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    Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats
    (2021)
    Andrea Tapia-Bustos
    ;
    Carolyne Lespay-Rebolledo
    ;
    Valentina Vío
    ;
    Ronald Pérez-Lobos
    ;
    Emmanuel Casanova-Ortiz
    <jats: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 characterized 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 occurring 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 transcriptional 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.</jats:p>
    Scopus© Citations 7  2
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    Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer
    (2021)
    Karen Toledo-Stuardo
    ;
    Carolina H. Ribeiro
    ;
    Andrea Canals
    ;
    Marcela Morales
    ;
    Valentina Gárate
    <jats:p>Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. <jats:italic>MICA</jats:italic> gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study <jats:italic>MICA</jats:italic> gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of <jats:italic>MICA</jats:italic> gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA<jats:sup>*</jats:sup>002 (<jats:sup>*</jats:sup>A9) as the most frequent allele in both, patients and controls, followed by MICA<jats:sup>*</jats:sup>008 allele (<jats:sup>*</jats:sup>A5.1). MICA<jats:sup>*</jats:sup>009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39–18.74], <jats:italic>p</jats:italic> = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA<jats:sup>*</jats:sup>A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12–0.98], <jats:italic>p</jats:italic> = 0.046). Survival analysis after gastrectomy showed that patients with MICA<jats:sup>*</jats:sup>002/002 or MICA<jats:sup>*</jats:sup>002/004 alleles had significantly higher survival rates than those patients bearing MICA<jats:sup>*</jats:sup>002/008 (<jats:italic>p</jats:italic> = 0.014) or MICA<jats:sup>*</jats:sup>002/009 (MICA<jats:sup>*</jats:sup>002/049) alleles (<jats:italic>p</jats:italic> = 0.040). The presence of threonine in the position MICA-181 (MICA<jats:sup>*</jats:sup>009/049 allele) was more frequent in GC patients than controls (<jats:italic>p</jats:italic> = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA<jats:sup>*</jats:sup>004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.</jats:p>
    Scopus© Citations 12  1