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Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology

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World Journal of Gastroenterology 2015年第24期21卷 7529-7544页

作者： nahum calvo Raúl Beltrán-Debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven Unitat de Recerca Biomèdica Hospital Universitari de Sant JoanInstitut d’Investigacio Sanitària Pere VirgiliUniversitat Rovira i VirgiliCampus of International Excellence Southern Catalonia Servei de Cirurgia General i de l’Aparell Digestiu Hospital Universitari de Sant Joan de ReusUniversitat Rovira i Virgili Metabolomics Platform Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas AsociadasIISPVUniversitat Rovira i Virgili Research and Collaborations General Electric Healthcare Metabolism and Cancer Group Transla-tional Research LaboratoryCatalan Institute of OncologyGirona Biomedical Research Institute

AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical ***: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected

关键词： Fatty liver disease Magnetic resonanceimaging Lipids Magnetic resonance spectroscopy Metabolomics Mitochondrial function Morbid obesity Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis

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Effect of processing parameters on in situ screen printing-assisted synthesis and electrical properties of Ti3SiC2-based structures

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Journal of Advanced Ceramics 2021年第1期10卷 129-138页

作者： Mylena LORENZ nahum TRAVITZKY Carlos R.RAMBO Department of Materials Science University of Erlangen-Nuremberg91058 ErlangenGermany Tomsk Polytechnic University 634050 TomskRussia Departm ent of Electrical and Electronic Engineering Federal University of Santa Catarina88040-900 FlorianopolisBrazil

This work reports on the development of pastes containing Ti,TiC,Si,and C elementary powders for in situ synthesis of Ti3SiC2 via screen *** paste compositions were manufactured using two powder mixtures(Ti/Si/C and Ti/TiC/Si/C)with different *** pastes were screen printed onto Al2O3 substrates and sintered at 1400℃in argon varying the dwell time from 1 to 5 *** printed pastes containing TiC and excess of Si exhibited the lowest surface roughness and after 5 h sintering comprised of Ti3SiC2 as the majority *** electrical conductivity of this sample was found to range from 4.63×10^(4)to 2.57×10^(5)S·m^(-1)in a temperature range of 25-400℃.

关键词： MAX phases Ti3SiC2 screen printing in situ synthesis electrical conductivity

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Why Is Being Nothing?An Apophatic Reading of Hegel's Opening to the Science of Logic

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Frontiers of Philosophy in China 2018年第4期13卷 518-534页

作者： nahum Brown Department of Philosophy Sun Yat-sen UniversityZhuhai 519000China

The aim of this article is to analyze Hegel’s famous transition from being to nothing in the opening of the Science of Logic, to outline a variety of interpretations from commentators, and to defend what I call the “indirect apophatic interpretation” as support for the conclusion that Hegel is an ambiguously apophatic thinker. One benefit of the “indirect apophatic interpretation” is that it leads to a reassessment of Hegel’s conception of totality. The prevailing understanding of “totality” as exclusionary exhaustion, completion, and finitude has often been attributed to Hegel’s thought. But the “indirect apophatic interpretation” of the transition from being to nothing that I defend prepares the way for an alternative reading of totality in his work: not as the exhaustion of all positive content, but as the coincidence of being and nothing, as the contradiction A is -A, and as the exhaustion of form and content by way of a dialectic with the apophatic.

关键词： Hegel being nothing apophasis beginning

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Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

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World Journal of Gastroenterology 2023年第25期29卷 3999-4008页

作者： Shreya C Pal nahum Méndez-Sánchez Faculty of Medicine National Autonomous University of MexicoMexico City 04510Mexico Liver Research Unit Medica Sur Clinic&FoundationMexico City 04510Mexico

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty *** is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple *** a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this *** is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of *** same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the *** complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the *** aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

关键词： Metabolic(dysfunction)-associated fatty liver disease Insulin resistance Adipose tissue Fatty liver Metabolic syndrome Adipokine

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Gut Microbiota in Metabolic-associated Fatty Liver Disease and in Other Chronic Metabolic Diseases

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 227-238页

作者： Winston Hernández-Ceballos Jacqueline Cordova-Gallardo nahum Mendez-Sanchez Plan of Combined Studies in Medicine(PECEM-MD/PhD) Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Department of Hepatology Service of Surgery and Obesity ClinicGeneral Hospital“Dr.Manuel Gea González”Mexico CityMexico Faculty of Medicine.National Autonomous University of Mexico Mexico CityMexico Liver Research Unit Medica Sur Clinic&FoundationMexico CityMexico

The gut microbiome plays a key role in the health-disease balance in the human *** its composition is unique for each person and tends to remain stable throughout lifetime,it has been shown that certain bacterial patterns may be determining factors in the onset of certain chronic metabolic diseases,such as type 2 diabetes mellitus(T2DM),obesity,metabolic-associated fatty liver disease(MAFLD),and metabolic *** gut-liver axis embodies the close relationship between the gut and the liver;disturbance of the normal gut microbiota,also known as dysbiosis,may lead to a cascade of mechanisms that modify the epithelial properties and facilitate bacterial *** of gut microbiota is fundamental to maintaining gut integrity,as well as the bile acids *** the present review,we summarize the current knowledge regarding the microbiota,bile acids composition and their association with MAFLD,obesity,T2DM and metabolic syndrome.

关键词： Metabolic-associated fatty liver disease Metabolic-associated steatohepatitis Gut microbiota Gut-liver axis Dysbiosis Bile acids

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Probiotics supplementation in the management of hepatocellular carcinoma

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Hepatobiliary Surgery and Nutrition 2019年第6期8卷 632-634页

作者： Ludovico Abenavoli Francesco Luzza nahum Mendez-Sanchez Department of Health Sciences University Magna GraeciaCatanzaroItaly Liver Research Unit Medica Sur Clinic&Foundation and Faculty of Medicine National Autonomous University of MexicoMexico CityMexico

Hepatocellular carcinoma(HCC,also known as primary liver cancer),is the fourth most frequent cancer and the third cause of deaths associated with cancer worldwide(1).HCC occurs in liver damaged tissue,due to chronic regenerative and inflammatory processes that contribute to the initiation and progression of the tumor(2).The main environmental factors associated with HCC are hepatotropic viral infection(hepatitis B and C,particularly),excessive consumption of alcohol,and exposure to aflatoxin through the ***,in the last 20 years,non-alcoholic fatty liver disease(NAFLD)has become a quickly emerging cause of end-stage liver disease ***,its hepatic injury starts with simple steatosis,which can progress to advanced stages such as non-alcoholic steatohepatitis(NASH),fibrosis and finally *** studies report that about 3-15%of the obese patients with NASH progress to cirrhosis,and about 4-27%of NASH patients with cirrhosis present HCC(1).

关键词： hepatic NAFLD finally

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From prediction to prevention:Machine learning revolutionizes hepatocellular carcinoma recurrence monitoring

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World Journal of Gastroenterology 2024年第7期30卷 631-635页

作者： Mariana Michelle Ramírez-Mejía nahum Méndez-Sánchez Plan of Combined Studies in Medicine Faculty of MedicineNational Autonomous University of MexicoDistrito Federal 04510Mexico Liver Research Unit Medica Sur Clinic&FoundationDistrito Federal 14050Mexico Faculty of Medicine National Autonomous University of MexicoDistrito Federal 04510Mexico

In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular *** carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative *** recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient *** predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC *** integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC *** study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC *** persist,including sample size constraints,issues with handling data,and the need for further validation and *** study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the *** these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology *** study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.

关键词： Hepatocellular carcinoma Early recurrence Machine learning XGBoost model Predictive precision medicine Clinical utility Personalized interventions

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Descemet stripping automated endothelial keratoplasty in phakic eyes:incision modification reducing cataract formation

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International Journal of Ophthalmology(English edition) 2018年第1期11卷 53-57页

作者： Jacqueline Beltz Silvana Madi Yoav nahum Paolo Santorum Massimo Busin Department of Ophthalmology Villa Igea Private HospitalForli 47122Italy Istituto Internazionale per la Ricerca e Formazione in Of talmologia(IRFO) Forli 47122Italy Department of Morphology Surgery and ExperimentalSurgeryUniversity of FerraraFerrara 44100Italy Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalMelbourne 3002Australia Department of Ophthalmology Alexandria University HospitalAlexandria 21527Egypt Department of Ophthalmology Rabin Medical CenterPetahTikva 49100Israel Sackler Faculty of Medicine Tel Aviv UniversityTel Aviv 69978Israel Department of Ophthalmology San Maurizio Regional HospitalBolzano 39100Italy

AIM： To evaluate the efficacy of a technical modification to reduce the incidence of traumatic cataract induced by Descemet stripping automated endothelial keratoplasty（DSAEK） performed in phakic eyes. METHODS： A retrospective cohort study. The records of all patients with a clear crystalline lens and endothelial failure that underwent modified DSAEK at our insitution were reviewed. In this modification, in order to avoid inadvertent touch of the insertion forceps against the exposed crystalline lens while passing across the anterior chamber, the incision sites were shifted from the standard 9 and 3 o＇clock positions, superiorly to the 10 and 2 o＇clock position respectively. Formation of typically traumatic, anterior subcapsular cataract in these patients was compared to that observed in a cohort including all the patients with a clear crystalline lens and endothelial failure that underwent conventional DSAEK at our ***： The study group included 49 eyes following modified DSAEK and the control group included 35 eyes following DSAEK with conventional incision sites. Anterior subcapsular cataract occurring 4 mo or less postoperatively was identified in 2 of 49（4%） eyes in the study group and 7 of 35（20%） eyes in the control group. The rates of traumatic cataract were significantly higher in the control group in comparison to the study group（P=0.03, RR=4.9, 95%CI 1.08-22.1）.CONCLUSION： Traumatic cataract formation following phakic DSAEK may be avoided with a simple modification to the position of the incision sites.

关键词： cornea Descemet stripping automated endothelial keratoplasty cataract lamellar keratoplasty

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Proteome profiling to advance management of metabolic dysfunction-associated fatty liver disease

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 147-149页

作者： Mohammed Eslam nahum Méndez-Sánchez Ming-Hua Zheng Storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNSWAustralia Liver Research Unit Medica Sur Clinic FoundationMexico CityMexico MAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a complex,heterogenous and progressive disease that is characterised by substantial phenotypic variability,which results in disparate clinical presentations and outcomes(1-4).Notably,only a proportion of patients with MAFLD progress to the more advanced stages of the ***,the identification of the subgroups that have a high risk of disease progression is of paramount importance for clinical care,as well as drug development and clinical trials(5).

关键词： Metabolic dysfunction-associated fatty liver disease(MAFLD) fatty liver disease(FLD) fibrosis proteome biomarkers

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Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

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World Journal of Gastroenterology 2016年第31期22卷 6965-6971页

作者： Priya Handa Akhila Vemulakonda Kris V Kowdley Misael Uribe nahum Méndez-Sánchez Senior Research Scientist Organ Care Research and Liver Care Network Swedish Medical Center Liver Research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

关键词： TLR9 Damage-associated molecular patterns Products of microbial metabolism produced by pathogens Mitochondrial DNA Hepatocytes Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease Inflammation Innate immune signaling Kupffer cells Therapy

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