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Bile-acid-induced cell injury and protection

World journal of Gastroenterology 2009年第14期15卷 1677-1689页

作者： maria j perez Oscar Briz Research Unit University Hospital of Salamanca Laboratory of Experimental Hepatology and Drug Targeting CIBERehd University of Salamanca E.D. 129 37007 Salamanca Spain

Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involvingoxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-N- methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.

关键词：肝细胞损伤胆汁酸保护肝细胞凋亡线粒体功能障碍熊去氧胆酸氧化损伤细胞毒性

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Interaction between diet and genetics in patients with inflammatory bowel disease

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World journal of Gastroenterology 2024年第12期30卷 1644-1650页

作者： Daniéla Oliveira Magro Ligia Yukie Sassaki júlio maria Fonseca Chebli Department of Surgery Faculty of Medical SciencesState University of Campinas(UNICAMP)Campinas 13083-970São PauloBrazil Department of Internal Medicine Medical SchoolSao Paulo State University(UNESP)Botucatu 18618-687São PauloBrazil Department of Medicine University Hospital of the Federal University of Juiz de ForaUniversity of Juiz de Fora School of MedicineJuiz de Fora 36036-247Minas GeraisBrazil

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of *** this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only ***,we provided dietary recommendations for patients with *** Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of *** the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)*** to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD *** patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red *** conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

关键词： Diet Genetics MicroRNAs Gastrointestinal microbiome Inflammatory bowel diseases Crohn’s disease

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Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： jose maria Martinez‑de‑la‑Casa Carlos Oribio‑Quinto Almudena Milans‑del‑Bosch Pilar perez‑Garcia Laura Morales‑Fernandez javier Garcia‑Bella jose Manuel Benitez‑del‑Castillo julian Garcia‑Feijoo David P.Pinero Ophthalmology Unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain Department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients *** current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop *** our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of ***:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye *** patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis *** in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after ***:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(SANDE)]as well as with the visual analogue scale(P<0.001).Mean change in OSDI was−15.0±11.3.A significant reduction was found after treatment in the corneal staining score(P<0.001).A significant reduction was found in tear film meniscus height(P=0.012),as well as in tear film osmolarity(P=0.001).A significant reduction was also found in meibomian gland expressibility(P=0.003),changing the percentage of grade 3 eyes from 44.4%before IPL to 17.2%after ***:IPL therapy combined with meibomian gland expression(MGX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface diseas

关键词： Glaucoma Intense pulsed light Dry eye Meibomian glands

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Plant triterpenoid saponins function as susceptibility factors to promote the pathogenicity of Botrytis cinerea

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Molecular Plant 2024年第7期17卷 1073-1089页

作者： Francisco j.Escaray Amelia Felipo-Benavent Cristian j.Antonelli Begona Balaguer maria Pilar Lopez-Gresa Pablo Vera Instituto de Biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.l.CCiudad Politecnica de la InnovacionEdificio 8Eacceso GIngeniero Fausto Elios/n46022ValenciaSpain

The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species,including high-value *** polyxenous nature and pathogenic success are due to its ability to perceive host signals in its *** this study,we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by *** to cause ***,poor-in-latex(pil)mutants,which lack laticifer cells,show full resistance to this pathogen,whereas lot-of-latex mutants,which produce more laticifer cells,are *** S factors are triterpenoid saponins,which are widely distributed natural products of vast structural *** downregulation of laticifer-specific oxydosqualene cyclase genes,which encode the first committed step enzymes for triterpene and,therefore,saponin biosynthesis,conferred disease resistance to ***,the Medicago truncatula Iha-1 mutant,compromised in triterpenoid saponin biosynthesis,showed enhanced ***,the application of different purified triterpenoid saponins pharmacologically complemented the diseaseresistant phenotype ofpil and hla-1 mutants and enhanced disease susceptibility in different plant *** found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in ***,leading to a change in its growth habit and infection strategy,culminating in the abundant formation of infection cushions,the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in *** together,these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote *** pathogenicity.

关键词： Euphorbia lathyris laticifer cell latex appressorium infection cushion necrotrophic fungi

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Experimental test of a building thermal system for preventive maintenance based on thermoeconomic analysis

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Energy Storage and Saving 2024年第1期3卷 42-51页

作者： I.Prol-Godoy A.Picallo-perez j.M.Sala-Lizarraga j.Rey-Martínez Research group ENEDI Department of Thermal EngineeringUniversity of the Basque Country(UPV/EHU)Bilbao48013Spain Research Group Termotecnia University of ValladolidValladolid47002Spain

An analysis of the sectorial structure of energy consumption shows that residential and tertiary sector buildings are the third-highest consumers,responsible for 29.5%of a city’s final energy *** Building Quality Control Laboratory of the Basque Government aims to promote quality,innovation,and sustainability in *** accomplish this goal,it has constructed an experimental facility with different energy generation technologies and a very versatile control system for testing different energy systems and operation *** this study,we tested a facility for supplying domestic hot water and heating for a multi-family house by means of a condensing boiler and an aerothermal heat pump(together with the corresponding control).This installation could reproduce the thermal demands required to be satisfied by the generation equipment through a programmed operation of the installation based on real ***,this installation was analyzed using thermoeconomics(TE)to solve problems unable to be solved using traditional energy analyses based on the First Law of *** problems include:(1)Determining the costs of the products of the installation based on physical criteria,(2)detecting the places where losses actually occur,evaluating their costs,and proposing cost-effective improvements,and(3)diagnosing issues in the *** a result,this paper suggests a solution to the preventive maintenance problems confronting the technical maintenance personnel for thermal installations in buildings by applying TE knowledge and using real data collected from sensors.

关键词： Experimental essay Energy savings in thermal systems Thermoeconomics Thermoeconomic costs Diagnosis

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Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease

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World journal of Gastroenterology 2024年第24期30卷 3022-3035页

作者： Marcia Henriques de Magalhães Costa Ligia Yukie Sassaki júlio maria Fonseca Chebli Department of Clinical Medicine Fluminense Federal UniversityRio de Janeiro 24210-200Brazil Department of Internal Medicine Medical SchoolSão Paulo State University(Unesp)Botucatu 18618-686São PauloBrazil Division of Gastroenterology Department of MedicineUniversity Hospital of The Federal University of Juiz de ForaUniversity of Juiz de Fora School of MedicineJuiz de Fora 36036-247Minas GeraisBrazil

Managing inflammatory bowel disease(IBD)is becoming increasingly complex and personalized,considering the advent of new advanced therapies with distinct mechanisms of *** mucosal healing(MH)is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares,hospitalization,surgery,intestinal damage,and colorectal *** proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation,even if subclinical,to alter the natural course of *** monitoring of fecal calprotectin(FC)levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD,assessing MH,and detecting subclinical ***,we comment on the article by Ishida et al Moreover,this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with ***,we intend to present some evidence on the role of these markers in future targets,such as histological and transmural *** prospective multicenter studies with a stricter MH criterion,standardized endoscopic and histopathological analyses,and virtual chromoscopy,potentially including artificial intelligence and other biomarkers,are desired.

关键词： Fecal calprotectin Endoscopic scores Mucosal healing Histological healing Ulcerative colitis Inflammatory bowel diseases

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Further understanding of mechanisms involved in liver cancer chemoresistance

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Hepatoma Research 2017年第1期3卷 22-26页

作者： Oscar Briz maria j.perez jose j.G.Marin Department of Physiology and Pharmacology University of Salamanca37007 SalamancaSpain

An important limitation for the success of chemotherapy in the treatment of primary liver cancer (hepatocellular carcinoma,hepatoblastoma and cholangiocarcinoma) is the marked efficacy of mechanisms of chemoresistance (MOC).These have been previously classified into five groups depending on whether they result in:a reduced drug uptake or enhanced drug export (MOC-1);poor intracellular activation of prodrugs or higher inactivation of active drugs (MOC-2);changes in the molecular targets that impairs the action of the drug by increasing the activity of the metabolic route to be inhibited or stimulating alternative routes (MOC-3);ability of tumor cells to repair drug-induced modifications in the target molecule,usually DNA (MOC-4);and the activation or inhibition of intracellular signaling pathways that lead to a change in the balance between proand anti-apoptotic factors favoring tumor cell survival (MOC-5).Nevertheless,novel information appeared over the last few years has recommended to consider two additional groups,MOC-6 and MOC-7,based on changes in tumor microenvironment,mainly hypoxia and acidity,and epithelial-mesenchymal transition,*** contribute to the defensive armamentaria developed or enhanced in liver cancer cells to resist the pharmacological attack,which accounts for a negligible beneficial effect of commonly used antitumor drugs and only a modest response to novel targeted therapies based on tyrosine kinase inhibitors,such as ***,further advances are urgently needed to better understand the molecular and cellular bases of the chemoresistant barrier and help scientists in this field to develop new tools able to overcome cancer cell defenses.

关键词： Chemotherapy cholangiocarcinoma hepatoblastoma hepatocellular carcinoma tumor environment epithelial-mesenchymal transition

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Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-perez jose j.Gil-Cosano Esther Ubago-Guisado Francisco j.Llorente-Cantarero juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino jonatan R.Ruiz Luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this ***,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar *** This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,***‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression *** regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass *** More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference *** strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all *** 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral *** Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all *** results suggest that interventions designed to improve muscle strength in t

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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Abnormal ACT in a Patient with Prekallikrein Deficiency Undergoing Cardiopulmonary Bypass

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Open journal of Anesthesiology 2024年第5期14卷 145-149页

作者： maria R. Fuertes Naila Ahmad Orlando perez-Franco Andrew Oster Marion Svendrowski Pin Yue Department of Anesthesiology and Critical Care Saint Louis University School of Medicine St. Louis MO USA

Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Thromboplastin Time and Activated Clotting Time in absence of anticoagulants or active bleeding. This case report describes the anesthesia management of a patient with Prekallikrein deficiency who underwent cardiac surgery with Cardiopulmonary Bypass for correction of a congenital cardiac malformation. We highlight the importance of understanding the different tests available for the diagnosis of coagulation factors deficiency during administration of heparin in the setting of cardiovascular procedures under general anesthesia.

关键词： Prekallikrein Deficiency Fletcher Factor Deficiency Cardiopulmonary Bypass Congenital Cardiac Malformation

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Structural performance of flexible freeform panelssubjected to wind loads

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Frontiers of Structural and Civil Engineering 2024年第6期18卷 851-869页

作者： Yong YOO Zaryab SHAHID Renzhe CHEN maria KOLIOU Anastasia MULIANA Negar KALANTAR Zachry Department of Civil and Environmental Engineering Texas A&M UniversityCollege StationTX 77843USA j.Mike Walker'66 Department of Mechanical Engineering Texas A&M UniversityCollege StationTX 77843USA Architecture Division California College of the ArtsSan FranciscoCA 94107USA

An increased number of hurricanes and tornadoes have been recorded worldwide in the last decade,while research efforts to reduce wind-related damage to structures become *** architecture,which focuses on generating complex curved shapes including streamlined shapes,has recently gained *** study focuses on investigating the potential of kerf panels,which have unique flexibility depending on the cut patterns and densities,to generate complex shapes for facades and their performance under wind *** investigate the kerf panel's potential capacity against wind loads,static and dynamic analyses were conducted for two kerf panel types with different cut densities and pre-deformed *** was observed that although solid panels result in smaller displacement amplitudes,stresses,and strains in some cases,the kerf panels allow for global and local cell deformations resulting in stress reduction in various locations with the potential to reduce damage due to overstress in *** the predeformed kerf panels,it was observed that both the overall stress and strain responses in kerf cut arrangements were lower than those of the flat-shaped *** study shows the promise of the use of kerf panels in achieving both design flexibility and performance demands when exposed to service *** that this newly proposed architectural configuration(design paradigm)for facades could revolutionize structural engineering by pushing complex freeform shapes to a standard practice that intertwines aesthetic arguments,building performance requirements,and material design considerations has the potential for significant practical applications.

关键词： freeform structure kerfing method wind load analysis cladding component

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