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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado mar.a JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri mar.a pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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Exosomes as mediators of neuron-glia communication in neuroinflammation

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Neural Regeneration Research 2020年第5期15卷 796-801页

作者： mar.a pascual Francesc Ibánez Consuelo Guerri Department of Molecular and Cellular Pathology of Alcohol Príncipe Felipe Research CenterValenciaSpain Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain

In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological *** nanovesicles (30–150 nm) contain proteins,RNAs and lipids,and their internalization by bystander cells could alter their normal *** review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous *** emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative *** the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and ***,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation.

关键词： biomarkers exosomes glial cells neuroinflammation neuron-glia commuication neurons neuropathology therapy

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Key biochar properties linked to denitrification products in a calcareous soil

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Biochar 2024年第1期6卷 1604-1619页

作者： mar.a L.Cayuela Oliver Spott mar.a B.pascual mar.a Sánchez-García Miguel A.Sánchez-Monedero Department of Soil and Water Conservation and Waste Management CEBAS-CSIC.Campus Universitario de Espinardo30100 MurciaSpain. SKW Stickstoffwerke Piesteritz GmbH.Agricultural Application Research 04451 BorsdorfGermany.

Meta-analyses show an overall decrease in soil N_(2)O emissions after biochar(BC)***,N_(2)O mitigation with BC cannot be extrapolated to every BC-soil combination,inasmuch as an increase in soil N_(2)O release has been occasionally *** hypothesized that BC characteristics are key,and performed two microcosm experiments to advance in the understanding of the properties *** first investigated how 22 well-characterized BCs affect N_(2)O emissions in a calcareous soil under denitrification *** most BCs decreased N_(2)O emissions,some substantially increased N_(2)O *** a second experiment,we selected and further characterized eight of the 22 previous *** applied the^(15)N-gas-flux method to study how these BCs affect denitrification products(N_(2)O and N_(2))in the same *** indicate that the interaction between BC and the denitrification process depends on the temperature of *** BCs produced at 400℃tended to increase total denitrification(N_(2)O+N_(2))by an average of 28%,BCs produced at 600℃significantly reduced total denitrification by 53%.Nevertheless,this decline in overall denitrification did not result in a decrease of N_(2)O emissions,as there was a strong shift in the N_(2)O/(N_(2)+N_(2)O)ratio favoring N_(2)O.A redundancy analysis revealed a direct correlation between carboxylic groups on BCs surface and N_(2)O *** research enhances our understanding of the interaction of BC with denitrification,particularly concerning the relevance of the temperature of pyrolysis,and opens up new paths for investigation,crucial for optimizing the application of BCs in different soil environments.

关键词： Nitrous oxide ^(15)N gas-flux method Denitrification Pyrogenic C

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Morphological determinants of jumping performance in the Iberian green frog

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Current Zoology 2020年第4期66卷 417-424页

作者： Gregorio Moreno-Rueda Abelardo Requeinia-Blaimco Francisco J.Zamora-Camacho mar Comas Guillem pascual Departamento de Zoologia Facultad de CienciasUniversidad de GranadaGranadaE-18071Spain Department of Biological Sciences Dartmouth CollegeHanoverNH03055USA Galanthus/Ctra.de Juia 46.17460 CelraSpain

Predation is one of the main selective forces in nature, frequently selecting potential prey for developing escape strategies. Escape ability is typically influenced by several morphological parameters, such as morphology of the locomotor appendices, muscular capacity, body mass, or fluctuating asymmetry, and may differ between sexes and age classes. In this study, we tested the relationship among these variables and jumping performance in 712 Iberian green frogs Pelophylax perezi from an urban population. The results suggest that the main determinant of jumping capacity was body size (explaining 48% of variance). Larger frogs jumped farther, but jumping performance reached an asymptote for the largest frogs. Once controlled by structural body size, the heaviest frogs jumped shorter distances, suggesting a trade-off between fat storage and jumping performance. Relative hind limb length also determined a small but significant percentage of variance (2.4%) in jumping performance-that is, the longer the hind limbs, the greater the jumping capacity. Juveniles had relatively shorter and less muscular hind limbs than adults (for a given body size), and their jumping performance was poorer. In our study population, the hind limbs of the frogs were very symmetrical, and we found no effect of fluctuating asymmetry on jumping performance. Therefore, our study provides evidence that jumping performance in frogs is not only affected by body size, but also by body mass and hind limb length, and differ between age classes.

关键词： body mass fluctuating asymmetry hind limb length hind limb width locomotor performance morphometry

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Dynamics of canopy-dwelling arthropods under different weed management options,including glyphosate,in conventional and genetically modified insect-resistant maize

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Insect Science 2021年第4期28卷 1121-1138页

作者： Esteban García-Ruiz Guillermo Cobos Ismael Sánchez-Ramos Susana pascual mar.a-Cristina Chueca mar.a-Concepción Escorial Inés Santín-Montanyá Íñigo Loureiro Manuel González-Núñez Plant Protection Department Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA)MadridSpain

The use of genetically modified varieties tolerant to herbicides(HT varieties)and resistant to insects(Bt varieties)in combination with application of a broad-spectrum herbicide such as glyphosate could be an effective option for the simultaneous control of weeds and pests in ***,the possible impact of these tools on nontarget arthropods still needs to be *** a field study in central Spain,potential changes in populations of canopy-dwelling arthropods in Bt maize under different weed management options,including glyphosate application,were ***-dwelling arthropods were sampled by visual inspection and yellow sticky *** Bt variety had no effect on any group of studied arthropods,except for the expected case of corn borers—the target pests of Bt *** the effects of herbicide regimes,the only observed difference was a lower abundance of Cicadellidae and Mymaridae on yellow sticky traps in plots not treated with pre-emergence *** effect was especially pronounced in a treatment involving two glyphosate *** decrease in Cicadellidae and Mymaridae populations was associated with a higher density of weeds in plots,which may have hindered colonization of the crop by *** differences,however,were only significant in the last year of the *** low likelihood of the use of glyphosate-and herbicide-tolerant varieties for weed control triggering important effects on the nontarget arthropod fauna of the maize canopy is discussed.

关键词： Bt maize canopy-dwelling arthropods GMHT maize glyphosate herbicide management parasitoids

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Healthcare staff as promoters of parental presence at anesthetic induction:Net Promoter Score survey

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World Journal of Clinical Pediatrics 2021年第6期10卷 159-167页

作者： mar.a Velayos Karla Estefanía mar.a Alvarez mar.a C Sarmiento Lucas Moratilla pascual Sanabria Francisco Hernández Manuel V López Santamar.a Servicio de Cirugía Pediátrica Hospital Universitario La PazMadrid 28046Spain Servicio de Anestesia y Reanimación Infantil Hospital Universitario La PazMadrid 28046Spain

BACKGROUND Surgical intervention is usually a traumatic event that causes stress and anxiety in the pediatric patient and the family *** reduce the harmful effects of presurgical anxiety,parental presence during induction of anesthesia(PPIA)is one of the more notable interventions used in medical ***,data on this measure are difficult to evaluate and often face resistance from healthcare *** To analyze the perception of the healthcare workers after the implementation of a PPIA *** A survey was developed and sent by email to all the healthcare staff working in the children’s area of a tertiary *** consisted of 14 items divided into positive aspects of PPIA and negative aspects of PPIA evaluated with the use of a Likert scale(1 to 5).The demographics of the respondents were included in the data *** answers to the questions were interpreted through the Net Promoter Score(NPS).The statistical analysis compared the differences in the responses to each question of the survey made by the different groups of health personnel *** A total of 141 surveys were sent out,with a response rate of 69%.Of the total number of responses,68%were from women and 32%from *** average age of the participants was 42.3±10.6 *** for the positive questions about the PPIA,83%had an NPS>50,and only one had a score between 0 and 50,which means that the quality of the service was rated as excellent or good by 100%of the *** the other hand,100%of the negative questions about the PPIA had a negative *** to the question“PPIA increases patient safety”were significantly different(P=0.037),with a lower percentage of pediatric surgeons(70%)thinking that PPIA increased patient safety,compared with anesthesiologists(90%),nursing(92%),and other medical personnel(96%).CONCLUSION The personnel who participated in the PPIA program at our center were in favor of *** were no validated arguments to

关键词： Parental presence Survey Anesthesia induction Patient-centered care Anxiety Surgery

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Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

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World Journal of Gastroenterology 2016年第48期22卷 10545-10556页

作者： Gloria Segarra Belén Cortina mar.a Dolores Mauricio Susana Novella Paloma Lluch Javier Navarrete-Navarro Inmaculada Noguera pascual Medina Department of Physiology University of Valencia and Institute of Health Research INCLIVAHospital Clínico Universitario Valencia Department of Gastroenterology and Hepatology and Institute of Health Research INCLIVA Hospital Clínico Universitario Valencia

AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic *** Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.

关键词： Portal hypertension Cirrhosis Nitric oxide Asymmetric dimethylarginine Nitric oxide inhibitors Dimethylarginine dimethylaminohydrolase

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Inflammatory bowel disease and celiac disease:Overlaps and differences

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World Journal of Gastroenterology 2014年第17期20卷 4846-4856页

作者： Virginia pascual Romina Dieli-Crimi Natalia López-Palacios Andrés Bodas Luz mar.a Medrano Concepción Nú?ez UGC de Inmunología Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain Servicio de Digestivo Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain Servicio de Pediatría Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain

Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

关键词： Disease susceptibility Gene-environment interaction Immune system Inflammation Microbiota Inflammatory bowel disease

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Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study

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World Journal of Cardiovascular Diseases 2016年第2期6卷 54-71页

作者： Joaquín Lasierra-Cirujeda mar.a José Aza pascual-Salcedo mar.a Mercedes Aza pascual-Salcedo C. Medicine Hematology Logrono Spain The Rioja and Pharmaceutical Act Ministry of Health The Rioja Regional Government Logrono Spain Aragon Health Service Zaragoza Spain

The purpose of this prospective study is to determine the relative incidence of Alzheimer’s disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol (n = 47, 78.21 ± 6.66 years old) in order to prevent primary and secondary venous thromboembolism and atherothrombotic disease. In the sulodexide group, there was an apparent prevention of cognitive and behavioural impairment (relative incidence: 2.02) compared with acenocoumarol group (relative incidence: 4.86). The favourable results in sulodexide group may be related to their pharmacodynamic actions of inhibition of PAI-1, which may interfere with the pathogenesis of Alzheimer’s disease, and to the role of glutathione and PAI-1 in the β-amyloid system in the brain.

关键词： Sulodexide Alzheimer’s Disease Glutathione t-PA PAI-1 Plasminogen Plasmin

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Analysis of the postoperative hemostatic profile of colorectal cancer patients subjected to liver metastasis resection surgery

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World Journal of Clinical Cases 2019年第17期7卷 2477-2486页

作者： Guillermo Perez Navarro Ana mar.a pascual Bellosta Sonia mar.a Ortega Lucea mario Serradilla martín Jose Manuel Ramirez Rodriguez Javier martinez Ubieto Department of Anesthesiology University Hospital Miguel ServetZaragoza 50009Spain Department of General Surgery University Hospital Miguel ServetZaragoza 50009Spain Department of General Surgery University Hospital Lozano BlesaZaragoza 50009Spain

BACKGROUND Liver resection surgery has advanced greatly in recent years,and the adoption of fasttrack programs has yielded good *** anesthesia (general anesthesia associated to epidural analgesia) is an anesthetic-analgesic strategy commonly used for the perioperative management of patients undergoing surgery of this kind,though there is controversy regarding the coagulation alterations it may cause and which can favor the development of spinal *** To study the postoperative course of liver resection surgery,an analysis was made of the outcomes of liver resection surgery due to colorectal cancer metastases in our centre in terms of morbiditymortality and hospital stay according to the anesthetic technique used (general vs combination anesthesia).METHODS A prospective study was made of 61 colorectal cancer patients undergoing surgery due to liver metastases under general and combination anesthesia between January 2014 and October *** patient characteristics,intraoperative variables,postoperative complications,evolution of hemostatic parameters,and stay in intensive care and in hospital were *** A total of 61 patients were included in two homogeneous groups: general anesthesia (n = 30) and combination anesthesia (general anesthesia associated to epidural analgesia)(n = 31).All patients had normal coagulation values before *** international normalized ratio (INR) in both the general and combination anesthesia groups reached maximum values at 2448 h (mean 1.37 and 1.45 vs 1.39 and 1.41,respectively),followed by a gradual *** was less intraoperative bleeding in the combination anesthesia group (769 mL) than in the general anesthesia group (1200 mL)(P < 0.05).Of the 61 patients,38.8% in the general anesthesia group experienced some respiratory complication vs 6.6% in the combination anesthesia group (P < 0.001).The time to gastrointestinal tolerance was significantly correlated to the type of anesthesia,though

关键词： Hepatectomy Epidural analgesia Perioperative complications Epidural hematoma Multimodal rehabilitation Outcomes

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