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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto Gomez-Carballa Maria Jose Curras-Tuala Sara Pischedda Miriam Cebey-Lopez Jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-Lasheras Antonio Justicia-Grande Julian Montoto-Louzao Alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga Jose RAntunez Rodolfo Gomez Federico Martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)gene.However,the molecular mechanisms underlying HO remain poorly understood.As a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli Kazim A.Sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba departamento de Química Biológica-Centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCK Y-27632

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Breaking paradigms: Long non-coding RNAs forming gene fusions with potential implications in cancer

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Genes & Diseases 2024年第3期11卷 311-323页

作者： David Sanchez-Marin Macrina Beatriz Silva-Cazares Fany Iris Porras-Reyes Rebeca Garcia-Roman Alma D.Campos-Parra Posgrado en Ciencias Biologicas Facultad de MedicinaUniversidad Nacional Autonoma de MexicoCiudad de MexicoC.P.04360Mexico Unidad Academica Multidisciplinaria Region Altiplano Universidad Autonoma de San Luis Potost(UASLP)Carretera a Cedral Km 5+600Ejido San Jose de la TrojesMatehualaSan Luis PotosiC.P.78760Mexico servicio de Anatomia Patologica Instituto Nacional de Cancerologia(INCan)Nino JesuisTlalpanCiudaddeMexicoC.P.14080Mexico Instituto de Salud Publica Universidad Veracruzana(UV)Av.Dr LuisDr.Castelazo Ayala s/nCol.Industrial AnimasXalapaVeracruzC.P.91190Mexico

Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory functions.They interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and progression.Recently,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding genes.However,their biological significance in the tumor phenotype is still uncertain.Therefore,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic targets.The present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential function.We address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.

关键词： Cancer Genefusions IncRNAs ncRNAs Therapy

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Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1705-1724页

作者： Damián Sánchez-Ramírez Mónica G Mendoza-Rodríguez Omar R Alemán Fernando A Candanedo-González Miriam Rodríguez-Sosa Juan JoséMontesinos-Montesinos Mauricio Salcedo Ismael Brito-Toledo Felipe Vaca-Paniagua Luis I Terrazas Unidad de Investigacion en Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autonoma de MexicoTlalnepantla 54090Estado de MexicoMexico department of Biology Facultad de QuimicaUniversidad Nacional Autonoma de MexicoCiudad UniversitariaMexico City 04510Mexico department of Pathology National Medical Center Century XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio de Células Troncales Mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Unidad de Investigacion en Biomedicina y Oncologia Genomica Instituto Mexciano del Seguro SocialMexico City 07300Mexico servicio de Colon y Recto Hospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio Nacional en Salud Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

关键词： Cancer-associated fibroblasts Signal transducer and activator of transcription signaling Colorectal cancer Immunity Immunosuppression

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David García-Bernal Diego García-Ayuso Manuel Vidal-Sanz 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 Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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Journal of Sport and Health Science 2024年第3期13卷 409-418页

作者： Jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes Mikael Croyal Bertrand Perret Sophie Guyonnet Bruno Vellas Laurent O.Martinez Philipe de Souto Barreto For the MAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France Centre d'Epidémiologie et de Recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France Service de Biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France BioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains unclear.Additionally,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase.We examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these associations.Methods:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included.IF1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year visit.Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations.Mediation analyses were conducted to examine whether apoA-I mediated these associations.Mixedeffect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA.Results:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly mediates this association.Additionally,this study f

关键词： Aging Apolipoprotein Bioenergetics Exerkine Mitochondria

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Environmental drivers of long-term variations in the abundance of the red hocicudo mouse (Oxymycterus rufus) in Pampas agroecosystems

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Integrative Zoology 2024年第1期19卷 37-51页

作者： Laura Mariel CALFAYAN Regino CAVIA Jimena FRASCHINA Juan Santiago GUIDOBONO Irene Laura GOROSITO María BUSCH Laboratorio de Ecología de Poblaciones Departamento de EcologíaGenética y EvoluciónFacultad de Ciencias Exactas y NaturalesUniversidad de Buenos Aires and Instituto de EcologíaGenética y Evolución de Buenos Aires(IEGEBA)Buenos AiresArgentina

During the 20th century,there has been an ongoing agricultural expansion and global warming,two of the main determinants influencing biodiversity changes in Argentina.The red hocicudo mouse(Oxymycterus rufus)inhabits subtropical grasslands and riparian habitats and has increased its abundance in recent years in central Argentina agroecosystems.This paper describes the long-term temporal changes in O.rufus abundance in Exaltación de la Cruz department,Buenos Aires province,Argentina,in relation to weatherfluctuations and landscape features,as well as analyzes the spatio-temporal structure of captures of animals.We used generalized liner models,semi-variograms,the Mantel test,and autocorrelation functions for the analysis of rodent data obtained from trappings conducted between 1984 and 2014.O.rufus showed an increase in abundance across the years of study,with its distribution depending on landscape features,such as habitat types and the distance tofloodplains.Capture rates showed a spatio-temporal aggregation,suggesting expansion from previously occupied sites.O.rufus was more abundant at lower minimum temperatures in summer,higher precipitation in spring and summer,and lower precip-itations in winter.Weather conditions affected O.rufus abundance,but there was local variation that differed from global patterns of climate change.

关键词： agroecosystems climate change linear habitats Oxymycterus rufus rodent

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Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： Antonio Molina Lucıa Jorda Miguel Angel Torres Marina Martın-Dacal Diego Jose Berlanga Patricia Fernandez-Calvo Elena Gomez-Rubio Sonsoles Martın-Santamarıa Centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain Centro de Investigaciones Biologicas Margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues.These wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress perception.Plant cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease resistance.Similarly,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI responses.The number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent years.However,the structural mechanisms underlying glycan recognition by plant PRRs remain limited.Currently,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological responses.Nevertheless,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide recognition.These include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and LRR-extensins.The characterization of structural basis of glycans recognition by these new plant receptors will shed light

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

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Common interacting genetic variation shapes susceptibility to type 1 diabetes in a Colombian Caribbean community:In search of shared genetic markers

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Genes & Diseases 2024年第4期11卷 106-108页

作者： Gloria Garavito-de Egea Alex Dominguez-Vargas Jorg e l.Velez Gustavo Aroca Luis Fagng Elkin Navarro-Quiroz Zilac Espitaleta Kenny del Toro-Camargo Leticia Martinez-Ariza Tatiana Gonzalez-Vargas Susana Garcia Mauricio Arcos-Burgos Eduardo Egea Universidad del Norte Division Ciencias de la SaludBarranquillaColombia Universidad Simon Bolivar Facultad de Ciencias de la SaludBarranquillaColombia Clinica de la Costa Grupo de Investigacion en NefrologiaBarranquillaColombia Universidad de Antioquia Grupo de Investigacion en Psiquiatria(GIPSI)Departamento de PsiquiatriaInstituto de Investigaciones MedicasFacultad de MedicinaMedellinColombia

Genome-wide association studies(GWASs)have identified hundreds of loci across the human genome conferring susceptibility to autoimmune diseases(AIDs),some of which are shared between more than two diseases.However,thi... 详细信息

关键词： susceptibility diseases diabetes

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