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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 damage.Mesenchymal 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 mice.Considering 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 drinking.We 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 mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken 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)

Qigong improves balance in young women: a pilot study

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Journal of Integrative Medicine 2013年第4期11卷 241-245页

作者： maría victoria gonzález lópez-Arza Enrique Varela-Donoso Jesús Montanero-Fernández Juan Rodríguez-Mansilla Blanca gonzález-Sánchez luis gonzález lópez-Arza Medicine and Surgery Department Extremadura University School of Medicine Adolor Research Group of the Extremadura University Physical and Rehabilitation Medicine Department Complutense University School of Medicine Mathematics Department Extremadura University School of Sciences Health Care Centre of Zafra

BACKGROUND： Balance problems are common in people of all ages and can lead to falls, thus causing fractures with consequent disability. Qigong practice has long been part of daily life in Chinese culture, and has good effects on physical health maintenance. OBJECTIVE： The present work describes the change in balance in young, healthy women after practising Qigong for eight weeks. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： The study took the form of a controlled, randomised longitudinal trial, and involved 30 women aged 18-25 years. The subjects had no prior experience of Qigong or Tai Chi and were unaware of the aims of the study. Subjects were randomly assigned to a Qigong intervention group or a control group. Those in the Qigong intervention group performed ＂exercises in 20 figures for health and long-life＂（Wang Ziping） for 1 h twice per week, for 4 weeks. The control group undertook no exercise at all. MAIN OUTCOME MEASURES： The main outcome measure was the stabilometry values. These were obtained in a unipodal support test, using a plantar pressure platform with optical sensors. RESUlTS： The Qigong subjects showed a significant improvement in their stabilometry results （40.1% pre-intervention and 56.4% post-intervention）（P〈0.045）, while no improvement was seen in the control group （51.2% pre-intervention and 53.5% post-intervention）. At the beginning of the intervention, the stabilometry values recorded for the Qigong intervention group were worse than those recorded for the control group （40.15% and 51.21% respectively; P=0.121）. However, a comparison of the post-intervention values between these groups showed that these differences have disappeared （P=0.653）. CONClUSION： Qigong can improve balance in healthy, young women.

关键词： Qigong musculoskeletal equilibrium women pilot projects

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2l,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2l RHBDF2

Damage Mechanism of CK2 and IKAROS in Philadelphia like Acute lymphoblastic leukemia

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Journal of Biosciences and Medicines 2024年第4期12卷 49-59页

作者： Ignacio Vélez-Rodríguez victoria Carranza-Aranda Facultad Mexicana de Medicina Universidad La Salle Tlalpan M&#233xico Hospital General de Mé xico Cuauht&#233moc M&#233xico

Acute lymphoblastic leukemia (All) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (All) with the presence of the Philadelphia chromosome (All Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABl fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).

关键词： Acute lymphoblastic leukemia IKAROS Dephosphorylation Philadelphia Chromosome CK2

Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage

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World Journal of Hepatology 2024年第1期16卷 1-11页

作者： Jorge Quarleri M victoria Delpino Instituto de Investigaciones Biomédicas en Retrovirus y Sida(INBIRS) Universidad de Buenos Aires(UBA)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Buenos Aires 1121Argentina

In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Viral RNA has been detected in hepatic tissues,and in situ hybridization revealed virions in blood vessels and endothelial cells.Electron microscopy confirmed viral particles in hepatocytes,emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury.Various factors contribute to liver injury,including direct cytotoxicity,vascular changes,inflammatory responses,immune reactions from COVID-19 and vaccinations,and druginduced liver injury.Although a typical hepatitis presentation is not widely documented,elevated liver biochemical markers are common in hospitalized COVID-19 patients,primarily showing a hepatocellular pattern of elevation.long-term studies suggest progressive cholestasis may affect 20%of patients with chronic liver disease post-SARS-CoV-2 infection.The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex.This“Editorial”highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells,the role of inflammatory responses,the impact of hypoxia,the involvement of the liver's vascular system,the infection of bile duct epithelial cells,the activation of hepatic stellate cells,and the contribution of monocyte-derived macrophages.It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19.Understanding the interaction of SARS-CoV-2 with the liver is still evolving,and further research is required.

关键词： SARS-CoV-2 COVID-19 Hepatotropism Angiotensin-converting enzyme-2

Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

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Neural Regeneration Research 2024年第1期19卷 55-61页

作者： Paula lzquierdo-Altarejos victoria Moreno-Manzano Vicente Felipo laboratory of Neurobiology Centro Investigación Príncipe FelipeValenciaSpain Neuronal and Tissue Regeneration laboratory Centro Investigación Príncipe FelipeValenciaSpain

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive molecules.Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation.The cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological situations.Extracellular vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative diseases.Extracellular vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the brain.This contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative diseases.The mechanisms involved are beginning to be unde rstood.For example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal rats.Identifying the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early detection.In contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor function.These extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target organs.Extracellular vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and hepatic encephalopathy.Extracellular vesicles f

关键词： extracellular vesicles inflammation cognitive function mesenchymal stem cells neurodegenerative diseases neuroinflammation therapy transforming growth factor-β

Medical management of urolithiasis: Great efforts and limited progress

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Asian Journal of Urology 2024年第2期11卷 149-155页

作者： victoria Jahrreiss Christian Seitz Fahad Quhal Department of Urology Comprehensive Cancer CenterMedical University of ViennaViennaAustria Department of Urology King Fahad Specialist HospitalDammamSaudi Arabia

Objective:To provide a comprehensive review on the existing literature on medical management of urolithiasis.Methods:A thorough literature review was performed using Medline,PubMed/PMC,Embase,and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis.Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed;studies on medical expulsive therapy were not included in this review.Results:Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies.While most treatment concepts have been long established,large randomized controlled trials are scarce.Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis.A major limitation for medical management of urolithiasis is poor patient compliance.Conclusion:Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones.Although medical management can be effective in limiting stone recurrence,medical interventions often fail due to poor compliance.

关键词： Medicalmanagement Medical therapy Urolithiasis Kidneystonedisease

Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： Courtney J.Rouse victoria N.Jensen Coy D.Heldermon lacerta Therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

A Tutorial on Federated learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.victoria luzón Nuria Rodríguez-Barroso Alberto Argente-Garrido Daniel Jiménez-lópez Jose M.Moyano Javier Del Ser Weiping Ding Francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(Fl)emerges as a relevant artificial intelligence field for developing machine learning(Ml)models in a distributed and decentralized environment.Fl allows Ml models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third parties.This paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data sources.By virtue of Fl,models can be learned from all such distributed data sources while preserving data privacy.The aim of this paper is to provide a practical tutorial on Fl,including a short methodology and a systematic analysis of existing software frameworks.Furthermore,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of Fl,describing the main components of Fl,from key elements to Fl categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for Fl deployment,devising a methodology to design a Fl scenario,and providing exemplary cases of study with source code for different Ml approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current Fl landscape.The ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of Fl in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks