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SARS-CoV-2 感染的子宫体子宫内膜癌患者的医学意义和白花丹醌的药理学特征。

Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin.

机构信息

Department of Gynecology, Guigang Maternal and Child Health Care Hospital, Guigang, China.

Department of Neurosurgery, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, China.

出版信息

Front Endocrinol (Lausanne). 2021 Oct 12;12:714909. doi: 10.3389/fendo.2021.714909. eCollection 2021.

Abstract

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 integrated analysis.

METHODS

The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, 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, 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 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.

摘要

背景

临床证据表明,感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的子宫体子宫内膜癌(UCEC)患者死亡率可能更高。然而,目前缺乏针对 UCEC/新型冠状病毒病 2019(COVID-19)的治疗方法。白花丹素(PLB)是一种具有药理活性的生物碱,是一种新兴的抗癌抑制剂。因此,本报告旨在通过整合分析,确定和表征 PLB 治疗感染 SARS-CoV-2 的 UCEC 患者的功能和机制。

方法

使用在线工具对 UCEC 和 COVID-19 患者的临床数据进行分析。同时,采用网络药理学和生物分子对接方法,筛选和表征 PLB 对 UCEC/COVID-19 的功能、生物靶标和作用机制。

结果

生物信息学数据揭示了感染 SARS-CoV-2 的 UCEC 患者的临床特征,包括特定基因、健康风险、生存率和预后指数。网络药理学研究发现,PLB 发挥抗 UCEC/COVID-19 作用是通过抑制增殖、诱导细胞毒性和细胞凋亡、抗炎、免疫调节以及调节与抗炎和免疫调节作用相关的一些关键分子途径来实现的。分子对接分析后,研究发现 PLB 抗 UCEC/COVID-19 的药理学生物靶标包括丝裂原活化蛋白激酶 3(MAPK3)、肿瘤坏死因子(TNF)和尿激酶型纤溶酶原激活物(PLAU)。

结论

基于本研究的生物信息学和实验结果,揭示了 UCEC/COVID-19 患者的临床特征。确定了 PLB 作用于 UCEC/COVID-19 的候选核心生物靶标和分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/547e/8547653/48f4b5b76521/fendo-12-714909-g001.jpg

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