Objective To identify genes of lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice base on bioinformatics and machine learning. Methods The acute lung injury dataset (GSE2411, GSE111241 and GSE18341) were download from the Gene Expression Database (GEO). Differential gene expression analysis was conducted. Gene ontology (GO) analysis, KEGG pathway analysis, GSEA enrichment analysis and protein-protein interaction analysis (PPI) network analysis were performed. LASSO-COX regression analysis and Support Vector Machine Expression Elimination (SVM-RFE) was utilized to identify key biomarkers. Receiver operator characteristic curve was used to evaluate the diagnostic ability. Validation was performed in GSE18341. Finally, CIBERSORT was used to analyze the composition of immune cells, and immunocorrelation analysis of biomarkers was performed. Results A total of 29 intersection DEGs were obtained after the intersection of GSE2411 and GSE111241 differentially expressed genes. Enrichment analysis showed that differential genes were mainly involved in interleukin-17, cytokine - cytokine receptor interaction, tumor necrosis factor and NOD-like receptor signaling pathways. Machine learning combined with PPI identified Gpx2 and Ifi44 were key biomarkers. Gpx2 is a marker of ferroptosis and Ifi44 is an type I interferon-induced protein, both of which are involved in immune regulation. Immunocorrelation analysis showed that Gpx2 and Ifi44 were highly correlated with Neutrophils, TH17 and M1 macrophage cells. Conclusion Gpx2 and Ifi44 have potential immunomodulatory abilities, and may be potential biomarkers for predicting and treating ALI in mince.
The morbidity and mortality of gallbladder cancer were rising. At present, there was no effective chemotherapy regimen, so it was of great practical significance to explore new therapy target. Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. In recent years, it had become a research hotspot. Many studies had been carried out on the relevant biological mechanisms such as liver cancer, breast cancer, pancreatic cancer, and other cancer. At present, there are still few studies on ferroptosis in gallbladder cancer, and its relevant mechanisms need further in-depth analysis, which opens up a new research direction for exploring the treatment of gallbladder cancer.
Neuropathic pain (NP) is a pathological state caused by damage or disease to the somatosensory nervous system. Programmed cell death (PCD) is an orderly process of cell death regulated by both intrinsic signals and external stimuli. In recent years, an increasing number of studies have shown that PCD plays a key regulatory role in the pathogenesis of NP. This article reviews the molecular mechanisms of various types of PCD and their specific roles in NP, in order to provide new research directions for the prevention, diagnosis, and treatment of NP.
Immunoglobulin A nephropathy (IgAN) is an immune-mediated chronic inflammatory disease with a complex pathogenesis and diverse clinical manifestations. Currently, there is no specific treatment plan. Programmed cell death is an active and orderly way of cell death controlled by genes in the body, which maintains the homeostasis of the body and the development of organs and tissues by participating in various molecular signaling pathways. In recent years, programmed cell death has played an important regulatory role in the occurrence and development of IgAN, involving complex signaling pathways. Under pathological conditions, it may relieve kidney damage through various pathways such as reducing oxidative stress, inhibiting inflammation, and improving energy metabolism. This article provides a review of the research progress of IgAN in apoptosis, autophagy, pyroptosis, ferroptosis,and cuproptosis in order to provide new therapeutic targets for IgAN.
ObjectiveTo summarize a comprehensive overview of the mechanism of ferroptosis and its associated microRNAs in the occurrence and development of hepatocellular carcinoma (HCC), and to offer novel insights and potential avenues for tumor marker screening and targeted treatment in clinical hepatocellular carcinoma patients. MethodThe literatures on the basic and clinical application research of ferroptosis and related microRNA in the occurrence, development and prognosis of HCC at home and abroad in recent years were reviewed and summarized, and the research progress of microRNA regulating ferroptosis in HCC was summarized. ResultsMicroRNA, a type of non-coding small RNA, had the ability to regulate gene expression at the post-transcriptional and translational levels. It held promising potential in the diagnosis and treatment of HCC. Ferroptosis, on the other hand, was a form of cell death triggered by iron-dependent lipid peroxidation. It played a crucial role in the development of HCC. A series of miRNAs related to ferroptosis might act as HCC growth regulators to regulate the growth of cancer cells, or reverse the drug resistance of cancer cells, thereby promoting or inhibiting the occurrence and progression of HCC. ConclusionsMicroRNA can regulate the occurrence and development of HCC through the ferroptosis pathway and may become tumor markers for the early diagnosis of HCC. Additionally, microRNA may also serve as a related therapeutic target and provide a new treatment option for HCC.
ObjectiveTo investigate the effect of Huaier extract on the proliferation, invasion, and ferroptosis pathways of colorectal cancer (CRC) cells. MethodsThe CRC cell line SW620 was cultured in vitro, and the cells were treated with Huaier extract solution at different concentrations (0, 5, 10, 20, and 50 mg/mL). The cell counting kit 8 was used to detect the proliferation of CRC cells at different concentrations to scree the test dose of the Huaier extract. The Transwell and the scratch assays were used to detect the cell invasion and migration. The reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) kits were used to detect the cellular oxidative stress level. The Western blot was used to detect the ferroptosis-related proteins levels, including glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (NRF2), and high mobility group box-1 (HMGB1). ResultsIn this study, it could statistically inhibit the proliferation of CRC cells after 48 h interfering with Huaier extract at 10, 20 mg/mL concentrations, so we chose 10, 20 mg/mL concentrations as the test dose, 0 mg/L as the control dose. Huaier extract effectively inhibited the migration and invasion abilities of SW620 cells in a dose-dependent manner (Transwell: F=480.0, P<0.001; scratch assay: F=24.3, P=0.001). The level of ROS in the SW620 cells increased with the increase of concentration in a dose-dependent manner (F=806.3, P<0.001). the level of GSH in the SW620 cells decreased with the increase of concentration in a dose-dependent manner (F=35.0, P=0.005), but the level of MDA was highest at 10 mg/mL (F=22.9, P=0.002) . Further the Huaier extract could effectively reduce the expressions of GPX4 (F=74.2, P<0.001), NRF2 (F=32.8, P=0.001), and HMGB1 (F=55.1, P<0.001) in a dose-dependent manner. ConclusionFrom the results of this study, Huaier extract at 10 and 20 mg/mL concentrations can inhibit the proliferation and invasion of CRC SW620 cells by inducing ferroptosis.
ObjectiveTo establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. MethodsFive AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analysis was performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene setenrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. ResultsA total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, regulation of interleukin 17, etc. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. ConclusionThe identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.
Objective To summarize the papers about the research status and prospects of ferroptosis in hepatocellular carcinoma (HCC) and its drug resistance in recent years in order to provide directions and ideas for the treatment of HCC. Method The relevant literatures at home and abroad in recent years about ferroptosis in HCC and its drug resistance were reviewed. Results The mechanism of ferroptosis in the development and drug resistance of HCC was complicated, involving multiple protein and molecular pathways. Ferroptosis played an important role in improving chemotherapy and sorafenib resistance, and it had a broad application prospect in HCC. Conclusions The molecular mechanism of ferroptosis in HCC and its drug resistance has not been fully elucidated. Further research on the mechanism of ferroptosis in HCC may provide new molecular therapeutic targets for HCC. Ferroptosis has a broad application prospect in the treatment of HCC.
ObjectiveTo understand the molecular mechanism of ferroptosis and its research progress and future prospects in pancreatic cancer. MethodThe relevant literature on the molecular mechanism of ferroptosis and its basic and clinical application in the occurrence and development of pancreatic cancer was retrievaled and reviewed. ResultsFerroptosis was a non-apoptotic form of cell death that depended on iron aggregation, and its molecular biological features included iron ion overload, reactive oxygen species accumulation, lipid peroxidation, and so on. Ferroptosis was closely related to cell metabolism, and the imbalance of ferroptosis caused by abnormal metabolism also existed during the tumorigenesis and progression of pancreatic cancer, which in turn triggered the abnormal proliferation of pancreatic cancer cells and leaded to their progression. By regulating the key molecular signaling pathways of ferroptosis, it was expected to find new drug targets and therapeutic pathways for pancreatic cancer treatment. The results of ferroptosis-related studies so far had shown the potential for future translational research in the field of pancreatic cancer treatment. ConclusionsThe mechanism of ferroptosis is of great value in pancreatic cancer research. At present, there are still many uncharted areas in the study of ferroptosis, and the molecular mechanisms involved are still poorly understood. In the future, as the study of ferroptosis continues, it is expected to provide new ideas for pancreatic cancer treatment and discover new targets for drug development.
Objective To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. Methods BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. Results The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. ConclusionVPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.