Browsing by Author "Maracaja, Vinicius"
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Publication Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen(2023) Huang, Ya-Lin; De Gregorio, Cristian; Silva, Verónica; Elorza, Álvaro; Léniz, Patricio; Aliaga, Víctor; Maracaja, Vinicius; Budini, Mauricio; Ezquer, Fernando; Ezquer, MarceloDrug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.Publication Characterization of microbial communities from gut microbiota of hypercholesterolemic and control subjects(2022) Morales, Cristian; Rojas, Gabriel; Rebolledo, Camilo; Rojas, Marcelo; Arias, Raúl; Cuadros, Sara; Maracaja, Vinicius; Saavedra, Kathleen; Leal, Pamela; Lanas, Fernando; Salazar, Luis; Saavedra, NicolasIntroduction: In recent years, several studies have evidenced the importance of the microbiome to host physiology as metabolism regulator, along with its potential role in triggering various diseases. In this study, we analyzed the gut microbiota in hypercholesterolemic (cases) and normocholesterolemic (controls) individuals to identify characteristic microbial signature for each condition. Methods: Stool samples were obtained from 57 adult volunteers (27 hypercholesterolemic and 30 controls). The taxonomic profiling of microbial communities was performed using high-throughput sequencing of 16S rRNA V3-V4 amplicons, followed by data analysis using Quantitative Insights Into Microbial Ecology 2 (QIIME2) and linear discriminant analysis (LDA) effect size (LEfSe). Results: Significant differences were observed in weight, height, body mass index (BMI) and serum levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol (LDL-C) between the groups (p<0.05). LEfSe showed differentially abundant prokaryotic taxa (α=0.05, LDA score > 2.0) in the group of hypercholesterolemic individuals (Methanosphaera, Rothia, Chromatiales, Clostridiales, Bacillaceae and Coriobacteriaceae) and controls (Faecalibacterium, Victivallis and Selenomonas) at various taxonomic levels. In addition, through the application of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2), the predominance of pathways related to biosynthesis in hypercholesterolemic patients was established, compared to controls in which degradation pathways were predominant. Finally, in the analysis of co-occurrence networks, it was possible to identify associations between the microorganisms present in both studied groups. Conclusion: Our results point out to unique microbial signatures, which likely play a role on the cholesterol metabolism in the studied population.