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Update in lean metabolic dysfunction-associated steatotic liver disease

World Journal of Hepatology 2024年第3期16卷 452-464页

作者： Karina Sato-Espinoza Perapa Chotiprasidhi Mariella R Huaman Javier Díaz-ferrer Division of Gastroenterology and Hepatology Department of MedicineMayo ClinicRochesterMN 55902United States Obesity and Metabolic Center for Obesity and Metabolic HealthLima 02002LimaPeru Hepatology Service Department of Digestive DiseasesHospital Nacional Edgardo Rebagliati MartinsLima 02002LimaPeru Medicine Faculty Universidad San Martin de PorresLima 02002LimaPeru Gastroenterology Service Clinica InternacionalLima 02002LimaPeru

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in *** condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase *** patients account for approximately 10%-15%of the MASLD ***,the pathogenesis is complex and is not well *** To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new *** We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD *** include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian *** We include 85 studies in our *** findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic *** risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean *** non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean *** modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser ***,lean NAFLD patients ex

关键词： Lean Non-obese Non-alcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Metabolic dysfunction-associated steatotic liver disease Guidelines Diagnosis Management Pathogenesis Treatment

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Identification and optimization of a potent and highly selective D3 dopamine receptor agonist

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中国药理学与毒理学杂志 2017年第10期31卷 950-951页

作者： Amy E MORITZ R Benjamin FREE Warren WEINER Muzna BACHANI Trevor DOYLE Noel SOUTHALL marc ferrer Jonathan A JAVITCH Joseph STEINER Ara ABRAMYAN Lei SHI Jeffrey AUBé Kevin FRANKOWSKI David R SIBLEY Molecular Neuropharmacology Section National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 University of North Carolina Chapel Hill NC27599 Neurotherapeutic Development Unit National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 National Center for Advancing Translational Sciences Rockville MD 20892 Columbia University New York NY 10032 Computational Chemistry and Molecular Biophysics Unit Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse National Institutes of Health Baltimore MD 21224

OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric *** available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays *** lab employed high throughput screening paradigms to discover highly selective modulators for the *** The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the *** and counter-screens assessed selectivity and mechanisms of *** identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining *** lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK *** neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell *** ML417 displays potent,DRD3-selective agonist activity in multiple functional *** and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other ***417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell *** We have discovered and characterized ML417,a potent and highly selective DRD3 *** compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.

关键词： Dopamine receptor high throughput screening subtype selectivity neuroprotection

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Cued aversive classical conditioning in humans: The role of trait-anxiety

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Open Journal of Psychiatry 2013年第2期3卷 230-237页

作者： óscar Andión Xavier Caseras Miquel àngel Fullana Alberto Fernandez-Teruel marc ferrer Miquel Casas Rafael Torrubia Departament de Psiquiatria i Medicina Legal Institut de Neurociencies Universitat Autonoma de Barcelona Bellaterra Spain Department of Psychological Medicine Cardiff University Cardiff United Kingdom Servei de Psiquiatria Hospital Vall d’Hebron Barcelona Spain

No study so far has specifically addressed the influence of individual differences in trait-anxiety on aversive classical conditioning as indexed by the startle reflex response. We compared the startle reflex responses between participants classified as high (n = 25) and low (n = 26) in trait-anxiety while undergoing a single-cue aversive classical conditioning procedure. High trait-anxiety group showed a greater startle response to the CS relative to the ITI at the post-acquisition compared with the pre-acquisition phase. Low trait-anxiety group did not show such a clear pattern of conditioning, and results from this group seem to be concealed by differences in the startle responses to the CS and the ITI during the pre-acquisition phase. However, a post-hoc analysis in which such differences at pre-conditioning were removed showed no conditioning effects in low trait-anxiety participants. Taking together, these results suggest differences between high and low trait-anxiety groups in the acquisition of the CS-US association. However, further research should clarify the unexpected pattern of responses shown by low trait-anxiety group.

关键词： Classical Conditioning Startle Reflex Trait-Anxiety Cued Conditioning Fear-Potentiated Startle

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Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

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Journal of Sport and Health Science 2024年第3期13卷 398-408页

作者： Pedro L.Valenzuela Alfredo Santalla Lidia B.Alejo Andrea Merlo Asuncion Bustos Laura Castellote-Belles Roser ferrer-Costa Nicola A.Maffiuletti David Barranco-Gil Tomas Pinos Alejandro Lucia Physical Activity and Health Research Group(“PaHerg”) Research Institute of Hospital“12 de Octubre”(“imas12”)Madrid 28041Spain Department of Systems Biology University of AlcalaMadrid 28871Spain Department of Sport and Computer Science Section of Physical Education and SportsFaculty of SportUniversidad Pablo de OlavideSevilla 41013Spain EVOPRED Research Group Universidad Europea de CanariasTenerife 38300Spain Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Gait&Motion Analysis Laboratory Sol et Salus HospitalTorre Pedrera di Rimini(RN)47922Italy Department of Clinical Biochemistry Laboratoris ClınicsHospital Universitari Vall d’HebronBarcelona 08035Spain Human Performance Lab Schulthess ClinicZurich 8008Switzerland Biomedical Research Networking Center on Rare Disorders(CIBERER) Barcelona 08035Spain Mitochondrial and Neuromuscular Disorders Unit Vall d’Hebron Institut de RecercaUniversitat Autonoma de BarcelonaBarcelona 08035Spain

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)***:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric *** a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were ***,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the ***,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle ***:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen *** of these benefits are dose dependent.

关键词： Endurance Glycogen storage disease Glycogenosis Nutrition Supplement

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Solar-assisted photocatalytic water splitting using defective UiO-66 solids from modulated synthesis

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Nano Research 2024年第5期17卷 4134-4150页

作者： Celia M.Rueda-Navarro María Cabrero-Antonino Paula Escamilla Valentín Díez-Cabanes Dong Fan Pedro Atienzar Belén ferrer Ignacio Vayá Guillaume Maurin Herme G.Baldoví Sergio Navalón Departamento de Química Universitat Politècnica de ValènciaCamino de Vera s/nValencia 46022Spain Instituto de Ciencia Molecular(ICMOL) Universitat de ValènciaPaterna 46980Spain ICGM Univ.MontpellierCNRSENSCMMontpellier34095France Instituto de Tecnología Química(UPV-CSIC) Universitat Politècnica de ValènciaAvenida de los Naranjos s/nValencia 46022Spain

Metal-organic frameworks(MOFs)are attracting increasing interests as photocatalysts for solar-driven hydrogen production from *** paper reports on a comparative study of using either acetic acid(AA)or trifluoroacetic acid(TFA)as the representative UiO-66 organic modulators for synthesizing visible light responsive UiO-66(Zr)-X(X:NH_(2) or NO_(2))photocatalysts for water *** results show that photocatalytic hydrogen generation from a water/methanol mixture can be improved by varying the nature and amount of the modulator employed to prepare the different UiO-66(Zr)-X(X:NH_(2) or NO_(2))solid ***-66(Zr)-NH_(2) was the most active photocatalyst,followed by UiO-66(Zr)-NO_(2),both prepared with 12 equivalents of AA with respect to the organic *** UiO-66(Zr)-NH_(2) solid was more active than the parent MOF in photocatalytic overall water splitting(OWS)(H_(2) and O_(2) production of 450 and 160μmol·g^(-1),respectively,in 5 h;apparent quantum yield(AQY)at 400 nm of 0.06%)in the absence of methanol and compares favourably with analogous *** on the photocatalytic activity of the most active solids of both series was obtained by means of a series of techniques,including ultraviolet-visible(UV-vis)diffuse reflectance,X-ray photoelectron spectroscopy(XPS),laser flash photolysis(LFP),electron spin resonance(ESR),photoluminescence and photoelectrochemical measurements together with density functional theory(DFT)*** results showed that organic acid modulators can be used to enhance the photocatalytic activity of missing linker UiO-66 defective materials in solar-powered water splitting.

关键词： heterogeneous photocatalysis metal-organic frameworks(MOFs) UiO-66 materials carboxylic acid modulators water splitting solar light

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History Teacher Training from Decolonial Curriculum Practices to Combat Racism at UniProjeção in the Federal District-A Secondary Publication

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Journal of Contemporary Educational Research 2024年第2期8卷 187-202页

作者： Karoline da Silva Ramos Cláudia Pinheiro Nascimento Francisca Carla Santos ferrer Faculty of Philosophy Languages and Human SciencesUniversity of São PauloSão PauloBrazil

This article aims to understand the training process of history undergraduates,to see if there are decolonial curricular practices to combat racism at the Centro Universitário e Faculdade Projeção(UniProjeção)in the Federal District,to understand how coloniality has corroborated the exclusion of different epistemologies and the erasure of different cultures,and how this exclusionary process of coloniality interferes in the training of history *** order to combat this practice,we are looking for alternatives that can break these suppressions carried out by *** this way,we turn to decolonial ideas that aim to break with the logic of *** can conclude that these practices are poorly developed in the institution,so we proposed active problem-based methodology and music as a didactic *** playful educational tools that strengthen the teaching-learning process,they are active agents in the decolonial work of combating racism,and it is essential to train responsible and ethical teachers in the fight against racism and any form of oppression.

关键词： Coloniality Decoloniality Education Curriculum practices Racism

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Extract of Codiaeum luzonicum Merr. overcomes multidrug resistance in human colon cancer cells by modulating P-glycoprotein

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Asian Pacific Journal of Tropical Biomedicine 2022年第9期12卷 400-410页

作者： Regina Joyce E.ferrer marc Justin C.Ong Sonia D.Jacinto Institute of Biology University of the Philippines DilimanQuezon CityMetro ManilaPhilippines

Objective:To investigate anti-multidrug resistance(MDR)activity and safety of the bioactive fraction(CL11)from Codiaeum luzonicum crude leaf ***:Cytotoxic activity of CL11 against MDR and nonresistant colon cancer cells was assessed using MTT *** of cell death was investigated by annexin V-propidium iodide staining,TUNEL,and JC-1 *** examine mechanism of action,the effect on the expression and function of the MDR-implicated protein P-glycoprotein was tested using Western blotting and calcein assay,***:CL11 had an EC50 of 0.18,1.03 and 38.52µg/mL against HCT-15,HCT-15/Dox and HCT116,*** was mediated by inhibition of P-glycoprotein function and *** mode of cell death involved mitochondrial membrane depolarization and was mostly non-apoptotic at EC50 concentrations against HCT-15 and HCT-15/***:Fraction CL11 of Codiaeum luzonicum induces nonapoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.

关键词： Natural product Leaf extract Codiaeum luzonicum MDR cancer P-gp inhibitor Colorectal cancer

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Germ-free, carefree: injured skin uses IL-24 to kick-start repair independent of pathogen-recognition

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5129-5131页

作者： Ruben A.ferrer Marta Torregrossa Sandra Franz Department of Dermatology Allergology and VenerologyUniversity LeipzigLeipzigGermany

Skin injury releases damage-associated molecular patterns(DAMPs)represented by tissue-components and intracellular contents as well as changes in the levels of certain molecules and metabolites that signal the“non-homeostatic”state of the *** addition,microorganisms entering a wound release molecules,which are sensed as“non-self”(pathogen-associated molecular patterns,PAMPs).Together,DAMPs and PAMPs initiate a complex and coordinated repair process aimed at restoring *** exciting work from Liu et *** of an additional novel mechanism by which a“non-homeostatic”state in murine cutaneous wounds elicits a response through IL-24 to mediate repair(Fig.1).

关键词： wound homeostasis release

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Effects of Imazethapyr-Based Herbicide Formulation in the Zebrafish (Danio rerio) Hepatocyte Cell Line (ZF-L): Cytotoxicity and Oxidative Stress

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Journal of Environmental Protection 2024年第6期15卷 747-765页

作者： Edila Maria Kickhöfel ferrer Milena Mattes Cerveira Pedro Henrique Flores Da Cruz Cleiton Jesus Andrade Pereira Lucas Moraes Berneira Claudio Martin Pereira de Pereira Nathalia Stark Pedra Roselia Maria Spanevello Jean Carlos Bauer Vieira Clarissa Piccinin Frizzo Mateus Tavares Kütter Janice Luehring Giongo Rodrigo de Almeida Vaucher Center of Chemical Pharmaceutical and Food Sciences Microorganism Biochemistry and Molecular Biology Research Laboratory (LAPEBBIOM) Federal University of Pelotas (UFPEL) Pelotas Rio Grande do Sul Brazil Center of Chemical Pharmaceutical and Food Sciences Laboratory for Lipidomic and Bio-Organic Research Bioforensic Research Group Federal University of Pelotas (UFPEL) Pelotas Rio Grande do Sul Brazil Center of Chemical Pharmaceutical and Food Sciences Neurochemistry Inflammation and Cancer Laboratory Federal University of Pelotas (UFPEL) Pelotas Rio Grande do Sul Brazil Department of Chemistry Heterocycle Chemistry Center (NUQUIMHE) Federal University of Santa Maria (UFSM) Santa Maria Rio Grande do Sul Brazil Department of Microbiology and Parasitology Biology Institute Federal University of Pelotas (UFPEL) Pelotas Rio Grande do Sul Brazil

Seizures of agrochemical formulations have increased in Brazil and Rio Grande do Sul is among the Brazilian states with the highest number of seizures of these products obtained illicitly. The use of illicit formulations can cause significant harm to agricultural production, the environment, and non-target species. This study evaluated the cytotoxicity and oxidative stress of a seized formulation containing the herbicide imazethapyr (IMZT). Characterization of the herbicide included gas chromatography-mass spectrometry (GC-MS) and thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC)). Hemolytic and cytotoxicity assays in ZF-L hepatic cells showed IC50 values of 12.75 µg/mL, 3.01 µg/mL, 2.67 µg/mL, and 1.61 µg/mL for erythrocytes, [3(4,5-dimethyl)-2 bromide-5 diphenyl tetrazolium] (MTT), neutral red (NR), and lactate dehydrogenase (LDH) assays, respectively. The median IC50 of 2.84 µg/mL was used in oxidative stress assays, revealing increased reactive oxygen species (ROS) production, reduced total sulfhydryl content, and decreased superoxide dismutase (SOD) and catalase (CAT) activity. This study is the first to report in vitro oxidative stress induced by IMZT in the ZF-L cell line, emphasizing the importance of in vitro assays for assessing the toxic effects of seized agrochemicals on human health and the environment.

关键词： Agrochemical Imidazolinone Zebrafish Cell Viability Oxidative Damage

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Resection *** for hepatocellular carcinoma:a never ending challenge

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 443-446页

作者： Joana ferrer-Fàbrega Jordi Bruix Barcelona Clínic Liver Cancer Group(BCLC) IDIBAPSBarcelonaSpain Hepatic Oncology Unit Hospital ClínicBarcelonaSpain Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit Department of SurgeryInstitute Clínic of Digestive and Metabolic Diseases(ICMDiM)Hospital ClínicBarcelonaSpain Department of Medicine and Departament of Surgery University of BarcelonaBarcelonaSpain CIBERehd BarcelonaSpain Liver Unit Institute Clínic of Digestive and Metabolic Diseases(ICMDiM)Hospital ClínicBarcelonaSpain

Liver transplantation(LT)is fully established in conventional clinical care for patients with hepatocellular carcinoma(HCC).The long-term survival of transplanted patients competes with the survival offered by surgical resection and this sets the scene for a debate for which a consensus answer based in evidence is not *** outcomes have steadily improved due a refined selection of patients and the availability of other effective options such as ablation or locoregional approach(chemoembolization or radioembolization)has allowed to avoid its indication as a last effective resource for desperate *** evolution has taken place for LT as it was early shown that if the tumor burden was reduced the survival results would be encouraging(1).

关键词： Hepatocellular carcinoma(HCC) liver resection liver transplantation(LT) survival recurrence

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