Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas.

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What's more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.

Identification of the Prognostic Significance of Somatic Mutation-Derived LncRNA Signatures of Genomic Instability in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a highly heterogeneous tumor with substantial somatic mutations and genome instability, which are emerging hallmarks of cancer. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in genomic instability. However, the identification of genome instability-related lncRNAs (GInLncRNAs) and their clinical significance has not been investigated in LUAD. Methods: We determined GInLncRNAs by combining somatic mutation and transcriptome data of 457 patients with LUAD and probed their potential function using co-expression network and Gene Ontology (GO) enrichment analyses. We then filtered GInLncRNAs by Cox regression and LASSO regression to construct a genome instability-related lncRNA signature (GInLncSig). We subsequently evaluated GInLncSig using correlation analyses with mutations, external validation, model comparisons, independent prognostic significance analyses, and clinical stratification analyses. Finally, we established a nomogram for prognosis prediction in patients with LUAD and validated it in the testing set and the entire TCGA dataset. Results: We identified 161 GInLncRNAs, of which seven were screened to develop a prognostic GInLncSig model (LINC01133, LINC01116, LINC01671, FAM83A-AS1, PLAC4, MIR223HG, and AL590226.1). GInLncSig independently predicted the overall survival of patients with LUAD and displayed an improved performance compared to other similar signatures. Furthermore, GInLncSig was related to somatic mutation patterns, suggesting its ability to reflect genome instability in LUAD. Finally, a nomogram comprising the GInLncSig and tumor stage exhibited improved robustness and clinical practicability for predicting patient prognosis. Conclusion: Our study identified a signature for prognostic prediction in LUAD comprising seven lncRNAs associated with genome instability, which may provide a useful indicator for clinical stratification management and treatment decisions for patients with LUAD.

Longitudinal association between cardiovascular health and arterial stiffness in the Chinese adult population.

OBJECTIVE: Arterial stiffness may be an intermediary biological pathway involved in the association between cardiovascular health (CVH) and cardiovascular disease. We aimed to evaluate the effect of CVH on progression of brachial-ankle pulse wave velocity (baPWV) over approximately 4 years. METHODS: We included 1315 cardiovascular disease-free adults (49±12 years) who had two checkups from 2010 to 2019. CVH metrics (current smoking, body mass index, total cholesterol, blood pressure, and fasting plasma glucose) were assessed at baseline, and the number of ideal CVH metrics and CVH score were calculated. Additionally, baPWV was examined at baseline and follow-up. RESULTS: Median baPWV increased from 1340 cm/s to 1400 cm/s, with an average annual change in baPWV of 15 cm/s. More ideal CVH metrics and a higher CVH score were associated with lower baseline and follow-up baPWV, and the annual change in baPWV, even after adjustment for confounding variables. Associations between CVH parameters and baseline and follow-up baPWV remained robust in different sex and age subgroups, but they were only able to predict the annual change in baPWV in men and individuals older than 50 years. CONCLUSIONS: Our findings highlight the benefit of a better baseline CVH profile for progression of arterial stiffness.

Metabolic characteristics of large and small extracellular vesicles from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy.

Pleural effusion is a common respiratory disease worldwide; however, rapid and accurate diagnoses of tuberculosis pleural effusion (TPE) and malignancy pleural effusion (MPE) remain challenging. Although extracellular vesicles (EVs) have been confirmed as promising sources of disease biomarkers, little is known about the metabolite compositions of its subpopulations and their roles in the diagnosis of pleural effusion. Here, we performed metabolomics and lipidomics analysis to investigate the metabolite characteristics of two EV subpopulations derived from pleural effusion by differential ultracentrifugation, namely large EVs (lEVs, pelleted at 20,000 × g) and small EVs (sEVs, pelleted at 110,000 × g), and assessed their metabolite differences between tuberculosis and malignancy. A total of 579 metabolites, including amino acids, acylcarnitines, organic acids, steroids, amides and various lipid species, were detected. The results showed that the metabolic profiles of lEVs and sEVs overlapped with and difference from each other but significantly differed from those of pleural effusion. Additionally, different type of vesicles and pleural effusion showed unique metabolic enrichments. Furthermore, lEVs displayed more significant and larger metabolic alterations between the tuberculosis and malignancy groups, and their differential metabolites were more closely related to clinical parameters than those of sEV. Finally, a panel of four biomarker candidates, including phenylalanine, leucine, phosphatidylcholine 35:0, and sphingomyelin 44:3, in pleural lEVs was defined based on the comprehensive discovery and validation workflow. This panel showed high performance for distinguishing TPE and MPE, particularly in patients with delayed or missed diagnosis, such as the area under the receiver-operating characteristic curve (AUC) >0.95 in both sets. We conducted comprehensive metabolic profiling analysis of EVs, and further explored the metabolic reprogramming of tuberculosis and malignancy at the level of metabolites in lEVs and sEVs, providing insight into the mechanism of pleural effusion, and identifying novel biomarkers for diagnosing TPE and MPE.

Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study.

BACKGROUND: Oseltamivir is a first-line antiviral drug, especially in primary hospitals. During the ongoing outbreak of coronavirus disease 2019 (COVID-19), most patients with COVID-19 who are symptomatic have used oseltamivir. Considering its popular and important role as an antiviral drug, it is necessary to evaluate oseltamivir in the treatment of COVID-19. OBJECTIVE: To evaluate the effect of oseltamivir against COVID-19. METHODS: Swiss-model was used to construct the structure of the N-terminal RNA-binding domain (NRBD) of the nucleoprotein (NC), papain-like protease (PLpro), and RNA-directed RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). TM-align program was performed to compare the structure of the viral proteins with the structure of the neuraminidase of influenza A. Molecular docking was used to analyze the theoretical possibility of effective binding of oseltamivir with the active centers of the viral proteins. In vitro study was used to evaluate the antiviral efficiency of oseltamivir against SARS-CoV-2. By clinical case analysis, we statistically evaluated whether the history of oseltamivir use influenced the progression of the disease. RESULTS: The structures of NRBD, PLpro, and RdRp were built successfully. The results from TM-align suggested that the S protein, NRBD, 3C-like protease (3CLpro), PLPrO, and RdRp were structurally similar to the influenza A neuraminidase, with TM-scores of 0.30077, 0.19254, 0.28766, 0.30666, and 0.34047, respectively. Interestingly, the active center of 3CL pro was found to be similar to the active center from the neuraminidase of influenza A. Through an analysis of molecular docking, we discovered that oseltamivir carboxylic acid was more favorable to bind to the active site of 3CLpro effectively, but its inhibitory effect was not strong compared with the positive group. Finally, we used in vitro study and retrospective case analysis to verify our speculations. We found that oseltamivir is ineffective against SARS-CoV-2 in vitro study and the clinical use of oseltamivir did not improve the patients' symptoms and signs and did not slow the disease progression. CONCLUSIONS: We consider that oseltamivir isn't suitable for the treatment of COVID-19. During the outbreak of novel coronavirus, when oseltamivir is not effective for the patients after they take it, health workers should be highly vigilant about the possibility of COVID-19.

Relationship between serum tumor markers and Anaplastic Lymphoma Kinase mutations in stage IV lung adenocarcinoma in Hubei province, Central China.

OBJECTIVE: The aim of this study was to explore the predictive value of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCAg), and neuron-specific enolase (NSE) in the prediction of anaplastic lymphoma kinase (ALK) mutations in advance stage non-small cell lung cancer (NSCLC). SUBJECTS AND METHODS: A total of 482 cases with untreated lung adenocarcinoma were retrospectively reviewed. Finally, 72 patients with stage IV were enrolled because of intact data of the detection of ALK rearrangement and serum tumor markers, as well they have not received any previous anticancer therapy. We used the one-way ANOVA analysis, correlation analysis, and multiple logistic regression analysis to evaluate the relationship between the level of serum tumor markers and ALK mutations. RESULTS: Fifteen cases with ALK mutations and 57 cases without mutations were identified. The result of the one-way ANOVA analysis showed only CEA was significantly associated with ALK mutations (95% CI:39.05-148.88; P = .001). The area under the ROC curve (AUC) of CEA was 0.705 (95%CI:0.567-0.843; P = .015). However, no significant association was observed between CEA and ALK mutations though the result of correlation analysis (P = .069) and multivariate logistic regression analysis (OR = 0.988, 95% CI: 0.972-1.003, P = .111). CONCLUSIONS: In our study, we performed on the patients with stage IV lung adenocarcinoma in our region and found preoperative serum levels of SCCAg, CYRF21-1, and NSE not suitable for the detection of ALK mutation. Although we observed a significant association between CEA and ALK mutations; however, it was not strong enough to distinguish ALK status for the patients in our region.

The role of adrenergic receptors in lung cancer.

Adrenergic receptors (ARs), especially ß-ARs, are constitutively expressed in most mammalian cells and are associated with various malignancies including lung cancer. Epidemiologic studies have reported that activation of ß-AR signalling promotes the development and progression of lung cancer and that pharmacological interference by ß-AR blockers could partially reverse lung cancer progression. In this review, we mainly focus on the role of ß-ARs in lung cancer and then reveal the possible application of AR blockers in anti-tumour therapy for lung cancer.

Potential roles of IL-1 subfamily members in glycolysis in disease.

The interleukin-(IL)-1 subfamily consists of IL-1α, IL-1ß, IL-1 receptor antagonist IL-1Ra and IL-33. These cytokines are the main members of the IL-1 family and have been widely recognized as having significant roles in pro-inflammatory and immunomodulatory actions. Mounting evidence has revealed that these cytokines also play key roles in the regulation of glycolysis, which is an important metabolic pathway in most organisms that provides energy. Dysregulation of glycolysis is associated with various diseases, including type 2 diabetes, rheumatoid arthritis (RA) and cancer. We reviewed studies addressing the important roles of IL-1 subfamily cytokines, with particular focus on their ability to regulate glycolysis in disease states. In this review, we summarize the potential roles of IL-1 subfamily members in glycolysis in disease states and address the underlying mechanisms. Furthermore, we discuss the potential of these cytokines as therapeutic targets in clinical applications to provide insight into possible therapeutic strategies for treatment, especially for cancers.