Examinando por Autor "Landskron, Glauben"

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    Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements.
    (Frontiers Media S.A., 2021-10-21) García-González, Paulina; Tempio, Fabian; Fuentes, Camila; Merino, Consuelo; Vargas, Leonardo; Simon, Valeska; Ramirez-Pereira, Mirliana; Rojas, Verónica; Tobar, Eduardo; Landskron, Glauben; Araya, Juan Pablo; Navarrete, Mariela; Bastias, Carla; Tordecilla, Rocío; Varas, Macarena A; Maturana, Pablo; Marcoleta, Andrés E; Allende, Miguel L; Naves, Rodrigo; Hermoso, Marcela A; Salazar-Onfray, Flavio; Lopez, Mercedes; Bono, María-Rosa; Osorio, Fabiola
    The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.
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    Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions
    (Frontiers Media S.A., 2024) Balboa, Elisa; Saud, Faride; Parra Ruiz, Claudia; De la Fuente, Marjorie; Landskron, Glauben; Zanlungo, Silvana
    The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%–30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.
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    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.
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    Regulation of the intestinal extra-adrenal steroidogenic pathway component LRH-1 by glucocorticoids in ulcerative colitis
    (MDPI, 2022-06-12) Landskron, Glauben; Dubois-Camacho, Karen; Orellana-Serradell, Octavio; De la Fuente, Marjorie; Parada-Venegas, Daniela; Bitrán, Mirit; Díaz-Jiménez, David; Tang, Shuang; Cidlowski, John A; Li, Xiaoling; Molina, Héctor; González, Carlos M; Simian, Daniela; Lubascher, Jaime; Pola, Victor; Montecino, Martín; Blokzijl, Tjasso; Faber, Klaas Nico; González, María-Julieta; Quera, Rodrigo; Hermoso, Marcela A
    Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GRβ) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GRiKO) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.
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    Tratamiento de sobrecrecimiento bacteriano en el intestino delgado en pacientes chilenos con síndrome de intestino irritable: un estudio prospectivo y comparativo
    (Elsevier, 2024-11-12) von Muhlenbrock, Christian; Landskron, Glauben; Madrid-Silva, Ana Maria
    Introducción y objetivos: Los pacientes con trastornos del eje intestino-cerebro, como el síndrome de intestino irritable (SII), a menudo muestran sobrecrecimiento bacteriano en el intestino delgado (SBID). Su tratamiento incluye rifaximina RF), ciprofloxacino (CF), neomicina, sulfametoxazol-trimetoprima y metronidazol (MZ). La RF es un antibiótico no absorbible, que se ha observado que tiene pocos efectos secundarios. Nuestro objetivo fue evaluar la respuesta sintomática y la erradicación del SBID en pacientes con SII, utilizando 3 regímenes antibióticos. Métodos: Se realizó un estudio doble ciego, aleatorizado y prospectivo con pacientes con SII mayores de 18 años, utilizando el cuestionario de Roma IV y la prueba de aliento con lactulosa. Los pacientes diagnosticados con SBID fueron asignados aleatoriamente para recibir tratamiento con antibiótico. El grupo A recibió tratamiento con RF, el grupo B con CF y el grupo C con MZ, cada uno durante 10 días. La respuesta al tratamiento fue evaluada en función de la tasa de erradicación del SBID 15 días después de completar la terapia, utilizando pruebas de aliento con hidrógeno y metano con lactulosa. Los síntomas autorreportados fueron registrados en una escala de Likert de 10 puntos, antes, durante y después del tratamiento. Resultados: Se incluyó a 97 pacientes con SII y SBID, de los cuales el 81% completó el tratamiento. El 59% de los pacientes tratados con RF logró la erradicación del SBID, frente al 53% y 79% de los pacientes tratados con CR y MZ, respectivamente. En el grupo de metronidazol los niveles de metano disminuyeron más que en los otros 2 grupos. Sin embargo, la mayor disminución en dolor abdominal e inflamación fue observada en el grupo de RF, con un menor porcentaje de eventos adversos. Conclusiones: Los pacientes con SII y SBID se benefician de la terapia con antibióticos. El MZ mostró la mejor tasa de erradicación de SBID, pero la RF mostró una mejoría sintomática más importante y una menor tasa de eventos adversos.