A Combined Risk Score Model to Assess Prognostic Value in Patients with Soft Tissue Sarcomas

A study by Tsvetkov et al. recently published a proposed novel form of copper-induced cell death in Science; however, few studies have looked into the possible mechanism in soft tissue sarcoma (STS). Herein, this study sought to investigate the function of cuproptosis-related genes (CRGs) in the development of tumor-associated immune cells and the prognosis of sarcoma. Herein, this study aimed to explore the role of cuproptosis-related genes (CRGs) in the development, tumor-associated immune cells, and the prognosis of sarcoma. Methods: The prognostic model was established via the least absolute shrinkage and selection operator (LASSO) algorithm as well as multivariate Cox regression analysis. The stromal scores, immune scores, ESTIMA scores, and tumor purity of sarcoma patients were evaluated by the ESTIMATE algorithm. Functional analyses were performed to investigate the underlying mechanisms of immune cell infiltration and the prognosis of CRGs in sarcoma. Results: Two molecular subgroups with different CRG expression patterns were recognized, which showed that patients with a higher immune score and more active immune status were prone to have better prognostic survival. Moreover, GO and KEGG analyses showed that these differentially expressed CRGs were mainly enriched in metabolic/ions-related signaling pathways, indicating that CRGs may have impacts on the immune cell infiltration and prognosis of sarcoma via regulating the bioprocess of mitochondria and consequently affecting the immune microenvironment. The expression levels of CRGs were closely correlated to the immunity condition and prognostic survival of sarcoma patients. Conclusions: The interaction between cuproptosis and immunity in sarcoma may provide a novel insight into the study of molecular mechanisms and candidate biomarkers for the prognosis, resulting in effective treatments for sarcoma patients

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort

BackgroundThe causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis.MethodsThe single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings.ResultsThe IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF.ConclusionThe study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA

Outer membrane vesicles from bacteria: Role and potential value in the pathogenesis of chronic respiratory diseases

Infectious diseases are the leading cause of death in both adults and children, with respiratory infections being the leading cause of death. A growing body of evidence suggests that bacterially released extracellular membrane vesicles play an important role in bacterial pathogenicity by targeting and (de)regulating host cells through the delivery of nucleic acids, proteins, lipids, and carbohydrates. Among the many factors contributing to bacterial pathogenicity are the outer membrane vesicles produced by the bacteria themselves. Bacterial membrane vesicles are being studied in more detail because of their potential role as deleterious mediators in bacterial infections. This review provides an overview of the most current information on the emerging role of bacterial membrane vesicles in the pathophysiology of pneumonia and its complications and their adoption as promising targets for future preventive and therapeutic approaches

Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling

Rationale: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity. In addition, LL-37 is involved in the regulation of tumor cell growth. However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood. Methods: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistological, immunofluorescence analysis, and enzyme-linked immunosorbent assay. The animal model of wild-type and Cramp knockout mice was employed to evaluate the tumorigenic effect of LL-37 in non-small cell lung cancer. The mechanism of LL-37 involving in the promotion of lung tumor growth was evaluated via microarray analyses, recombinant protein treatment approaches in vitro, tumor immunohistochemical assays, and intervention studies in vivo. Results: LL-37 produced by myeloid cells was frequently upregulated in primary human lung cancer tissues. Moreover, its expression level correlated with poor clinical outcome. LL-37 activated Wnt/β-catenin signaling by inducing the phosphorylation of protein kinase B and subsequent phosphorylation of glycogen synthase kinase 3β mediated by the toll-like receptor-4 expressed in lung tumor cells. LL-37 treatment of tumor cells also decreased the levels of Axin2. In contrast, it elevated those of an RNA-binding protein (tristetraprolin), which may be involved in the mechanism through which LL-37 induces activation of Wnt/β-catenin. Conclusion: LL-37 may be a critical molecular link between tumor-supportive immune cells and tumors, facilitating the progression of lung cancer

Bronchoalveolar Lavage Fluid-Derived Exosomes: A Novel Role Contributing to Lung Cancer Growth

Exosomes are nanovesicles produced by a number of different cell types and regarded as important mediators of cell-to-cell communication. Although bronchoalveolar lavage fluid (BALF) has been shown to be involved in the development of tumors, its role in lung cancer (LC) remains unclear. In this article, we systemically studied BALF-derived exosomes in LC. C57BL/6 mice were injected with Lewis lung carcinoma cells and exposed to non-typeable Haemophilus influenza (NTHi) lysate. The analysis showed that the growth of lung tumors in these mice was significantly enhanced compared with the control cohort (only exposure to air). Characterization of the exosomes derived from mouse BALF demonstrated elevated levels of tumor necrosis factor alpha and interleukin-6 in mice exposed to NTHi lysates. Furthermore, abnormal BALF-derived exosomes facilitated the development of LC in vitro and in vivo. The internalization of the BALF-derived exosomes contributed to the development of LC tumors. Collectively, our data demonstrated that exosomes in BALF are a key factor involved in the growth and progression of lung cancer

A random maintenance last model with preventive maintenance for the product under a random warranty

Although renewing pro-rate replacement warranty (RPRW) can help producers obtain some compensation from users, there seldom exists a two-dimensional random RPRW with a refund (2D-RRPRW with R) where a refund can guarantee the fairness of users. In addition, although random periodic replacement last (RPRL) can extend the service span after the expiry of the warranty, RPRL considering preventive maintenance (PM) has been seldom modeled to further lengthen the service span after the expiry of the warranty. In view of these, a 2D-RRPRW with R is devised to guarantee the fairness of users by integrating the limited job cycles and a refund into RPRW. Under the case where 2D-RRPRW with R warrants products with job cycles, a RPRL with PM is modeled to further lengthen the service span after the expiry of the warranty and reduce the failure frequency. It shows that to shorten the warranty period can makes the warranty cost of 2D-RRPRW with R to be less than the warranty cost of classic RPRW; and the performance of RPRL with PM outperforms the performance of classic RPRL

An Optimal Random Hybrid Maintenance Policy of Systems under a Warranty with Rebate and Charge

Facilitated by advanced digital technologies, reliability managers can monitor system working cycles during the whole life cycle. Such a technological realization can help reliability managers ensure system reliability in real time by monitoring working cycles. In this paper, by incorporating a limited random working cycle, rebate and charge into warranty theory, a random free repair warranty with rebate and charge (RFRW-RC) is devised to ensure system reliability during the warranty stage. Under RFRW-RC, the rebate removes manufacturers’ responsibility for continuing to ensure system reliability, while the charge is a support where manufacturers continue to ensure system reliability. The warranty cost of RFRW-RC is derived, and a random discrete free repair warranty (RDFRW) is presented by simplifying RFRW-RC. By mixing random age replacement last (RARL) and classic age replacement (CAR), a random hybrid age replacement (RHAR) is designed in order to ensure system reliability during the post-warranty stage. In such an RHAR, RARL is applied to extend the replacement time during the post-warranty stage in order to maximize the remaining life of the system through warranty, and CAR is used to lower the maintenance cost of the system through warranty. The cost rate of RHAR is modeled, and the cost rate of RDFRW is offered as well by discussing parameter values. The decision variable is optimized by minimizing the cost rate model. The properties of the presented models are explored from numerical perspectives

The Function and Molecular Mechanism of Commensal Microbiome in Promoting Malignant Progression of Lung Cancer

The human commensal microbiome existing in an internal environment is relatively consistent with that of the host. The presence of bacterial dysbiosis, on the other hand, promptly results in the termination of this symbiotic association. The altered microbial structure in the lung may be responsible for the development of lung cancer by controlling the host’s inflammatory response and influencing a variety of immunological pathways. More and more studies have pointed to the fact that the commensal microbiota plays a vital role in both the development of tumors and the body’s response to lung cancer treatment. Microbiome dysbiosis, genotoxicity, virulence effect, and epigenetic dysregulations are some of the potential mechanisms that may lie behind the process of tumorigenesis that is mediated by microbiome. Other potential mechanisms include regulating host immune activity through a variety of pathogenic factors, dysregulating host metabolism as a result of microbiome alterations, and microbiome dysbiosis. In this historical overview, we go through some of the more recent mechanistic discoveries into the biological processes that are involved in lung cancer that are caused by bacteria. Without a question, obtaining a greater knowledge of the dynamic link between the lung microbiome and lung cancer has the potential to inspire the development of innovative early detection and customized treatment methods for lung cancer

Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer

Abstract Background and aims This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk. Materials and methods There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis. Results Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis. Conclusion Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk

LINC02163 promotes colorectal cancer progression via miR-511-3p/AKT3 axis

AbstractLong non-coding RNAs and microRNAs are functional regulators in tumour progression. Herein, we revealed the level LINC02163 was up-regulated in CRC tissues and cell lines, and the expression of LINC02163 negatively correlated with prognosis of CRC patients. Functional experiments demonstrated knockdown of LINC02163 significantly attenuated CRC cells proliferation and metastasis. Mechanism analysis showed miR-511-3p could bind LINC02163 and AKT3, and the expressional level of miR-511-3p negatively correlated with the abundance of LINC02163 and AKT3. Inhibition of LINC02163 suppressed cell proliferation, while transfection of miR-511-3p inhibitor or AKT3 in LINC02163-depletion cells restored cell growth and abolished the cell cycle arrest in G0/G1 phase. Therefore, it was indicated that LINC02163 exerted pro-tumour effect through miR-511-3p/AKT3 axis and was prognostic marker for colorectal cancer