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Liver tissue microbiota in nonalcoholic liver disease:a change in the paradigm of host-bacterial interactions

Hepatobiliary Surgery and Nutrition 2021年第3期10卷 337-349页

作者： Silvia Sookoian carlos j.pirola School of Medicine Institute of Medical Research A LanariUniversity of Buenos AiresCiudad Autónoma de Buenos AiresArgentina Department of Clinical and Molecular Hepatology Institute of Medical Research(IDIM)National Scientific and Technical Research Council(CONICET)University of Buenos AiresCiudad Autónoma de Buenos AiresArgentina Department of Molecular Genetics and Biology of Complex Diseases Institute of Medical Research(IDIM)National Scientific and Technical Research Council(CONICET)University of Buenos AiresCiudad Autónoma de Buenos AiresArgentina

Nonalcoholic fatty liver disease(NAFLD)pathogenesis is explained by the complex relationship among diet and lifestyle-predisposing factors,the genetic variance of the nuclear and mitochondrial genome,associated phenotypic traits,and the yet not fully explored interactions with epigenetic and other environmental factors,including the *** the wealth of knowledge gained from molecular and genome-wide investigations in patients with NAFLD,the precise mechanisms that explain the variability of the histological phenotypes are not fully *** studies of the gut microbiota in patients with NAFLD and nonalcoholic steatohepatitis(NASH)provided clues on the role of the fecal microbiome in the disease ***,the composition of the gut microbiota does not fully explain tissue-specific mechanisms associated with the degree of disease severity,including liver inflammation,ballooning of hepatocytes,and *** liver acts as a key filtration system of the whole body by receiving blood from the hepatic artery and the portal ***,not only microbes would become entrapped in the complex liver anatomy but,more importantly,bacterial derived products that are likely to be potentially powerful stimuli for initiating the inflammatory ***,the study of liver tissue microbiota offers the opportunity of changing the paradigm of host-NAFLD-microbial interactions from a“gut-centric”to a“liver-centric”***,we highlight the evidence on the role of liver tissue bacterial DNA in the biology of NAFLD and ***,we provide evidence of metagenomic findings that can serve as the seed of further hypothesis-raising studies as well as can be leveraged to discover novel therapeutic targets.

关键词： Nonalcoholic fatty liver disease(NAFLD) nonalcoholic steatohepatitis(NASH) HSD17B13 microbiota microbiome proteobacteria lipopolysaccharide(LPS) drug prediction

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Tackling the complexity of nonalcoholic steatohepatitis treatment:challenges and opportunities based on systems biology and machine learning approaches

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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 495-498页

作者： carlos j.pirola Silvia Sookoian School of Medicine Institute of Medical Research A LanariUniversity of Buenos AiresCiudad Autonoma de Buenos AiresArgentina Department of Molecular Genetics and Biology of Complex Diseases Institute of Medical Research(IDIM)University of Buenos Aires-National Scientific and Technical Research Council(CONICET)Ciudad Autónoma de Buenos AiresArgentina Department of Clinical and Molecular Hepatology Institute of Medical Research(IDIM)University of Buenos Aires-National Scientific and Technical Research Council(CONICET)Ciudad Autónoma de Buenos AiresArgentina

Nonalcoholic fatty liver disease(NAFLD)is regarded as the most frequent cause of chronic liver damage(1,2).The natural history of the disease presents a complex scenario of potential progression into severe clinical outcomes,including nonalcoholic steatohepatitis(NASH),NASH-fibrosis,cirrhosis,and hepatocellular carcinoma(1,2).In addition,NAFLD is closely associated with comorbidities of the metabolic syndrome(MetS),including type 2 diabetes,obesity,arterial hypertension,and dyslipidemia,which together aggravate the morbidity and mortality associated with the disease.

关键词： NAFLD liver arterial damage

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Nonalcoholic steatohepatitis pharmacotherapy and predictors of response: dual role of aminotransferases as biosensors of metabolism and biomarkers of histological improvement

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 381-385页

作者： Silvia Sookoian carlos j.pirola School of Medicine Institute of Medical Research A.LanariUniversity of Buenos AiresBuenos AiresArgentina Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council(CONICET)and University of Buenos AiresInstitute of Medical Research(IDIM)Buenos AiresCiudad Autónoma de Buenos Aires(C1427ARN)Argentina Department of Molecular Genetics and Biology of Complex Diseases National Scientific and Technical Research Council(CONICET)and University of Buenos AiresInstitute of Medical Research(IDIM)Buenos AiresCiudad Autónoma de Buenos Aires(C1427ARN)Argentina

Nonalcoholic steatohepatitis (NASH)—the severe histological form of nonalcoholic fatty liver disease (NAFLD)—is regarded as a major health problem worldwide (1,2). The disease can progress to liver cirrhosis and eventually to hepatocellular carcinoma (1,3). Treatment of NASH and NASH-fibrosis is thus increasingly being given priority in the clinical field. Yet, these efforts face challenges not only related to the design and validation of novel pharmacological agents, but also to the need to optimize treatment options as well as improve access to therapies. In fact, while many drugs are currently being tested for safety and efifcacy, only a few approved options for the treatment of NASH presently exist (4,5). It is thus expected that, in the near future, emphasis will be given to selecting the right drug for treating NASH patients from a wide spectrum of treatment choices. Hence, identiifcation of early predictors of treatment response represents an unmet and relevant need.

关键词： metabolism histological drugs

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Supercritical fluid technology as a sustainable alternative method for textile dyeing:An approach on waste,energy,and CO_(2)emission reduction

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journal of Environmental Sciences 2024年第6期140卷 123-145页

作者： carlos Rafael Silva de Oliveira Patrícia Viera de Oliveira Leandro Pellenz Catia Rosana Lange de Aguiar Afonso Henrique da Silva júnior Federal University of Santa Catarina Textile Engineering Department2514 João Pessoa St.BlumenauSC89036-004Brazil Federal University of Santa Catarina Chemical Engineering DepartmentS/n Biotério Central St.FlorianópolisSC88040-900Brazil

The clothing industry is considered one of the most polluting industries on the planet due to the high consumption of water,energy,chemicals/dyes,and high generation of solid waste and *** with environmental concerns,the textile ennoblement sector is the most critical of the textile production chain,especially the traditional dyeing *** an alternative to current problems,dyeing with supercritical CO_(2)(scCO_(2))has been presented as a clean and efficient process for a sustainable textile *** fluid dyeing(SFD)has shown a growing interest due to its significant impact on environmental preservation and social,economic,and financial *** main SFD benefits include economy and reuse of non-adsorbed dyes;reduction of process time and energy expenditure;capture of atmospheric CO_(2)(greenhouse gas);use and recycling of CO_(2)in SFD;generation of carbon credits;water-free process;effluent-free process;reduction of CO_(2)emission and auxiliary *** being still a non-scalable and evolving technology,SFD is the future of *** review presented a comprehensive overview of the environmental impacts caused by traditional processes and confronted the advantages of *** SFD technique was introduced,along with its latest advances and future *** and environmental gains were also discussed.

关键词： Textile industry Supercritical dyeing Sustainable processes Water free dyeing Energy saving Cleaner production

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Mortality rate after total knee arthroplasty or total hip arthroplasty in patients with a history of liver transplant

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World journal of Orthopedics 2024年第4期15卷 310-311页

作者： E carlos Rodriguez-Merchan Department of Orthopedic Surgery La Paz University Hospital-IdiPazMadrid 28046Spain

In this editorial I comment on the article by Ahmed et al published in a recent issue of the World j Orthop 2023;14:*** is well known that patients who have undergone a liver transplant(LT)may need to have a total hip arthroplasty(THA)or total knee arthroplasty(TKA)*** et al stated that the mortality rate in these patients was similar to the one of the general ***,there are three articles previously published that found higher mortality in LT patients who experienced THA/TKA than in the general population(individuals without LT).Therefore,in this Editorial I would like to point out that there is controversy in the literature regarding whether LT patients undergoing THA/TKA have higher mortality than the general ***,future research should attempt to resolve this controversy.

关键词： Liver transplant Total knee arthroplasty Total hip arthroplasty Results Mortality

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Repurposing drugs to target nonalcoholic steatohepatitis

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World journal of Gastroenterology 2019年第15期25卷 1783-1796页

作者： Silvia Sookoian carlos j.pirola Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council (CONICET) University of Buenos Aires Institute of Medical Research (IDIM) Department of Molecular Genetics and Biology of Complex Diseases National Scientific and Technical Research Council (CONICET) University of Buenos Aires Institute of Medical Research (IDIM)

Nonalcoholic fatty liver disease(NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack of approved pharmacological interventions for the treatment of nonalcoholic steatohepatitis(NASH) and NASH-fibrosis-the severe histological forms. Over the past decade,tremendous advances have been made in NAFLD research, resulting in the discovery of disease mechanisms and novel therapeutic targets. Hence, a large number of pharmacological agents are currently being tested for safety and efficacy. These drugs are in the initial pharmacological phases(phase 1 and 2),which involve testing tolerability, therapeutic action, and pharmacological *** is thus reasonable to assume that the next generation of NASH drugs will not be available for clinical use for foreseeable future. The expected delay can be mitigated by drug repurposing or repositioning, which essentially relies on identifying and developing new uses for existing drugs. Here, we propose a drug candidate selection method based on the integration of molecular pathways of disease pathogenesis into network analysis tools that use OMICs data as well as multiples sources, including text mining from the medical literature.

关键词： Drug discovery Drug repositioning Fibrosis Genetics Treatment Systems biology

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Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

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World journal of Gastroenterology 2018年第15期24卷 1601-1615页

作者： carlos j.pirola Silvia Sookoian Department of Genetics and Molecular Biology of Complex Diseases. University of Buenos Aires Institute of Medical Research A Lanari Buenos Aires Argentina National Scientific and Technical Research Council-University of Buenos Aires. Institute of Medical Research (IDIM) Clinical and Molecular Hepatology University of Buenos Aires Institute of Medical Research A Lanari Buenos Aires Argentina National Scientific and Technical Research Council-University of Buenos Aires. Institute of Medical Research (IDIM)

This review intends to uncover how information from large-scale genetic profiling(whole genome sequencing, and whole exome sequencing) of nonalcoholic fatty liver disease(NAFLD), as well as information from circulating transcriptomics(cell-free mi RNAs) and metabolomics, contributes to the understanding of NAFLD pathogenesis. A further aim is to address the question of whether OMICs information is ready to be implemented in the clinics. The available evidence suggests that any new knowledge pertaining to molecular signatures associated with NAFLD and nonalcoholic steatohepatitis should be promptly translated into the clinical setting. Nevertheless, rigorous steps that must include validation and replication are mandatory before utilizing OMICs biomarkers in diagnostics to identify patients at risk of advanced disease, including liver cancer.

关键词： nonalcoholic steatohepatitis Fibrosis Liver biopsy Genetics PNPLA3 TM6SF2 Metabolomics Proteomics Transcriptomics nonalcoholic fatty liver disease miR122

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Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

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Plant Diversity 2024年第4期46卷 491-501页

作者： Guillermo Bañares-de-Dios Manuel j.Macía Gabriel Arellano Íñigo Granzow-de la Cerda julia Vega-álvarez Itziar Arnelas carlos I.Espinosa Norma Salinas Luis Cayuela Departamento de Biología y Geología Física y Química InorgánicaUniversidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain Departamento de Biología Área de BotánicaUniversidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Centro de Investigación en Biodiversidad y Cambio Global(CIBC-UAM) Universidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Ecology and Evolutionary Biology University of MichiganAnn ArborMI 48109USA Oikobit LLC ***AlbuquerqueNM87120USA Real jardín Botánico–CSIC Plaza Murillo 2MadridES-28014Spain Departamento de Biología Animal EcologíaParasitologíaEdafología y Química AgrícolaUniversidad de SalamancaCalle Donantes de Sangre s/nSalamancaES-37007Spain Departamento de Biodiversidad Ecología y EvoluciónUniversidad Complutense de MadridCalle JoséAntonio Nováis 12Ciudad UniversitariaES-28040Spain Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de LojaA.P.11-01-608 LojaEcuador Sección Química Pontificia Universidad Católica del PerúA.P.Lima 32LimaPeru ECI School of Geography and EnvironmentUniversity of OxfordOX13QYOxfordshireUnited Kingdom Instituto de Investigación en Cambio Global(IICG-URjC) Universidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short *** research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be *** first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary *** investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill *** exception was a slight increase in phylogenetic diversity when dominant species were *** decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional ***,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional *** phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate *** could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

关键词： Altitudinal gradients Andes Environmentalﬁltering Out of the Tropical Lowlands Functional rarity Tropical Niche Conservatism

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Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system

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World journal of Gastroenterology 2021年第4期27卷 305-320页

作者： carlos jose pirola Adrian Salatino Silvia Sookoian Department of Molecular Genetics and Biology of Complex Diseases National Scientific and Technical Research Council(CONICET)University of Buenos AiresInstitute of Medical Research(IDIM)Ciudad Autónoma de Buenos Aires C1427AROArgentina Institute of Medical Research A Lanari University of Buenos AiresSchool of MedicineCiudad Autónoma de Buenos AiresCiudad Autónoma de Buenos Aires C1427AROArgentina Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council(CONICET)University of Buenos AiresInstitute of Medical Research(IDIM)Ciudad Autónoma de Buenos Aires C1427AROArgentina

Genome-wide association studies of complex diseases,including nonalcoholic fatty liver disease(NAFLD),have demonstrated that a large number of variants are implicated in the susceptibility of multiple traits—a phenomenon known as pleiotropy that is increasingly being explored through phenome-wide association *** focused on the analysis of pleiotropy within variants associated with hematologic traits and *** used information retrieved from large public National Health and Nutrition Examination Surveys,Genome-wide association studies,and phenome-wide association studies based on the general population and explored whether variants associated with NAFLD also present associations with blood cell-related ***,we applied systems biology approaches to assess the potential biological connection/s between genes that predispose affected individuals to NAFLD and nonalcoholic steatohepatitis,and genes that modulate hematological-related traits—specifically platelet *** reasoned that this analysis would allow the identification of potential molecular mediators that link NAFLD with *** associated with platelet count are most highly expressed in the liver,followed by the pancreas,heart,and ***,genes associated with NAFLD presented high expression levels in the brain,lung,spleen,and *** mapping,gene prioritization,and functional analysis of the most significant loci(P<1×10-8)revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance *** conclusion,variants in genes influencing NAFLD exhibit pleiotropic associations with hematologic traits,particularly platelet ***,significant enrichment of related genes with variants influencing platelet traits was noted in metabolic-related ***,this approach yields novel mechanistic insights into NAFLD pathogenesis.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Platelets Leukocytes Hematologic traits Genetics

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Complexed amino acid minerals ***-glycinate chelated minerals:Impact on the performance of old laying hens

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Animal Nutrition 2024年第1期16卷 395-408页

作者： Marcos j.B.Santos Maria C.M.M.Ludke Leandro M.Silva carlos B.V.Rabello Mércia R.Barros Fabiano S.Costa Clariana S.Santos jamille S.S.Wanderley Department of Animal Science Rural Federal University of PernambucoRecifePEBrazil Department of Veterinary Science Rural Federal University of PernambucoRecifePEBrazil

The present study was to evaluate the effect of trace minerals(Zn,Mn,and Cu)from complexed amino acid minerals(ZMCAA)and bis-glycinate chelated minerals(ZMCGly)in laying hen diets on performance,internal and external egg quality,yolk mineral deposition,intestinal morphometry,and bone *** 78 to 98 weeks of age,400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per *** were distributed in a 2×2 factorial arrangement using either Zn,Mn,and Cu of ZMCAA or ZMCGly source at 2 levels:low(20,20,and 3.5 mg/kg of Zn,Mn,and Cu,respectively)or high(40,40,and 7 mg/kg of Zn,Mn,and Cu,respectively).The analysis of variance was performed,and in cases where differences were observed,the means were compared using Tukey?s test(P<0.05).The source and level of trace mineral supplementation had a significant impact on the performance of laying *** fed ZMCAA had higher egg production(P=0.01),egg weight(P=0.02),egg mass(P=0.01),and lower feed conversion ratio(P=0.05)compared to those fed *** ZMCAA supplementation showed higher albumen height(P=0.01),albumen weight(P=0.01),and eggshell thickness(P<0.01).The deposition of Zn(P<0.01),Mn(P<0.01),and Cu(P<0.01)in the egg yolk was greater for hens received *** weight(P=0.04)and bone densitometry(P<0.01)in the tibia were higher with ZMCAA *** the small intestine,ZMCAA resulted in longer villi(P=0.02)and shorter crypt depth(P=0.01)in the *** and ileum measurements were influenced by the level and source of trace minerals(P<0.05).Laying hens fed ZMCAA exhibited superior performance,egg quality,deposition of trace minerals in the egg yolk,and bone density compared to hens fed *** this study,older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

关键词： Bis-glycinates Metal-amino acids Radiodensity Trace minerals

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