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Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

World Journal of Hepatology 2018年第1期10卷 124-133页

作者： Edilmar Alvarado-Tapias Carlos Guarner-Argente Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román mar concepción maria Poca Cristina Gely Oana Pavel Juan Camilo nieto Cándido Juárez Carlos Guarner Germán Soriano Department of Gastroenterology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Instituto de Salud Carlos III Institut de Recerca IIBSant PauUniversitat Autònoma de BarcelonaBellaterra(Cerdanyola del Vallès)08193Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Department of Immunology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Escola Universitària d’Infermeria EUI-Sant Pau Hospital de la Santa Creu i Sant PauBarcelona 08025Spain

AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. COnCLUSIOn Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

关键词： Cirrhosis Genetic polymorphisms Toll-like receptor 4 Bacterial infections Ascites

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From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： Juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio maría del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean Gabriel Gonzáles-Yovera maría Alejandra Quispe-Flores Luis Alberto concepción-Urteaga Alejandro Román-González José Paz-Ibarra marcio José concepción-Zavaleta non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

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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 maría-Cristina Chueca maría-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 maize.nevertheless,the possible impact of these tools on nontarget arthropods still needs to be evaluated.In 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 investigated.Canopy-dwelling arthropods were sampled by visual inspection and yellow sticky traps.The Bt variety had no effect on any group of studied arthropods,except for the expected case of corn borers—the target pests of Bt maize.Regarding 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 herbicides.This effect was especially pronounced in a treatment involving two glyphosate applications.The 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 leafhoppers.These differences,however,were only significant in the last year of the study.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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Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

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World Journal of Gastroenterology 2024年第14期30卷 1982-1989页

作者： Julieta Trinks maría F Mascardi Adrián Gadano Sebastián marciano Instituto de Medicina Traslacional e Ingeniería Biomédica-Consejo nacional de Investigaciones Científicas y Técnicas-Instituto Universitario del Hospital Italiano-Hospital Italiano de Buenos Aires Ciudad Autónoma de Buenos Aires C1199ACLArgentina Consejo nacional de Investigaciones Científicas y Técnicas Ciudad Autónoma de Buenos Aires C1425FQBArgentina Liver Unit Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina Department of Research Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

关键词： Metabolic dysfunction-associated steatotic liver disease non-alcoholic steatohepatitis Biomarker Risk stratification Omics

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Vigorous,but differential mononuclear cell response of cirrhotic patients to bacterial ligands

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World Journal of Gastroenterology 2011年第10期17卷 1317-1325页

作者： Varenka J Barbero-Becerra maría concepción Gutiérrez-Ruiz Carmen Maldonado-Bernal Félix I Téllez-Avila Roberto Alfaro-Lara Florencia Vargas-Vorácková Department of Gastroenterology Instituto Nacional de Ciencias Médicasy Nutrición Salvador Zubirán Laboratorio de Fisiología Celular División de Ciencias de la Salud Universidad Autónoma Metropolitana-Iztapalapa Unidad de Investigación Médica en Enfermedades Infecciosasy Parasitarias Hospital de Pediatría Unidad de Investigación en Enfermedades Oncológicas Hospital Infantil de México Federico Gómez

AIM: To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS: Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis.Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor (TnF) α, interleukin (IL)-1β, IL-6, IL-12 and IL-10 secretion in supernatants was determined by ELISA. RESULTS: Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononuclear cells from cirrhotic patients, (P nd lipoteichoic acid induced a further increase in CD14 expression (P nd a decrease in Toll-like receptor 2 (P nd Toll-like receptor 4 (P n. With the exception of TnFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions (P nce exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former (P nFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P nFα; P nse of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. COnCLUSIOn: Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide, suggesting that immune regulation mechanisms are still pr

关键词：单核细胞肝硬化细菌性患者外周血单个核细胞 Toll样受体4 配体肿瘤坏死因子

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez maría Fernanda González Ana maría Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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neural Regeneration Research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier Ramos Laboratorio de neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRnAs or lncRnA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Relationship between D90 and D100 with Biochemical and Local Failure in Low-risk Prostate Cancer Treated with Low-rate Brachytherapy(LDR)

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Journal of Oncology Research 2022年第2期4卷 1-12页

作者： marta Domínguez Morcillo Carmen Ibáñez Villoslada Joaquín navarro Castellón Paula Sáez Bueno Eliseo Carrasco Esteban Andrea Matas Escamillas Zigor Zalabarría Zarrabeitia maría concepción López Carrizosa Department of Radiation Oncology Hospital Central de la DefensaUniversidad de Alcaláde HenaresMadridSpain

Low dose rate brachytherapy(LDR)is an accepted,effective treatment with few local side effects,used as monotherapy in patients with low-risk prostate cancer(PC).The aim of this paper is to analyse 245 patients treated with LDR in the Radiation Oncology Department of the Hospital Gómez Ulla,from 2004 to 2016,evaluating the relationship of dosimetric parameters with biochemical and local recurrence as well as genitourinary and gastrointestinal toxicity derived from the technique.The results obtained show a clear relationship between the dose used and biochemical and local failure.

关键词： Brachytherapy Prostate Cancer Dose Failure Biochemical Local

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Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán maría Dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and Liver Transplantation Unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.

关键词： Machine learning Liver surgery Artificial intelligence Random forest Prediction model

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The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1042-1048页

作者： maría Ximena núñez Andrea Acosta-Ortega Guillermo Raul Vera-Duarte Catalina Gómez-Duarte Unit of Cornea Cataract and Refractive SurgeryVision Sana Research GroupClínica de Oftalmología de CaliFaculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Faculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Hospital de ClínicasNational University of AsunciónAsunción 111421Paraguay

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)ofn the lower eyelid of each eye,and non-invasive tear break-up time(nI-TBUT)ndomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with Pnalysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,nIBUT,and OSDI.There was a significant difference between ILux®and MMGE(Pnth in MGS,nI-BUT,and OSDI scores.no adverse events were reported.COnCLUSIOn:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

关键词： meibomian gland dysfunction ILux® ocular surface dry eye

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