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Immunogenicity and mechanisms impairing the response to vaccines in inflammatory bowel disease

World Journal of Gastroenterology 2015年第40期21卷 11273-11281页

作者： alicia c marín Javier P Gisbert maría chaparro Gastro- enterology Unit Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria PrincesaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas28021 MadridSpain

Inflammatory bowel disease(IBD) is an immunological disorder that is usually treated with immunosuppressive therapy,potentially leading to increases in vulnerability to infections. Although many infections can be pre-vented by vaccination,vaccination coverage in these patients in clinical practice is insufficient. Therefore,the seroprotection condition should be verified,even for routine vaccines,such as hepatitis B or pneu-mococcus. Response to vaccines in IBD patients is thought to be impaired due to the immunological alterations generated by the disease and to the immunomodulatory treatments. The immunogenicity of hepatitis B,influenza,and pneumococcal vaccines is impaired in IBD patients,whereas the response to papillomavirus vaccine seems similar to that observed in the healthy population. On the other hand,data on the immunogenicity of tetanus vaccine in IBD patients are conflicting. Studies assessing the response to measles-mumps-rubella,varicella,and herpes zoster vaccines in IBD patients are scarce. The cellular and molecular mechanisms responsible for the impairment of the response to vaccination in IBD patients are poorly understood. Studies aiming to assess the response to vaccines in IBD patients and to identify the mechanisms involved in their immunogenicity are warranted. A better understanding of the immune response,specifically to vaccines,in patients with immune-mediated diseases(such as IBD),is crucial when developing vaccines that trigger more potent immunologic responses.

关键词： crohn’s disease Inflammatory bowel disease Tumor n

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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

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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)

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： carina Hromada Patrick Heimel markus Kerbl LászlóGál Sylvia nürnberger Barbara Schaedl James Ferguson nicole Swiadek Xavier Monforte Johannes c.Heinzel Antal nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tnGcs). However, the use of tnGcs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tnGc would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tnGcs and compared the various features of these improved silk^(+) tnGcs with the tubes without holes(silk^(–) tnGcs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tnGcs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tnGcs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tnGcs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tnGcs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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Hepatoprotective effects of antioxidants in chronic hepatitis c

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World Journal of Gastroenterology 2010年第15期16卷 1937-1938页

作者： Ricardo Moreno-Otero maría Trapero-marugán Digestive Diseases Service and cIBEREHD (Instituto de Salud carlos Ⅲ) University Hospital La Princesa Autonomous University of Ma-drid

We have read with interest the paper published in issue 2, volume 16 of World Journal of Gastroenterology 2010 by nakamura et al, demonstrating that the antioxidant resveratrol (RVT) enhances hepatitis c virus (HcV) replication, consequently, they conclude that RVT is not a suitable antioxidant therapy for HcV chronic infection. The data raise some concern regarding the use of complementary and alternative medicine since the most frequent supplements taken by these patients are antioxidants or agents that may be beneficial for different chronic liver diseases. A recent study by Vidali et al on oxidative stress and steatosis in the progression of chronic hepatitis c concludes that oxidative stress and insulin resistance contribute to steatosis, thus accelerating the progression of fibrosis. We are particularly interested in investigating how the oxidative and nitrosative stress mechanisms are involved in the pathogenesis of different chronic liver diseases.

关键词： Antioxidant chronic hepatitis c Resveratrol Sadenosylmethionine nitric oxide nacetylcysteine

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Long-term outcome of chronic hepatitis c patients with sustained virological response to peginterferon plus ribavirin

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World Journal of Gastroenterology 2011年第4期17卷 493-498页

作者： maría Trapero-marugán Jorge Mendoza maría chaparro Leticia González-Moreno José Andrés Moreno-Monteagudo maría Jesús Borque Ricardo Moreno-Otero Gastroenterology-Hepatology Department University Hospital La Princesa and Princesa Research Institute Autonomous University of Madrid and CIBERehd (Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas)

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis c (cHc) patients with a sustained virological response (SVR) after peginterferon (PEG-IFn) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFn plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. clinical anamnesis, biochemical analysis, hepatitis c virus RnA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. no patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. cOncLUSIOn: The long-term outcome of 153 cHc patients with SVR to PEG-IFn plus ribavirin was good. no evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

关键词： chronic hepatitis c Peginterferon Ribavirin Sustained virological response Long-term effects

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Effects of six months losartan administration on liver fibrosis in chronic hepatitis c patients: A pilot study

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World Journal of Gastroenterology 2005年第48期11卷 7560-7563页

作者： Silvia Sookoian maría Alejandra Fernández Gustavo casta(n|~)o Instituto de Investigaciones Médicas A.Lanari cathedra of Physiopathology Gastroenterology Section

AIM： TO evaluate the safety and efficacy of chronic administration of Iosartan on hepatic fibrosis in chronic hepatitis c patients.METHODS： Fourteen patients with chronic hepatitis c non-responders （n = 10）, with contraindications （n = 2） or lack of compliance （n = 2） to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after Iosartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies （interval 6-14 mo）. Histological activity index （HAI） with fibrosis stage was assessed under blind conditions by means of Ishak＇s score. Subendothelial fibrosis was evaluated by digital image analyses.RESULTS： The changes in the fibrosis stage were significantly different between Iosartan group （decrease of 0.5±1.3） and controls （increase of 0.89±1.27; P〈0.03）. In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients （P〈0.04）. A decrease in sub-endothelial fibrosis was observed in the Iosartan group. no differences were found in HAI after Iosartan administration. Acute and chronic decreases in systolic arterial pressures （P〈0.05） were observed after the Iosartan administration, without changes in mean arterial pressure or renal function.cOncLUSIOn： chronic AT-Ⅱ type 1 receptor （AT1R） blockade may reduce liver fibrosis in patients with chronic hepatitis c.

关键词： Hepatitis c Liver fibrosis Losartan AT1R chronic liver disease Angiotensin Ⅱ

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Oleanolic acid:a promising neuroprotective agent for cerebral ischemia

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neural Regeneration Research 2015年第4期10卷 540-541页

作者： caltana Laura nieto maría Luisa Brusco alicia Instituto de Biología celulary neurociencia IBCN(UBA-CONICET)Buenos AiresArgentina Instituto Biologíay Genética Molecular CSIC-UVAValladolidSpain

Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such as smoking, obesity and nutritional disbalance. Disability affects 75% of stroke survivors through severe mental and/or physical impairment depending on the affected brain area （Go et al., 2014）.

关键词： acid Oleanolic acid

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro martín-Belmonte Sergi Ferré Francisco ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats

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World Journal of Gastroenterology 2006年第26期12卷 4149-4155页

作者： Soledad Gonzales maría Julia Pérez Juan c Perazzo maría Luján Tomaro Department of Biological chemistry School of Pharmacy and Biochemistry University of Buenos AiresBuenos Aires 1113Argentina Laboratory of Portal Hypertension Department of Biological Science School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos Aires 1113Argentina

AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male rats, weighing 200-250 g, were divided at random into two groups： one group with prehepatic portal hypertension （PH） induced by regulated prehepatic portal vein ligation （PPVL） and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured. RESULTS： In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances （TBARS） content and a decrease in reduced glutathione （GSH） levels. The activities of liver antioxidant enzymes, superoxide dismutase （SOD）, catalase （cAT） and glutathione peroxidase （GSH-Px） were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin （5μmol/kg body weight） 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX （Sn-PPIX）（100 μg/kg body weight, i.p.）, a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect cOncLUSIOn： These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.

关键词： Heme oxygenase-1 Portal hypertensive rats Liver oxidative stress

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