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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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ECIEN-2020 study:the effect of COVID-19 on admissions for non-COVID-19 diseases

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World Journal of Pediatrics 2021年第1期17卷 85-91页

作者： beatriz Ramos-Lacuey Mercedes Herranz Aguirre Clara Calderón Gallego Andrea Ilundain López de Munain Eva Gembero Esarte Laura Moreno-Galarraga department of Pediatrics CHNComplejo Hospitalario de NavarraServicio Navarro de SaludC/Irunlarrea 331080 PamplonaSpain Pediatric Infectious Diseases department CHNComplejo Hospitalario de NavarraServicio Navarro de SaludPamplonaSpain Pediatric Hospitalization Department of PediatricsCHNComplejo Hospitalario de NavarraServicio Navarro de SaludPamplonaSpain IdiSNA Navarra Institute for Health ResearchPamplonaSpain department of Preventive Medicine and Public Health School of MedicineUniversity of NavarraPamplonaSpain Pediatric Pulmonology Department of PediatricsCHNComplejo Hospitalario de NavarraServicio Navarro de SaludPamplonaSpain

background The pandemic caused by severe acute respiratory coronavirus 2(SARS-CoV-2)has had great effects on health systems worldwide,not only in relation to coronavirus disease 2019(COVID-19)cases but also affecting patients with other *** ECIEN-2020 is an observational study conducted in a tertiary referral hospital in navarra,*** describes the effects of COVID-19 pandemic and the preventive measures adopted,in pediatric admissions for non-COVID-19 *** during March-June 2020(first wave of the COVID-19 pandemic in spain)are described and compared with the same quarter in 2019.A sub-analysis was performed delving into *** characteristics(age,sex,past medical history),disease characteristics(symptoms,duration of symptoms,previous consultation in Primary Care Health Center),and admission characteristics(place and average stay)were *** A 33% reduction in the number of pediatric hospital admissions was observed,decreasing from 529 hospitaliza-tions in 2019 to 353 in 2020(Pdepartment rose from 5.1%in 2019 to 10.9% in 2020,whereas the total number of consultations in the emergency department decreased by 68%.Conclusion The pandemic and the measures adopted due to SARS-CoV-2 have significantly decreased pediatric admissions for non-COVID-19 diseases,especially due to a reduction in the hospitalization for respiratory diseases.

关键词： Admission COVID-19 Hospitalization SARS-CoV-2

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Parental perception of child's weight,their attitudes towards child's dietary habits and the risk of obesity

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World Journal of Pediatrics 2022年第7期18卷 482-489页

作者： Lorena Garcia-blancol Arantxa berasaluce Andrea Romanos-Nanclares Miguel Angel Martinez-Gonzalez Laura Moreno-Galaraga Nerea Martin-Calvo San Juan Primary Care Health Center.Servicio Navarro de Salud-Osasunbidea PamplonaSpain IdisNA.Instituto de Investigacion Sanitaria de Navrra.pamplona Spain department of Preventive Medicine and Public Health School of Medicine.University of NavarraC/Irunlarrea l.31080 Pamplona.Spain biomedical Research Centre Network On Obesity and Nutrition(CIBERobn).Physiopathology of Obesity and NutritionInstituteof Health Carlos Ⅲ.Av.Monforte de Lemos.3-528029 MadridSpain department of Nutrition.Harvard T.H.Chan School of Public Health Boston.MA 02115.USA department of pediatrices.complejo hospialario de navarra b.pamplona.spain

background The association between parental perception of child's weight and their attitudes towards his/her dietary habits has not been reported *** study aimed to assess the association between parental underestimation of child's weight and parental attitudes towards child's dietary *** We conducted a cross-sectional analysis of SENDO cohort participants recruited between January 2015 and June *** information was collected through online questionnaires completed by *** calculated crude and multivariable-adjusted odds ratio(OR)and 95%confidence intervals(CI)for unhealthy attitudes towards child's dietary habits associated with parental underestimation of child's *** Sixteen percent of children in the SENDO project had parents who underestimated their *** who under-estimated their child's weight status were more likely to have unhealthy attitudes toward his/her dietary habits[OR 3.35;95%CI(1.71-6.53)].Conclusions Parental underestimation of child's weight was associated with unhealthy attitudes towards child's dietary *** and public health practitioners should pay attention to the parental perception of child's weight to identify parents who underestimate it as an at-risk group in which to inquire about lifestyle and dietary habits.

关键词： Childhood obesity Dietary atitudes Eating habits Overweight Weight perception

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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

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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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Auricular embryonal rhabdomyosarcoma

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World Journal of Pediatrics 2022年第5期18卷 358-360页

作者： Javier Arredondo Montero Monica bronte Anaut Sara Hernandez-Martin Juan Carlos Lopez-Gutierrez Pediatric Surgery department Complejo Hospitalario de NavarraCalle Irunlarrea 331008 PamplonaNavarraSpain Pathology department Complejo Hospitalario de NavarraPamplonaSpain Pediatric Surgery department Hospital Universitario La PazMadridSpain

A 13-month-old girl presented with a red-violaceous tumor of 13 mm in diameter on the inner side of the root of the right helix,with increased temperature and cystic consistency(Fig.1).No pulse was palpable in the *** ultrasonography was performed,showing a 1.6 cm rounded lesion with well-defined margins,hypoechogenic and homogeneous,compatible with *** treatment with oral propranolol was started without improve-ment.

关键词： sarcoma ultrasonography showing

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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(Pbesity-associated T2D(Pbese patients with T2D exhibited increased(Pb 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(Pby downregulating the mRNA levels of CCL2,IL1b,IL6,IL8,S100A8,S100A9,TLR4 and TNF as well as inhibiting(Pblocking NLRP3 attenuated(Pbrosis(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

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Everything that is not given is lost

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World Journal of Pediatrics 2021年第6期17卷 566-567页

作者： Javier Arredondo Montero Carlos bardajf Pascual Pediatric Surgery department Complejo Hospitalario de NavarraCalle Irunlarrea 331008 Pamplona.NavarraSpain

A small health center is located in Velingara,*** is approximately 7 o'clock in the *** the old,dusty room that constitutes the operating room,a soft beeping sound,like that of a kettle,begins to be heard between the rhythmic beats of the heart *** oxygen cylinder has started to ***,one of us approaches and applies Teflon,controlling the *** a while,the electrical current is cut ***,the anesthesiologist continues to hand ventilate the patient with her ambu,and we all turn on our *** is no more electric scalpel,but the activity does not stop.

关键词： problem cylinder approximate

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Long-term outcomes after stenting as a"bridge to surgery"for the management of acute obstruction secondary tocolorectal cancer

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World Journal of Gastrointestinal Oncology 2016年第1期8卷 105-112页

作者： javier suárez javier jimenez-pérez department of general surgery coloproctology unitcomplejo hospitalario de navarra31008 PamplonaSpain department of gastroenterology endoscopy unithospital de la ribera46600 AlziraSpain

Obstructive symptoms are present in 8% of cases at the time of initial diagnosis in cases of colorectal cancer. Emergency surgery has been classically considered the treatment of choice in these patients. However, in the majority of studies, emergency colorectal surgery is burdened with higher morbidity and mortality rates than elective surgery, and many patients require temporal colostomy which deteriorates their quality of life and becomes permanent in 10%-40% of cases. The aim of stenting by-pass to surgery is to transform emergency surgery into elective surgery in order to improve surgical results, obtain an accurate tumoral staging and detection of synchronous lesions, stabilization of comorbidities and performance of laparoscopic surgery. Immediate results were more favourable in patients who were stented concerning primary anastomosis, permanent stoma, wound infection and overall morbidity, having the higher surgical risk patients the greater benefit. However, some findings laid out the possible implication of stenting in long-term results of oncologic treatment. Perforation after stenting is related to tumoral recurrence. In studies with perforation rates above 8%, higher recurrences rates in young patients and lower disease free survival have been shown. On the other hand, after stenting the number of removed lymph nodes in the surgical specimen is larger, patients can receive adjuvant chemotherapy earlier and in a greater percentage and the number of patients who can be surgically treated with laparoscopic surgery is larger. Finally, there are no consistent studies able to demonstrate that one strategy is superior to the other in terms of oncologic benefits. At present, it would seem wise to assume a higher initial complication rate in young patients without relevant comorbidities and to accept the risk of local recurrence in old patients(> 70 years) or with high surgical risk(ASA Ⅲ/Ⅳ).

关键词： Self-expanding metallic stent Colorectalcancer Obstructive colorectal cancer Colorectal cancerchemotherapy Colorectal cancer surgery

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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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