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    Paw Skin as a Translational Model for Investigating Fibrotic and Inflammatory Wound Healing Defects in Recessive Dystrophic Epidermolysis Bullosa
    (MDPI AG, 2025-04-30)
    DE GREGORIO CONCHA, CRISTIAN ALEJANDRO  
    ;
    Giselle Ramos-Gonzalez
    ;
    Bernardo Morales-Catalán
    ;
    EZQUER, EDUARDO FERNANDO  
    ;
    EZQUER, EDUARDO MARCELO  
    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic disease caused by COL7A1 mutations. It leads to skin fragility, chronic inflammation, and impaired wound healing. The condition often results in fibrotic scarring, pseudosyndactyly, and cutaneous squamous cell carcinoma (SCC). However, current animal models fail to fully replicate chronic RDEB wounds. In this study, we used Collagen VII-hypomorphic mice (Col7a1flNeo/flNeo) and created full-thickness wounds on their paw skin, an area prone to fibrosis due to mechanical stress. We analyzed the healing process using histology, immunofluorescence, and electron microscopy. The RDEB mice showed delayed wound closure, increased inflammation, and poor granulation tissue formation. At 30 days post-injury, we observed persistent fibrosis, with elevated levels of Collagen I, α-SMA+ myofibroblasts, and tenascin-C. These mice also had fewer intraepidermal nerve fibers, which may help explain the neuropathic pain associated with RDEB. Our model reproduces the main features of chronic RDEB wounds. It offers a useful tool for evaluating therapies aimed at reducing inflammation, fibrosis, and tumor risk in these patients.
    Scopus© Citations 3  4
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    Digital Bowen disease: a case report and systematic review
    (JLE, 2024-12)
    CABRERA MORAGA, RAUL ALEJANDRO  
    ;
    Cristóbal Lecaros
    ;
    Edinson López
    ;
    Nelson Lobos
    ;
    Nadia Vega
      5
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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
    <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>
      1Scopus© Citations 3
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    Extranodal Follicular Dendritic Cell Sarcoma Presenting on the Skin
    (2024)
    Rosario Agüero
    ;
    RECULE GONZALEZ, FRANCISCA  
    ;
    Jaime Pérez
    ;
    CASTRO MENDEZ, ALEX  
    <jats:title>Abstract:</jats:title> <jats:p>Follicular dendritic cell sarcoma is a rare intermediate-grade malignancy characterized by a proliferation of ovoid to spindle-shaped cells with morphologic and immunophenotypic features similar to normal follicular dendritic cells. It may develop in lymph nodes or extranodal sites. Its presentation in extranodal tissues is a diagnostic challenge. It requires a high index of suspicion because follicular dendritic cell markers are not included in the routine immunohistochemical panels used for differential diagnosis. In an extensive review of the English literature, we found 3 cases of follicular dendritic cell sarcoma developing on the skin. We report a case of a primary cutaneous follicular dendritic cell sarcoma in a 28-year-old man, which presented as a 6-mm skin-colored nodule on the right forearm. We describe the morphologic and immunohistochemical features and a review of the literature.</jats:p>
      4
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    ERCC1 (Excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor
    (2011)
    Roa, Ivan
    ;
    Lantadilla, Soledad
    ;
    Xabier De Aretxabala
    ;
    Munoz, Sergio
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    Expresión y amplificación del gen HER2 en el cáncer gástrico avanzado
    (2013)
    Iván Roa
    ;
    Jeannie Slater
    ;
    Daniel Carvajal  
    ;
    Kurt Schalper
    ;
    Gonzalo de Toro
    Scopus© Citations 3  1
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      1
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      1
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    A solitary nodule in the palm of a newborn
    (2022)
    Hasbún Zegpi, María
    ;
    Britzmann, Joanna
    ;
    RECULE GONZALEZ, FRANCISCA  
    ;
    Alfaro-Sepúlveda, Daniela
    ;
    CASTRO MENDEZ, ALEX  
      2
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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