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

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-Sanz 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

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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-Sanz 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

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Effect of Senescence Retardants on the Quality of Persian Lime Fruits

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Phyton-international Journal of Experimental Botany 2024年第8期93卷 1805-1818页

作者： rafael Ariza-Flores rafael Ambriz-Cervantes Pedro Cadena-iñiguez Luis A.Gálvez-Marroquín Miguel A.Cano-García national institute of Forestry Agriculture and Livestock Research(INIFAP)South Pacific Regional CenterSanto Domingo Barrio BajoVilla de EtlaOaxaca68200México national institute of Forestry Agriculture and Livestock Research(INIFAP)Zacatepec Research StationZacatepecMorelos62780México national institute of Forestry Agriculture and Livestock Research(INIFAP)Central Chiapas Research StationOcozocoautlaChis29140México national institute of Forestry Agriculture and Livestock Research(INIFAP)Oaxaca Central Valley Research StationSanto Domingo Barrio BajoVilla de EtlaOaxaca68200México

The objective of this study consisted of evaluating the effect of the application of chitosan(Q),1-methylcyclopropene(1-MCP)under two controlled temperatures on some physical,physiological,and chemical parameters contributing to the quality of Persian lime Citrus latifolia *** treatments were evaluated,resulting from the combination of four senescence retardant applications(Q,1-MCP,1-MCP+Q,and without application)on fruits stored at two temperatures(12/20℃.Epidermis color(luminosity,chromaticity,and hue),fruit appearance,respiration,weight loss,total juice content,total soluble solids,and titratable acidity were registered during the *** results indicate that the 1-MCP and Q combination favored fruit postharvest quality conditions such as reducing respiration rate;maintaining fruit good appearance,turgidity,and brighter fruit chromaticity;fruits treated with chitosan and stored at 12℃,favored total soluble *** the other hand,Variables such as weight loss,juice content,acidity,phenols,flavonoids,antioxidant activity,and hue values were favored by a 12℃ storing temperature regardless of the *** general,the use of modified atmospheres,senescence retardants,and refrigeration as postharvest methods,can increase Persian lime shelf life.

关键词： Citrus latifolia quality conservation organic alternatives

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Solution of the Center Problem for a Class of Polynomial Differential Systems

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1685-1696页

作者： Chang Jian Liu jaume Llibre rafael Ramírez Valentín Ramírez School of Mathematics(Zhuhai) Sun Yat-sen UniversityZhuhai519086P.R.China Departament de Matemàtiques Universitat Autònoma de Barcelona08193BellaterraBarcelonaCataloniaSpain Departament d’Enginyeria informàtica i Matemàtiques Universitat Rovira i VirgiliAvinguda dels Paiïsos Catalans 2643007TarragonaCataloniaSpain

Consider the polynomial differential system of degree m of the form x=-y(1+μ(a_(2)x-a_(1)y))+x(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),y=x(1+μ(a_(2)x-a_(1)y))+y(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),whereμandνare real numbers such that(μ^(2)+v^(2))(μ+v(m-2))(a_(1)^(2)+a_(2)^(2))≠m>2 andΩ_(m−1)(x,y)is a homogenous polynomial of degree m−1.A conjecture,stated in *** Equations 2019,suggests that whenν=1,this differential system has a weak center at the origin if and only if after a convenient linear change of variable(x,y)→(X,Y)the system is invariant under the transformation(X,Y,t)→(−X,Y,−t).For every degree m we prove the extension of this conjecture to any value ofνexcept for a finite set of values ofμ.

关键词： Center problem polynomial differential system

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Topical ocular administration of DPP-Ⅳ inhibitors:a new approach for treating diabetes-induced retinal neurodegeneration

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neural Regeneration Research 2024年第4期19卷 713-714页

作者： rafael Simó Cristina Hernández Diabetes and Metabolism Research Unit Vall d’Hebron Research Institute(VHIR) Department of Medicine Autonomous University of Barcelona Centro de investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CiBERDEM) Instituto de Salud CarlosⅢ(ICSⅢ)

Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable *** fact,the American Diabetes Association has defined DR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider DR as merely a microvascular *** this regard,the term diabetic retinal disease(DRD)has been proposed as a broader term comprising microangiopathy and ***,there are currently no treatments available that directly target the neurodegenerative changes of *** paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase iV(GLP-1/DPP-iV)inhibitors.

关键词： neurodegeneration ocular insight

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Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： rafael Calleja Manuel Durán María Dolores Ayllón Ruben Ciria javier Briceño Hepatobiliary Surgery and Liver Transplantation Unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of ***,we must be cautious with the *** this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the *** the future faces significant challenges,it also holds a great potential.

关键词： Machine learning Liver surgery Artificial intelligence Random forest Prediction model

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Children with obesity have poorer circadian health as assessed by a global circadian health score

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World Journal of Pediatrics 2024年第8期20卷 787-800页

作者： María Rodríguez-Martín nuria Martínez-Lozano Vicente Santaclara-Maneiro Antonio Gris-Peñas Diego Salmerón rafael Ríos Asta Tvarijonaviciute Marta Garaulet Department of Physiology Regional Campus of International Excellence University of Murcia 30100 Murcia CP Spain Biomedical Research institute of Murcia IMIB-Arrixaca-UMU University Clinical Hospital 30120 Murcia Spain Health Area of Lorca Lorca Murcia Spain Health and Social Sciences Department University of Murcia Murcia Spain Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain interdisciplinary Laboratory of Clinical Analysis (interlab-UMU) University of Murcia Murcia Spain Division of Sleep and Circadian Disorders Brigham and Women’s Hospital (BWH) and Division of Sleep Medicine Harvard Medical School Boston MA 02115 USA

Background Circadian health refers to individuals’well-being and balance in terms of their circadian *** is influenced by external *** adults,a close relationship between circadian-related alterations and obesity has been ***,studies in children are scarce,and circadian health and its association with obesity have not been evaluated *** aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score(GCS)in a school-age *** Four hundred and thirty-two children(7–12 years)were recruited in ***-invasive tools were used to calculate the GCS:(1)7-day rhythm of wrist temperature(T),activity(A),position(P),an integrative variable that combines T,A,and P(TAP);(2)cortisol;and(3)7-day food and sleep *** mass index,body fat percentage,waist circumference(WC),melatonin concentration,and cardiometabolic marker levels were *** Circadian health,as assessed by the GCS,differed among children with obesity,overweight,and normal weight,with poorer circadian health among children with *** with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health,respectively,than did those with normal weight or low *** percentage of rhythmicity,a marker of the robustness of the TAP rhythm,and the amplitude,both components of the GCS,decreased with increasing *** lifestyle behaviors were involved in the association between circadian health and obesity,particularly protein intake(P=0.024),physical activity level(P=0.076)and chronotype(P=0.029).Conclusions The GCS can capture the relationship between circadian health and obesity in school-age *** intake,physical activity level,and chronotype were involved in this *** intervention based on improving circadian health may help to prevent childhood obesity.

关键词： Children Chronodisruption Circadian Lifestyle Obesity

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Three-dimensional seismic face stability of shield tunnels inundrained clay

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Underground Space 2024年第2期15卷 26-43页

作者： Milad Davoodi Salvador Senent Amin Keshavarz rafael Jimenez Civil Engineering Department School of EngineeringPersian Gulf UniversityBushehr ***Iran Universidad Polite´cnica de Madrid C/Prof.Aranguren s/nMadrid 28040Spain

Tunnel face stability has received increasing research interest over the past few decades. However, computing time-efficient and safethree-dimensional solutions under seismic loading is still an unsolved problem, while case studies indicate that seismic loading can be onecritical destabilizing factor affecting tunnel stability. The primary objective of this work is to fill this gap in knowledge by providing compromisingand computationally efficient solutions, along with their respective lower and upper bounds, to compute face stability underseismic conditions. The analyses employ the finite element limit analysis method to evaluate the limit support pressure in undrained clay,considering horizontal pseudo-static seismic forces pointing outwards from the face. Moreover, the analyses employ both constant andlinearly increasing shear strengths with depth. The results are summarized as dimensionless stability charts and tables to facilitate theirinterpretation and future use for tunnel design. A new design equation has been developed to evaluate the stability of the tunnel faceconsidering the effect of seismic forces. Additionally, the effects of different parameters on the shape of the failure mechanism have beeninvestigated by analysing the distribution of shear dissipation.

关键词： Tunnel face stability Finite element limit analysis Undrained clay Seismic stability

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Olfactory receptors in neural regeneration in the central nervous system

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neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： rafael Franco Claudia Garrigós Toni Capó Joan Serrano-Marín rafael Rivas-Santisteban jaume Lillo Molecular neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain Ciberned network Center for Biomedical Research in neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Telomeric DnA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： Katrina n.Estep John W.Tobias rafael J.Fernandez Brinley M.Beveridge F.Brad Johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DnA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal *** engineer human iPSCs with an inducible TRF1-Foki fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-Foki DSBs activate an ATR-dependent DnA damage response,which leads to p53-independent cell cycle arrest in *** CRiSPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-Foki-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).in contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZSCAn4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-Foki *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DnA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DnA damage double-strand breaks

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