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Mesenchymal stromal cell therapy for damaged retinal ganglion cells, is gold all that glitters?

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Neural Regeneration Research 2019年第11期14卷 1851-1857页

作者： Fernando Lucas-ruiz Caridad Galindo-Romero David García-Bernal María Norte-Munoz Kristy T. rodríguez-Ramírez Manuel Salinas-Navarro Jose E. Millán-Rivero Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Oftalmologia Experimental Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain Department of Talmologia Universidad de MurciaMurciaSpain Unidad de Terapia Celular y Trasplante Hematopoyetico Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain Department of Medicina Interna Universidad de MurciaMurciaSpain

Mesenchymal stromal cells are an excellent source of stem cells because they are isolated from adult tissues or perinatal derivatives, avoiding the ethical concerns that encumber embryonic stem cells. In preclinical models, it has been shown that mesenchymal stromal cells have neuroprotective and immunomodulatory properties, both of which are ideal for central nervous system treatment and repair. Here we will review the current literature on mesenchymal stromal cells, focusing on bone marrow mesenchymal stromal cells, adipose-derived mesenchymal stromal cells and mesenchymal stromal cells from the umbilical cord stroma, i.e.,Wharton’s jelly mesenchymal stromal cells. Finally, we will discuss the use of these cells to alleviate retinal ganglion cell degeneration following axonal trauma.

关键词： stem cells adipose stem cells umbilical cord bone marrow Wharton's jelly optic nerve axotomy neuroprotection

Mechanisms implicated in the contralateral effect in the central nervous system after unilateral injury:focus on the visual system

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Neural Regeneration Research 2021年第11期16卷 2125-2131页

作者： Fernando Lucas-ruiz Caridad Galindo-Romero Virginia Albaladejo-García Manuel Vidal-Sanz marta Agudo-Barriuso Departamento de Oftalmología Facultad de MedicinaUniversidad de Murcia and Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca(IMIBArrixaca)MurciaSpain

The retina,as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new *** the last decade is becoming clear that unilateral lesions in bilateral areas of the central nervous system trigger an inflammatory response in the contralateral uninjured *** effect has been better studied in the visual system where,as a rule,one retina is used as experimental and the other as *** retinas in unilateral models of retinal injury show neuronal degeneration and glial *** mechanisms by which this adverse response in the central nervous system occurs are discussed in this review,focusing primarily on the visual system.

关键词： bilateral effect brain glaucoma inflammation mirror effect optic nerve axotomy optic nerve crush retina spinal cord

Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2

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Journal of Molecular Cell Biology 2014年第4期8卷 299-311页

作者： Lucia Garcia-Guerra Rocio Vila-Bedmar marta Carrasco-Rando marta Cruces-Sande Mercedes Martin Ana ruiz-Gomez Mar ruiz-Gomez Margarita Lorenzo Sonia Fernandez-Veledo Federico Mayor Jr. Cristina Murga Iria Nieto-Vazquez Department of Biochemistry and Molecular Biology II School of Pharmacy Complutense University 28040 Madrid Spain CIBER de Diabetes y Enfermedades Metab61icas Asociadas (CIBERDEM) 08017 Barcelona Spain Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM) 28029 Madrid Spain CIBER de enfermedades neurodegenerativas (CIBERNED) 28049 Madrid Spain Departament of Molecular Biology and Centro de Biologia Molecular Severo Ochoa (CSIC-UAM) 28049 Madrid Spain Instituto de Investigacion Sanitaria la Princesa 28006 Madrid Spain Centro de Biologia Molecular Severo Ochoa (UAM-CSIC) 28049 Madrid Spain Hospital Universitari de Tarragona Joan XXIII. IISPV. Universitat Rovira i Virgili 43007 Tarragona Spain

G protein-coupled receptor kinase 2 （GRK2） is an important serine/threonine-kinase regulating different membrane receptors and intraceUular proteins. Attenuation of Drosophila Gprk2 in embryos or adult flies induced a defective differentiation of somatic muscles, loss of fibers, and a flightless phenotype. In vertebrates, GRK2 hemizygous mice contained less but more hypertrophied skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts, overexpression of a GRK2 kinase-deficient mutant （K220R） caused precocious differentiation of ceUs into immature myotubes, which were wider in size and contained more fused nuclei, while GRK2 overexpression blunted differentiation. Moreover, p38MAPK and Akt pathways were activated at an earlier stage and to a greater extent in K220R-expressing cells or upon kinase downregulation, while the activation of both kinases was impaired in GRK2-overexpressing cells. The impaired differentiation and fewer fusion events promoted by enhanced GRK2 levels were recapitulated by a p38MAPK mutant, which was able to mimic the inhibitory phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation observed in GRK2-expressing clones was rescued in the presence of a constitutively active upstream stimulator of the p38MAPK pathway. These results suggest that balanced GRK2 function is necessary for a timely and complete myogenic process.

关键词： GRK2 p38MAPK Akt skeletal muscle myogenesis

Intravitreal fluorogold tracing as a method to label retinal neurons and the retinal pigment epithelium

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Neural Regeneration Research 2021年第10期16卷 2000-2001页

作者： Francisco Javier Valiente-Soriano Fernando Lucas-ruiz Juan A.Miralles de Imperial-Ollero Manuel Vidal-Sanz marta Agudo-Barriuso Departamento de Oftalmología Facultad de MedicinaUniversidad de Murcia and Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca(IMIB-Arrixaca)MurciaSpain

Techniques to label the neuroretina and the retinal pigment epithelium(RPE)have been the topic of many studies for *** reliability and reproducibility of these techniques are essential to investigate retinal alterations of ocular pathologies and possible *** particular,the study of the integrity of the RPE is of great importance in pathologies such as retinitis pigmentosa or age-related macular degeneration(Gu et al.,2012;Fisher and Ferrington,2018;Zhang et al.,2019).The most common approaches use antibodies to identify different cell ***,we have described a novel technique to study the integrity of the neuroretina and the RPE,as well as the functionality of the RPE in rats(Valiente-Soriano et al.,2020).

关键词： epithelium al. alterations

Comparison of clinical outcomes between unrelated single umbilical cord blood and"ex-vivo"T-cell depleted haploidentical transplantation in children with hematological malignancies

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World Journal of Pediatrics 2021年第6期17卷 609-618页

作者： Carmen Gomez-Santos marta Gonzalez-Vicent Blanca Molina Natalia Deltoro Blanca Herrero Julia ruiz Antonio Perez-Martinez Miguel A Diaz Department of Pediatrics Hematopoietic Stem Cell Transplantation UnitHospital Infantil Universitario"Nino Jesus"Menedez Pelayo 6528009 MadridSpain Hospital Infantil Universitario"La Pa"Madrid MadridSpain

Background Over the last two decades,umbilical cord blood(UCB)and haploidentical transplantation(HaploHSCT)have emerged as alternative sources of hematopoietic stem cell for allogeneic *** are few retrospective studies and no prospective studies comparing both types of alternative transplantation in pediatric *** We analyzed the data of 134 children with hematological malignancies who received a hematopoietic stem cell transplantation from a single umbilical cord blood(UCB)(n=42)or an"tex-vivo"T-cell depleted transplant from a haploi-dentical-related donor(HaploHSCT)(n=92)between 1996 and *** recovery was faster after HaploHSCT than the UCB transplant group(median times to neutrophil and platelet recovery:13 vs.16 days,10 vs.57 days,respectively)(P<0.001).The HaploHSCT group had a significantly early immune reconstitution based on NK and CD8+T cells compared with the UCB ***,after the first year *** had a lower number of CD4+ T and B lymphocytes compared with the UCB transplant *** cumulative incidence of TRM was 29±8%in the HaploHSCT group versus 40±5%in the UCB *** incidence was 21±7%in the HaploHSCT group and 19±8%in the UCB *** of DFS was 58±8%in the HaploHSCT group versus 40±9%in the UCB group(P=0.051).Conclusions TCD haploidentical transplant is associated with advantages in terms of engraftment and early immune reconstitution *** haploidentical transplant was associated with lower incidence of infectious and non-infectious complications,especially in the early phases of the transplant compared with UCB transplant ***,there are no advantages in transplant outcomes compared with UCB transplant.

关键词： Children Cord blood transplant Hematologic malignancies Immune reconstitution TCD haploidentical transplant

Pan-retinal ganglion cell markers in mice, rats, and rhesus macaques

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Zoological Research 2023年第1期44卷 226-248页

作者： Francisco M.Nadal-Nicolás Caridad Galindo-Romero Fernando Lucas-ruiz Nicholas Marsh-Amstrong Wei Li Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Oftalmología Experimental Instituto Murciano de Investigación Biosanitaria Pascual Parrilla(IMIB)Murcia 30120Spain Dpto.Oftalmología Facultad de MedicinaUniversidad de MurciaMurcia 30120Spain Retinal Neurophysiology Section National Eye InstituteNational Institutes of HealthBethesdaMaryland 20892-2510USA Department of Ophthalmology and Vision Science University of CaliforniaDavisCA 95817USA

Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.

关键词： RGC Optic nerve crush BM88 BRN3A Estrogen-related receptorβ ERRβ NEUN Neurofilament-L PGP9.5 RBPMS γ-SYN βIII-tubulin TUJ1

Use of new technologies for the promotion of physical activity in patients with mental illness:A systematic review

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World Journal of Psychiatry 2023年第4期13卷 182-190页

作者： Margarita Guerrero-Jiménez marta ruiz Luis Gutiérrez-Rojas Laura Jiménez-Muñoz Enrique Baca-Garcia Alejandro Porras-Segovia Department of Psychiatry Hospital Clínico San CecilioGranada 18014Spain Department of Psychiatry Hospital Rey Juan CarlosMóstoles 28933MadridSpain Department of Psychiatry Hospital Universitario Jiménez DíazMadrid 28040Spain Department of Psychiatry Fundación Jiménez DiazMadrid 28040Spain

BACKGROUND Physical exercise is an underutilized tool for the management of mental *** technologies have made a breakthrough in health care,and one of its possible applications(apps)could be that of customizing exercise programs for special populations,such as patients with mental ***,the app of the so-called e-health to mental health care is still *** To know the efficacy of apps to promote physical activity in patients with mental *** We conducted a systematic review of the PubMed and Embase databases with the aim of exploring the use of new technologies for the enhancement of physical exercise in patients with a psychiatric *** the selection process,10 articles were included in the *** The most commonly used devices in this type of intervention are wearable devices and web *** results in terms of effectiveness and acceptability were obtained in most of the *** Our findings suggest that the use of new technologies in mental health represents a feasible strategy with great potential in clinical practice.

关键词： e-health m-health Physical exercise Mobile applications Wearable device

Bull spermatozoa selected by thermotaxis exhibit high DNA integrity,specific head morphometry,and improve ICSI outcome

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Journal of Animal Science and Biotechnology 2023年第3期14卷 1001-1011页

作者： Sara ruiz-Diaz Rosane Mazzarella Paula Navarrete-Lopez Raul Fernandez-Gonzalez Celia de Frutos Maria Maroto Claudia Cucala Paula Beltran-Brena marta Lombo Dimitrios Rizos Alfonso Gutierrez-Adan Department of Animal Reproduction INIA-CSIC28040 MadridSpain Mistral Fertility Clinics S.L Clinica TambreCalle Tambre828002 MadridSpain

Background Sperm migration by thermotaxis is a guidance mechanism that operates along the oviduct and it has proved to be a valid method for selecting spermatozoa with low DNA fragmentation(SDF)in mice,humans,and *** study aimed to analyse if bull spermatozoa could be selected by thermotaxis and to assess their quality in terms of SDF as well as determine the presence of a specific sperm subpopulation based on sperm morphometry and assess their fertilizing capacity by *** We used frozen-thawed sperm from 6 bulls and sperm selection by thermotaxis was performed with TALP medium supplemented with 25 mmol/L of HEPES and 5 mmol/L of *** these conditions,sperm selection was achieved,obtaining a net thermotaxis of 3.6%.Subsequently,we analysed the SDF of the migrated and not-migrated spermatozoa using the neutral COMET assay,and we evaluated the size of the sperm head using Hemacolor■ staining with Motic Images Plus 3 ***,migrated and not-migrated spermatozoa by thermotaxis were used to fertilize bovine in vitro matured(IVM)oocytes by ICSI,a very inefficient procedure in cattle that is only successful when the oocyte is artificially *** The results showed lower SDF(χ^(2),P<0.001,13.3%reduction,n=8)and lower head size parameters(length and width,P<0.01;and perimeter and area,P<0.001;n=4)in those spermatozoa migrated in comparison to those *** distribution of sperm subpopulations structure varied between groups,highlighting cluster 2,characterized by spermatozoa with small head size,and high ellipticity and elongated heads,as the most abundant in the thermotaxis migrated *** performed ICSI(without oocyte artificial activation)with the thermotactic sperm,the blastocyst rate was 32.2%±9.3%in the group microinjected with the thermotactic spermatozoa vs.8.3%±7.8%in the group of not-migrated sperm(χ^(2),P<0.05).Conclusion Our results showed that bull sperm selection by thermotaxis has a much higher D

关键词： ART Bovine Sperm morphometry Sperm selection Thermotaxis

Robust transcriptional indicators of immune cell death revealed by spatiotemporal transcriptome analyses

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Molecular Plant 2022年第6期15卷 1059-1075页

作者： Jose Salguero-Linares Irene Serrano Nerea ruiz-Solani marta Salas-Gómez Ujjal Jyoti Phukan Victor Manuel González MartíBernardo-Faura Marc Valls David Rengel Nuria S.Coll Centre for Research in Agricultural Genomics(CRAG) CSIC-IRTA-UAB-UBCampus UABBellaterra08193 BarcelonaSpain LIPM Universitéde ToulouseINRACNRS84195 Castanet-TolosanFrance INRAE GeT-PlaGeGenotoul31326 Castanet-TolosanFrance Department of Genetics Universitat de Barcelona08028 BarcelonaSpain Consejo Superior de Investigaciones Científicas(CSIC) BarcelonaSpain Department of Plant Molecular Biology and Physiology.Albrechtvon Haller Institute for Plant Sciences niversity of GottingenJulia-Lermontowa-Weg3.37077 GottingenGrmany Institut de Phammacologie et de Biologie Structurale IPBS Universite deToulouse CNRSUPSBP 64182205 route de Nartxonne310077 Toulouse Cedex 04France

Recognition of a pathogen by the plant immune system often triggers a form of regulated cell death traditionally known as the hypersensitive response(HR).This type of cell death occurs precisely at the site of pathogen recognition,and it is restricted to a few *** research has shed light on how plant immune receptors are mechanistically ***,two central key questions remain largely unresolved:how does cell death zonation take place,and what are the mechanisms that underpin this phenomenon?Consequently,bona fide transcriptional indicators of HR are lacking,which prevents deeper insight into its mechanisms before cell death becomes macroscopic and precludes early or live *** this study,to identify the transcriptional indicators of HR we used the paradigmatic Arabidopsis thaliana–Pseudomonas syringae pathosystem and performed a spatiotemporally resolved gene expression analysis that compared infected cells that will undergo HR upon pathogen recognition with bystander cells that will stay alive and activate *** data revealed unique and time-dependent differences in the repertoire of differentially expressed genes,expression profiles,and biological processes derived from tissue undergoing HR and that of its ***,we generated a pipeline based on concatenated pairwise comparisons between time,zone,and treatment that enabled us to define 13 robust transcriptional HR *** these genes,the promoter of an uncharacterized AAA-ATPase was used to obtain a fluorescent reporter transgenic line that displays a strong spatiotemporally resolved signal specifically in cells that will later undergo pathogen-triggered cell *** valuable set of genes can be used to define cells that are destined to die upon infection with HR-triggering bacteria,opening new avenues for specific and/or high-throughput techniques to study HR processes at a single-cell level.

关键词： Arabidopsis thaliana cell death indicator effector-triggered immunity hypersensitive response pattern-triggered immunity plant immunity Pseudomonas syringae