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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)

Steatosis and insulin resistance in hepatitis c: A way out for the virus?

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World Journal of gastroenterology 2009年第40期15卷 5014-5019页

作者： josé A Del campo Manuel Romero-gómez Unit for The clinical Management of Digestive Diseases and cIBERehd Hospital Universitario de Valme

The hepatitis c virus (HcV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HcV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HcV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HcV promotes steatosis as an eff icient mechanism for stable viral replication. chronic HcV in-fection can also induce insulin resistance. In patients with HcV, insulin resistance is more strongly associated with viral load than visceral obesity. HcV seems to lead to insulin resistance through interference of intracellular insulin signalling by HcV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HcV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOcS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

关键词： Steatosis Insulin resistance Hepatitis cvirus

Is interferon-beta an alternative treatment for chronic hepatitis c?

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World Journal of gastroenterology 2006年第17期12卷 2730-2736页

作者： Ricardo Moreno-Otero María Trapero-Marugán Elena gómez-Domínguez Luisa garcía-Buey joséA Moreno-Monteagudo Unit of Hepatology Hospital Universitario de La Princesa Universidad Autónoma de MadridSpain

The treatment of chronic hepatitis c （cHc） is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α （IFNα） plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβ could represent an interesting alternative for treating cHc patients. controversial data about IFNβ efficacy in cHc exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNα. Additionally, the good tolerability of IFNβ represents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβ plus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.

关键词： Hepatitis c Hepatitis c virus Interferon beta Ribavirin

Modulation of host lipid metabolism by hepatitis c virus: role of new therapies

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World Journal of gastroenterology 2015年第38期21卷 10776-10782页

作者： josé A Del campo Manuel Romero-gómez Digestive Diseases and cIBERehd Valme University Hospital

It is well established that hepatitis c virus(HcV) infection and replication relies on host lipid metabolism. HcV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides,circulating infective particles are associated with verylow-density lipoprotein. On the other hand,higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HcV infection,suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy(> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HcV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review,host genetic factors,viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

关键词： Hepatitis c virus Lipid metabolism Direct acting a

VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

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cellular & Molecular Immunology 2018年第4期15卷 353-366页

作者： Laura gómez-Jaramillo Raquel Romero-garcía gema Jiménez-gómez Lisa Riegle Ana Belén Ramos-Amaya joséAntonio Brieva Marie Kelly-Worden Antonio campos-caro Unidad de Investigación Hospital Universitario Puerta del MarCádizSpain Department of Biology Ball State UniversityMuncieINUSA

The production and secretion of antibodies by human plasma cells(Pcs)are two essential processes of humoral *** secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors(SNAREs),which are located in the plasma membrane(t-SNAREs)and in the antibody-carrying vesicle membrane(v-SNARE),and mediate the fusion of both *** have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody ***,using human Pcs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMP)isoforms,demonstrating that all isoforms(with the exception of VAMP1)are expressed by the referenced ***,the functional role in antibody secretion of each expressed VAMP isoform was tested using *** results show that VAMP2 may be the v-SNARE involved in vesicular antibody *** further support this conclusion,we used tetanus toxin light chain to cleave VAMP2,conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in situ interaction of VAMP2 with *** together,these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.

关键词： exocytosis human immunoglobulin plasma cells VAMP proteins

A stable anthraquinone-derivative cathode to develop sodium metal batteries: The role of ammoniates as electrolytes

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Journal of Energy chemistry 2023年第2期77卷 572-580,I0015页

作者： Débora Ruiz-Martínez josé M.Orts Roberto gómez Departament de Química Física i Institut Universitari d’Electroquímica Universitat d’AlacantApartat 99Alicante E-03080Spain

Rechargeable sodium metal batteries constitute a cost-effective option for energy storage although sodium shows some drawbacks in terms of reactivity with organic solvents and dendritic *** we demonstrate that an organic dye,indanthrone blue,behaves as an efficient cathode material for the development of secondary sodium metal batteries when combined with novel inorganic *** electrolytes are ammonia solvates,known as liquid ammoniates,which can be formulated as NaI·3.3NH_(3) and NaBF_(4)·2.5NH_(3).They impart excellent stability to sodium metal,and they favor sodium non-dendritic growth linked to their exceedingly high sodium ion *** advantage is complemented by a high specific *** battery described here can last hundreds of cycles at 10 c while keeping a coulombic efficiency of 99%from the first *** of the high capacity of the cathode and the superior physicochemical properties of the electrolytes,the battery can reach a specific energy value as high as 210 W h kgIB^(-1),and a high specific power of 2.2 kW kgIB^(-1),even at below room temperature(4℃).Importantly,the battery is based on abundant and cost-effective materials,bearing promise for its application in large-scale energy storage.

关键词： Sodium metal batteries Anthraquinone-based cathode Vat dye Indanthrone blue Inorganic electrolytes Liquid ammoniates

Mulching as best management practice to reduce surface runoff and erosion in steep clayey olive groves

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International Soil and Water conservation Research 2021年第1期9卷 26-36页

作者： giuseppe Bombino Pietro Denisi joséAlfonso gómez Demetrio Antonio Zema Mediterranea University of Reggio calabria Department"Agraria"LocalitàFeo di Vito1-89122Reggio CalabriaItaly Institute for Sustainable Agriculture(IAS-cSIc) Agronomy DepartmentAvenida Menéndez Pidal s/nE-14004CórdobaSpain

No-tillage and soil mulching with pruning residues,applied in olive groves of the semi-arid Mediter-ranean environment,as erosion control practices still practice not fully *** study has evaluated the saturated hydraulic conductivity(Ksat),surface runoff(SR)and soil erosion(SL)under rainfall at plot scale throughout two years in four different management practices,total soil cover with a net(SP),mechanical tillage(MT)and mulching by vegetal residues at 3,5·10^(3) and 17,5·10^(3) kg ha^(-1) of dry matter(NTR350 and NTR1750),in an olive grove of Southern *** varied between 1.6(MT)and 25.1(NTR1750)mm/h.A clear reduction in runoff and soil losses was detected for the mulch-based practices when compared to MT,from 20 to 32%in the runoff coefficient and 75-80%in SL,with higher reductions in the *** reduction in SL can be mainly explained by the reduction in SR and rain-splash,interrill and rill erosion,due to protection by mulch residues,which increased the vegetal cover and organic matter content of mulched *** vegetal cover was on average higher in SP(33%),NTR1750(25%)and NTR350(22%),and lower in MT(12%).The mean organic matter content of soil was 2.01%,1.69%,1.34%and 0.82%for NTR1750,NTR350,SP and MT ***,the results quantify the impact of soil mulching with pruning residues at different doses,which will provide guidelines to control and mitigate the hydrological response of clayey and steep soils in Mediterranean olive groves,analysing the associated environmental and economic benefits.

关键词： Pruning residues Tillage Soil loss Vegetal cover Organic matter Soil hydraulic conductivity

Entry of hepatitis c virus into the cell: A therapeutic target

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World Journal of gastroenterology 2012年第33期18卷 4481-4485页

作者： josé Antonio Del campo ngela Rojas Manuel Romero-gómez Unit for Medical and Surgical Management of Digestive Diseases Center for Biomedical Research in Digestive and Liver Diseases Network (CIBERehd) Valme University Hospital University of Seville E-41014 Sevilla Spain

Several receptors have been identified as implicated on viral entry into the hepatocyte; and, this interaction between the virus and potential receptors could modulate infection, spontaneous viral clearance, persistence of the infection and the widespread of the virus as outbreak. Nevertheless, the playing role of each of them remains controversial. The NiemannPick type c1 like 1 gene (NPc1L1) receptor has been recently implicated on hepatitis c virus (HcV) entry into the cell and ezetimibe, an anti-cholesterol drug seems to block that, emerging the idea to control hepatitis c outbreak modulating lipid-related receptors. Hepatitis c infection seems to modulate lipid metabolism according to host genetic background. Indeed, it circulates like a lipoviroparticle. The main aim of this field of vision would be to discuss the role of hepatocyte receptors implicated on virus entry, especially NPc1L1 and the therapeutic options derived from the better knowledge about HcV-lipidsreceptors interaction.

关键词： Hepatitis c virus entry Niemann-Pick type c1 like 1 gene Lipid metabolism Ezetimibe

In-depth analysis of soil management and farmers’perceptions of related risks in two olive grove areas in southern Spain

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International Soil and Water conservation Research 2021年第3期9卷 461-473页

作者： josé A.gòmez Ana Sanchez Montero gema guzman Marfa-Auxiliadora Soriano a Institute for Sustainable Agriculture CSICCordobaSpain Agronomy Department University of CordobaCordobaSpain

This manuscript presents a questionnaire-based study aimed to provide a detailed analysis on the different soil management carried out by olive farmers in two representative olive-growing areas in southern Spain(cordoba and Estepa),their perceptions on cover crop use and the possible influence of the different types of farms and farmers’typologies on these *** results show a relatively large variability of soil management,with fourteen options,as a result of a combination of different alternatives for bare soil and cover crops with the use or not of pruning residues,but with a great similarity between both *** results indicate a high adoption of soil conservation measures in the two study areas,with 63%of farmers using cover crops and 80%a mulch of pruning residues,higher than that reported in previous studies in Southern Spain,and a trend of lower use of these techniques by less experienced and younger *** high penetration of soil conservation measures resulted in a significant reduction of soil erosion risk,as indicated by the relatively low values for the cover and management factor(c)of RUSLE,also calculated and presented in this study,but also the possibility of focusing further efforts on fanners with less *** results indicate the persistence of a minor,but relevant,percentage of farmers using bare soil management(37%)and no mulching(20%),with a moderate concern on the impact of soil erosion on soil degradation and provision of ecosystem *** suggests the need to concentrate efforts also on this cluster of farmers to enhance the success of what seems to be a remarkable expansion of the use of soil conservation measures in recent decades in Southern Spain,but also in similar areas in the Mediterranean basin.

关键词： Tillage cover crops Olive yield Erosion risk Irrigation Questionnaire