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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David garcía-Bernal diego garcía-ayuso Manuel Vidal-Sanz Marta Agudo-Barriuso 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 Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical *** stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and *** studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional ***,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous ***,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

Bone marrow-derived mononuclear stem cells in the treatment of retinal degenerations

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Neural Regeneration Research 2022年第9期17卷 1937-1944页

作者： diego garcía-ayuso Johnny Di Pierdomenico David garcía-Bernal Manuel Vidal-Sanz María P.Villegas-Pérez Departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaCampus de Ciencias de la saludMurciaSpain Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca) MurciaSpain Servicio de Hematología Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain

Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the *** present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal ***,these diseases are nowadays one of the greatest challenges in the field of ophthalmological *** marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor *** cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor ***,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent *** intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect ***,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.

关键词： age-related macular degeneration bone marrow stem cells intravitreal injection macroglia microglia photoreceptor degeneration retinal ganglion cells retinitis pigmentosa subretinal injection transplant

Role of microglial cells in photoreceptor degeneration

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Neural Regeneration Research 2019年第7期14卷 1186-1190页

作者： Johnny Di Pierdomenico diego garcía-ayuso Marta Agudo-Barriuso Manuel Vidal-Sanz María Paz Villegas-Pérez Departamento de Oftalmología Facultad de MedicinaUniversidad de Murciaand Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca)

Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the *** comprise various diseases,but retinitis pigmentosa is the most frequently *** pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily *** mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of *** the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration *** cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a *** this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor *** also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial *** inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor ***,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.

关键词： Royal College of Surgeons RCS P23H-1 microglia minocycline photoreceptor retinal degeneration retinitis pigmentosa

Taurine:an essential amino sulfonic acid for retinal health

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Neural Regeneration Research 2023年第4期18卷 807-808页

作者： Johnny Di Pierdomenico Ana Martínez-Vacas Serge Picaud María P.Villegas-Pérez diego garcía-ayuso Departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca)MurciaSpain(Di Pierdomenico JMartínez-Vacas AVillegas-Pérez MPGarcía-Ayuso D)INSERMCNRSInstitut de la VisionSorbonne UniversitéParisFrance(Picaud S)

Taurine(2-amino-ethanesulfonic acid)is a naturally occurring amino sulfonic acid derived from cysteine and methionine *** common name derives from the ox,as it was first isolated from the bile of an ox(Froger et al.,2014).The molecular structure of taurine differs from that of amino acids by the presence of a sulfonic acid,instead of the more common carboxylic acid group in the structure of amino acids.

关键词： sulfonic structure ethane

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

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

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)

5DGWO-GAN:A Novel Five-Dimensional Gray Wolf Optimizer for Generative Adversarial Network-Enabled Intrusion Detection in IoT Systems

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Computers, Materials & Continua 2025年第1期82卷 881-911页

作者： Sarvenaz Sadat Khatami Mehrdad Shoeibi Anita Ershadi Oskouei diego Martín Maral Keramat Dashliboroun Department of Data Science Engineering University of HoustonHoustonTX 77204USA The WPI Business School Worcester Polytechnic InstituteWorcesterMA 01609USA School of Systems and Enterprises Stevens Institute of TechnologyHobokenNJ 07030USA Department of Computer Science Escuela de Ingeniería Informática de SegoviaUniversidad de ValladolidSegovia40005Spain Ernest G.Welch School of Art&Design Georgia State UniversityAtlantaGA 30303USA

The Internet of Things(IoT)is integral to modern infrastructure,enabling connectivity among a wide range of devices from home automation to industrial control *** the exponential increase in data generated by these interconnected devices,robust anomaly detection mechanisms are *** detection in this dynamic environment necessitates methods that can accurately distinguish between normal and anomalous behavior by learning intricate *** paper presents a novel approach utilizing generative adversarial networks(GANs)for anomaly detection in IoT ***,optimizing GANs involves tuning hyper-parameters such as learning rate,batch size,and optimization algorithms,which can be challenging due to the non-convex nature of GAN loss *** address this,we propose a five-dimensional Gray wolf optimizer(5DGWO)to optimize GAN *** 5DGWO introduces two new types of wolves:gamma(γ)for improved exploitation and convergence,and theta(θ)for enhanced exploration and escaping local *** proposed system framework comprises four key stages:1)preprocessing,2)generative model training,3)autoencoder(AE)training,and 4)predictive model *** generative models are utilized to assist the AE training,and the final predictive models(including convolutional neural network(CNN),deep belief network(DBN),recurrent neural network(RNN),random forest(RF),and extreme gradient boosting(XGBoost))are trained using the generated data and AE-encoded *** evaluated the system on three benchmark datasets:NSL-KDD,UNSW-NB15,and *** conducted on diverse IoT datasets show that our method outperforms existing anomaly detection strategies and significantly reduces false *** 5DGWO-GAN-CNNAE exhibits superior performance in various metrics,including accuracy,recall,precision,root mean square error(RMSE),and convergence *** proposed 5DGWO-GAN-CNNAE achieved the lowest RMSE values across the NSL-KDD,UNSW-NB15,and

关键词： Internet of things intrusion detection generative adversarial networks five-dimensional binary gray wolf optimizer deep learning

Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta garcía-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

Functional evolution of thyrotropin-releasing hormone neuropeptides: Insights from an echinoderm

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Zoological Research 2025年第01期 236-248页

作者： Yingqiu Zheng Huachen Liu Xin Dang Juan diego Gaitán-Espitia Muyan Chen The Key Laboratory of Mariculture Ministry of Education Ocean University of China The Swire Institute of Marine Science and School of Biological Sciences The University of Hong Kong

Feeding behavior is regulated by a complex network of endogenous neuropeptides. In chordates, this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH). However,whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans, and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin(CCK, known as a satiety signal), remain unclear. This study investigated the TRH signaling system in the echinoderm Apostichopus japonicus. Bioinformatic analyses and ligand-binding assays identified a functional TRH receptor(AjTRHR) that activated signaling via the MAPK/ERK1/2pathways. Experimental administration of TRH significantly reduced feeding activity, while up-regulating CCK expression. RNA interference(RNAi) experiments confirmed that both CCK and TRH are essential components of satiety signaling, working synergistically to mediate feeding inhibition. Evolutionary analysis of TRHtype peptides revealed greater conservation of the short isoform of TRH compared to the long isoform, probably driven by strong selection acting on the functional redundancy. These findings provide compelling evidence of a TRH-mediated signaling system in non-chordate deuterostomes,expandingourunderstandingof neuropeptide-regulated feeding mechanisms in marine invertebrates.

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