Browsing by Author "Echeverria, Cesar"

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    In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma
    (2022) Echeverria, Cesar; Martin, Aldo; Simon, Felipe; Salas, Cristian O.; Nazal, Mariajesus; Varela, Diego; Perez-Castro, Ramon A.; Santibanez, Juan F.; Valdes-Valdes, Ricardo O.; Forero-Doria, Oscar; Echeverria, Javier
    Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species. Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models. Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo. Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth. Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.
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    INTERACTION OF CHALCONES WITH CT-DNA BY SPECTROPHOTOMETRIC ANALYSIS AND THEORETICAL SIMULATIONS
    (2016) Zarate, Ximena; Schott Verdugo, Eduardo Enrique; Escobar, Carlos A.; Lopez Castro, Roberto; Echeverria, Cesar; Alvarado Soto, Leonor; Ramirez Taglea, Rodrigo
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    Preventive leptin administration protects against sepsis through improving hypotension, tachycardia, oxidative stress burst, multiple organ dysfunction, and increasing survival
    (2018) Vallejos, Alejandro; Olivares, Pedro; Varela, Diego; Echeverria, Cesar; Cabello Verrugio, Claudio Alejandro; Pérez Leighton, Claudio; Simon, Felipe
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    Procoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death
    (2023) Prado, Yolanda; Perez, Lorena; Eltit, Felipe; Echeverria, Cesar; Llancalahuen, Felipe M.; Tapia, Pablo; Gonzalez, Pablo A.; Kalergis, Alexis M.; Cabello-Verrugio, Claudio; Simon, Felipe
    Background: Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. Methods: Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. Results: OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creat-inine, urea, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. Conclusion: Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that as-sociates with acute kidney injury and increased risk of death.