In the past few decades, coronaviruses have risen as a global threat to public health.Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Our pooled results suggested that MSC treatment could significantly reduce the mortality rate, without increasing the incidence of severe complications.
Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database.Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses.Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system.Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.
The high incidence and vulnerability to recurrence of bladder urothelial carcinoma (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in bladder cancer has not been elucidated. In this study, NFE2L3 expression was significantly increased in bladder cancer samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival (OS) and metastasis-free survival (MFS) in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited bladder cancer cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition (EMT) in bladder cancer cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.
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