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Direct or collateral liver damage in SARS-CoV-2-infected patients

2020 , Lizardo-Thiebaud, María José , Cervantes-Álvarez, Eduardo , Limón-de la Rosa, Nathaly , Tejeda Domínguez, Farid , Palacios-Jiménez, Mildred , Méndez-Guerrero, Osvely , Delaye-Martínez, Marco , Rodríguez-Álvarez, Fátima , Romero-Morales, Beatriz , Wei-Hui, Liu , Huang, Christene A. , Kershenobich, David , Navarro Álvarez, Nalu

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease. © 2020 American Institute of Physics Inc.. All rights reserved.

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Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients

2022 , Cervantes-Álvarez, Eduardo , Limón-de la Rosa, Nathaly , Salgado-de la Mora, Moisés , Valdez-Sandoval, Paola , Palacios-Jiménez, Mildred , Rodríguez-Álvarez, Fátima , Vera-Maldonado, Brenda I. , Aguirre-Aguilar, Eduardo , Escobar-Valderrama, Juan Manuel , Alanis-Mendizabal, Jorge , Méndez-Guerrero, Osvely , Tejeda Domínguez, Farid , Torres-Ruíz, Jiram , Gómez-Martín, Diana , Colborn, Kathryn L. , Kershenobich, David , Huang, Christene A. , Navarro Álvarez, Nalu

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47–9.20),  < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79–0.91, < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

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Tumour growth inhibitory effect of Ibervillea sonorae phytopreparations in cervical cancer xenografts

2024 , Max Vidal-Gutiérrez , Heriberto Torres-Moreno , Víctor M. Arenas-Luna , María Lilia Loredo-Mendoza , Tejeda Domínguez, Farid , Carlos Velazquez , Wagner Vilegas , Ana Luisa Gutiérrez-salomón , Ramón E. Robles-Zepeda

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Standardized phytopreparations and cucurbitacin IIb from Ibervillea sonorae (S. Watson) greene induce apoptosis in cervical cancer cells by Nrf2 inhibition

2022 , Vidal-Gutiérrez, Max , Torres-Moreno, Heriberto , Arenas Luna, Victor Manuel , Loredo Mendoza, María Lilia , Velazquez, Carlos , Tejeda Domínguez, Farid , Vilegas, Wagner , Robles-Zepeda, Ramón E. , Hernández Gutiérrez, Salomón

Ethnopharmacology relevance: Ibervillea sonorae (S. Watson) Greene is a plant from northwestern Mexico, known as “Wereke” or “Guareque”, used by the Mayo ethnic group to treat diabetes and cancer. Cucurbitacin IIb (CIIb), isolated from I. sonorae has apoptotic and antitumor activity in a model of cervical cancer with the HeLa cell line. One pathway affected by cucurbitacins is Nrf2, a glutathione transferase (GST) transcription factor, important in the regulation of mitochondrial oxidative stress (MOS). A signal of MOS is the change in the mitochondrial membrane potential (ΔΨm), which has been detected in HeLa in the presence of CIIb. Fito-Ison-EtOH (Etanison) and Fito-Ison-EtOAc (Acetison) are phytopreparations from I. sonorae standardized according to their CIIb content (6.7 mg/g and 18.4 mg/g of CIIb, respectively). Etanison and Acetison have been reported to induce morphological changes in HeLa like those induced by CIIb. Aim of the study: To evaluate the apoptotic and Nrf2 inhibition activity of the phytopreparations Acetison and Etanison from Ibervillea Sonorae in the HeLa cervical cancer cell line. Materials and methods : Antiproliferative activity was evaluated by the MTT method at 24, 48, and 72 h. For Acetison and Etanison, serial concentrations from 6.25 μg/mL to 100 μg/mL were tested, and for CIIb from 1.56 μg/mL to 50 μg/mL. The expression of Nrf2, caspase 3, and caspase 9 was evaluated by western blot, using concentrations of 30 μg/mL for Acetison, 50 μg/mL for Etanison, and 15 μg/mL for CIIb. Cisplatin was used as a positive control.

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Galectin-3 as a Biomarker of Disease Severity in Acute-on-Chronic Liver Failure

2020 , Cervantes-Álvarez, Eduardo , Limón-de la Rosa, Nathaly , Vilatoba, Mario , Pérez-Monter, Carlos , Hurtado-Gómez, Sahara , Martínez-Cabrera, Cynthia , Argemi, Josepmaria , Alatorre-Arenas, Elisa , Yarza-Regalado, Susana , Tejeda Domínguez, Farid , Méndez-Guerrero, Osvely , Lizardo-Thiebaud, María José , Gamboa-Domínguez, Armando , Aguilar-Salinas, Carlos A. , Huang, Christene A. , Kershenobich, David , Bataller, Ramon , Torre, Aldo , Navarro Álvarez, Nalu

*Purpose: A matter of great importance is the discovery of alternative diagnostic measures that can detect liver disease at an early stage, especially when at risk of developing acute on chronic liver failure (ACLF), to optimize outcome and survival. Galectin-3 (Gal-3) is a lectin that binds to β-galactosides and can be secreted to the systemic circulation, regulating inflammation and fibrosis. Due to its direct role in inflammation and fibrosis, levels of this lectin can reflect the progression of liver damage and the possible consequent multiorgan failure, which is a distinctive characteristic of ACLF. The purpose of this study is to determine if liver Gal-3 expression is a useful biomarker of disease progression. *Methods: Liver samples from cirrhotic patients with compensated, decompensated cirrhosis and ACLF were collected at the time of liver transplant. The liver from donors was used as controls. RNA was extracted and liver Gal-3 expression was analyzed by quantitative polymerase chain reaction (qPCR). The values obtained were correlated with clinical and biochemical parameters using Pearson’s and Spearman’s correlation coefficients. A comparison among 3 different groups was performed using the Kruskal-Wallis test with Dunn’s multiple comparisons test.

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Galectin‐3 is overexpressed in advanced cirrhosis and predicts post‐liver transplant infectious complications

2022 , Cervantes‐Alvarez, Eduardo , Limón-de la Rosa, Nathaly , Vilatoba, Mario , Pérez Nicomedes, Carlos , Hurtado‐Gomez, Sahara , Martínez‐Cabrera, Cynthia , Argemi, Josepmaria , Alatorre‐Arenas, Elisa , Yarza‐Regalado, Susana , Tejeda Domínguez, Farid , Lizardo-Thiebaud, María José , Mendez‐Guerrero, Osvely , Gamboa‐Dominguez, Armando , Aguilar‐Salinas, Carlos A. , Huang, Christene A. , Kershenobich, David , Bataller, Ramon , Torre, Aldo , Navarro Álvarez, Nalu

Background & aims: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a β-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. Methods: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections.