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Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

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World Journal of Stem Cells 2020年第12期12卷 1667-1690页

作者： marta camacho-cardenosa JoséManuel Quesada-Gómez Alba camacho-cardenosa Alejo Leal GabrielDorado Bárbara Torrecillas-Baena Antonio Casado-Díaz Facultad Ciencias del Deporte Universidad De ExtremaduraCáceres 10003Spain CIBER De Fragilidad Y Envejecimiento Saludable(CIBERFES) Unidad De Gestión Clínica De Endocrinología Y NutriciónInstituto Maimónides De Investigación Biomédica De CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Servicio de Traumatología Hospital de CáceresCáceres 10004Spain Departamento Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de Córdoba-CIBERFES14071 CórdobaSpain

BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and *** tend to differentiate into adipocytes,instead of osteoblasts,with *** favors the loss of bone mass and development of *** induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and *** allows a better adaptation to low O2 *** hypoxia has negative effects on bone metabolism,favoring bone ***,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in *** To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in *** MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,*** addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain *** in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray *** CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,***,both parameters were not significantly affected by the other shorter hypoxia times *** longest periods of hypoxia downregulated the expression of genes related to extracellular matrix

关键词： Normobaric cyclic hypoxia Mesenchymal stem cells Cellular differentiation Osteoblasts Adipocytes Bone health

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Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

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World Journal of Stem Cells 2022年第7期14卷 453-472页

作者： Victoria Pulido-Escribano Bárbara Torrecillas-Baena marta camacho-cardenosa Gabriel Dorado MaríaÁngeles Gálvez-Moreno Antonio Casado-Díaz Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17 Instituto Maimónides de Investigación Biomédica de CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Dep.Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their *** properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and ***,the regenerative effect of MSC is partly due to their paracrine *** has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient ***,contents of EV can be modulated by preconditioning MSC under different culture *** them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) *** has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell *** of these genes is reflected in the contents of secreted ***,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under *** this review,we show the implications of hypoxia responses in relation to tissue *** addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

关键词： Cell priming Extracellular vesicles Hypoxia Hypoxia-inducible factor Mesenchymal stemcells Regenerative medicine

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The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni marta Busnelli Silvia Bassani CNR Institute of Neuroscience Vedano al LambroItaly NeuroMi Milan Center for Neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： marta Chierichetti Riccardo Cristofani Valeria Crippa Veronica Ferrari marta Cozzi Elena Casarotto Paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient

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World Journal of Gastroenterology 2015年第36期21卷 10475-10479页

作者： Maria Salvado Victor Vargas marta Vidal Macarena Simon-Talero Jessica camacho Josep Gamez ALS Unit Neurology DepartmentHospital Universitari Vall d'HebronVall d'Hebron Research InstituteAutonomous University of Barcelona Liver Unit Department of MedicineHospital Universitari Vall d'HebronVall d'Hebron Research InstituteAutonomous University of BarcelonaBarcelona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)Instituto de Salud Carlos IIIMadridSpain Pathology Department Hospital Universitari Vall d’HebronVall d’HebronAutonomous University of Barcelona

We report a case of acute severe hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib,a tyrosine kinase inhibitor,is usually transient with mild elevation of transaminases,although acute hepatitis has been not reported to date. The hepatitis was resolved after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal values five months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liver injury is discussed. Physicians should be aware of this potential complication.

关键词： Drug-induced liver injury Masitinib Amyotrophic la

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Not only myelination: the immune-inflammatory functions of oligodendrocytes

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Neural Regeneration Research 2022年第12期17卷 2661-2663页

作者： marta Boccazzi Stefano Raffaele marta Fumagalli Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilanItaly

Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve *** formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of *** addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS *** their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.

关键词： myelin cytes homeostasis

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Evolution of temperature indices in the periglacial environment of the European Alps in the period 1990-2019

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Journal of Mountain Science 2021年第11期18卷 2842-2853页

作者： NIGRELLI Guido CHIARLE marta National Research Council Research Institute for Geo-hydrological ProtectionStrada delle Cacce73–TorinoItaly

Air temperature in the European Alps shows warming over recent decades at an average rate of 0.3℃/10 years,therebyoutpacing the global warming rate of 0.2℃/10 *** periglacial environment of the Alps is particularly important for several aspects(*** production,tourism,natural hazards,indicator of global warming).However,there is a lack of specific and updated studies relating to temperature change in this *** order to fill this gap,the recent temperature trends in the periglacial environment of the Alps were ***/maximum/minimum daily air temperatures recorded by 14 land-based meteorological stations were used,and the temperature indices for the period 1990-2019 were *** periglacial environment of the Alps showed a warming rate of 0.4℃/10 years,0.6℃/10 years and 0.8℃/10 years for the mean/maximum/minimum temperatures,*** warming rates are higher than that observed for the entire Alpine *** 2050 many glaciers of the Alps below 3000 m altitude are expected to be extinct,and all the areas previously occupied by glaciers will become *** order to manage and adapt to these changes,more in-depth climate analyses are *** is necessary for all the mountainous areas of the world,which are undergoing similar changes.

关键词： Mountain climate Cryosphere Climate change Extreme temperature Air temperature trend

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