Examinando por Autor "Silva, Verónica"

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    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
    (Cells, 2023-02) Huang, Ya-Lin; De Gregorio, Cristian; Silva, Verónica; Elorza, Álvaro A.; Léniz, Patricio; Aliaga-Tobar, Víctor; Maracaja-Coutinho, Vinicius; Budini, Mauricio; Ezquer, Fernando; Marcelo, Ezquer
    Drug-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.
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    Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells
    (Nature Research, 2020-12) Lobos-González, Lorena; Bustos, Rocío; Campos, América; Silva, Valeria; Silva, Verónica; Jeldes, Emanuel; Salomon, Carlos; Varas-Godoy, Manuel; Cáceres-Verschae, Albano; Duran, Eduardo; Vera, Tamara; Ezquer, Fernando
    During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can infuence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown afects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model
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    Instrumento para el desarrollo del razonamiento clínico
    (Sociedad Medica de Santiago, 2018) Silva, Verónica; McColl, Peter; Pérez, Carolina; Searle, Mariana; Goset, Jessica
    Background: Teaching clinical reasoning is a challenge in medical education. Aim: To design a clinical reasoning assessment instrument. Material and Methods: Structured interviews were carried out to six physicians with at least five years experience. The Grounded Theory method was used to determine the relevant categories of the clinical reasoning process and the modified Delphi expert judgment method to validate the categories, the definition of observable behaviors and the format of the instrument. Results: The relevant reasoning categories were the reason for consultation, medical history, physical examination, additional tests, diagnosis, therapeutic options and reasoning reassessment capacity. Expert judgment assessed at a level of “strongly agree” and “agree” the sufficiency, clarity and pertinence of all categories, related observable behaviors and instrument format. The internal Kappa consistency yielded an index of 0.92. Conclusions: The resulting instrument was constructed with the following axes derived from the main categories and subcategories: reason for consultation, history, physical examination, additional tests, diagnosis, therapeutic options and reassessment capacity. © 2018, Sociedad Medica de Santiago. All rights reserved.
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    Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model
    (Impact Journals LLC, 2017) Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A.; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O.
    Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma. © Borgna et al.