RESUMO
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.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Carcinoma Endometrioide , Neoplasias do Endométrio , Interações Hospedeiro-Patógeno , Naftoquinonas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/genética , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Endometrioide/complicações , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/genética , Biologia Computacional , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Estudos de Associação Genética , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Humanos , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Simulação de Acoplamento Molecular/métodos , Naftoquinonas/uso terapêutico , Prognóstico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismo , Útero/patologia , Útero/virologiaRESUMO
This study was designed to understand the pivotal anti-cerebral ischemia/reperfusion injury (CIRI) targets and pathways of calycosin through network pharmacology and molecular docking analyses. In this study, bioinformatics tools were employed to characterize and identify the pharmacological functions and mechanisms of calycosin for CIRI management. The network pharmacology data identified potential, merged CIRI-associated targets of calycosin including tumor protein p53 (TP53), protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), interleukin 6, tumor necrosis factor (TNF), and mitogen-activated protein kinase 1 (MAPK1). Molecular docking analysis indicated the binding efficacy of calycosin with three of the targets, namely TP53, AKT1, and VEGFA. The biological processes of calycosin for the treatment of CIRI are mainly involved in the improvement of endothelial cell proliferation and growth, inflammatory development, and cellular metabolism. In addition, the anti-CIRI actions of calycosin were primarily through suppression of the toll-like receptor, PI3K-AKT, TNF, MAPK, and VEGF signaling pathways. Taken together, the current bioinformatic findings revealed pivotal targets, biological functions, and pharmacological mechanisms of calycosin for the treatment of CIRI. In conclusion, calycosin, a functional phytoestrogen, can be potentially used for the treatment of CIRI in future clinical trials.