EZQUER, EDUARDO FERNANDO
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EZQUER, EDUARDO FERNANDO
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eezquer@udd.cl
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8614146900

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Morphine self-administration is inhibited by the antioxidant N‐acetylcysteine and the anti-inflammatory ibudilast; an effect enhanced by their co-administration

2024 , María Elena Quintanilla , Paola Morales , Daniela Santapau , Javiera Gallardo , Rocío Rebolledo , Gabriel Riveras , Tirso Acuña , Mario Herrera-Marschitz , Yedy Israel , EZQUER, EDUARDO FERNANDO , Shao-Jun Tang

Background The treatment of opioid addiction mainly involves the medical administration of methadone or other opioids, aimed at gradually reducing dependence and, consequently, the need for illicit opioid procurement. Thus, initiating opioid maintenance therapy with a lower level of dependence would be advantageous. There is compelling evidence indicating that opioids induce brain oxidative stress and associated glial activation, resulting in the dysregulation of glutamatergic homeostasis, which perpetuates drug intake. The present study aimed to determine whether inhibiting oxidative stress and/or neuroinflammation reduces morphine self-administration in an animal model of opioid dependence. Methods Morphine dependence, assessed as voluntary morphine self-administration, was evaluated in Wistar-derived UChB rats. Following an extended period of morphine self-administration, animals were administered either the antioxidant N-acetylcysteine (NAC; 40 mg/kg/day), the anti-inflammatory ibudilast (7.5 mg/kg/day) or the combination of both agents. Oxidative stress and neuroinflammation were evaluated in the hippocampus, a region involved in drug recall that feeds into the nucleus accumbens, where the levels of the glutamate transporters GLT-1 and xCT were further assessed. Results Daily administration of either NAC or ibudilast led to a mild reduction in voluntary morphine intake, while the co-administration of both therapeutic agents resulted in a marked inhibition (-57%) of morphine self-administration. The administration of NAC or ibudilast markedly reduced both the oxidative stress induced by chronic morphine intake and the activation of microglia and astrocytes in the hippocampus. However, only the combined administration of NAC + ibudilast was able to restore the normal levels of the glutamate transporter GLT-1 in the nucleus accumbens. Conclusion Separate or joint administration of an antioxidant and anti-inflammatory agent reduced voluntary opioid intake, which could have translational value for the treatment of opioid use disorders, particularly in settings where the continued maintenance of oral opioids is a therapeutic option.

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Spatial maps and oscillations in the healthy hippocampus of Octodon degus, a natural model of sporadic Alzheimer’s disease

2022 , Matias Mugnaini , Diana Polania , Yannina Diaz , EZQUER, EDUARDO MARCELO , EZQUER, EDUARDO FERNANDO , Robert M. J. Deacon , Patricia Cogram , Emilio Kropff

AbstractThe Octodon degus is a South American rodent that is receiving increased attention as a potential model of aging and sporadic late-onset Alzheimer’s disease (AD). Impairments in spatial memory tasks in Octodon degus have been reported in relation to either advanced AD-like disease or hippocampal lesion, opening the way to investigate how the function of hippocampal networks affects behavior across AD stages. However, no characterization of hippocampal electrophysiology exists in this species. Here we describe in young, healthy specimens the activity of neurons and local field potential rhythms during spatial navigation tasks with and without objects. Our findings show similarities between the Octodon degus and laboratory rodents. First, place cells with characteristics similar to those found in rats and mice exist in the CA1 subfield of the Octodon degus. Second, the introduction of objects elicits novelty-related exploration and an increase in activity of CA1 cells, with location specific and unspecific components. Third, oscillations of the local field potential are organized according to their spectral content into bands similar to those found in laboratory rodents. These results suggest a common framework of underlying mechanisms, opening the way to future studies of hippocampal dysfunction in this species associated to aging and disease.

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Could cancer and infection be adverse effects of mesenchymal stromal cell therapy?

2015 , Martha L Arango-Rodriguez , EZQUER, EDUARDO FERNANDO

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MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

2012 , EZQUER, EDUARDO MARCELO , EZQUER, EDUARDO FERNANDO , Martha L Arango-Rodríguez , Paulette A Conget

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Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats

2024 , María Elena Quintanilla , Daniela Santapau , Eugenio Diaz , Ignacio Valenzuela Martinez , Nicolas Medina , Glauben Landskron , Antonia Dominguez , Paola Morales , David Ramírez , Marcela Hermoso , Belén Olivares , Pablo Berríos-Cárcamo , EZQUER, EDUARDO MARCELO , Mario Herrera-Marschitz , Yedy Israel , EZQUER, EDUARDO FERNANDO

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Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells

2020 , Lorena González-sánchez , Rocío Bustos , América Campos , Valeria Silva , Verónica Silva , Emanuel Jeldes , Carlos Salomon , Manuel Varas-Godoy , Albano Cáceres-Verschae , Eduardo Duran , Tamara Vera , EZQUER, EDUARDO FERNANDO , EZQUER, EDUARDO MARCELO , Verónica A. Burzio , Jaime Villegas

AbstractDuring intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence 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 affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.

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Intracerebral Stem Cell Administration Inhibits Relapse-like Alcohol Drinking in Rats

2016 , Yedy Israel , EZQUER, EDUARDO FERNANDO , María Elena Quintanilla , Paola Morales , EZQUER, EDUARDO MARCELO , Mario Herrera-Marschitz

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Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

2023 , María Elena Quintanilla , Paola Morales , Daniela Santapau , Alba Ávila , Carolina Ponce , BERRIOS CARCAMO, PABLO ANDRES , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Javiera Gallardo , Yedy Israel , EZQUER, EDUARDO FERNANDO

Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

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Corrigendum: Contribution of Connexin Hemichannels to the Decreases in Cell Viability Induced by Linoleic Acid in the Human Lens Epithelial Cells (HLE-B3)

2020 , Vania A. Figueroa , Oscar Jara , Carolina A. Oliva , EZQUER, EDUARDO MARCELO , EZQUER, EDUARDO FERNANDO , RETAMAL LUCERO, MAURICIO ANTONIO , Agustín D. Martínez , Guillermo A. Altenberg , Aníbal A. Vargas

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Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

2017 , Carolina Oses , OLIVARES, MARIA BELEN , EZQUER, EDUARDO MARCELO , Cristian Acosta , BOSCH PÉREZ, PAUL JESÚS , Macarena Donoso , Patricio Léniz , EZQUER, EDUARDO FERNANDO

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