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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

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer m.colón-mercado Aranza I.Torrado-Tapias Iris K.Salgado jose m.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA national Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Gut epithelial barrier dysfunction in humanimmunodeficiency virus-hepatitis C virus coinfectedpatients:Influence on innate and acquired immunity

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World Journal of Gastroenterology 2016年第4期22卷 1433-1448页

作者： mercedes márquez Clotilde Fernández Gutiérrez delÁlamo joséAntonio Girón-González Department of Internal medicine Infectious Disease UnitPuerta del Mar University HospitalUniversity of Cadiz11009 CádizSpain Servicio de medicina Interna Hospital Universitario Puerta del Mar11009 CádizSpain

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

关键词： human immunodeficiency virus infection hepatitis C virus infection Innate immunity Acquiredimmunity Gut barrier

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： maría norte-muñoz maría Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega mar Pérez josémCabrera-maqueda Javier Sierra manuel Vidal-Sanz maría Teresa moreno-Flores 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 SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(mHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

multiparameter resonant imaging for studying cell interactions

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Light(Science & Applications) 2018年第1期7卷 652-653页

作者： joséJuan-colás Thomas F Krauss Department of Physics The University of YorkHeslignton YO105DDUK Department of Electronic Engineering The University of YorkHeslignton YO105DDUK

The development of optical microscopy techniques has provided major insights into the machinery of life,from molecules to cells to tissues and *** techniques have been particularly successful in this respect by elucidating biological pathways and helping us understand the complex relationships that underpin all living *** example,the first use of fluorescence as an analytical tool in 18641 paved the way for the study of biological entities and interactions,but it was not until nearly 60 years later,in the 1930s,that fluorophores were first employed to perform biological investigations into specific tissue components and bacteria that do not *** advances led to the first labeling of an antibody with a visible label in 19413,which gave birth to the field of immunofluorescence and allowed us obtain unprecedented insight into antibody structure.

关键词： organs insight visible

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-inflammatory effects of mangifera indica *** in a model of colitis

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World Journal of Gastroenterology 2010年第39期16卷 4922-4931页

作者： Lucía márquez Beatriz G Pérez-nievas Icíar Gárate Borja García-Bueno josé Lm madrigal Luis menchén Gabino Garrido Juan C Leza Department of Pharmacology School of MedicineUniversity Complutense and Centro de Investigación en Red de Salud Mental(CIBERSAM) Pharmaceutical Chemistry Center and University of La Habana Health Research Institute Hospital 12 de Octubre(I+12) Gastroenterology Service Hospital General Universitario Gregorio Maraón and CIBEREHD Department of Chemistry and Pharmacy University Católica del Norte

AIm:To investigate the effect of aqueous extract from mangifera indica L.(mIE)on dextran sulfate sodium (DSS)-induced colitis in ***:mIE(150 mg/kg)was administered in two different protocols:(1)rectally,over 7 d at the same time as DSS administration;and(2)once daily over 14 d (by oral gavage,7 d before starting DSS,and rectally for 7 d during DSS administration).General observations of clinical signs were ***-inflammatory activity of mIE was assessed by myeloperoxidase(mPO)activity. colonic lipid peroxidation was determined by measuring the levels of thiobarbituric acid reactive substances (TBARS).Reduced glutathione(GSH)levels,expression of inflammatory related mediators[inducible isoforms of nitric oxide synthase(inOS)and cyclooxygenase (COX)-2,respectively]and cytokines[tumor necrosis factor(TnF)-αand TnF receptors 1 and 2]in colonic tissue were also ***(IL)-6 and TnF-α serum levels were also measured. RESULTS:The results demonstrated that mIE has anti-inflammatory properties by improvement of clinical signs,reduction of ulceration and reduced mPO activity when administered before *** addition,administration of mIE for 14 d resulted in an increase in GSH and reduction of TBARS levels and inOS,COX-2, TnF-αand TnF R-2 expression in colonic tissue,and a decrease in IL-6 and TnF-αserum levels. COnCLUSIOn:mIE has anti-inflammatory activity in a DSS-induced rat colitis model and preventive administration(prior to DSS)seems to be a more effective protocol.

关键词： Oxidative stress Ulcerative colitis Inflammation Polyphenols mangifera indica Antioxidants

Hepatitis C: Problems to extinction and residual hepatic and extrahepatic lesions after sustained virological response

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World Journal of Hepatology 2022年第1期14卷 62-79页

作者： Sara Cuesta-Sancho mercedes márquez-Coello Francisco Illanes-Álvarez Denisse márquez-Ruiz Ana Arizcorreta Fátima Galán-Sánchez natalia montiel manuel Rodriguez-Iglesias josé-Antonio Girón-González medicina Interna Hospital Universitario Puerta del MarFacultad de MedicinaUniversidad de CádizInstituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz(INiBICA)Cádiz 11009Spain microbiología Hospital Universitario Puerta del MarFacultad de MedicinaUniversidad de CádizInstituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz(INiBICA)Cádiz 11009Spain

Loss of follow-up or reinfections hinder the expectations of hepatitis C eradicationdespite the existence of highly effective treatments. moreover, the elimination ofthe infection does not imply the reversion of those chronic alterations derivedfrom the previous infection by hepatitis C virus (HCV). This review analyzes therisk factors associated with loss to follow-up in diagnosis or treatment, and thepossibility of reinfection. Likewise, it assesses the residual alterations induced bychronic HCV infection considering the liver alterations (inflammation, fibrosis,risk of decompensation, hepatocellular carcinoma, liver transplantation) and, onthe other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia,non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, boneand cognitive alterations). Peculiarities present in subjects coinfected with humanimmunodeficiency virus are analyzed in each section.

关键词： Hepatitis C virus Sustained virological response Direct antiviral agents Human immunodeficiency virus Cirrhosis decompensation Hepatocarcinoma Extrahepatic complications

Phasor-domain Dynamic model of Asymmetric Current Injection Controller for Converter-interfaced Generator

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Journal of modern Power Systems and Clean Energy 2021年第6期9卷 1269-1278页

作者： Victor A.F.Almeida Glauco n.Taranto josé m.T.marinho Electrical Engineering Department of the Federal University of Rio de Janeiro(COPPE/UFRJ) Petrobras S.A.

This paper presents a controller model of asymmetric current injection for converter-interfaced generators suitable for root-mean-square(RmS)phasor-domain,fundamentalfrequency,three-phase,and dynamic simulation *** effectiveness of the proposed controller is assessed with simulations in test systems with high percentage of converter-interfaced *** simulations focus on the operation of protection relays that use negative-sequence quantities in their directional *** paper also presents and compares two strategies to limit reactive negative-sequence currents,and active and reactive positive-sequence currents.A tutorial test system and a regional system part of the actual Brazilian Interconnected Power System are used to assess the correctness of the proposed controller in three-phase fundamental-frequency RmS dynamic simulations.

关键词： Converter-interfaced generator three-phase model power system protection negative-sequence current injection negative-sequence current protection unbalanced fault three-phase root-mean-square(RmS)dynamic simulation