Publicaciones 2011-2020

@article{RN392,
title = {Photothermally Controlled Methotrexate Release System Using Beta-Cyclodextrin and Gold Nanoparticles},
author = { N. Silva and A. Riveros and N. Yutronic and E. Lang and B. Chornik and S. Guerrero and J. Samitier and P. Jara and M.J. Kogan},
url = {/brokenurl#<Go to ISI>://WOS:000455323100023},
doi = {10.3390/nano8120985},
issn = {2079-4991},
year = {2018},
date = {2018-01-01},
journal = {Nanomaterials},
volume = {8},
number = {12},
abstract = {The inclusion compound (IC) of cyclodextrin (CD) containing the antitumor drug Methotrexate (MTX) as a guest molecule was obtained to increase the solubility of MTX and decrease its inherent toxic effects in nonspecific cells. The IC was conjugated with gold nanoparticles (AuNPs), obtained by a chemical method, creating a ternary intelligent delivery system for MTX molecules, based on the plasmonic properties of the AuNPs. Irradiation of the ternary system, with a laser wavelength tunable with the corresponding surface plasmon of AuNPs, causes local energy dissipation, producing the controlled release of the guest from CD cavities. Finally, cell viability was evaluated using MTS assays for beta-CD/MTX and AuNPs + beta-CD/MTX samples, with and without irradiation, against HeLa tumor cells. The irradiated sample of the ternary system AuNPs + beta-CD/MTX produced a diminution in cell viability attributed to the photothermal release of MTX.},
keywords = {binding, citrate complex, compound, cyclodextrin, delivery delivery, gold hepatotoxicity, inclusion irradiation, laser, methotrexate, nanoparticles, oxidative photothermal release, stabilization, stress, system, therapy},
pubstate = {published},
tppubtype = {article}
}

@article{RN385,
title = {Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: A Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?},
author = { M. Herrera-Marschitz and R. Perez-Lobos and C. Lespay-Rebolledo and A. Tapia-Bustos and E. Casanova-Ortiz and P. Morales and J.L. Valdes and D. Bustamante and B.K. Cassels},
url = {/brokenurl#<Go to ISI>://WOS:000422640700020},
doi = {10.1007/s12640-017-9795-9},
issn = {1029-8428},
year = {2018},
date = {2018-01-01},
journal = {Neurotoxicity Research},
volume = {33},
number = {2},
pages = {461-473},
abstract = {Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult., PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1 alpha (HIF-1 alpha) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD(+) exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-kappa B subunit p65, overexpression of the pro-inflammatory cytokines IL-1 beta and TNF-alpha, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss evidence showing that (i) inhibition of PARP-1 overactivation by nicotinamide and (ii) inhibition of extrasynaptic NMDA receptor overactivation by memantine can prevent the short- and long-term consequences of PA. These hypotheses have been evaluated in a rat preclinical model of PA, aiming to identify the metabolic cascades responsible for the long-term consequences induced by the insult, also assessing postnatal vulnerability to recurrent oxidative insults. Thus, we present and discuss evidence demonstrating that PA induces long-term changes in metabolic pathways related to energy and oxidative stress, priming vulnerability of cells with both the neuronal and the glial phenotype. The effects induced by PA are region dependent, the substantia nigra being particularly prone to cell death. The issue of short- and long-term consequences of PA provides a framework for addressing a fundamental issue referred to plasticity of the CNS, since the perinatal insult triggers a domino-like sequence of events making the developing individual vulnerable to recurrent adverse conditions, decreasing his/her coping repertoire because of a relevant insult occurring at birth.},
keywords = {basal brain-damage, cell cell-death, cultures, death, delayed encephalopathy encephalopathy, factor-i, ganglia, gfap, hypoxia, hypoxic hypoxic-ischemic inducible ischaemic leukomalacia, map-2, memantine, n-acetylcysteine neonatal niacinamide, nitric-oxide nmda nnos, organotypic oxidative rat rat, receptors, stress, substantia-nigra, synthase, tunel},
pubstate = {published},
tppubtype = {article}
}

@article{RN387,
title = {Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine},
author = { S.K. Noureini and M. Kheirabadi and F. Masoumi and F. Khosrogerdi and Y. Zarei and C. Suarez-Rozas and J. Salas-Norambuena and B.K. Cassels},
url = {/brokenurl#<Go to ISI>://WOS:000434978700318},
doi = {10.3390/ijms19041239},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {International Journal of Molecular Sciences},
volume = {19},
number = {4},
abstract = {Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations.},
keywords = {apoptosis, assay binding boldine, cells, derivative, domain, inhibition, n-benzylsecoboldine, site, stress, telomerase},
pubstate = {published},
tppubtype = {article}
}

@article{RN338,
title = {Role of Sfk1 Gene in the Filamentous Fungus Penicillium Roqueforti},
author = { C. Torrent and C. Gil-Duran and J.F. Rojas-Aedo and E. Medina and I. Vaca and P. Castro and R.O. Garcia-Rico and M. Cotoras and L. Mendoza and G. Levican and R. Chavez},
url = {/brokenurl#<Go to ISI>://WOS:000417142700001},
doi = {10.3389/fmicb.2017.02424},
issn = {1664-302x},
year = {2017},
date = {2017-01-01},
journal = {Frontiers in Microbiology},
volume = {8},
abstract = {The sfk1 (suppressor of four kinase) gene has been mainly studied in Saccharomyces cerevisiae, where it was shown to be involved in growth and thermal stress resistance. This gene is widely conserved within the phylum Ascomycota. Despite this, to date sfk1 has not been studied in any filamentous fungus. Previously, we found that the orthologous of sfk1 was differentially expressed in a strain of Penicillium roqueforti with an altered phenotype. In this work, we have performed a functional characterization of this gene by using RNAi-silencing technology. The silencing of sfk1 in P. roqueforti resulted in decreased apical growth and the promotion of conidial germination, but interesting, it had no effect on conidiation. In addition, the attenuation of the sfk1 expression sensitized the fungus to osmotic stress, but not to thermal stress. RNA-mediated gene-silencing of sfk1 also affected cell wall integrity in the fungus. Finally, the silencing of sfk1 depleted the production of the main secondary metabolites of P. roqueforti, namely roquefortine C, andrastin A, and mycophenolic acid. To the best of our knowledge this is the first study of the sfk1 gene in filamentous fungi.},
keywords = {alpha-subunit, biosynthesis, botrytis-cinerea, changes, chrysogenum, expression, four gene germination, growth kinase, metabolites, of pathways, penicillium phenotypic protein rna-mediated roqueforti, saccharomyces-cerevisiae, secondary signaling silencing, stress, suppressor},
pubstate = {published},
tppubtype = {article}
}