Susceptibility of acute myeloid leukemia cells to ferroptosis and evasion strategies

Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a 5-year survival rate of less than 30%. Continuous updating of diagnostic and therapeutic strategies has not been effective in improving the clinical benefit of AML. AML cells are prone to iron metabolism imbalance due to their unique pathological characteristics, and ferroptosis is a novel cell death mode that is dominated by three cellular biological processes: iron metabolism, oxidative stress and lipid metabolism. An in-depth exploration of the unique ferroptosis mechanism in AML can provide new insights for the diagnosis and treatment of this disease. This study summarizes recent studies on ferroptosis in AML cells and suggests that the metabolic characteristics, gene mutation patterns, and dependence on mitochondria of AML cells greatly increase their susceptibility to ferroptosis. In addition, this study suggests that AML cells can establish a variety of strategies to evade ferroptosis to maintain their survival during the process of occurrence and development, and summarizes the related drugs targeting ferroptosis pathway in AML treatment, which provides development directions for the subsequent mechanism research and clinical treatment of AML

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study

BackgroundPatients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear.MethodsUsing a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality.ResultsAfter adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000–1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found.ConclusionThis study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer

Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents

T cell senescence: a new perspective on immunotherapy in lung cancer

T cell senescence is an indication of T cell dysfunction. The ability of senescent T cells to respond to cognate antigens is reduced and they are in the late stage of differentiation and proliferation; therefore, they cannot recognize and eliminate tumor cells in a timely and effective manner, leading to the formation of the suppressive tumor microenvironment. Establishing methods to reverse T cell senescence is particularly important for immunotherapy. Aging exacerbates profound changes in the immune system, leading to increased susceptibility to chronic, infectious, and autoimmune diseases. Patients with malignant lung tumors have impaired immune function with a high risk of recurrence, metastasis, and mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, and other immune checkpoints is promising for treating lung malignancies. However, T cell senescence can lead to low efficacy or unsuccessful treatment results in some immunotherapies. Efficiently blocking and reversing T cell senescence is a key goal of the enhancement of tumor immunotherapy. This study discusses the characteristics, mechanism, and expression of T cell senescence in malignant lung tumors and the treatment strategies

NaTi2(PO4)3/N‐Doped Hard Carbon Nanocomposites with Sandwich Structure for High‐Performance Na‐Ion Full Batteries

The well‐matched technology of cathode and anode in Na‐ion full batteries is highly challenging yet critically important in practical applications. Here, the high‐performance Na‐ion full batteries are developed by using NaTi2(PO4)3/N‐doped mesoporous hard carbon hybrid anode and porous Na3V2(PO4)3 cathode. The different anodes are designed for well‐matched Na‐ion full batteries. The unique sandwich and mesoporous structural features endow the hybrid anode with a high reversible capacity (240 mAh g−1 at 1 C), high rate performance (109.7 mAh g−1 at 100 C), ultrahigh energy/power densities (76.56 Wh kg−1/5104 W kg−1) and a long cycle‐life (capacity retention of 92.1 % after 1000 cycles at 100 C) in a half cell. In a full battery this hybrid anode can also deliver a higher capacitive contribution (79.5–87.7 %) and high energy/power densities (104 Wh kg−1/5256 W kg−1). This design provides a promising pathway for developing high performance and low‐cost Na‐ion full batteries

Identifying the Antiproliferative Effect of Astragalus Polysaccharides on Breast Cancer: Coupling Network Pharmacology With Targetable Screening From the Cancer Genome Atlas

Background:Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumorigenesis.Methods: We obtained breast cancer genetic data from The Cancer Genome Atlas (TCGA) database, network pharmacology to further clarify its biological properties. Survival analysis and molecular docking techniques were implemented for the final screening to obtain key target information. Our experiments focused on the detection of intervention effects of APS on BC cells (MCF-7 and MDA-MB-231), and quantitative RT-PCR (qRT-PCR) was used to assess the expression of key targets.Results: A total of 1,439 differentially expressed genes (DEGs) were identified by TCGA and used to build disease networks. Module analysis, gene ontology and pathway analysis revealed characteristic of the DEGs network. Topological properties were used to identify key targets, survival analysis and molecular docking finally found that the targets of APS regulation of BC cells may be CCNB1, CDC6, and p53. Through cell viability, migration and invasion assays, we found that APS interferes with the development of breast cancer in MCF7 and MDA-MB-231 cells in a dose-dependent manner. Furthermore, qRT-PCR verification suggested that the expression of CCNB1 and CDC6 in breast cancer cells was significantly downregulated in response to APS, while expression of the tumor suppressor gene P53 was significantly increased.Conclusion: Results of this study suggest therapeutic potential for APS in BC treatment, possibly through interventions with CCNB1, CDC6, and P53. Furthermore, these findings illustrate the feasibility of using network pharmacology to connect large-scale target data as a way to discover the mechanism of natural products interfering with disease

The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method.

Background: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC

Development approach of a programmable and open software package for power system frequency response calculation

Abstract Dynamic behaviour of frequency is crucial for power system operation and control. Several frequency response models have been proposed to reveal frequency dynamics from different aspects. A comprehensive software package incorporating major frequency response models is needed for analysis and control of power system frequency dynamics. In this paper, an approach for developing a programmable and open software package for frequency response studies is proposed. The framework of the package is extendable with reduced frequency response models. Essential models for frequency response study are included, e.g., generator, load, and under-frequency load shedding (UFLS). The provided application program interfaces (APIs) enable simulation with high-level languages by calling dynamic link library and makes the package programmable. An advanced application module is developed for quantitative assessment of transient frequency deviation. APIs can also be used for model extension and secondary development. To demonstrate the usage of the package, several examples are illustrated to explain how to perform simulations with the package, and to perform advanced applications using scripting with the provided APIs

Identification of lncRNAs associated with lung squamous cell carcinoma prognosis in the competitive endogenous RNA network

Background Long noncoding RNAs (lncRNAs) play a role in the formation, development, and prognosis of various cancers. Our study aimed to identify prognostic-related lncRNAs in lung squamous cell carcinoma (LUSC), which may provide new perspectives for individualized treatment of patients. Materials and Methods The RNA sequencing (lncRNA, microRNA (miRNA), mRNA) data and clinical information related to LUSC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA sequences were used to construct the competitive endogenous RNA (ceRNA) network. In present study, we mainly used two prognostic verification methods, Cox analysis and survival analysis, to identify the prognostic relevance of specific lncRNAs and construct prognostic model of lncRNA. Results Datasets on 551 samples of lncRNA and mRNA and 523 miRNA samples were retrieved from the TCGA database. Analysis of the normal and LUSC samples identified 170 DElncRNAs, 331 DEmiRNAs, and 417 DEmRNAs differentially expressed RNAs. The ceRNA network contained 27 lncRNAs, 43 miRNAs, and 11 mRNAs. Furthermore, we identified seven specific lncRNAs (ERVH48-1, HCG9, SEC62-AS1, AC022148.1, LINC00460, C5orf17, LINC00261) as potential prognostic factors after correlation analysis, and five of the seven lncRNAs (AC022148.1, HCG9, LINC00460, C5orf17, LINC00261) constructed a prognostic model of LUSC. Conclusion In present study, we identified seven lncRNAs in the ceRNA network that are associated with potential prognosis in LUSC patients, and constructed a prognostic model of LUSC which can be used to assess the prognosis risk of clinical patients. Further biological experiments are needed to elucidate the specific molecular mechanisms underlying them