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Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

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World Journal of Gastroenterology 2018年第48期24卷 5454-5461页

作者： Rafael I Jaén Patricia Prieto marta Casado paloma martín-s.nz Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Department of Biomedicine Instituto de Biomedicina de Valencia (CSIC) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares y Hepáticas y DigestivasISCⅢ Unidad Asociada IIBMULPGC Universidad de las Palmas de Gran Canaria (ULPGC)

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGs2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGs2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGs2 inhibitors, termed coxibs, have been generated and widely used. PTGs2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGs1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGs2 occurs at the transcription level. In addition to this, the stability of the mRnA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR nAs to proteins that control mR nA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGs2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

关键词： Prostaglandins Prostaglandin-endoperoxide synthase 2 Post-translational modifications Glycosylation Colorectal cancer Inflammation

Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-serrano Estefanía nú?ez María Fernández-Velasco paloma martín-s.nz sergio Alonso Jesús Vázquez sebastián Cerdán Miguel ángel Peinado Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación sanitaria del Hospital Universitario la Paz(IdiPaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUnD Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in *** To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic *** Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide n-glycosidase F(PnGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELIsA. 1 H high resolution magic angle spinning(HRMAs) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-Ms/Ms) using a QExactive HF orbitrap *** Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after Pn

关键词： Colon Carcinoma Cyclooxygenase Prostaglandin Proteomics High resolution magic angle spinning

Pyrenetetraone-based covalent organic framework as an effective electrocatalyst for oxygen reduction reaction

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nano Research 2022年第5期15卷 3907-3912页

作者： paloma Garcia-Arroyo Emiliano martinez-Perinan Jorge J.Cabrera-Trujillo Elena salagre Enrique G.Michel Jose I.martinez Encarnacion Lorenzo Jose L.segura Departamento de Quimica Organica I Facultad de CC.QuimicasUniversidad Complutense de Madrid28040 MadridSpain Departamento de Quimica Analitica y Analisis Instrumental Facultad de CienciasUniversidad Autónoma de Madrid28049 MadridSpain Departamento de Fisica de la Materia Condensada Universidad Autónoma de Madrid28049 MadridSpain Condensed Matter Physics Center(IFIMAC) Universidad Autónoma de Madrid28049 MadridSpain Departamento de nanoestructuras SuperficiesRecubrimientos y Astrofisica MolecularInstituto de Ciencia de Materiales de Madrid(ICMMCSIC)28049 MadridSpain Instituto Madrileno de Estudios Avanzados en nanociencia(IMDEA-nanociencia) 28049 MadridSpain Institute for Advanced Research in Chemical sciences(IAdChem) Universidad Autonoma de Madrid28049 MadridSpain

A novel porous and crystalline two-dimensional(2D)electrochemically active covalent organic framework(COF)based on ortho-quinone units has been prepared as an innovative approach towards the development of organic cathode materials with multiple redox sites as an efficient electrocatalyst for the oxygen reduction reaction(ORR).In contrast with most of the previously reported COFs as electrocatalysts for the ORR,the electrocatalytic application of this material towards ORR has been investigated without adding any metal or conductive supporting material and avoiding any additional carbonization ***,the electrochemical properties of the COF material have been compared with two analogue amorphous frameworks with similar chemical composition,which points out the important role of the enhanced crystallinity and porosity of the COF network in its superior performance as an electrocatalyst towards ORR.

关键词： electrocatalysis oxygen reduction reaction metal free pyrenetetraone covalent organic framework

Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-Rodríguez María Jesús Borque Leticia González-Moreno Yolanda Real-martínez Luisa García-Buey Ricardo Moreno-Otero paloma s.nz-Cameno Gastroenterology service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODs Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELIsA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).REsULTs Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P ng2 was significantly increased as CHC progressed to the end stage of liver disease(P nsequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P nterestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area under the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

Post-Hospital syndrome and Hyponatremia

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Health 2021年第8期13卷 846-856页

作者： José Bellod-Tonda Julio Blázquez-Encinar María Dolores Jover-Ríos Carmen seguí-Pérez Juan Méndez-Mora Francisco Caparrós-Hernández Álex Méndez-Jover Marc seguí-Pérez David Baláž Leticia Espinosa del Barrio Jesús Corbacho-Redondo Carles García-Cervera Juan Manuel núñez-Cruz Isidro Hernández-Isasi Javier Guzmán-martínez Angie Gómez-Uranga Pedro Esteve-Atiénzar Jorge Peris-García Veronica martínez-sempere Eliana Damonte-White Óscar Hernando Ruiz-Ariza Juan Carlos López-Corbalán Lourdes Lajara-Villar Andrea Riaño-Pérez paloma Chazarra-Pérez María Escamilla-Espínola Maria Luisa Asensio-Tomás Miguel Ángel Auladell-Alemany Laura serna-Torres Asunción Pérez-Fullana Amparo Gómez-siurana sergio Menargues-Irles José Miguel seguí-Ripoll Internal Medicine Department University Hospital of San Juan Alicante Spain Internal Medicine Department Torrevieja University Hospital Alicante Spain Internal Medicine Department Hospital La Vega Baja of Orihuela Alicante Spain CEU Cardinal Herrera University Veterinary Hospital Valencia Spain secondary school Marist Brothers High School Alicante Spain Department of Clinical Medicine Miguel Hernández University Elche Spain Primary Care Medicine Benilloba Spain sub-Delegation of the Government Alicante Spain Chemical Engineering Department University of Alicante Alicante Spain

Introduction: Post-hospital syndrome (PHs) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the mo... 详细信息

strong>Introduction:strong> Post-hospital syndrome (PHs) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the most frequent hydroelectrolytic disorder in hospitalized patients and may be related to the appearance of PHs. strong>Objective: strong>The objective is to estimate the prevalence of PHs that is assessed as the rate of readmissions in the first 30 days after discharge, in patients with hyponatremia. strong>Material and Methods:strong> It is a descriptive observational study of patients with hyponatremia who were discharged from 1 september 2010 to 2 February 2020 at the Internal Medicine service of the Hospital University of san Juan (Alicante, spain). strong>Results:strong> Of the 25 included patients, 5 (20%) were readmitted within a month of discharge, after a mean of 11.4 days (standard deviation [sD] 5.1). The overall mortality of the study was 20% (n = 5), with one case of death in the first 30 days post-hospitalization (4%). In 12 patients (48%) the origin of the hyponatremia was undetermined. The most frequently recorded etiology for the condition was pharmacological (n = 7, 28%), and there was pronounced variability in its clinical and laboratory study. The most widely used corrective measure was drug withdrawal, in 16 patients (64%). Water intake restriction was the most common treatment after discharge (5 patients, 20%), followed by urea (2 patients, 8%), while tolvaptan was not used. strong>Conclusion: strong>Hyponatremia may be the cause of PHs, which could increase the rate of early readmission. Hyponatremia is an underdiagnosed and undertreated entity, so it is necessary to apply an appropriate system to optimize its management and, in future studies, to assess its impact on PHs.

关键词： Hospitalization Hyponatremia Patient Readmission Inappropriate ADH syndrome

Role of double-balloon enteroscopy in malignant small bowel tumors

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World Journal of Gastrointestinal Endoscopy 2015年第6期7卷 652-658页

作者： Enrique Pérez-Cuadrado Robles Pilar Esteban Delgado paloma Bebia Conesa Blanca martínez Andrés Milivoj Franulic Guggiana Eduardo Alcaraz Mateos Mariana Fernández Caballero José Luis Rodrigo Agudo silvia Chacón martínez Rafael Latorre Federico soria Juan Manuel Herrerías Gutiérrez Enrique Pérez-Cuadrado martínez Department of Gastroenterology Morales Meseguer Hospital Department of Radiology Morales Meseguer Hospital Department of Pathology Morales Meseguer Hospital Department of Hematology and Oncology Morales Meseguer Hospital Department of Anatomy University of Murcia Centre Jesus Usón Hospital Universitario Virgen Macarena

AIM: To assess the double-balloon enteroscopy(DBE) role in malignant small bowel tumors(MsBT).METHODs: This is a retrospective descriptive study performed in a single center. All consecutive patients who underwent a DBE with final diagnosis of a malignant neoplasm from 2004 to 2014 in our referral center were included. Patient demographic and clinical pathological characteristics were recorded and reviewed. MsBT diagnosis was achieved either by DBE directed biopsy with multiple tissue sampling, endoscopic findings or histological analysis of surgical specimen. We have analyzed double-balloon enteroscopy impact in outcome and clinical course of these patients. REsULTs: Of 627 patients, 28(4.5%)(mean age = 60 ± 17.3 years) underwent 30 procedures(25 anterograde, 5 retrograde) and were diagnosed of a malignant tumor. Patients presented with obscure gastrointestinal bleeding(n = 19, 67.9%), occlusion syndrome(n = 7, 25%) and diarrhea(n = 1, 3.6%). They were diagnosed by DBE biopsy(n = 18, 64.3%), histological analysis of surgical specimen(n = 7, 25%) and unequivocal endoscopic findings(n = 2, 7.1%). Gastrointestinal stromal tumor(n = 8, 28.6%), adenocarcinoma(n = 7, 25%), lymphoma(n = 4, 14.3%), neuroendocrine tumor(n = 4, 14.3%), metastatic(n = 3, 10.7%) and Kaposi sarcoma(n = 1, 3.6%) were identified. DBE modified outcome in 7 cases(25%), delaying or avoiding emergency surgery(n = 3), modifying surgery approach(n = 2) and indicating emergency sB partial resection instead of elective approach(n = 2).COnCLUsIOn: DBE may be critical in the management of MsBT providing additional information that may be decisive in the clinical course of these patients.

关键词： Double balloon enteroscopy Malignantsmall bowel tumors Obscure gastrointestinal bleeding Gastrointestinal stromal tumor Occlusion syndrome

Absolute parameters of young stars:PU Pup

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Research in Astronomy and Astrophysics 2021年第10期21卷 151-163页

作者： Ahmet Erdem Derya surgit Timothy s.Banks Burcu Ozkardes Edwin Budding Canakkale Onsekiz mart University Astrophysics Research Center and Ulupinar ObservatoryTR-17100CanakkaleTurkey Department of Physics Faculty of Arts and SciencesCanakkale Onsekiz Mart UniversityTerzioglu KampusuTR-17100CanakkaleTurkey Department of space sciences and Technologies Faculty of Arts and SciencesCanakkale Onsekiz Mart UniversityTerzioglu KampusuTR-17100CanakkaleTurkey Data science Nielsen200 W JacksonChicagoIL 60606USA Physics&Astronomy Harper College1200 W Algonquin RdPalatineIL 60067USA Visiting astronomer Mt.John ObservatoryUniversity of CanterburyPrivate Bag 4800Christchurch 8140NZ Carter Observatory Wellington 6012New Zealand school of Chemical&Physical sciences Victoria University of WellingtonWellington 6012New Zealand Variable stars south RASNZPO Box 3181WellingtonNew Zealand

We present combined photometric and spectroscopic analyses of the southern binary star PU ***-resolution spectra of this system were taken at the University of Canterbury *** Observatory in the years 2008 and again in *** find the light contribution of the secondary component to be only 2%of the total light of the system in optical wavelengths,resulting in a single-lined spectroscopic *** TEss data revealed grazing eclipses within the light minima,though the tidal distortion,examined also from Hipparcos data,remains the predominating light curve *** model shows PU Pup to have the more massive primary relatively close to filling its Roche *** Pup is thus approaching the rare‘fast phase’of interactive(Case B)*** adopted absolute parameters are as follows:M_(1)=4.10(±0.20)M_(⊙),M_(2)=0.65(±0.05)M_(⊙),R_(1)=6.60(±0.30)R_(⊙),R_(2)=0.90(±0.10)R_(⊙);T_(1)=11500(±500)K,T_(2)=5000(±350)K;photometric distance=186(±20)pc,age=170(±20)*** less-massive secondary component is found to be significantly oversized and overluminous compared to standard main sequence *** discuss this discrepancy referring to heating from the reflection effect.

关键词： (stars:)binaries(including multiple):close stars:early-type stars:individual(PU Pup) Galaxy:stellar content