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miR-99a-5p modulates doxorubicin resistance via the COX-2/ABCG2 axis in triple-negative breast cancer: from the discovery to in vivo studies

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Cancer Communications 2022年第12期42卷 1412-1416页

作者： Iris Garrido-Cano Anna Adam-Artigues Ana Lameirinhas Juan F.Blandez Vicente Candela-noguera Federico Rojo Sandra Zazo Juan madoz-Gúrpide Ana Lluch Begoña Bermejo Felix Sancenón Juan Miguel Cejalvo ramón martínez-mañez Pilar Eroles Biomedical Research Institute InCLIVA Valencia 46010Spain Bioengineering Biomaterials and Nanomedicine Networking Biomedical Research Centre(CIBER-BBN)Madrid 28029Spain Interuniversity Research Institute for Molecular Recognition and Technological Development(IDM) Polytechnic University of ValenciaUniversity of ValenciaValencia 46010Spain Joint Unit CIPF-UPV of Mechanisms of Diseases and nanomedicine ValenciaPolytechnic University of ValenciaPrince Felipe Research CenterValencia 46012Spain Joint Research Unit in nanomedicine and Sensors Polytechnic University of ValenciaMedical Research Institute Hospital La FeValencia 46026Spain Biomedical Research networking Center in Oncology(CIBEROnC) Madrid 28029Spain Department of Pathology Fundación Jiménez Díaz University Hospital Health Research InstituteMadrid 28040Spain Department of Clinical Oncology University Clinical Hospital of ValenciaValencia 46010Spain Department of Medicine University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain

Dear Editor,Breast cancer(BC)is the most commonly diagnosed cancer and the fifth cause of cancer-related death worldwide[1].Despite the advances in BC targeted therapies,cytotoxic chemotherapy is still widely used[2].However,around 20%-30%of BC patients develop metastasis after treatment as a consequence of drug resistance[3].In this context,microRnAs have emerged as potential therapeutic targets to overcome therapy resistance[4].Therefore,we aimed to elucidate the molecular mechanisms underlying resistance to doxorubicin,one of the most effective chemotherapeutic agents used in BC.Methods are detailed in Supplementary materials.

关键词： doxorubicin ABCG2 chemotherapy

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-martínez mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Photosynthetic Gas Exchange and nitrogen Assimilation in Green Bean Plants Supplied with Two Sources of Silicon

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Phyton-International Journal of Experimental Botany 2024年第5期93卷 963-980页

作者： Julio C.Anchondo-Páez Esteban Sánchez Carlos A.ramírez-Estrada Alondra Salcido-martínez Erick H.Ochoa-Chaparro Department of Plant Physiology Centro de Investigación en Alimentación y DesarrolloCiudad Delicias33089México

Beans contain a wide range of vitamins,proteins,calcium,and zinc which make them an important food source for many countries.To meet the demand for bean production worldwide,large amounts of fertilizers and pesticides are used.However,the cost of production and environmental impact increases.To produce food sustainably,the use of beneficial nutrients such as silicon as a biostimulant has been proposed.However,information about the effect of different sources of silicon on the metabolism of bean plants is scarce.Bean plants cv.Strike were grown in pots for 60 days and the effect of foliar application of silicon nanoparticles and the silicon-based biostimulant Codasilat 4 concentrations(0,1,2,and 4 mM)on total biomass,yield,photosynthetic pigment concentration,photosynthetic activity,stomatal conductance,transpiration rate,chlorophyll fluorescence,and nitrogen assimilation were evaluated.The results obtained showed that the supply of silicon at a dose of 1 mM functioned as a biostimulant,favoring gas exchange and nitrogen assimilation within the plant,which stimulated growth and yield.The results of this research work allowed a better comprehension of the effects of silicon application through silicon nanoparticles and the biostimulant Codasilon the physiology of green bean plants.

关键词： nanoparticles silicon Phaseolus vulgaris L.

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Reuse of port industrial heritage in tourist cities:Shipyards as case studies

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Frontiers of Architectural Research 2024年第1期13卷 164-183页

作者： maría J.Andrade Eduardo Jiménez-Morales Rachel Rodríguez-ramos Pablo martínez-ramírez Department of Art and Architecture School of ArchitectureMalaga UniversityMalaga 29013Spain

The progressive deindustrialisation of many western cities since the 1980s has led to many industrial zones linked to port activities being abandoned or falling into disuse.Cities such as Barcelona,naples,Lisbon,Amsterdam,and Hamburg have port industrial complexes of high tangible and intangible heritage value that could totally or partially disappear,resulting in an irreparable loss of their scientific,architectural,social,technological,and historical values.With that in mind,Adaptive Reuse(AR)of the built heritage allows the industrial memory of the ports to be preserved by turning them into new functional centres within the existing urban structure.That occurs in the context of the contemporary challenges of those cities,such as touristification,the circular economy and climate change,while guaranteeing the life cycle of those buildings.This article analyses two case studies—the nederlandsche Scheepsbouw maatschappij(nDSM)and the Rotterdamsche Droogdok maatschappij(RDM)shipyards,both in the netherlands—in order to contribute to the knowledge of AR of Port Industrial Heritage.They are two examples of good practices in port industrial heritage interventions,where the factors behind their acclaim can be easily highlighted.A multi-scale methodology is therefore used and tailored to the case of port industrial heritage,based on analysing previous studies of the heritage in different spheres and on different scales.A relationship matrix tool is thus defined.It enables a comparative study to be conducted,using key variables and indicators,and considering qualitative and quantitative data.That provides extensive output information for each case study,which is summarised in the most favourable factors for the success of the AR of this port industrial heritage.

关键词： Industrial heritage Port-city Adaptive reuse Best practices Circular economy HUL Touristification

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Output feedback adaptive super twisting sliding mode control for quadrotor UAVs

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Control Theory and Technology 2024年第1期22卷 92-105页

作者： Oscar Salas-Peña Jesus DeLeón-Morales Susana V.Gutiérrez-martínez École Centrale de nantes-LS2n UMR 6004 CNRS44300NantesFrance Facultad de Ingeniería Mecánica y Eléctrica Universidad Autónoma de Nuevo León66451San Nicolás de Los GarzaMexico

In this paper, a sliding mode control with adaptive gain combined with a high-order sliding mode observer to solve the tracking problem for a quadrotor UAV is addressed, in presence of bounded external disturbances and parametric uncertainties. The high order sliding mode observer is designed for estimating the linear and angular speed in order to implement the proposed scheme. Furthermore, a Lyapunov function is introduced to design the controller with the adaptation law, whereas an analysis of finite time convergence towards to zero is provided, where sufficient conditions are obtained. Regarding previous works from literature, one important advantage of proposed strategy is that the gains of control are parameterized in terms of only one adaptive parameter, which reduces the control effort by avoiding gain overestimation. numerical simulations for tracking control of the quadrotor are given to show the performance of proposed adaptive control–observer scheme.

关键词： Adaptive super twisting controller High-order sliding modes observer UAV

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Chiral forces in longitudinally invariant dielectric photonic waveguides

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Photonics Research 2024年第3期12卷 431-443页

作者： JOSEP martÍnez-ROMEU IAGO DIez SEBASTIAn GOLAT FRAnCISCO J.RODRÍGUez-FORTUÑO ALEJAnDRO martÍnez nanophotonics Technology Center Universitat Politècnica de ValènciaValencia 46022Spain Department of Physics King’s College LondonLondon WC2R 2LSUK

We calculate numerically the optical chiral forces in rectangular cross-section dielectric waveguides for potential enantiomer separation.Our study considers force strength and time needed for separating chiral nanoparticles,mainly via quasi-TE guided modes at short wavelengths(405 nm)and the 90°-phase-shifted combination of quasi-TE and quasi-TM modes at longer wavelengths(1310 nm).Particle tracking simulations show successful enantiomer separation within two seconds.These results suggest the feasibility of enantiomeric separation of nanoparticles displaying sufficient chirality using simple silicon photonic integrated circuits,with wavelength selection based on the nanoparticle size.

关键词： dielectric forces quasi

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Austrian syndrome:Resurgence of an old and deadly triad

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Journal of Intensive Medicine 2024年第2期4卷 261-264页

作者： Kristian Rivera Dolors Viles marta Zielonka Carlos Izurieta Tania ramírez martínez Diego Menéndez Department of Cardiology University Hospital Arnau de VilanovaInstitut de Recerca Biomèdica de Lleida(IRBLleida)LleidaSpain

Introduction The Gram-positive bacterium,Streptococcus pneumoniae(S.pneumoniae),often colonizes the nasopharynx;however,it is one of the major microorganisms that cause pneumonia and meningitis.[[1],[2],[3]]It presents several virulence factors,such as surface proteins and enzymes,pneumolysin toxin,and a polysaccharide capsule,which is mainly responsible for the immune response;the capsule also facilitates classification of the bacterium into several serotypes.[1,2]In vulnerable individuals,the bacterium may lead to the development of invasive pneumococcal disease(IPD),which is defined as an infection of normally sterile locations.

关键词： capsule sterile infection

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5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

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neural Regeneration Research 2024年第2期19卷 302-308页

作者： Joaquín martí-Clúa Unidad de Citología e Histología.Departament de Biologia Cel·lular de Fisiologia i d’Immunologia.Facultad de Biociencias.Institut de Neurociències.Universidad Autónoma de Barcelona08193 BellaterraBarcelonaSpain

The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DnA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DnA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DnA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.

关键词： 5-bromo-2′-deoxyuridine adult neurogenesis human adult neurogenesis labeling pitfalls prenatal neurogenesis proliferation S-phase suturing S-phase toxicity

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： ramón Pérez-núñez maría Fernanda González Ana maría Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Are we ready to use new endoscopic scores for ulcerative colitis?

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World Journal of Gastroenterology 2024年第10期30卷 1466-1469页

作者： Rodrigo Quera Paulina núñez F Universidad de los Andes Inflammatory Bowel Disease ProgramClinica Universidad de los AndesDigestive Disease CenterSantiago 7600976RMChile Digestive Disease Center Inflammatory Bowel Disease ProgramClínica Universidad de los AndesSantiago 7620157Chile Department of Gastroenterology Universidad de Chile-Hospital San Juan de DiosSantiago 770123Chile

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

关键词： Ulcerative colitis Sigmoidoscopy Colonoscopy Score index

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