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Communication between bone marrow mesenchymal stem cells and multiple myeloma cells:Impact on disease progression

World Journal of Stem Cells 2023年第5期15卷 421-437页

作者： Daniel García-Sánchez Alberto González-González ana alfonso-fernández Mónica Del Dujo-Gutiérrez Flor M Pérez-Campo Department of Molecular Biology_IDIVAL Faculty of MedicineUniversity of CantabriaSantander 39011CantabriaSpain Servicio de Traumatología y Cirugía Ortopédica Hospital Universitario Marqués de ValdecillaInstituto de Investigación Sanitaria Valdecilla(IDIVAL)Facultad de MedicinaUniversidad de CantabriaSantander 39008CantabriaSpain

Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this *** data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological *** relation of MM cells with the resident BM-MSCs is a two-way *** modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence *** turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease *** interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other ***,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling ***,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.

关键词： Multiple myeloma Mesenchymal stem cells Bone marrow microenvironment Soluble factors Extra-cellular vesicles Cells adhesion molecules Tunnellingnanotubes

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Planetary Gear Profile Modification Design Based on Load Sharing Modelling

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Chinese Journal of Mechanical Engineering 2015年第4期28卷 810-820页

作者： IGLESIAS Miguel fernández DEL RINCóN alfonso DE-JUAN ana Magdalena GARCIA Pablo DIEZ Alberto VIADERO fernando Mechanical Engineering Research Group University of Cantabria

In order to satisfy the increasing demand on high performance planetary transmissions, an important line of research is focused on the understanding of some of the underlying phenomena involved in this mechanical system. Through the development of models capable of reproduce the system behavior, research in this area contributes to improve gear transmission insight, helping developing better maintenance practices and more efficient design processes. A planetary gear model used for the design of profile modifications ratio based on the levelling of the load sharing ratio is presented. The gear profile geometry definition, following a vectorial approach that mimics the real cutting process of gears, is thoroughly described. Teeth undercutting and hypotrochoid definition are implicitly considered, and a procedure for the incorporation of a rounding arc at the tooth tip in order to deal with corner contacts is described. A procedure for the modeling of profile deviations is presented, which can be used for the introduction of both manufacturing errors and designed profile modifications. An easy and flexible implementation of the profile deviation within the planetary model is accomplished based on the geometric overlapping. The contact force calculation and dynamic implementation used in the model are also introduced, and parameters from a real transmission for agricultural applications are presented for the application example. A set of reliefs is designed based on the levelling of the load sharing ratio for the example transmission, and finally some other important dynamic factors of the transmission are analyzed to assess the changes in the dynamic behavior with respect to the non-modified case. Thus, the main innovative aspect of the proposed planetary transmission model is the capacity of providing a simulated load sharing ratio which serves as design variable for the calculation of the tooth profile modifications.

关键词： transmission planetary gear load sharing relief profile modification

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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： ana Milena Silva Olaya fernanda Martins Almeida ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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A long-term record of land use change impacts on sediments in Oualidia lagoon,Morocco

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International Journal of Sediment Research 2014年第1期29卷 1-10页

作者： Mehdi MAanaN ana Carolina RUIZ-fernndez Mohamed MAanaN Paul FATTAL Bendahhou ZOURARAH Mohamed SAHABI Géolittomer UMR 6554 LETG Université de Nantes Marine Geosciences Laboratory URAC 45Earth Sciences departmentFaculty of Sciences Universidad Nacional Autónoma de México.Instituto de Ciencias del Mary Limnología

An integrated approach,involving land use patterns and heavy metal contents of the surficial and cored sediment,was proposed to detect the characteristic spatial and temporal scale of point and non-point source human disturbances on the Oualidia lagoon in *** and description of the temporal and spatial distributions of the main contamination sources of heavy metals are analyzed using statistics and GIS *** results show that surficial sediments are highly enriched in heavy metals compared to their preindustrial background ***-use types affected lagoon sediment pollution in different ways:1) agricultural areas had the highest potential for sediment contamination by heavy metals,particularly Pb,Cu and Hg,2) Ni and Cr are the main pollutants originating from urban sewage and 3) oyster farming and traditional land uses such as salt flats,pastures showed low levels of others *** enrichment factors(normalized by Al) obtained from the sediment cores indicated that the lagoon is(strongly/moderately) polluted by all metals which were attributed to agricultural activities and wastewater discharges from urbanized areas.

关键词： Land use change(LUC) Geographical information systems(GIS) Sediment pollution Risk assessment

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Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

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Cell Research 2005年第7期15卷 495-503页

作者： ana GARCíA-SACRISTáN■,María J. fernández-NESTOSA,Pablo HERNández,Jorge B.SCHVARTZMAN,Dora B. KRIMER Department of Cell and Developmental Biology Centro de Investigaciones Biológicas Consejo Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Instiute of Molecular Medicine 1649-028 Lisbon Medical School Lisbon Portugal Department of Cell and Developmental Biology Centro de Investigaciones Biológicas Consejo Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental Biology Centro de Investigaciones Biológicas Consejo Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental Biology Centro de Investigaciones Biológicas Consejo Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental Biology Centro de Investigaciones Biológicas Consejo Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain

Clk/STY is a LAMMER protein kinase capable to phosphorylate serine/arginine-rich (SR) proteins that modulate pre-mRNA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalyti-cally inactive protein. Here we showed that clk/STY, as well as other members of the family (e.g. clk2, clk3 and clk4),are up-regulated during HMBA-induced erythroleukemia cell differentiation. mRNAs coding for the full-length and thetruncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed forthe ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundantwhereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly,overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest thatclk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between thesetwo isoforms.

关键词： clk/STY LAMMER kinase alternative splicing erythroleukemia cells.

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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 *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** 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 *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** 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 *** 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 *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

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

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Retinal microglial activation in glaucoma:evolution over time in a unilateral ocular hypertension model

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Neural Regeneration Research 2022年第4期17卷 797-799页

作者： JoséA.fernández-Albarral ana I.Ramírez Rosa de Hoz Juan J.Salazar Instituto de Investigaciones Oftalmológicas Ramón Castroviejo Universidad Complutense de MadridMadridSpain Facultad deÓptica y Optometría Departamento de InmunologíaOftalmología y ORLUniversidad Complutense de MadridMadridSpain

Glaucoma is a neurodegenerative chronic pathology,characterized by the loss of retinal ganglion cells(RGC),which leads to an irreversible vision field *** increased intraocular pressure(IOP)constitutes its main risk ***,the main treatments for glaucoma are focused on decreasing IOP;nevertheless,the progression of the disease continues,despite IOP *** fact shows the existence of other factors that could contribute to the advance of glaucomatous *** early diagnostics,the use of neuroprotective therapies,and knowledge of the pathological processes are the major challenges associated with the management of this *** pathogenic mechanisms have been proposed to be responsible for RGC death,including oxidative stress,mitochondrial dysfunction,glutamate excitotoxicity,and neuroinflammation(Casson et al.,2012).

关键词： irreversible oxidative activation

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Intestinal pseudo-obstruction caused by herpes zoster:Case report and pathophysiology

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World Journal of Clinical Cases 2018年第6期6卷 132-138页

作者： Roberto anaya-Prado José V Pérez-Navarro ana Corona-Nakamura Michelle M anaya-fernández Roberto anaya-fernández Marian Eliza Izaguirre-Pérez Department of Surgery at Western Medical Center the Mexican Institute of Social Security Division of Research at Autonomous University of Guadalajara Department of Infectious Diseases at Western Medical Center the Mexican Institute of Social Security Division of Research at University of Guadalajara

Herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be consideredwhen dealing with non-obstructive(adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery.

关键词： Ogilvie’s symdrome Herpes zoster virus Neuropathies Intestinal pseudo-obstruction

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Weak crossed biproducts and weak projections

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Science China Mathematics 2012年第7期55卷 1321-1352页

作者： fernndez VILABOA Jose Manuel GONZLEZ RODRíGUEZ Ramon RODRíGUEZ RAPOSO ana Belen Departamento de lxebra Universidad de Santiago de Compostela Departamento de Matemtica Aplicada II Universidade de Vigo Departamento de Matemticas Universidade da Coruna

In this paper, we present the general theory and universal properties of weak crossed biproducts. We prove that every weak projection of weak bialgebras induces one of these weak crossed structures. Finally, we comput... 详细信息

关键词： braided monoidal category preunit crossed product weak Hopf algebra weak projection weakcrossed biproduct

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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 *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** 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 *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** 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 *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** 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 ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,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 ***,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 *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

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

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