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Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease:A crosssectional study

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World Journal of Gastroenterology 2025年第7期31卷 63-73页

作者： Yolanda Real Martinez Carlos Ernesto Fernandez-Garcia Esther Fuertes-Yebra Mario Calvo Soto Angela Berlana Vicente Barrios Maria Caldas Leticia Gonzalez Moreno Luisa Garcia-Buey Begoña Molina Baena Miguel Sampedro-Nuñez Maria J Beceiro C García-Monzón Águeda González-Rodríguez Servicio Aparato Digestivo Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Unidad de Investigación Hospital Universitario Santa CristinaInstituto de Investigación Sanitaria La PrincesaMadrid 28009Spain department of Endocrinology Department of PediatricsHospital Infantil Universitario Niño JesúsInstituto de Investigación La PrincesaMadrid 28009Spain Centro de Investigación Biomédica en red de Fisiopatología de la Obesidad y Nutrición Instituto de Salud Carlos IIIMadrid 28029Spain Servicio de Endocrinología y Nutrición Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Instituto de Investigaciones Biomédicas Sols-Morreale(IIBM) CSIC-UAMMadrid 28029Spain Centro de Investigación Biomédica en red de Diabetes y Enfermedades Metabólicas Asociadas Madrid 28029Spain

BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these ***,their actual prevalence and pathophysiology remain to be *** To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with *** Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level *** degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional *** and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD *** analysis was performed comparing results according to liver fibrosis and *** No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver ***,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD *** serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.

关键词： Skeletal muscle alterations Myokines Metabolic dysfunction-associated steatotic liver disease Liver fibrosis Hepatosteatosis

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Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases

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Neural Regeneration Research 2020年第9期15卷 1631-1638页

作者： Kevin Puertas-Neyra Ricardo Usategui-Martín Rosa MCoco Ivan Fernandez-Bueno Instituto Universitario de Oftalmobiologia Aplicada Universidad de ValladolidValladolidSpain Centro en red de Medicina Regenerativa y Terapia Celular de Castilla y Leon ValladolidSpain red Tematica de Investigacion Cooperativa en salud OftaredInstituto de Salud CarlosⅢValladolidSpain

Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.

关键词： clinical trials growth factors intraocular injection intravitreal injection neuroprotection paracrine properties photoreceptors preclinical models retinal diseases stem cells

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Neuroprotective therapy for retinal neurodegenerative diseases by stem cell secretome

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Neural Regeneration Research 2021年第1期16卷 117-118页

作者： Ricardo Usategui-Martín Ivan Fernandez-Bueno Instituto Universitario de Oftalmobiología Aplicada(IOBA) Retina GroupUniversidad de ValladolidValladolidSpain Centro en red de Medicina Regenerativa y Terapia Celular de Castilla y León Red Temática de Investigación Cooperativa en SaludOftaredInstituto de Salud Carlos IIIValladolidSpain

Retinal neurodegenerative diseases like agerelated macular degeneration,glaucoma,diabetic retinopathy or retinitis pigmentosa are the most frequent causes of incurable low vision and blindness *** had been estimated that the prevalence of these diseases varies between 1/750 and 1/5000 depending on the region,the level of consanguinity or ethnicity(Na et al.,2017).The functional and structural complexity of the retina makes it susceptible to multiple types of pathogenic damage.

关键词： diseases protective degenerative

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Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

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Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： Instituto de salud Carlos III Irene Villalón-García Suleva Povea-Cabello MónicaÁlvarez-Córdoba Marta Talaverón-Rey Juan MSuárez-Rivero Alejandra Suárez-Carrillo Manuel Munuera-Cabeza Diana Reche-López Paula Cilleros-Holgado Rocío Piñero-Pérez JoséA.Sánchez-Alcázar Centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation *** dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these ***,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is *** this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular *** vicious cycle established between both pathological alterations may lead to the development of ***,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict *** addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress PLA2G6-associated neurodegeneration

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Precision medicine in pantothenate kinase-associated neurodegeneration

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Neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： Mónica álvarez-Córdoba Marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan M.Suárez-Rivero Marta Talaverón-Rey Javier Abril-Jaramillo Ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar Centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ Centro de Neurología Avanzada Centro Civet

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAN fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme ***,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

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Anti-inflammatory effects of Mangifera indica *** in a model of colitis

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World Journal of Gastroenterology 2010年第39期16卷 4922-4931页

作者： Lucía Márquez Beatriz G Pérez-Nievas Icíar Gárate Borja García-Bueno José LM Madrigal Luis Menchén Gabino Garrido Juan C Leza department of Pharmacology School of MedicineUniversity Complutense and Centro de Investigación en Red de Salud Mental(CIBERSAM) Pharmaceutical Chemistry Center and University of La Habana Health Research Institute Hospital 12 de Octubre(I+12) Gastroenterology Service Hospital General Universitario Gregorio Maraón and CIBEREHD department of Chemistry and Pharmacy University Católica del Norte

AIM:To investigate the effect of aqueous extract from Mangifera indica L.(MIE)on dextran sulfate sodium (DSS)-induced colitis in ***:MIE(150 mg/kg)was administered in two different protocols:(1)rectally,over 7 d at the same time as DSS administration;and(2)once daily over 14 d (by oral gavage,7 d before starting DSS,and rectally for 7 d during DSS administration).General observations of clinical signs were ***-inflammatory activity of MIE was assessed by myeloperoxidase(MPO)activity. Colonic lipid peroxidation was determined by measuring the levels of thiobarbituric acid reactive substances (TBARS).reduced glutathione(GSH)levels,expression of inflammatory related mediators[inducible isoforms of nitric oxide synthase(iNOS)and cyclooxygenase (COX)-2,respectively]and cytokines[tumor necrosis factor(TNF)-αand TNF receptors 1 and 2]in colonic tissue were also ***(IL)-6 and TNF-α serum levels were also measured. RESULTS:The results demonstrated that MIE has anti-inflammatory properties by improvement of clinical signs,reduction of ulceration and reduced MPO activity when administered before *** addition,administration of MIE for 14 d resulted in an increase in GSH and reduction of TBARS levels and iNOS,COX-2, TNF-αand TNF R-2 expression in colonic tissue,and a decrease in IL-6 and TNF-αserum levels. CONCLUSION:MIE has anti-inflammatory activity in a DSS-induced rat colitis model and preventive administration(prior to DSS)seems to be a more effective protocol.

关键词： Oxidative stress Ulcerative colitis Inflammation Polyphenols Mangifera indica Antioxidants

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Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism

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World Journal of Gastroenterology 2017年第28期23卷 5246-5252页

作者： Fernando Díaz-Fontenla Marta Castillo-Pradillo Arantxa Díaz-Gómez Luis Ibanez-Samaniego Pilar Gancedo Juan Adan Guzmán-de-Villoria Pilar Fernández-García Rafael Banares-Canizares Rita García-Martínez Unidad de Hepatología Servicio de Aparato DigestivoHospital General Universitario Gregorio Maranón Instituto de Investigación Sanitaria Hospital Gregorio Maranón Servicio de Aparato Digestivo Hospital Santa Bárbara Servicio de Radiodiagnóstico Hospital General Universitario Gregorio Maranón Centro de Investigación Biomédica en red de salud mental Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas Facultad de Medicina Universidad San Pablo CEU

Hepatic encephalopathy(HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events(i.e.,portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here,we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment,hyperammonaemia,electroencephalograph alterations,impaired neuropsychological performance,and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE,paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

关键词： Hepatic encephalopathy Hypothyroidism Cognitive impairment Cirrhosis Portosystemic shunt Magnetic resonance spectroscopy

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Central nervous system-derived extracellular vesicles:the next generation of neural circulating biomarkers?

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Translational Neurodegeneration 2024年第1期13卷 674-691页

作者： Rocío del Carmen Bravo-Miana Jone Karmele Arizaga-Echebarria David Otaegui Multiple Sclerosis Group Neuroscience AreaBiodonostia Health Research InstituteSan Sebastián 20014Spain Centro de Investigación Biomédica en red de Enfermedades Neurodegenerativas Instituto de Salud CarlosⅢMadrid 28029Spain

The central nervous system(CNS)is integrated by glial and neuronal cells,and both release extracellular vesicles(EVs)that participate in CNS *** could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos,which are protected during systemic circulation of *** a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS *** raises a particular point of interest:can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases?L1 cell adhesion molecule(L1CAM)is a widely reported biomarker to identify CNS-derived EVs in peripheral ***,it has been demonstrated that L1CAM is also expressed outside the *** that principal data related to neurodegenerative diseases,such as multiple sclerosis,amyotrophic lateral sclerosis,Parkinson’s disease and Alzheimer’s disease were obtained using L1CAM-positive EVs,efforts to overcome present challenges related to its specificity are *** this sense,other surface biomarkers for CNS-derived EVs,such as glutamate aspartate transporter(GLAST)and myelin oligodendrocyte glycoprotein(MOG),among others,have started to be *** a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of *** review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases,focusing on the reported biomarkers and the technical possibilities for their *** are emerging as a mirror of brain physiopathology,reflecting both localized and systemic ***,when the technical hindrances for EV research and clinical applications are overcome,novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to pe

关键词： Extracellular vesicles Circulating biomarkers Central nervous system-derived EVs Neural-derived EVs Brain-derived EVs Cerebrospinal fluid EVs Plasma EVs Neurodegenerative diseases

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Genetics of adult attachment:An updated review of the literature

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World Journal of Psychiatry 2021年第9期11卷 530-542页

作者： Leire Erkoreka Mercedes Zumarraga Aurora Arrue M Isabel Zamalloa Ainara Arnaiz Olga Olivas Teresa Moreno-Calle Estela Saez Jon Garcia Elena Marin Noemi Varela Ana Gonzalez-Pinto Nieves Basterreche department of Psychiatry Galdakao-Usansolo HospitalOsakidetza Basque Health ServiceGaldakao 48960Spain grupo red de salud mental Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain department of Neurosciences University of the Basque Country UPV/EHULeioa 48940Spain department of Neurochemical Research Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceBarakaldo 48903Spain Erandio mental Health Center Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceErandio 48950Spain Zaldibar Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceZaldibar 48250Spain Zamudio Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceZamudio 48170Spain Bermeo Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceBermeo 48370Spain department of Psychiatry BioAraba Research InstituteAraba University HospitalUniversity of the Basque Country(UPV/EHU)CIBERSAMVitoria-Gasteiz 01004Spain grupo de investigacion integradora en salud mental Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain

Attachment style,which has been theorized to be rooted in childhood bonding experiences,influences adult cognitive,emotional and interpersonal *** its relationship with early experiences,research indicates that the continuity of attachment style across childhood and adulthood is only partial,being a malleable tendency that is shaped throughout development,with an increasing influence of genetics,as it occurs in other cognitive and behavioral *** research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes,but the precise mechanisms remain unclear.A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin,dopaminergic pathways,serotonergic pathways and brainderived neurotrophic factor in adult attachment,with both vulnerability and differential susceptibility approaches,yielding mixed *** highlight the lack of genome-wide studies and the scarcity of epigenetic *** on the existing data,we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.

关键词： Genetics Adult attachment Oxytocin Dopamine Serotonin Brain-derived neurotrophic factor Methylation

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Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

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Neural Regeneration Research 2018年第2期13卷 239-240页

作者： ivan fernandez-bueno yolanda diebold instituto universitario de oftalmobiología aplicada university of valladolidValladolidSpain red temática de investigación cooperativa en salud(retics) oftaredinstituto de salud carlos IIIMadridSpain biomedical research networking center on bioengineering biomaterials and nanomedicineciber-bbnValladolidSpain

Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.

关键词： Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

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