Examinando por Autor "Dominguez, Antonia"

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    Ítem
    Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats
    (Springer Nature, 2024-11-26) Quintanilla, Maria Elena; Santapau, Daniela; Diaz, Eugenio; Valenzuela Martinez, Ignacio; Medina, Nicolas; Landskron, Glauben; Dominguez, Antonia; Morales, Paola; Ramírez, David; Hermoso, Marcela; Olivares, Belén; Berríos-Cárcamo, Pablo; Ezquer, Marcelo; Herrera-Marschitz, Mario; Israel, Yedy; Ezquer, Fernando
    Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression of alcohol use disorder. Among the different protective molecules that could mediate this communication, short chain fatty acids (SCFAs) have emerged as attractive candidates, since these gut microbiota-derived molecules have multi-target effects that could normalize several of the functional and structural parameters altered by chronic alcohol abuse. The present study, conducted in male alcohol-preferring UChB rats, shows that the initiation of voluntary ethanol intake was inhibited in 85% by the intragastric administration of a combination of SCFAs (acetate, propionate and butyrate) given before ethanol exposure, while SCFAs administration after two months of ethanol intake induced a 90% reduction in its consumption. These SCFAs therapeutic effects were associated with (1) a significant reduction of ethanol-induced intestinal inflammation and damage; (2) reduction of plasma lipopolysaccharide levels and hepatic inflammation; (3) reduction of ethanol-induced astrocyte and microglia activation; and (4) attenuation of the ethanol-induced gene expression changes within the nucleus accumbens. Finally, we determined that among the different SCFAs evaluated, butyrate was the most potent, reducing chronic ethanol intake in a dose–response manner. These findings support a key role of SCFAs, and especially butyrate, in regulating AUD, providing a simple, inexpensive, and safe approach as a preventive and intervention-based strategy to address this devastating disease.
  • Miniatura
    Ítem
    Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival
    (Elsevier, 2024) Fierro Arenas, Aaron; Landskron, Glauben; Camhi-Vainroj, Ilan; Basterrechea, Benjamin; Parada Venegas, Daniela; Lobos Gonzalez, Lorena; Dubois Camacho, Karen; Araneda, Catalina; Romero, Camila; Dominguez, Antonia; Vasquez, Gonzalo; Lopez K, Francisco; Alvarez, Karin; Gonzalez, Carlos M; Hager Ribeiro, Carolina; Balboa, Elisa; Eugenin, Eliseo; Hermoso, Marcela A; De la Fuente, Marjorie
    Aims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stagedependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.