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Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： matheus Truccolo michalczuk Larisse Longo melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari joséEduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIm07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(mASLD).AIm To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(mmp2),and metalloproteinases-9(mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(map1 Lc3b),and p62/sequestosome-1(p62/SQSTm1)-*** with controls,map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(Pm1 was lower in HCC compared to RIF(Pmmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(Pm1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(PmiR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(Pmong groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma metabolic dysfunction-associated steatotic liver disease Rifaximin

Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： Laura García-mendívil maría Pérez-Zabalza Antoni Oliver-Gelabert josémaría Vallejo-Gil Javier Fañanás-mastral manuel Vázquez-Sancho Javier AndréBellido-morales Alexánder Sebastián Vaca-Núñez Carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental medicine and Biology of Cuyo(ImBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

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考古植物遗存中的碳稳定同位素

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东方考古 2024年第1期 146-179页

作者： Juan Pedro Ferrio mònica Aguilera Jordi Voltas josé Luis Araus 褚黎明阿拉贡研究与发展机构(ARAID) 阿拉贡农业研究与技术中心(CITA)森林资源部 CTFC-AGROTECNIO联合研究单位莱里达大学农作物与森林科学系巴塞罗那大学生物学院植物生理学部综合作物生理生态学组农业技术研究中心(AGROTECNIO) 山东大学文化遗产研究院

考古植物遗存是了解关于过去社会经历的社会和环境条件的宝贵信息来源。植物遗存巨大潜力的充分开发需要分析技术的应用。在这一背景下,考古植物遗存的碳稳定同位素组成或许能够提供关于环境条件、农业管理、食物网和饮食偏好等多方面... 详细信息

考古植物遗存是了解关于过去社会经历的社会和环境条件的宝贵信息来源。植物遗存巨大潜力的充分开发需要分析技术的应用。在这一背景下,考古植物遗存的碳稳定同位素组成或许能够提供关于环境条件、农业管理、食物网和饮食偏好等多方面的线索。本文全面介绍了分析植物遗存的碳稳定同位素在考古学中的潜在应用。在对决定植物碳稳定同位素特性的广泛生理和环境因素进行解释之后,对最相关的方法问题进行了讨论。其中,本文对样品的前处理方式、与大气变化有关的不确定性以及植物遗存在土壤中沉积前后经历的潜在变化进行了评述。以选定的案例研究为例,为碳稳定同位素在考古学中的应用提供了方法和概念上的线索。同时,也强调了依旧存在的挑战。

关键词：碳稳定同位素植物考古环境农业

Expanding the Boundaries of the Chemical Space of DNA methyltransferase 1 modulators

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Computational molecular Bioscience 2024年第1期14卷 1-16页

作者： massyel S. martínez-Cortés Diana L. Prado-Romero josé L. medina-Franco DIFACQUIm Research Group Department of Pharmacy School of Chemistry Universidad Nacional Autónoma de México Avenida Universidad 3000 Mexico City México

DNA methyltransferase 1 (DNmT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNmT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNmT1 inhibitors. However, only a limited number of DNmT1 activators have been disclosed because, at least in part, DNmT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNmT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNmT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.

关键词： Chemical multiverse Chemoinformatics Epigenetics Pharmacophore Hypothesis Small molecules

The Nikola Tesla Constant and Its Relation to the Circumference Inscribed in a Square

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Journal of Applied mathematics and Physics 2024年第1期12卷 277-283页

作者： Javier mendoza Navarrete josé Ismael Ojeda Campaña Huetzin Perez Gabriel Luna-Sandoval Victor Verdugo Ricardo Jiménez Garcia Departamento de matemáticas CBTis 256 DGETI Cabo San Lucas México División de Ingeniería en Sistemas Computacionales Tecnológico Nacional de México/ITES de Los Cabos Cabo San Lucas México DCI Departamento de Física médica Universidad de Guanajuato León México Departamento de Ingeniería Industrial en manufactura Universidad Estatal de Sonora Navojoa México Departamento de Eléctrica-Electrónica Tecnológico Nacional de México Campus Mexicali Mexicali México

This research work relates the surface of a square and the area circumscribed by a circle, resulting in a value called Nikola Tesla constant. This constant starts with the calculation of the areas of the square and the inscribed circle, giving a ratio of 9/40 and from which a residual area of the area proportions of the geometric figures described is obtained. Plotting smooth curves, particularly those in round shapes, can be represented efficiently with the use of Nikola Tesla constant, reducing complex mathematical calculus.

关键词： Tesla Numbers Prime Number Circle Binary Area

multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto Gomez-Carballa maria jose Curras-Tuala Sara Pischedda miriam Cebey-Lopez jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-Lasheras Antonio Justicia-Grande Julian montoto-Louzao Alba Camino-mera Isabel Ferreiros-Vidal maximo Fraga jose RAntunez Rodolfo Gomez Federico martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain Department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)***,the molecular mechanisms underlying HO remain poorly *** a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

Venopulmonary ECmO Improved Hypoxemia and Supported the Right Ventricle in a Patient with Decompensated Eisenmenger Syndrome

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World Journal of Cardiovascular Surgery 2024年第1期14卷 7-19页

作者： Daniel manzur-Sandoval Gian manuel Jiménez-Rodríguez Edgar García-Cruz Ramón Espinosa-Soto Erika Yamali Ramirez-marcano Yessenia máyory Téllez-López josé Luis Elizalde-Silva Gustavo Rojas-Velasco Cardiovascular Critical Care Unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Adult Congenital Heart Disease Unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Cardiology Department Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico

mechanical circulatory and/or respiratory assistance with extracorporeal membrane oxygenation (ECmO) has become a standard of care for patients with circulatory (venoarterial) and/or respiratory (venovenous) failure refractory to standard therapies. Adult patients with congenital heart disease are an increasingly recognized and growing population and include various groups, such as undiagnosed cases in childhood and palliated and/or corrected cases, which require subsequent care because of residual lesions, cardiac arrest/insufficiency, and arrhythmias, among other conditions. In addition, these patients are prone to developing pathologies that are typical of adulthood with a generally increased risk of morbidity and mortality because of their low reserves and organic damage associated with the underlying heart disease, which makes them candidates for ECmO. These patients represent an additional challenge in this therapy because malformations and the presence of a shunt can generally affect the usual cannulation methods and hemodynamic and oximetry monitoring. Thus, the configuration decision must be made on a case-by-case basis. Here, we present a cannulation method, venopulmonary artery ECmO, which provides hemodynamic and respiratory support, and may be ideal for patients with shunts and/or right ventricular dysfunction. To our knowledge, this is the first report of this configuration in patients with congenital heart diseases.

关键词： Eisenmenger Syndrome Venopulmonary Artery ECmO Refractory Hypoxemia Right Ventricular Dysfunction

Evidence-Based Complementary and Alternative medicine Effects of Capybara Oil on Cardiac Remodeling of C57bl/6 mice

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Journal of Biosciences and medicines 2024年第5期12卷 213-232页

作者： Rafael m. Almeida Wagner D. Giannetti Guilherme R. Silveira Carolina R. Castilho Renata V. Lisboa Bianca T. Ciambarella Rodrigo N. Ferreira Jorge josé de Carvalho Laboratory of Ultrastructure and Tissue Biology Institute of Biology State University of Rio de Janeiro Rio de Janeiro Brazil Higher Education Center of Valenç a Dom Andr&#233 Arcoverde Educational Foundation Valen&#231a Brazil

Cardiovascular diseases are the main cause of morbidity and mortality in the world, and obesity and the metabolic syndrome are risk factors for its development. One of the therapies to reduce cardiovascular risk is the use of polyunsaturated fatty acids. In Brazil, a source of such acid is the oil extracted from the fat of the capybara. The objective of this work is to study the effects of the capybara oil on lipid and glucose metabolism, as well as its effects on the adipose tissue and cardiac remodeling. We assessed the effects of capybara oil treatment on body mass, lipid and carbohydrate metabolism, systolic blood pressure, adipose tissue and cardiac remodeling, and performed an ultrastructural evaluation of the myocardium in C57Bl/6 mice treated with high-fat diet. Treatment with capybara oil reduced total cholesterol and triglyceride levels, systolic blood pressure, visceral and subcutaneous adipose tissue, and adipocyte diameter. In addition, cardiac remodeling was attenuated, preserving cardiomyocytes, increasing vascularization, reducing cardiomyocyte hypertrophy and the extracellular matrix, and preserving the morphological integrity of mitochondria. Capybara oil has several beneficial effects on the cardiovascular and metabolic system, and further studies are needed to better understand its role in the prevention or treatment of cardiovascular diseases.

关键词： Capybara Oil Cardiac Remodeling Polyunsaturated Fatty Acids Obesity metabolic Syndrome

Induced and heavy aggregation operators with distance measures

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Journal of Systems Engineering and Electronics 2010年第3期21卷 431-439页

作者： josé m.merigó montserrat Casanovas Department of Business Administration University of Barcelona

This paper introduces a new aggregation model by using induced and heavy aggregation operators in distances measures such as the Hamming *** is called the induced heavy ordered weighted averaging（OWA） distance（IHOWAD） *** paper studies some of its main properties and a wide range of particular cases such as the induced heavy OWA（IHOWA） operator,the induced OWA distance（IOWAD） operator and the heavy OWA distance（HOWAD） *** approach is generalized by using generalized and quasi-arithmetic means obtaining the induced generalized IHOWAD（IGHOWAD） operator and the Quasi-IHOWAD *** application of the new approach in a decision making problem regarding the selection of strategies is developed.

关键词： distance measures aggregation operators decision making OWA operator.