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Front Endocrinol (Lausanne) ; 12: 714909, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1497067

RESUMEN

Background: Clinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis. Methods: The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB. Results: The bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU). Conclusions: Based on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Carcinoma Endometrioide , Neoplasias Endometriales , Interacciones Huésped-Patógeno , Naftoquinonas/farmacología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/genética , Proteínas de Unión al Calcio/efectos de los fármacos , Proteínas de Unión al Calcio/metabolismo , Carcinoma Endometrioide/complicaciones , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/genética , Biología Computacional , Ensayos de Selección de Medicamentos Antitumorales/métodos , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Estudios de Asociación Genética , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Humanos , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteína Quinasa 3 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Simulación del Acoplamiento Molecular/métodos , Naftoquinonas/uso terapéutico , Pronóstico , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Útero/efectos de los fármacos , Útero/metabolismo , Útero/patología , Útero/virología
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