Examinando por Autor "Morales, P."

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    Genome sequencing and transcriptomic analysis of the Andean killifish Orestias ascotanensis reveals adaptation to high-altitude aquatic life
    (Elsevier, 2022-01) Di Genova, A.; Nardocci, G.; Maldonado-Agurto, R.; Hodar, Ch.; Valdivieso, C.; Valdivieso, C.; Morales, P.; Gajardo, F.; Marina, R.; Gutiérrez, R.; Orellana, A.; Cambiazo, V.; Cambiazo, V.; González, M.; Glavic, A.; Mendez, M.; Maass, A.; Allende, M.; Montecino, M.
    Orestias ascotanensis (Cyprinodontidae) is a teleost pupfish endemic to springs feeding into the Ascotan saltpan in the Chilean Altiplano (3,700 m.a.s.l.) and represents an opportunity to study adaptations to high-altitude aquatic environments. We have de novo assembled the genome of O. ascotanensis at high coverage. Comparative analysis of the O. ascotanensis genome showed an overall process of contraction, including loss of genes related to G-protein signaling, chemotaxis and signal transduction, while there was expansion of gene families associated with microtubule-based movement and protein ubiquitination. We identified 818 genes under positive selection, many of which are involved in DNA repair. Additionally, we identified novel and conserved microRNAs expressed in O. ascotanensis and its closely-related species, Orestias gloriae. Our analysis suggests that positive selection and expansion of genes that preserve genome stability are a potential adaptive mechanism to cope with the increased solar UV radiation to which high-altitude animals are exposed to.
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    Intranasal administration of mesenchymal stem cell secretome reduces hippocampal oxidative stress, neuroinflammation and cell death, improving the behavioral outcome following perinatal asphyxia
    (MDPI AG, 2020-10) Farfan, N.; Carril, J.; Redel, M.; Zamorano, M.; Araya, M.; Monzón, E.; Alvarado, R.; Contreras, N.; Tapia-Bustos, A.; Quintanilla, M.E.; Ezquer, F.; Valdes, J.L.; Israel, Y.; Herrera-Marschitz, M.; Morales, P.
    PerinatalAsphyxia (PA) is a leading cause ofmotor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-ff+IFN- (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 ffC for 21 min. Thereafter, 16 ffL of MSC-S (containing 6 ffg of protein derived from 2 ff 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-ffB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia. © 2020 by the authors.
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    Neonatal mesenchymal stem cell treatment improves myelination impaired by global perinatal asphyxia in rats
    (MDPI AG, 2021-03) Tapia-bustos, A.; Lespay-rebolledo, C.; Vío, V.; Pérez-lobos, R.; Casanova-ortiz, E.; Ezquer, F.; Herrera-marschitz, M.; Morales, P.
    The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period char-acterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)- treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk oc-curring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 μL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 tran-scriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.