for the potential use of struvite as a P fertilizer in contrasting soils.

关键词： bacteria fungi environmental factor operational taxonomic unit phosphorus fertilizer phosphorus fraction phosphorus solubilization soil fertility soil property

An update on iron physiology

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World Journal of Gastroenterology 2009年第37期15卷 4617-4626页

作者： Manuel Muoz Isabel Villar josé antonio garcía-Erce Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain department of Hospital Pharmacy University Hospital Miguel Servet Zaragoza 50009 Spain Hematology and Hemotherapy University Hospital Miguel Servet Zaragoza 50009 Spain

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (Id) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional Id), and anemia of chronic disease (ACd), which can evolve to ACd plus true Id (ACd + Id). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of Id status and anemia.

关键词： Iron metabolism Iron deficiency Functionaliron deficiency, Hepcidin Anemia of chronic disease

Elastic Smart Contracts in Blockchains

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IEEE/CAA Journal of Automatica Sinica 2021年第12期8卷 1901-1912页

作者： Schahram dustdar Pablo Fernández joséMaría garcía antonio Ruiz-Cortés distributed Systems Group Vienna University of TechnologyWien 1040Austria Smart Computer Systems Research and Engineering Lab Research Institute of Computer EngineeringUniversity of SevillaSevilla 41012Spain

In this paper,we deal with questions related to blockchains in complex Internet of Things(IoT)-based *** ecosystems are typically composed of IoT devices,edge devices,cloud computing software services,as well as people,who are decision makers in scenarios such as smart *** decisions related to analytics can be based on data coming from IoT sensors,software services,and ***,they are typically based on different levels of abstraction and *** poses a number of challenges when multiple blockchains are used together with smart *** work proposes to apply our concept of elasticity to smart contracts and thereby enabling analytics in and between multiple blockchains in the context of *** propose a reference architecture for Elastic Smart Contracts and evaluate the approach in a smart city scenario,discussing the benefits in terms of performance and self-adaptability of our solution.

关键词： Blockchain elasticity Internet of Things(IoT) smart cities smart contracts virtual chains

Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

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World Journal of Gastroenterology 2009年第37期15卷 4686-4694页

作者： josé antonio garcía-Erce Fernando Gomollón Manuel Muoz Transfusion Medicine and Apheresis Unit Haematology and Haemotherapy Regional Service "Miguel Servet" University Hospital Zaragoza 50009 Spain Gastroenterology Unit University Clinical Hospital and Biomedical Investigation Center at Digestive and Hepatic Disease Network c/San Juan Bosco 15 Zaragoza 50009 Spain Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain

Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBd), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a f ixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient' s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidencebased clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABd) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABd in surgical IBd patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within wellconstructed protocols will offer better prospe

关键词： Anaemia Blood transfusion Autologous blood transfusion Inflammatory bowel diseases Risk assessment