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Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

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Engineering 2021年第10期7卷 1393-1412页

作者： Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio Carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano Maria Gamella Rebeca Magnolia Torrente-Rodríguez miren alonso-navarro Vivian de los Ríos J.Ignacio Casal Gemma Domínguez Ana Guzman-Aranguez Alberto Peláez-García JoséManuel Pingarrón Susana Campuzano Rodrigo Barderas Chronic Disease Program(UFIEC) Carlos III Health InstituteMadrid E-28220Spain Department of Biochemistry and Molecular Biology Faculty of Optics and OptometryComplutense University of MadridMadrid E-28040Spain Gastroenterology Unit San Carlos Clinical HospitalMadrid E-28040Spain Surgical Pathology Department San Carlos Clinical HospitalMadrid E-28040Spain Translational Oncology Division OncoHealth InstituteJimenez Diaz Foundation University HospitalMadrid E-28040Spain Department of Biochemistry Faculty of MedicineAlberto Sols Institute of Biomedical ResearchCSIC-UAMMadrid E-28029Spain Department of Analytical Chemistry Faculty of Chemical SciencesComplutense University of MadridMadrid E-28040Spain Center for Biological Research Spanish National Research Council(CSIC)MadridE-28040Spain Molecular Pathology and Therapeutic Targets Group La Paz University Hospital(IdiPAZ)Madrid E-28046Spain

Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)de

关键词： Autoantibodies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response Point of care Biosensors

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Competitive effect, but not competitive response, varies along a climatic gradient depending on tree species identity

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Forest Ecosystems 2024年第2期11卷 142-151页

作者： Teresa Valor Lluís Coll David I.Forrester Hans Pretzsch miren del Río Kamil Bielak Bogdan Brzeziecki Franz Binder Torben Hilmers Zuzana Sitková Roberto Tognetti Aitor Ameztegui Department of Agricultural and Forest Sciences and Engineering(DCEFA) University of LleidaAv.Alcalde Rovira Roure 191E25198 LleidaSpain Joint Research Unit CTFC-AGROTECNIO-CERCA Ctra.Sant LlorençKm.225280SolsonaSpain Swiss Federal Institute of Forest Snow and Landscape Research WSLZürcherstrasse 1118903BirmensdorfSwitzerland CSIRO Land and Water GPO Box 1700CanberraACT2601Australia Chair of Forest Growth and Yield Science School of Life Sciences WeihenstephanTechnical University of MunichHans-Carl-Von-Carlowitz-Platz 285354FreisingGermany Forest Research Center INIA-CSICCtra.A Coruña Km 7.528040MadridSpain IuFOR Sustainable Forest Management Research InstituteUniversity of Valladolid&INIASpain Department of Silviculture Institute of Forest SciencesWarsaw University of Life SciencesNowoursynowska 159/3402776WarsawPoland Bavarian State Institute of Forestry(LWF) Hans-Carl-von-Carlowitz-Platz 1D-85354FreisingGermany National Forest Centre Forest Research InstituteT.G.Masaryka 2296001ZvolenSlovakia Faculty of Agricultural Environmental and Food SciencesFree University of Bozen-Bolzano Piazza Università1 I-39100Bolzano

Background: Understanding the role of species identity in interactions among individuals is crucial for assessing the productivity and stability of mixed forests over time. However, there is limited knowledge concerning the variation in competitive effect and response of different species along climatic gradients. In this study, we investigated the importance of climate, tree size, and competition on the growth of three tree species: spruce(Picea abies), fir(Abies alba), and beech(Fagus sylvatica), and examined their competitive response and effect along a climatic gradient.Methods: We selected 39 plots distributed across the European mountains with records of the position and growth of 5,759 individuals. For each target species, models relating tree growth to tree size, climate and competition were proposed. Competition was modelled using a neighbourhood competition index that considered the effects of inter-and intraspecific competition on target trees. Competitive responses and effects were related to climate.Likelihood methods and information theory were used to select the best model.Results: Our findings revealed that competition had a greater impact on target species growth than tree size or climate. Climate did influence the competitive effects of neighbouring species, but it did not affect the target species? response to competition. The strength of competitive effects varied along the gradient, contingent on the identity of the interacting species. When the target species exhibited an intermediate competitive effect relative to neighbouring species, both higher inter-than intraspecific competitive effects and competition reduction occurred along the gradient. Notably, species competitive effects were most pronounced when the target species' growth was at its peak and weakest when growing conditions were far from their maximum.Conclusions: Climate modulates the effects of competition from neighbouring trees on the target tree and not the susceptibility of the target tree to competition. The modelling appr

关键词： Competition coefficient Competition reduction Interspecific competition Intraspecific competition Mixing effects Mixed species forest Neighbourhood models Plant-plant interactions

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AASLD practice guidance on drug,herbal,and dietary supplement-induced liver injury:also useful for hepatobiliary surgeons

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 746-751页

作者： Jose María Pinazo-Bandera miren García-Cortés Raúl J.Andrade Service of Gastroenterology and Hepatology University Hospital Virgen de la VictoriaInstituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BionandUniversidad de MálagaMálagaSpain Centro de Investigación Biomédico en Red Enfermedades Hepáticas y Digestivas(CIBERehd) MadridSpain

Drug-induced liver injury(DILI)is a term used to describe an unexpected liver reaction to drugs,but also to herbal products and dietary supplements(HDS).In the current therapeutic armamentarium,only a small number of available drugs are still capable of causing liver damage in overdose.These include,in addition to paracetamol-the prototypical example of this group-niacin(now rarely used to treat hypercholesterolaemia),intravenous methotrexate and probably ketamine(an intravenous hypnotic used in critically ill patients for rapid sequence induction)(1).

关键词： Drug-induced liver injury(DILI) hepatotoxicity causality assessment Revised Electronic Causality Assessment Method(RECAM)

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Potential preventive disease-modifying pharmacological strategies to delay late onset Alzheimer’s disease

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Neural Regeneration Research 2019年第10期14卷 1721-1725页

作者： miren Ettcheto Oriol Busquets Antoni Camins Departament de Farmacologia Toxicologia i Química TerapèuticaFacultat de Farmàcia i Ciències de l’AlimentacióUniversitat de BarcelonaBarcelonaSpain Departament de Bioquímica i Biotecnologia Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain Institut de Neurociències Universitat de BarcelonaBarcelonaSpain Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED) MadridSpain

Alzheimer’s disease(AD)is a progressive neurodegenerative disease that was histopathologically characterized in the brain by the presence of extracellular senile plaques made of amyloid β peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated Tau protein.Over the years,AD has been classified in two subgroups:early onset or familial AD and late onset or sporadic AD.On the one hand,familial AD has been described to be the result of genetic mutations that cause,in some cases,for the overproduction of amyloid β.On the other,the cause of late onset or sporadic AD is still unclear even though several hypotheses have been proposed to explain the process of severe and progressive memory and cognitive loss.In the present review,some of the current hypotheses that try to explain the origin of late onset or sporadic AD have been summarized.Also,their potential implication in the development of new drugs for the presymptomatic treatment of late onset or sporadic AD has been considered.

关键词： Alzheimer's disease beta-secretase neuroinflammation Tau amyloid N-methyl-D-aspartate glutamate

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Implications of denitrification in the ecological status of an urban river using enzymatic activities in sediments as an indicator

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Journal of Environmental Sciences 2019年第1期31卷 255-268页

作者： Jessica Unda-Calvo miren Martínez-Santos Estilita Ruiz-Romera Juan Luis Lechuga-Crespo Department of Chemical and Environmental Engineering University of the Basque Country

A better understanding of the effects of a number of environmental factors on denitrification is vital for analyzing its role as nitrogen sink and providing deeper knowledge about the ecological status of a nitrate-rich ecosystem. Since few studies have addressed the occurrence and implications of denitrification in river sediments, and complexity of interactions among all these environmental factors makes comprehension of the process difficult, the potential of sediments from the Deba River to attenuate nitrate excess through denitrification was investigated. For this purpose, we adapted an in vitro method to measure activities of two enzymes contributing to the entire multiple-step nitrate reduction: Nitrate Reductase and Nitrite Reductase. The environmental features that influence both or single enzymatic activities were identified as oxygen availability,regulated directly by the moisture content or indirectly through the aerobic respiration,organic matter and nitrate content of sediments, and electrical conductivity and exchangeable sodium percentage of water. Additionally, our results showed that Nitrate Reductase catalyzes the principal limiting step of denitrification in sediments. Therefore,taking this enzymatic activity as an indicator, the southern part of the Deba River catchment presented low potential to denitrify but nitrate-limited sediments, whereas the middle and northern parts were characterized by high denitrification potential but nitraterich sediments. In general, this study on denitrifying enzymatic activities in sediments evaluates the suitability of the management of the effluents from wastewater treatment plants and municipal sewages to ensure a good ecological status of the Deba River.

关键词： Urban catchment Sediments Denitrification Enzymatic activity Ecological status

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Stand-level biomass models for predicting C stock for the main Spanish pine species

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Forest Ecosystems 2021年第2期8卷 387-402页

作者： Ana Aguirre miren del Río Ricardo Ruiz-Peinado Sonia Condés Department of Natural Systems and Resources School of Forest Engineering and Natural ResourcesUniversidad Politécnica de MadridMadridSpain INIA Forest Research CenterDepartment of Forest Dynamics and ManagementMadridSpain iuFOR Sustainable Forest Management Research InstituteUniversity of Valladolid and INIAValladolidSpain

Background:National and international institutions periodically demand information on forest indicators that are used for global reporting.Among other aspects,the carbon accumulated in the biomass of forest species must be reported.For this purpose,one of the main sources of data is the National Forest Inventory(NFI),which together with statistical empirical approaches and updating procedures can even allow annual estimates of the requested indicators.Methods:Stand level biomass models,relating the dry weight of the biomass with the stand volume were developed for the five main pine species in the Iberian Peninsula(Pinus sylvestris,Pinus pinea,Pinus halepensis,Pinus nigra and Pinus pinaster).The dependence of the model on aridity and/or mean tree size was explored,as well as the importance of including the stand form factor to correct model bias.Furthermore,the capability of the models to estimate forest carbon stocks,updated for a given year,was also analysed.Results:The strong relationship between stand dry weight biomass and stand volume was modulated by the mean tree size,although the effect varied among the five pine species.Site humidity,measured using the Martonne aridity index,increased the biomass for a given volume in the cases of Pinus sylvestris,Pinus halepensis and Pinus nigra.Models that consider both mean tree size and stand form factor were more accurate and less biased than those that do not.The models developed allow carbon stocks in the main Iberian Peninsula pine forests to be estimated at stand level with biases of less than 0.2 Mg·ha^(-1).Conclusions:The results of this study reveal the importance of considering variables related with environmental conditions and stand structure when developing stand dry weight biomass models.The described methodology together with the models developed provide a precise tool that can be used for quantifying biomass and carbon stored in the Spanish pine forests in specific years when no field data are available.

关键词： Martonne aridity index Dry weight biomass Carbon stock National Forest Inventory Peninsular pine forest Biomass expansion factor

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Hitting a moving target:inhibition of the nuclear export receptor XPO1/CRM1 as a therapeutic approach in cancer

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Cancer Drug Resistance 2018年第3期1卷 139-163页

作者： Maria Sendino miren Josu Omaetxebarria Jose Antonio Rodríguez Department of Genetics Physical Anthropology and Animal PhysiologyUniversity of the Basque Country(UPV/EHU)Leioa48940Spain. Department of Biochemistry and Molecular Biology University of the Basque Country(UPV/EHU)Leioa 48940Spain

Cellular homeostasis crucially relies on the correct nucleocytoplasmic distribution of a vast number of proteins and RNA molecules,which are shuttled in and out of the nucleus by specialized transport receptors.The nuclear export receptor XPO1,also called CRM1,mediates the translocation of hundreds of proteins and several classes of RNA to the cytoplasm,and thus regulates critical signaling pathways and cellular functions.The normal function of XPO1 appears to be often disrupted in malignant cells due to gene mutations or,most commonly,aberrant overexpression.Due to its important physiological roles and its frequent alteration in human tumors,XPO1 is a promising target for cancer therapy.XPO1 inhibitors have undergone extensive testing as therapeutic agents in preclinical models of cancer,with promising results.One of these inhibitors,Selinexor,is currently being evaluated in multiple clinical trials of different types of solid tumors and hematological malignancies.Here,we review several key aspects of XPO1 function,as well as the mechanisms that may lead to its alteration in cancer,and provide an update on the status of XPO1 inhibitors being developed as drugs for cancer therapy,including the definitive results of the first clinical trials with Selinexor that have been recently published.

关键词： XPO1 CRM1 nucleocytoplasmic transport Selinexor

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Heterogeneous Fenton Catalyst for the Efficient Removal of Azo Dyes in Water

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American Journal of Analytical Chemistry 2014年第8期5卷 490-499页

作者： miren Blanco Amaia Martinez Arrate Marcaide Estíbaliz Aranzabe Ana Aranzabe Chemistry of the Surface Unit IK4-TEKNIKER Eibar Gipuzkoa Spain

Heterogeneous Fenton/photo Fenton type processes using a Fe-exchanged zeolite of Y-type have been applied for the degradation of a model textile synthetic water based on Black B azodye. Research work has been directed to compare process efficiency and to establish their advantages over corresponding homogenous Fenton type processes. By optimizing the amount of reactants and process conditions, a complete decolorization of the effluent and a reduction greater than 80 per cent in the total organic carbon content is achieved. The influence of solar radiation on the heterogeneous process has been also studied. Homogeneous and heterogeneous Fenton processes yielded similar decolorization and mineralization, but the concentration of Fe ions in the bulk after the treatment was not significant in the latter case. Moreover, the catalyst support can be reused in successive cycles without significant loss of effectiveness. The use of solar radiation as a source of energy for operating the process accelerates the decomposition of azodye, making the process economical and environmentally sustainable.

关键词： Zeolite Heterogeneous Fenton Catalyst Wastewater Treatment Dyes

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管道压浆浆液外加剂类型及掺量影响研究

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地质与勘探 2023年第2期59卷 398-407页

作者：戎密仁薛志坤李向国刘喜坤李帅河北地质大学城市地质与工程学院河北石家庄050031 河北省地下人工环境智慧开发与管控技术创新中心河北石家庄050031 石家庄铁道大学土木工程学院河北石家庄050043 河北省建筑科学研究院有限公司河北石家庄050227

预应力管道压浆浆液外加剂种类及配合比的选取是管道压浆工艺的重要部分。为研究减水剂和矿物掺和料对管道压浆浆液的影响及作用机理,进而研制一种流动性、保水性及力学性能优异的管道压浆浆液,本研究采用单组分掺和试验的方法,对掺有... 详细信息

预应力管道压浆浆液外加剂种类及配合比的选取是管道压浆工艺的重要部分。为研究减水剂和矿物掺和料对管道压浆浆液的影响及作用机理,进而研制一种流动性、保水性及力学性能优异的管道压浆浆液,本研究采用单组分掺和试验的方法,对掺有减水剂与矿物掺合料两种不同压浆浆料进行流动性、压力泌水率、沉积密度比、抗压及抗折性能试验研究,并得到不同掺量外加剂对压浆浆液和易性与力学性能的影响和作用机理,以及合适的外加剂掺量配比。研究表明:聚羧酸减水剂30 min与60 min流动度最佳,且压力泌水率表现也较为良好,综合考虑聚羧酸减水剂为压浆浆液的优良减水剂;聚羧酸减水剂掺量在0.4%~0.5%时,浆液的流动性与保水性表现良好,随掺量的继续增加,流动性提升较小;微珠由于其物理性质以及化学性质,对提高压浆浆液和易性与力学性能的效果较为明显;微珠掺量在10%~15%时,压浆浆液的和易性达到临界状态。

关键词：压浆浆液单组分掺和试验外加剂和易性力学性能

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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 progression.PD-L1 possesses two main pro-oncogenic functions.First,PD-L1 is a strong immunosuppressive molecule that inactivates tumor-specific T cells by binding to the inhibitory receptor PD-1.Second,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 interferons.Here,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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