Sensitivity of polyamine metabolism to glucose deprivation is increased in neuroblastoma cells with N-myc amplification

Ornithine-derived polyamines are essential for cell proliferation, and their levels are elevated in many human tumors. Neuroblastoma, the most frequent extra-cranial solid tumor in children, harbors amplification of n-myc oncogene (which enhances polyamine metabolism) in 25% of the cases. In the present communication, the relevance of n-myc amplification in several metabolic features of human neuroblastoma cell lines is studied. A previously unknown linkage between glycolysis impairment and polyamine reduction, related to n-myc amplification, is unveiled. Results show that glycolysis inhibition is able to trigger signaling events leading to the reduction of N-Myc protein levels and subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. Metabolism-targeted therapies are emerging as new approaches for cancer treatment. New anti-tumor strategies could take advantage of the direct relationship between glucose deprivation and PA metabolism impairment leading to cell death described in the present work, and its apparent dependence on n-myc amplification in the case of neuroblastoma. Combined therapies targeting glucose metabolism and polyamine synthesis could be effective in the treatment of n-myc amplified tumors.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been funded by Grants SAF2011-26518 (Ministerio de Economía y Competitividad, Spain), Excellence Projects CTS-1507 and CVI-06585 (Junta de Andalucía, Spain) and BIO-267 (fondos PAIDI, Junta de Andalucía, Spain). MVRP was the recipient of a FPU long-term fellowship (Ministerio de Educación, Cultura y Deporte, Spain) and a “III Plan Propio de Investigación” short-term fellowship (University of Málaga). CIBERER is an initiative of Instituto de Salud Carlos III. This communication has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"

Novel Fluorescent Labeled Octasilsesquioxanes Nanohybrids as Potential Materials for Latent Fingerprinting Detection

The recent demand for fluorescent labeled materials (FLMs) in forensic security concepts such as latent fingerprints (LFs) that encodes information for anti-counterfeiting and encryption of confidential data makes necessary the development of building new and innovative materials. Here, novel FLMs based on Polyhedral Oligomeric Silsesquioxanes (POSS) functionalized with fluorophores via “click” reactions have been successfully synthesized and fully characterized. A comprehensive study of their photophysical properties has displayed large Stokes’s shift together with good photostability in all cases, fulfilling the fundamental requisites for any legible LF detection on various surfaces. The excellent performance of the hetero-bifunctional FLM in the visualization of LF is emphasized by their legibility, selectivity, sensitivity and temporal photostability. In this study, development mechanisms have been proposed and the overall concept constitute a novel approach for vis-à-vis forensic investigations to trace an individual’s identity.Alexander von Humboldt FoundationGeneralitat ValencianaUniversität RegensburgUniversidad de La LagunaMinisterio de Ciencia, Innovación y Universidade

Sap flow response to olive water stress: a comparative study with trunk diameter variations and leaf turgor pressure

11 pages, 3 figures, 19 references.-- VIII International Symposium on Sap Flow, celebrado del 8-12 de mayo 2011, en Volterra, Italia.The aim of this work was to evaluate the potential of used sap flow (SF), trunk diameter variation (TDV) and leaf turgor (LT) sensors for assessing water stress in a `Arbequina¿ hedgerow olive orchard with 1667 trees ha-1. Measurements were made in control trees irrigated to replace 100% of the crop water needs, and in trees under two regulated deficit irrigation strategies, 60RDI and 30RDI, in which irrigation replaced ca. 60% and 30% of the control, respectively. From the SF and TDV measurements we calculated the daily difference, both for tree water consumption (DEp) and maximum trunk diameter (DMXTD), between RDI trees and control trees. With the LT sensors we recorded the leaf patch output pressure (Pp), which is related to the leaf turgor pressure. Both DEp and DMXTD responded quickly and markedly to changes in water stress. The seasonal dynamics of both indices agreed with that of the stem water potential. A decrease in the reliability of DEp was recorded on days of highly variable atmospheric demand. The LT sensors also showed to be highly sensitive to changes on water stress. Any of the three methods have a potential as indicators for precise irrigation in hedgerow olive orchards with high plant density and low soil water-holding capacity.This experiment was funded by the Spanish Ministry of Science and Innovation, research project AGL2009-11310/AGR.Peer Reviewe

Patterns of Change in Dietary Habits and Physical Activity during Lockdown in Spain Due to the COVID-19 Pandemic

Background: Lockdown due to COVID-19 influenced food habits and lifestyles with potential negative health impact. This study aims to identify patterns of change in eating habits and physical activity during COVID-19 lockdown in Spain and to identify associations with sociodemographic factors and usual habits. Methods: This cross-sectional study included 1155 adults recruited online to answer a 10-section questionnaire. The protocol assessed usual diet by means of a semi-quantitative food frequency questionnaire, usual physical activity (PA) and supplement use, dietary changes, sedentary time, PA, exposure to sunlight, sleep quality, and smoking during confinement. Patterns of dietary change were identified by factor analysis. Factor scores were included in cluster analysis together with change in PA. Results: Six patterns of dietary change were identified that together with PA changes during lockdown defined three clusters of lifestyle change: a cluster less active, a more active cluster, and a third cluster as active as usual. People who were usually less active were more likely to be classified in the cluster that increased physical activity in confinement. Scores of the Healthy Mediterranean-Style dietary pattern were higher in this group. Conclusions: Different patterns of change in lifestyles in confinement suggest the need to tailor support and advice to different population groups.This research received no external funding. J.A.T. was funded by Instituto de Salud Carlos III through the Fondo de Investigacion para la Salud (CIBEROBN CB12/03/30038) which was co-funded by the European Regional Development Fund

Symbolic Recurrence Analysis of RR Interval to Detect Atrial Fibrillation

Atrial fibrillation (AF) is a sustained cardiac arrhythmia associated with stroke, heart failure, and related health conditions. Though easily diagnosed upon presentation in a clinical setting, the transient and/or intermittent emergence of AF episodes present diagnostic and clinical monitoring challenges that would ideally be met with automated ambulatory monitoring and detection. Current approaches to address these needs, commonly available both in smartphone applications and dedicated technologies, combine electrocardiogram (ECG) sensors with predictive algorithms to detect AF. These methods typically require extensive preprocessing, preliminary signal analysis, and the integration of a wide and complex array of features for the detection of AF events, and are consequently vulnerable to over-fitting. In this paper, we introduce the application of symbolic recurrence quantification analysis (SRQA) for the study of ECG signals and detection of AF events, which requires minimal pre-processing and allows the construction of highly accurate predictive algorithms from relatively few features. In addition, this approach is robust against commonly-encountered signal processing challenges that are expected in ambulatory monitoring contexts, including noisy and non-stationary data. We demonstrate the application of this method to yield a highly accurate predictive algorithm, which at optimal threshold values is 97.9% sensitive, 97.6% specific, and 97.7% accurate in classifying AF signals. To confirm the robust generalizability of this approach, we further evaluated its performance in the implementation of a 10-fold cross-validation paradigm, yielding 97.4% accuracy. In sum, these findings emphasize the robust utility of SRQA for the analysis of ECG signals and detection of AF. To the best of our knowledge, the proposed model is the first to incorporate symbolic analysis for AF beat detection.This research was funded by projects AIM, ref. TEC2016-76465-C2-1-R (AEI/FEDER, UE), e-DIVITA, ref.20509/PDC/18 (Proof of Concept, 2018) and it is the result of the activity performed under the program Groups of Excellence of the Region of Murcia (Spain), the Fundación Séneca, Science and Technology Agency of the region of Murcia project under grant 19884/GERM/15 and ATENTO, ref. 20889/PI/18. All remaining errors are our responsibility

Dietary and Lifestyle Patterns in the Spanish Pediatric Population (One to <10 Years Old): Design, Protocol, and Methodology of the EsNuPI Study

The interest in a healthy diet and lifestyle during the early stages of life increased, pointing out its role in the development of noncommunicable chronic diseases throughout adult life. Dietary habits and dietary patterns begin to be established in early childhood and persist during adulthood. Therefore, the EsNuPI (“Nutritional Study in Spanish Pediatric Population”) study aims to depict the dietary patterns, physical activity, and sedentary behaviors in Spanish children aged from one to <10 years old. This prospective, cross-sectional, observational study recruited a total of 1514 children from Spanish cities with >50,000 inhabitants, stratified by Nielsen areas. Participants were involved in one face-to-face survey, followed by a telephone survey after at least one week. Information about dietary intake and habits was obtained using a quantitative food frequency questionnaire and two 24-h dietary recalls. Physical activity and sedentary behaviors were registered using a specific questionnaire based on a seven-day record. Data were processed and stratified by categorical variables to be statistically analyzed in order to meet the study objectives. This study is the first of its kind in a Spanish reference population of this age range and the first to evaluate whether the consumption of adapted milk formulas and dairy products is associated with healthier dietary patterns and better diet quality and lifestyles in this group.This research was funded by Instituto Puleva de Nutrición (IPN)

Poesía y cuidados: una herramienta para las emociones

El objetivo de este trabajo es desarrollar una herramienta de reflexión y sentimientos que contribuyan a la gestión emocional de los alumnos de enfermería en sus prácticas clínicas. Se ha empleado un grupo de poemas derivados de experiencias clínicas como base para la identificación y análisis de emociones y sentimientos. Se utilizó la taxonomía de Heller (1989) para facilitar su análisis. Los principales resultados afirman el gran reto que tenemos los docentes en dotar a los futuros enfermeros de la capacidad cognitiva y las destrezas emocionales necesarias para gestionar el aluvión de sentimientos complejos e intensos que emergen durante la aplicación del proceso de enfermería con el fin de prepararlos para el trabajo emocional inherente a su trabajo y disminuir el riesgo de “burnout”. Con lo que podemos concluir que los poemas inspirados en experiencias clínicas constituyen una herramienta pertinente para facilitar el trabajo emocional y de sentimientos generados durante las prácticas clínicas

Investigation of metabolite-protein interactions by transient absorption spectroscopy and in silico methods

[EN] Transient absorption spectroscopy in combination with in silico methods has been employed to study the interactions between human serum albumin (HSA) and the anti-psychotic agent chlorpromazine (CPZ) as well as its two demethylated metabolites (MCPZ and DCPZ). Thus, solutions containing CPZ, MCPZ or DCPZ and HSA (molar ligand:protein ratios between 1:0 and 1:3) were submitted to laser flash photolysis and the Delta A(max) value at lambda = 470 nm, corresponding to the triplet excited state, was monitored. In all cases, the protein-bound ligand exhibited higher Delta Amax values measured after the laser pulse and were also considerably longer-lived than the non-complexed forms. This is in agreement with an enhanced hydrophilicity of the metabolites, due to the replacement of methyl groups with H that led to a lower extent of protein binding. For the three compounds, laser flash photolysis displacement experiments using warfarin or ibuprofen indicated Sudlow site I as the main binding site. Docking and molecular dynamics simulation studies revealed that the binding mode of the two demethylated ligands with HSA would be remarkable different from CPZ, specially for DCPZ, which appears to come from the different ability of their terminal ammonium groups to stablish hydrogen bonding interactions with the negatively charged residues within the protein pocket (Glu153, Glu292) as well as to allocate the methyl groups in an apolar environment. DCPZ would be rotated 180 degrees in relation to CPZ locating the aromatic ring away from the Sudlow site I of HSA. (C) 2019 Elsevier B.V. All rights reserved.Financial support from Ministerio de Economia, Industria y Competitividad (CTQ2016-78875-P, SAF2016-75638-R, BES-2011-043706), Generalitat Valenciana (Prometeo 2017/075), Xunta de Galicia [Centro Singular de Investigacion de Galicia accreditation 2016-2019 (ED431G/09, ED431B 2018/04) and post-doctoral fellowship to E. L.] and European Union (European Regional Development Fund-ERDF) is gratefully acknowledged. I. A. holds a "Miguel Servet" contract (CP1116/00052) funded by the Carlos III Health Institute. We are grateful to the Centro de Supercomputacion de Galicia (CESGA) for computational facilities.Limones Herrero, D.; Palumbo, F.; Vendrell Criado, V.; Andreu Ros, MI.; Lence, E.; González-Bello, C.; Miranda Alonso, MÁ.... (2020). Investigation of metabolite-protein interactions by transient absorption spectroscopy and in silico methods. Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy. 226:1-8. https://doi.org/10.1016/j.saa.2019.117652S18226Yang, G. X., Li, X., & Snyder, M. (2012). Investigating metabolite–protein interactions: An overview of available techniques. Methods, 57(4), 459-466. doi:10.1016/j.ymeth.2012.06.013S. Hage, D., Anguizola, J., Barnaby, O., Jackson, A., J. Yoo, M., Papastavros, E., … Tong, Z. (2011). Characterization of Drug Interactions with Serum Proteins by Using High-Performance Affinity Chromatography. Current Drug Metabolism, 12(4), 313-328. doi:10.2174/138920011795202938Matsuda, R., Bi, C., Anguizola, J., Sobansky, M., Rodriguez, E., Vargas Badilla, J., … Hage, D. S. (2014). Studies of metabolite–protein interactions: A review. Journal of Chromatography B, 966, 48-58. doi:10.1016/j.jchromb.2013.11.043López-Muñoz, F., Alamo, C., cuenca, E., Shen, W., Clervoy, P., & Rubio, G. (2005). History of the Discovery and Clinical Introduction of Chlorpromazine. Annals of Clinical Psychiatry, 17(3), 113-135. doi:10.1080/10401230591002002Beckett, A. H., Beaven, M. A., & Robinson, A. E. (1963). Metabolism of chlorpromazine in humans. Biochemical Pharmacology, 12(8), 779-794. doi:10.1016/0006-2952(63)90108-4Chetty, M., Moodley, S. V., & Miller, R. (1994). Important Metabolites to Measure in Pharmacodynamic Studies of Chlorpromazine. Therapeutic Drug Monitoring, 16(1), 30-36. doi:10.1097/00007691-199402000-00004Hubbard, J. W., Midha, K. K., Hawes, E. M., McKAY, G., Marder, S. R., Aravagiri, M., & Korchinski, E. D. (1993). Metabolism of Phenothiazine and Butyrophenone Antipsychotic Drugs. British Journal of Psychiatry, 163(S22), 19-24. doi:10.1192/s0007125000292556García, C., Oyola, R., Piñero, L. E., Arce, R., Silva, J., & Sánchez, V. (2005). Substitution and Solvent Effects on the Photophysical Properties of Several Series of 10-Alkylated Phenothiazine Derivatives. The Journal of Physical Chemistry A, 109(15), 3360-3371. doi:10.1021/jp044530jNavaratnam, S., Parsons, B. J., Phillips, G. O., & Davies, A. K. (1978). Laser flash photolysis study of the photoionisation of chlorpromazine and promazine in solution. Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 74(0), 1811. doi:10.1039/f19787401811Palumbo, F., Garcia-Lainez, G., Limones-Herrero, D., Coloma, M. D., Escobar, J., Jiménez, M. C., … Andreu, I. (2016). Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites. Toxicology and Applied Pharmacology, 313, 131-137. doi:10.1016/j.taap.2016.10.024Garcia, C., Smith, G. A., McGimpsey, W. G., Kochevar, I. E., & Redmond, R. W. (1995). Mechanism and Solvent Dependence for Photoionization of Promazine and Chlorpromazine. Journal of the American Chemical Society, 117(44), 10871-10878. doi:10.1021/ja00149a010Nath, S., & Sapre, A. V. (2001). Photoinduced electron transfer from chloropromazine and promethazine to chloroalkanes accompanied by cleavage of C–Cl bond. Chemical Physics Letters, 344(1-2), 138-146. doi:10.1016/s0009-2614(01)00685-6Joshi, R., Ghanty, T. K., & Mukherjee, T. (2008). Reactions and structural investigation of chlorpromazine radical cation. Journal of Molecular Structure, 888(1-3), 401-408. doi:10.1016/j.molstruc.2008.01.025He, X. M., & Carter, D. C. (1992). Atomic structure and chemistry of human serum albumin. Nature, 358(6383), 209-215. doi:10.1038/358209a0Sharples, D. (1974). The binding of chlorpromazine to human serum albumin. Journal of Pharmacy and Pharmacology, 26(8), 640-641. doi:10.1111/j.2042-7158.1974.tb10679.xVerbeeck, R. K., Cardinal, J.-A., Hill, A. G., & Midha, K. K. (1983). Binding of phenothiazine neuroleptics to plasma proteins. Biochemical Pharmacology, 32(17), 2565-2570. doi:10.1016/0006-2952(83)90019-9Silva, D., Cortez, C. M., & Louro, S. R. W. (2004). Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Brazilian Journal of Medical and Biological Research, 37(7), 963-968. doi:10.1590/s0100-879x2004000700004Lázaro, E., Lowe, P. J., Briand, X., & Faller, B. (2008). New Approach To Measure Protein Binding Based on a Parallel Artificial Membrane Assay and Human Serum Albumin. Journal of Medicinal Chemistry, 51(7), 2009-2017. doi:10.1021/jm7012826Kaddurah-Daouk, R., Kristal, B. S., & Weinshilboum, R. M. (2008). Metabolomics: A Global Biochemical Approach to Drug Response and Disease. Annual Review of Pharmacology and Toxicology, 48(1), 653-683. doi:10.1146/annurev.pharmtox.48.113006.094715Korkuć, P., & Walther, D. (2015). Physicochemical characteristics of structurally determined metabolite-protein and drug-protein binding events with respect to binding specificity. Frontiers in Molecular Biosciences, 2. doi:10.3389/fmolb.2015.00051Ohnmacht, C. M., Chen, S., Tong, Z., & Hage, D. S. (2006). Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin. Journal of Chromatography B, 836(1-2), 83-91. doi:10.1016/j.jchromb.2006.03.043Roelofs, K. G., Wang, J., Sintim, H. O., & Lee, V. T. (2011). Differential radial capillary action of ligand assay for high-throughput detection of protein-metabolite interactions. Proceedings of the National Academy of Sciences, 108(37), 15528-15533. doi:10.1073/pnas.1018949108Jimenez, M., & Miranda, M. (2015). Triplet Excited States as a Source of Relevant (Bio)Chemical Information. Current Topics in Medicinal Chemistry, 14(23), 2734-2742. doi:10.2174/1568026614666141216100907Jiménez, M. C., Miranda, M. A., & Vayá, I. (2005). Triplet Excited States as Chiral Reporters for the Binding of Drugs to Transport Proteins. Journal of the American Chemical Society, 127(29), 10134-10135. doi:10.1021/ja0514489Vayá, I., Bueno, C. J., Jiménez, M. C., & Miranda, M. A. (2006). Use of Triplet Excited States for the Study of Drug Binding to Human and Bovine Serum Albumins. ChemMedChem, 1(9), 1015-1020. doi:10.1002/cmdc.200600061Vayá, I., Jiménez, M. C., & Miranda, M. A. (2008). Transient Absorption Spectroscopy for Determining Multiple Site Occupancy in Drug−Protein Conjugates. A Comparison between Human and Bovine Serum Albumins Using Flurbiprofen Methyl Ester as a Probe. The Journal of Physical Chemistry B, 112(9), 2694-2699. doi:10.1021/jp076960qPérez-Ruiz, R., Bueno, C. J., Jiménez, M. C., & Miranda, M. A. (2010). In situ Transient Absorption Spectroscopy to Assess Competition between Serum Albumin and Alpha-1-Acid Glycoprotein for Drug Transport. The Journal of Physical Chemistry Letters, 1(5), 829-833. doi:10.1021/jz1000227Nuin, E., Jiménez, M. C., Sastre, G., Andreu, I., & Miranda, M. A. (2013). Drug–Drug Interactions within Protein Cavities Probed by Triplet–Triplet Energy Transfer. The Journal of Physical Chemistry Letters, 4(10), 1603-1607. doi:10.1021/jz400640sAlonso, R., Yamaji, M., Jiménez, M. C., & Miranda, M. A. (2010). Enhanced Photostability of the Anthracene Chromophore in Aqueous Medium upon Protein Encapsulation. The Journal of Physical Chemistry B, 114(34), 11363-11369. doi:10.1021/jp104900rAlonso, R., Jiménez, M. C., & Miranda, M. A. (2011). Stereodifferentiation in the Compartmentalized Photooxidation of a Protein-Bound Anthracene. Organic Letters, 13(15), 3860-3863. doi:10.1021/ol201209hKitamura, K., Fujitani, K., Takahashi, K., Tanaka, Y., Hirako, S., Kotani, C., … Takegami, S. (2000). Synthesis of [N-13CH3] drugs (chlorpromazine, triflupromazine and promazine). Journal of Labelled Compounds and Radiopharmaceuticals, 43(9), 865-872. doi:10.1002/1099-1344(200008)43:93.0.co;2-eGhuman, J., Zunszain, P. A., Petitpas, I., Bhattacharya, A. A., Otagiri, M., & Curry, S. (2005). Structural Basis of the Drug-binding Specificity of Human Serum Albumin. 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Factors related to the development of health-promoting community activities in Spanish primary healthcare: two case-control studies.

Objective Spanish primary healthcare teams have the responsibility of performing health-promoting community activities (CAs), although such activities are not widespread. Our aim was to identify the factors related to participation in those activities. Design Two case–control studies. setting Performed in primary care of ve Spanish regions. subjects In the rst study, cases were teams that performed health-promoting CAs and controls were those that did not. In the second study (on case teams from the rst study), cases were professionals who developed these activities and controls were those who did not. Main outcome measures Team, professional and community characteristics collected through questionnaires (team managers/professionals) and from secondary sources. results The rst study examined 203 teams (103 cases, 100 controls). Adjusted factors associated with performing CAs were percentage of nurses (OR 1.07, 95% CI 1.01 to 1.14), community socioeconomic status (higher vs lower OR 2.16, 95% CI 1.18 to 3.95) and performing undergraduate training (OR 0.44, 95% CI 0.21 to 0.93). In the second study, 597 professionals responded (254 cases, 343 controls). Adjusted factors were professional classi cation (physicians do fewer activities than nurses and social workers do more), training in CAs (OR 1.9, 95% CI 1.2 to 3.1), team support (OR 2.9, 95% CI 1.5 to 5.7), seniority (OR 1.06, 95% CI 1.03 to 1.09), nursing tutor (OR 2.0, 95% CI 1.1 to 3.5), motivation (OR 3.7, 95% CI 1.8 to 7.5), collaboration with non-governmental organisations (OR 1.9, 95% CI 1.2 to 3.1) and participation in neighbourhood activities (OR 3.1, 95% CI 1.9 to 5.1). Conclusions Professional personal characteristics, such as social sensitivity, profession, to feel team support or motivation, have in uence in performing health-promoting CAs. In contrast to the opinion expressed by many professionals, workload is not related to performance of health-promoting CAs

Extracellular vesicles from pristane-treated CD38-deficient mice express an antiinflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice

In CD38-deficient (Cd38-/-) mice intraperitoneal injection of pristane induces a lupus-like disease, which is milder than that induced in WT mice, showing significant differences in the inflammatory and autoimmune processes triggered by pristane. Extracellular vesicles (EV) are present in all body fluids. Shed by cells, their molecular make-up reflects that of their cell of origin and/or tissue pathological situation. The aim of this study was to analyze the protein composition, protein abundance, and functional clustering of EV released by peritoneal exudate cells (PECs) in the pristane experimental lupus model, to identify predictive or diagnostic biomarkers that might discriminate the autoimmune process in lupus from inflammatory reactions and/or normal physiological processes. In this study, thanks to an extensive proteomic analysis and powerful bioinformatics software, distinct EV subtypes were identified in the peritoneal exudates of pristane-treated mice: 1) small EV enriched in the tetraspanin CD63 and CD9, which are likely of exosomal origin; 2) small EV enriched in CD47 and CD9, which are also enriched in plasma-membrane, membrane-associated proteins, with an ectosomal origin; 3) small EV enriched in keratins, ECM proteins, complement/coagulation proteins, fibrin clot formation proteins, and endopetidase inhibitor proteins. This enrichment may have an inflammation-mediated mesothelial-tomesenchymal transition origin, representing a protein corona on the surface of peritoneal exudate EV; 4) HDL-enriched lipoprotein particles. Quantitative proteomic analysis allowed us to identify an anti-inflammatory, Annexin A1- enriched pro-resolving, neutrophil protein signature, which was more prominent in EV from pristane-treated Cd38-/- mice, and quantitative differences in the protein cargo of the ECM-enriched EV from Cd38-/- vs WT mice. These differences are likely to be related with the distinct inflammatory outcome shown by Cd38-/- vs WT mice in response to pristane treatment. Our results demonstrate the power of a hypothesis-free and data-driven approach to transform the heterogeneity of the peritoneal exudate EV from pristanetreated mice in valuable information about the relative proportion of different EV in a given sample and to identify potential protein markers specific for the different small EV subtypes, in particular those proteins defining EV involved in the resolution phase of chronic inflammation.Proyecto del plan estatal, Ministerio de Ciencia e Innovacion PT13/0001/011CSIC PT17/0019/0010 PID2020-119567RB-I0