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Context-dependent role of sirtuin 2 in inflammation

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

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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

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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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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

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The immune system:uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan JoséLasarte Immunology and Immunotherapy Program Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Pathology Anatomy and Physiology DepartmentSchool of MedicineUniversity of NavarraIDISNAPamplonaSpain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth *** perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological *** addition to the direct effects of sense-induced mediators in the brain.

关键词： prompt system transmitting

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SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta Department of Pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective *** this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative *** review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative *** role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's ***,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific *** studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological *** will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

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Interactivity software tools for teaching in ophthalmology

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Annals of Eye Science 2024年第1期9卷 10-23页

作者： Jesús Barrio-Barrio Department of Ophthalmology Navarra University Clinic HospitalNavarra Institute for Health ResearchIdiSNAPamplonaSpain

The use of interactive audience software,such as audience response systems(ARS),in medical education has become increasingly popular in recent *** technology allows instructors to engage students in real time,encouraging active participation and promoting effective *** benefits of interactive audience software in medical education include increased student engagement,promotion of active learning,and enhanced learning ***,there are also several challenges to its implementation,including technical difficulties,careful planning and preparation,over-reliance on technology,and ethical concerns related to privacy and data *** cost of implementing interactive audience software may also be a barrier for some *** paper specifically reviews six interactive software platforms,including Socrative,Quizizz,Pear Deck,Slido,Wooclap and *** platforms allow for real-time assessment of student understanding,feedback,and *** also enable instructors to adjust their teaching strategies based on student responses and ***,interactive audience software has shown great potential to enhance learning and engagement in medical *** is important for instructors to carefully consider the benefits and challenges of its *** the cost of implementing interactive audience software may be a barrier for some institutions,there are free and low-cost options available.

关键词： Interactive audience software mobile software audience response systems(ARS) medical education

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Olfactory proteotyping: towards the enlightenment of the neurodegeneration

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Neural Regeneration Research 2019年第6期14卷 979-981页

作者： Joaquín Fernández-Irigoyen Enrique Santamaría Proteored-Institute of Health Carlos Ⅲ (ISCⅢ) Clinical Neuroproteomics UnitNavarrabiomedNavarra Health DepartmentPublic University of NavarraNavarra Institute for Health Research (IdiSNA)

Although phylogenetically ancient,the olfactory system has received less attention than other sensorial ***,olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases(NDs)(Doty,2012;Attems et al.,2014),which may vary from severe smell loss(e.g.,Alzheimer’s and Parkinson’s diseases)to relatively moderate loss(e.g.,progressive supranuclear palsy)(Doty,2017).Recently,a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb(OB)during the neurodegenerative process(Attems et al.,2014;Rey et al.,2018).For instance,the double-transgenic APP/PS1 mouse model of Alzheimer’s disease(AD)develops early proteomic disturbances accompanied by a specific modulation of the focal adhesion kinase(FAK)and mitogen-activated protein kinase(MAPK)dynamics at the level of the OB,demonstrating that olfactory molecular alterations occur prior toβ-amyloid plaque appearance and memory impairments in APP/PS1 transgenic mice(Lachen-Montes et al.,2016).

关键词： Although phylogenetically olfactory system considered

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The intracellular signalosome of PD-L1 in cancer cells

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Signal Transduction and Targeted Therapy 2018年第1期3卷 72-80页

作者： David Escors Maria Gato-Canas Miren Zuazo Hugo Arasanz María Jesus García-Granda Ruth Vera Grazyna Kochan Navarrabiomed Complejo Hospitalario de NavarraIdISNAIrunlarrea 331008 PamplonaNavarraSpain Rayne Institute Division of Infection and ImmunityUniversity College London5 University StreetWC1E 6JF LondonUK Oncology Department Complejo Hospitalario de NavarraIdISNAIrunlarrea 331008 PamplonaNavarraSpain

Programmed cell death-1 ligand-1(PD-L1)overexpression in cancer cells accelerates tumor ***-L1 possesses two main pro-oncogenic ***,PD-L1 is a strong immunosuppressive molecule that inactivates tumor-specific T cells by binding to the inhibitory receptor ***,PD-L1 function relies on the delivery of intrinsic intracellular signals that enhance cancer cell survival,regulate stress responses and confer resistance toward pro-apoptotic stimuli,such as ***,we review the current knowledge on intracellular signal transduction pathways regulated by PD-L1,describe its associated signalosome and discuss potential combinations of targeted therapies against the signalosome with PD-L1/PD-1 blockade therapies.

关键词： cancer targeted signal

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Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

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Journal of Sport and Health Science 2023年第2期12卷 147-157页

作者： Antonio García-Hermoso Robinson Ramírez-Vélez Javier Díez Arantxa González Mikel Izquierdo Navarrabiomed Public University of Navarra(UPNA)Health Research Institute of Navarra(IdiSNA)University Hospital of NavarraPamplona 310008Spain CIBER of Frailty and Healthy Aging(CIBERFES) Carlos Ⅲ Institute of HealthMadrid 28029Spain Institute for Health Research of Navarra(idisna) Pamplona 31008Spain Program of Cardiovascular Diseases Center for Applied Medical ResearchUniversity of NavarraPamplona 31008Spain Centre for Biomedical Research in Cardiovascular Disease Network Carlos Ⅲ Institute of HealthMadrid 28029Spain Departments of Nephrology and Cardiology University of Navarra ClinicPamplona 31008Spain

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise ***:A systematic search for relevant studies was performed in 3 *** controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and ***:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to *** exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per ***:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

关键词： Adipokines Exercise training Hepatokines Myokines

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Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis:a systematic review

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World Journal of Pediatrics 2022年第2期18卷 91-99页

作者： Javier Arredondo Montero Carlos Bardaji Pascual Monica Bronte Anaut Natalia Lopez-Andres Giuseppa Antona Nerea Martin-Calvo Pediatric Surgery Department Complejo Hospitalario de NavarraCalle Irunlarrea 331008 PamplonaNavarraSpain Pathology Department Complejo Hospitalario de NavarraPamplonaSpain Cardiovascular Translational Research Navarrabiomed(Miguel Servet Foundation)Complejo Hospitalario de Navarra(CHN)Universidad Publica de Navarra(UPNA)IdiSNAPamplonaSpain Department of Preventive Medicine and Public Health Instituto de Investigacion Sanitaria de Navarra(IdiSNA).University of Navarra.PamplonaSpain CIBER Fisiopatologia de la Obesidad y Nutricion(CIBERobn) Health Institute CarlosⅢMadridSpain

Background Despite the radiological and analytical advances of the last decades,there is still a significant rate of diagnostic error in pediatric acute *** recent years,multiple biomarkers have emerged as potential diagnostic *** study aimed to examine the diagnostic performance of serum interleukin-6 in pediatric acute *** We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography(Medline,PubMed,Web of Science and SciELO).Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion *** quality of the selected article was rated using the QUADAS2 *** extraction was performed by two independent *** The research in the medical bibliography databases resulted in 68 *** removed 26 *** the remaining 42 articles,we excluded 33 following the inclusion and exclusion *** the final 9 studies included in this review,8 provided measured serum interleukin-6 values,and all of them reported significant differences between groups,but inconsistent results regarding sensitivity and *** The diagnostic performance of interleukine-6 alone for the diagnosis of acute appendicitis in children is *** sensitivity and specificity of interleukine-6 for the diagnosis of non-complicated acute appendicitis in the pediatric population are moderate but increased in complicated *** seems to be a direct relationship between serum level of interleukin-6 and the hours of evolution of abdominal pain in children with acute *** increasingly widespread use of non-operative management of acute appendicitis warrants further exploration of the classificatory potential of this marker between complicated and uncomplicated *** consider that this may be an avenue of research to explore in the future.

关键词： Acute appendicitis Children Interleukin-6 Pediatric Sensitivity Specificity Systematic review

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