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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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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria S.Aymerich Universidad de navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de navarra PamplonaSpain IdiSnA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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Stem cell therapy in the management of shoulder rotator cuff disorders

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World Journal of Stem Cells 2015年第4期7卷 691-699页

作者： Maria Valencia Mora Miguel A Ruiz Ibán Jorge Díaz Heredia Raul Barco Laakso Ricardo Cuéllar Mariano García Arranz Unidad de Hombro y Codo Hospital Universitario Ramón y Cajal Hospital Universitario La Paz departamento de Traumatología y Cirugía Ortopédica Hospital Universitario Donostia instituto de investigación sanitaria fundación jiménez diaz departamento de Cirugía Universidad Autónoma de Madrid

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.

关键词： Rotator cuff Enthesis Biologic Stem cells

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Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-Rodríguez María Jesús Borque Leticia González-Moreno Yolanda Real-Martínez Luisa García-Buey Ricardo Moreno-Otero Paloma Sanz-Cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P ng2 was significantly increased as CHC progressed to the end stage of liver disease(P nsequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P nterestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area under the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

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Further the liquid biopsy:Gathering pieces of the puzzle of genometastasis theory

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World Journal of Clinical Oncology 2017年第5期8卷 378-388页

作者： Ana García-Casas Dolores C García-Olmo Damián García-Olmo Universidad Complutense de Madrid Centre de Recerca Experimental Biomèdica Aplicada(CREBA) IRBLLEIDA department of Surgery Universidad Autónoma de MadridInstituto de Investigación SanitariaFundación Jiménez Díaz

Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism,not yet fully *** is almost beyond doubt is that circulatory system is crucial for cancer *** this system,much attention has been recently paid to liquid *** technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic,prognostic and follow-up of *** CTCs tend to be scarce in serum and plasma from cancer patient,abundant circulating nucleic acids can be detected in the same *** fact,together with the genetic origin of cancer,stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis,a recently discovered phenomenon called *** innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory *** is more,many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of *** this review,we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this *** objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

关键词： Genometastasis Cancer metastasis Circulating nucleic acids:Circulating tumor cells Liquid biopsy Exosomes Virtosomes

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Association between urinary concentrations of bisphenol A substitutes and diabetes in adults

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World Journal of Diabetes 2022年第7期13卷 521-531页

作者： Rafael Moreno-Gómez-Toledano Esperanza Vélez-Vélez María I Arenas Marta Saura Ricardo J Bosch Universidad de Alcalá Department of Biological Systems/Physiology UnitAlcaláde Henares 28871Spain fundación jiménez Díaz School of nursing Jiménez Díaz FoundationAutonomous University of MadridMadrid 28040Spain Universidad de Alcalá Department of Biomedicine and BiotechnologyAlcaláde Henares 28871Spain Centro de investigación en Red de Enfermedades Cardiovasculares Instituto Ramón y Cajal de Investigación SanitariaMadrid 28034Spain

BACKGROUnD Due to new restrictions on the use of bisphenol A(BPA),industries are beginning to replace it with derived molecules such as bisphenol S and F(BPS and BPF).There is extensive evidence in the academic literature on the potential health effects of BPA,which is known to be a diabetogenic ***,there are few publications related to new compounds derived from *** To perform an epidemiological study of urinary BPS and BPF in the American national Health and nutrition Examination Survey(nHAnES)cohort,and analyze their possible relationship with diabetes *** nHAnES datasets from 2013 to 2016 were used due to the urinary BPF and BPS *** from 3658 adults were analyzed to perform regression analysis exploring the possible relationship between BPA-derived compounds and *** descriptive statistics,linear regression modeling,and logistic regression analysis revealed a significant relationship between urinary BPS,but not BPF,and diabetes ***,a relationship was observed between both compounds and hypertension and a slight relationship between BPF and *** In the present study,a strong relationship between urinary BPS,not BPF,and diabetes risk has been *** substitute molecules do not exempt the population from potential health risks.

关键词： Bisphenol S Bisphenol F Diabetes mellitus national Health and nutrition Examination Survey Urine

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Stem cell therapy for faecal incontinence: Current state and future perspectives

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World Journal of Stem Cells 2018年第7期10卷 82-105页

作者： Jacobo Trébol Ana Carabias-Orgaz Mariano García-Arranz Damián García-Olmo General and Digestive Tract Surgery department Salamanca University Healthcare Centre Anaesthesiology department Complejo Asistencial de ávila new Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez Díaz General and Digestive Tract Surgery department Quiron-Salud Hospitals Surgery department Universidad AutónomaMadrid

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

关键词： Faecal incontinence Anal sphincter Cell implantation Tissue engineering Cell therapy Stem cells

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Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding

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World Journal of Clinical Cases 2018年第13期6卷 611-623页

作者： José Ignacio Fortea ángela Puente Patricia Ruiz Iranzu Ezcurra Javier Vaquero Antonio Cuadrado María Teresa Arias-Loste Joaquín Cabezas Susana Llerena Paula Iruzubieta Carlos Rodríguez-Lope Patricia Huelin Fernando Casafont Emilio Fábrega Javier Crespo Servicio de Aparato Digestivo Hospital Universitario Marques? de Valdecilla instituto de investigación sanitaria Marqués de Valdecilla Centro de investigación Biomédica Red de Enfermedades Hepáticas y Digestivas Laboratorio de investigación en Hepatología y Gastroenterología Hospital General Universitario Gregorio Mara?ón-Instituto de Investigación Sanitaria Gregorio Mara?ón

AIM To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers(nSBBs) and acute nonresponders received *** Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional nSBB(i.e. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic *** Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation(nSBB: 0%, 13.7%, 26.1% vs carvedilol: 0%, 20%, 20%, P = 0.968) or further decompensation(21.2%, 26.1%, 40.9% vs 21.2%, 50.0%, 50.0%, P = 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation [hazard ratio(95% confidence interval): 8.03(2.76-23.37)]. Mortality rates were similar in acute responders and acute nonresponders with compensated(P = 0.428) or decompensated cirrhosis(P = 0.429). no clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional nSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated(r = 0.59, P = 0.001). Up to 69.2% of acute nonresponders gained chronic response with *** Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects fo

关键词： Gastrointestinal hemorrhage Propranolol Carvedilol Liver cirrhosis Portal hypertension

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Rat model of anal sphincter injury and two approaches for stem cell administration

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World Journal of Stem Cells 2018年第1期10卷 1-14页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Luz Vega-Clemente Ignacio García-Gómez Ana Carabias-Orgaz Mariano García-Arranz Damián García-Olmo department of General and Digestive Tract Surgery University Hospital“La Paz”Madrid 28046Spain department of General and Digestive Tract Surgery Villalba General HospitalMadrid 28400Spain new Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Hektoen Institute of Medicine ChicagoIL 60612United States department of Anaesthesiology Complejo Asistencial deávilaávila 05004Spain new Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain department of General and Digestive Tract Surgery Quiron-Salud HospitalsMadrid 28040Spain department of Surgery Madrid Autonomous UniversityMadrid 28029Spain

AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured *** Adipose-derived stem cells(ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein(GFP) for cell tracking. Biosutures(sutures covered with ASCs) were prepared with 1.5 × 10~6 GFPASCs, and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole(commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for:(1) Cell injection without repair;(2) biosuture repair; and(3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical *** With the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of "plateaus" with multiple twitches(peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min(mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean numb

关键词： Fecal incontinence Experimental rat model Anal sphincter Cell implantation Cell therapy Stem cells Mesenchymal stem cell

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Plasma betatrophin levels in patients with liver cirrhosis

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World Journal of Gastroenterology 2015年第37期21卷 10662-10668页

作者： Maria Teresa Arias-Loste Maria Teresa García-Unzueta Susana Llerena Paula Iruzubieta Angela Puente Joaquín Cabezas Carmen Alonso Antonio Cuadrado José Antonio Amado Javier Crespo Emilio Fábrega Gastroenterology and Hepatology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria ValdecillaAvenida Valdecilla s/n 39008 Santander Cantabria Spain Endocrinology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria Valdecilla Avenida Valdecilla s/n 39008 Santander Cantabria Spain

AIM: To investigate the plasma levels of betatrophin in patients with ***: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or histological criteria were *** severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched *** blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were nd normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility werend n levels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(Pnd in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation(P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P n the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P n observed, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P n time(r =-0.44;P nsulin

关键词： Liver cirrhosis Betatrophin Insulin resistance Bet

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