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neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria S.Aymerich Universidad de navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de navarra PamplonaSpain IdiSnA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

Context-dependent role of sirtuin 2 in inflammation

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neural Regeneration Research 2025年第3期20卷 682-694页

作者： noemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-delgado Elena Puerta department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain navarra Institute for Health Research(IdiSnA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(nAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(nLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation nLRP3 nuclear factorκB sirtuin 2

Mutated trimeric RBD vaccines:a platform against variants of concern

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2038-2040页

作者： Belén Aparicio Juan J.Lasarte Pablo Sarobe Programa de Inmunología e Inmunoterapia Centro de Investigación Médica Aplicada(CIMACCUN)Universidad de NavarraPamplona31008Spain Centro de investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD) Pamplona31008Spain IdiSnA Instituto de Investigación Sanitaria de NavarraPamplona31008Spain

He et *** reported in nature Communications1 the development of a protein vaccine against SASR-CoV-2 Omicron variant consisting of a trimer of the spike protein receptor-binding domain(RBD)of the delta variant fused to heptad-repeat sequences 1 and *** vaccine induced broad-spectrum neutralizing antibodies and fully protected mice and non-human primates against challenge with live delta and Omicron virus.

关键词： vaccine vaccines

nLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling

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Cellular & Molecular Immunology 2021年第4期18卷 1045-1057页

作者： Xabier Unamuno Javier Gomez-Ambrosi Beatriz Ramirez Amaia Rodriguez Sara Becerril Victor Valenti Rafael Moncada Camilo Silva Javier Salvador Gema Fruhbeck Victoria Catalan Metabolic Research Laboratory Clfnica Universidad de NavarraPamplonaSpain CIBER Fisiopatologfa de la Obesidad y nutricion(CIBEROBn) Instituto de Salud Carlos ⅢPamplonaSpain Obesity and Adipobiology Group Instituto de Investigaci6n Sanitaria de Navarra(IdiSNA)PamplonaSpain department of Surgery Clinica Universidad de NavarraPamplonaSpain department of Anesthesia Clinica Universidad de NavarraPamplonaSpain department of Endocrinology&nutrition Clfnica Universidad de NavarraPamplonaSpain

The nLRP3-IL-1β pathway plays an important role in adipose tissue(AT)-induced inflammation and the development of obesityassociated *** aimed to determine the impact of nLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix(ECM)*** obtained from 98 subjects were used in a case-control *** expression of different components of the inflammasome as well as their main effectors and inflammation-and ECM remodeling-related genes were *** impact of blocking nLRP3 using siRnA in lipopolysaccharide(LPS)-mediated inflammation and ECM remodeling signaling pathways was *** demonstrated that obesity(Pnd nAFLD(Pncreased the expression of different com ponents of the inflammasome as well as the expression and release of IL-1β and IL-18 in *** also found that obese patients with T2D exhibited increased(Pne expression levels of nLRP3,IL1B and *** showed that nLRP3,but not nLRP1,is regulated by inflammation and hypoxia in visceral *** revealed that the inhibition of nLRP3 in human visceral adipocytes significantly blocked(Pnduced inflammation by downregulating the mRnA levels of CCL2,IL1B,IL6,IL8,S100A8,S100A9,TLR4 and TnF as well as inhibiting(Pn of IL1-β into the culture ***,blocking nLRP3 attenuated(Pnduced expression of important molecules involved in AT fibrosis(COL1A1,COL4A3,COL6A3 and MMP2).These novel findings provide evidence that blocking the expression of nLRP3 reduces AT inflammation with significant fibrosis attenuation.

关键词： nLRP3 Inflammasone Inflammation Obesity Type 2 diabetes nonalcoholic fatty liver disease

Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children:a prospective validation study

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World Journal of Pediatrics 2022年第12期18卷 810-817页

作者： Javier Arredondo Montero Giuseppa Antona Adriana Rivero Marcotegui Carlos BardajíPascual Mónica Bronte Anaut Raquel Ros Briones Amaya Fernández-Celis natalia López-Andrés nerea Martín-Calvo Pediatric Surgery department Hospital Universitario de NavarraIrunlarrea 331008PamplonaSpain Clinical Analysis department Hospital Universitario de NavarraPamplonaSpain Pathology department Hospital Universitario de NavarraPamplonaSpain Cardiovascular Translational Research NavarraBiomed(Miguel Servet Foundation)Hospital Universitario de NavarraUniversidad Pública de Navarra(UPNA)IdiSNAPamplonaSpain School of Medicine Department of Preventive Medicine and Public HealthUniversity of NavarraPamplonaSpain CIBER Fisiopatología de la Obesidad y nutrición(CIBERobn) Health Institute Carlos IIIMadridSpain instituto de investigación sanitaria de navarra IdiSNAPamplonaNavarraSpain

Background Serum interleukin-6(IL-6)has a moderate diagnostic performance in pediatric acute appendicitis(PAA).The evidence regarding its capacity to discern between complicated and uncomplicated PAA is *** We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated *** study included 205 patients divided into three groups:(1)patients who underwent major outpatient surgery(n=57);(2)patients with non-surgical abdominal pain(nSAP)in whom the diagnosis of PAA was excluded(n=53),and(3)patients with a confirmed diagnosis of PAA(n=95).The PAA patients were further classified as uncomplicated or complicated ***-6 concentration was determined in all patients at *** statistical analysis was performed using the Mann-Whitney U test,the Fisher exact test and the Kruskall Wallis *** area under the receiver operating characteristic curves(AUC)were *** Median(interquartile range,IQR)serum IL-6 values were 2 pg/mL(2.0–3.4)in group 1,3.9 pg/mL(2.4–11.9)in group 2,and 23.9 pg/mL(11.1–61.0)in group 3(Png the participants in group 3,those with uncomplicated PAA had median(IQR)serum IL-6 values of 17.2 pg/mL(8.5–36.8),and those with complicated PAA had 60.25 pg/mL(27.1–169)serum IL-6(Pnt of 19.55 pg/mL,the AUC for the discrimination between patients in group 2 vs.3 was 0.83[95%confidence interval(CI)0.76–0.90],with a sensitivity of 61.3%and a specificity of *** AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77(95%CI 0.68–0.86)and the cut-off point was 25.90 pg/mL,with a sensitivity and specificity of 84.6%and 65.6%,*** Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA.A score including clinical and radiological variables may increase the diagnostic performance of this molecule.

关键词： Acute Appendicitis Complicated Diagnostic Interleukin-6 Pediatric Uncomplicated

SARS-CoV-2 infection in children requiring hospitalization: the experience of navarra, Spain

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World Journal of Pediatrics 2020年第6期16卷 614-622页

作者： Laura Moreno-Galarraga Maria Urretavizcaya-Martinez Josune Alegria Echauri Marcos Garcia Howard Eva Ruperez Garcia Sergio Aguilera-Albesa Valentin Alzina de Aguilar Mercedes Herranz Aguirre Pediatric Pulmonology Department of PediatricsCHNComplejo Hospitalario de NavarraServicio Navarro de SaludC/Irunlarrea 331080 PamplonaSpain IdiSnA.navarra Institute for Health Research PamplonaSpain department of Preventive Medicine and Public Health.School of Medicine.University of navarra Pamplona.wSpain department of Pediatrics CHNComplejo Hospitalario de NavarraServicio Navarro de Salud.Pamplona.Spain Pediatric Cardiology Department of PediatricsCHN.Complejo Hospitalario de NavarraServicio Navarro de SaludPamplonaSpain Pediatric neurology Department of PediatricsCHN.Complejo Hospitalario de NavarraServicio Navarro de SaludPamplonaSpain department of Pediatrics CUN.Clfnica Universidad de NavarraPamplona.Spain department of Pediatrics School of MedicineUniversity of NavarraPamplona.Spain

Background Coronavirus disease 2019 in children,or pediatric COVID-19,initially was described as an acute respiratory syndrome similar to the adult presentation but with less severe *** We describe the clinical characteristics,disease presentation,treatments and outcomes of all pediatric cases with COVID-19 admitted to the reference hospitals in navarra,Spain during the first wave of the COVID-19 outbreak(February-May 2020).Results We found a low number of hospitalized cases in infants and children compared to adults with a hospitalization ratio of 1:*** of these hospitalized cases did not suffer from severe *** 80%of infections reported household contacts,and the mother was the known-contact in 83%of these cases.72%of hospitalized cases were previously healthy *** describe how symptoms in pediatric cases are nonspecific and how COVID-19 can be presented with a wide range and variety of *** symptoms are not always present,and severe neurological and cardiac features can occur in previously healthy *** Epidemiological description and case reports will be key to a better recognition and to adequate treatment of pediatric patients with COVID-19.

关键词： Coronavirus disease 2019 Hospitalization Severe acute respiratory syndrome coronavirus 2

FnDC4 and FnDC5 reduce SARS-CoV-2 entry points and spike glycoprotein S1-induced pyroptosis, apoptosis, and necroptosis in human adipocytes

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Cellular & Molecular Immunology 2021年第10期18卷 2457-2459页

作者： Gema Frühbeck Victoria Catalán Víctor Valentí Rafael Moncada Javier Gómez-Ambrosi Sara Becerril Camilo Silva Piero Portincasa Javier Escalada Amaia Rodríguez Metabolic Research Laboratory Clínica Universidad de NavarraPamplonaSpain CIBER Fisiopatología de la Obesidad y nutrición(CIBEROBn) Instituto de Salud Carlos IIIMadridSpain Obesity and Adipobiology Group Instituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain department of Endocrinology and nutrition Clínica Universidad de NavarraPamplonaSpain department of Surgery Clínica Universidad de NavarraPamplonaSpain department of Anesthesia Clínica Universidad de NavarraPamplonaSpain department of Biomedical Sciences and Human Oncology Clinica Medica“A.Murri”University of Bari Medical SchoolPoliclinico HospitalBariItaly.

A sedentary lifestyle and obesity are important risk factors for severe COVID-19 complications and death[1,2].Excessive adipose tissue(AT)might contribute to more extensive viral spread with increased shedding,immune activation,and cytokine amplification[3].Several factors secreted by contracting muscle,termed myokines,mediate the beneficial effects of exercise in a wide range of diseases,including obesity[4].Thus,we conducted a study to explore the potential role of myokines of the fibronectin type III domain-containing family,FnDC4 and FnDC5,in mechanisms underlying the increased susceptibility to COVID-19 complications in obesity.

关键词： FnDC5 obesity FnD

Rebooting Synthetic Phage-Inducible Chromosomal Islands:One Method to Forge Them All

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Biodesign Research 2020年第1期2020卷 34-47页

作者： Rodrigo Ibarra-Chávez Andreas F.Haag Pedro Dorado-Morales Iñigo Lasa JoséR.Penadés Institute of Infection Immunity and InflammationCollege of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowUK Laboratory of Microbial Pathogenesis NavarrabiomedComplejo Hospitalario de Navarra-Universidad Pública de Navarra(UPNA)Instituto de Investigación Sanitaria de Navarra(IDISNA)31008 PamplonaSp

Phage-inducible chromosomal islands(PICIs)are a widespread family of mobile genetic elements,which have an important role in bacterial *** elements mobilize among bacterial species at extremely high frequencies,representing an attractive tool for the delivery of synthetic ***,tools for their genetic manipulation are limited and timing ***,we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host *** proof of concept,we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI *** biotechnological purposes,we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted *** results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.

关键词： proof eliminate generating

Endoscopic anti-reflux therapy for gastroesophageal reflux disease

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World Journal of Gastroenterology 2021年第39期27卷 6601-6614页

作者： Enrique Rodríguez de Santiago Eduardo Albéniz Fermin Estremera-Arevalo Carlos Teruel Sanchez-Vegazo Vicente Lorenzo-Zúñiga department of Gastroenterology and Hepatology Hospital Universitario Ramón y CajalInstituto Ramón y Cajal de Investigación Sanitaria(IRYCIS)Madrid 28034Spain Endoscopy Unit Gastroenterology DepartmentHospital Universitario de Navarra.Gastrointestinal Endoscopy Research UnitNavarrabiomed Biomedical Research Center.PamplonaSpain Endoscopy Unit Gastroenterology DepartmentHospital Universitari i Politècnic La FeInstituto de Investigación Sanitaria La Fe(IIS La Fe)Valencia 46026Spain

Gastroesophageal reflux disease has an increasing incidence and prevalence worldwide.A significant proportion of patients have a suboptimal response to proton pump inhibitors or are unwilling to take lifelong medication due to concerns about long-term adverse *** anti-reflux therapies offer a minimally invasive option for patients unwilling to undergo surgical treatment or take lifelong *** best candidates are those with a good response to proton pump inhibitors and without a significant sliding hiatal *** incisionless fundoplication and nonablative radiofrequency are the techniques with the largest body of evidence and that have been tested in several randomized clinical ***-assisted ligation techniques,anti-reflux mucosectomy,antireflux mucosal ablation,and new plication devices have yielded promising results in recent noncontrolled ***,the role of endoscopic procedures remains controversial due to limited long-term and comparative data,and no consensus exists in current clinical *** review provides an updated summary focused on the patient selection,technical details,clinical success,and safety of current and future endoscopic anti-reflux techniques.

关键词： Treatment Gastroesophageal reflux Transoral incisionless fundoplication Anti-reflux mucosectomy Anti-reflux mucosal ablation Stretta