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.
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 A series of bioinformatics methods were used to identify ferroptosis related biomarkers in lupus nephritis (LN). Methods We retrieved sequencing data of GSE112943 from the GEO (Gene Expression Omnibus) database and screened LN differentially expressed genes. We searched for ferroptosis-related gene (FRG) through FerrDb database, and screened LN-FRG. We conducted enrichment analysis on the LN-FRGs using David online bioinformatics database and screened the core LN-FRG using cytoHubba. We used external data sets to verify the core LN-FRGs, constructed competing endogenous RNA networks, and conducted molecular docking analysis. Results A total of 37 LN-FRGs were selected through screening. These genes are mainly enriched in inflammation, immune regulation and ferroptosis related signaling pathways. Through the cytoHubba and external dataset validation, the key core LN-FRG of ATF3 (activating transcription factor 3) was ultimately identified, and its expression was significantly increased in LN (P<0.05). Molecular docking analysis showed that ATF3 was closely bound to SLC7A11 and NRF2, and may participate in the occurrence and development of LN through the microRNA-27-ATF3 regulation axis. Conclusion The pivotal gene ATF3 may participate in the inflammation and immune injury of LN through ferroptosis.
ObjectiveTo construct a prognostic prediction model for hepatocellular carcinoma (HCC) based on disulfidptosis-associated genes (DAGs) and ferroptosis-associated genes (FAGs) using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and explore the immune characteristics and antitumor drug sensitivity of HCC patients with high- and low-risk score. MethodsThe transcriptomic and clinical data of HCC were downloaded from the TCGA and ICGC databases. The expression levels of DAGs and FAGs were extracted. Subsequently, the differentially expressed and prognostically relevant DAGs and FAGs (DFAGs) were screened through differential expression and prognostic analysis. A prognostic prediction model for HCC was constructed by LASSO regression analysis. The prognostic value of risk factors was evaluated using univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, receiver operating characteristic curves, principal component analysis, and t-distributed stochastic neighbor embedding. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to further elucidate the mechanisms of genes associated with HCC prognosis. The impact of risk factors on immune cells and immune cells functions was analyzed using single-sample gene set enrichment analysis. Based on the Genomics of Drug Sensitivity in Cancer database, the oncoPredict package was used to predict responses to antitumor drugs in for different risk groups. ResultsFour DFAGs (SLC7A11, SLC1A5, G6PD, and LRPPRC) with respective risk coefficients of 0.0350, 0.0442, 0.1597, and 0.0132 were selected to construct the prognostic prediction model. The risk score of prognostic prediction model was calculated as: Risk score =(0.0350×SLC7A11 expression level) + (0.0442×SLC1A5 expression level) + (0.159 7×G6PD expression level) + (0.013 2×LRPPRC expression level). The multivariate Cox regression analysis indicated that a high-risk score was an independent risk factor for HCC patient survival [HR (95%CI) = 5.414 (1.918, 15.279), P<0.001]. Both TCGA and ICGC datasets demonstrated that the high-risk patients had significantly worse survival than low-risk patients (P<0.001 and P=0.003, respectively). Enrichment analysis revealed that the risk-associated genes influenced HCC progression through multiple pathways, such as immune response, cell cycle, glycolysis, gluconeogenesis. Immune analysis showed that the high-risk patients exhibited increased infiltration of immunosuppressive cells, such as activated dendritic cells, macrophages, and regulatory T cells, while natural killer cell infiltration was significantly reduced. The drug sensitivity analysis suggested that the high-risk HCC patients might respond better to 5-fluorouracil, afatinib, cyclophosphamide, and lapatinib, whereas the low-risk patients might benefit more from oxaliplatin and sorafenib. ConclusionsHCC prognosis prediction model based on DFAGs in this study suggests a certain predictive value for the survival of HCC patients in the data from both TCGA and ICGC datasets. There are significant differences in pionts of immune cells infiltration and immune cells functions between high-risk and low-risk HCC patients. Additionally, significant differences exist in sensitivity to targeted drugs and chemotherapeutic drugs. This model can provide some references for immunotherapy, personalized treatment, and prognosis evaluation of HCC patients.
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.
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.
Objective To observe the expression of hepcidin-ferroportin (FPN) pathway in adenine-induced chronic kidney disease (CKD) rat model and to explore the mechanism of its involvement in renal fibrosis in CKD. Methods A total of 20 6-week-old male SD rats without specific pathogen were selected. The rats were divided into control group and CKD group, with 10 rats in each group, using a simple random method. Rats were sacrificed at the end of the second and sixth weeks after modeling. The levels of serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urine protein quantification were measured. The pathological changes of rats were observed. The iron content of rat kidney tissue was detected by colorimetric method, and the level of serum hepcidin-25 was detected by enzyme linked immunosorbent assay method in both groups. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to detect the renal protein and mRNA expression of α-smooth muscle actin (α-SMA), collagen type Ⅰ (Col-Ⅰ), FPN1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) P65. Results Compared with the control group, the levels of Scr, BUN, and 24 h urine protein quantification were higher in the CKD group at the end of the second and sixth weeks of modeling (P<0.05). The results of renal tissue staining showed that the CKD group had obvious glomerular structural disorders, tubular dilation, and interstitial collagen fiber deposition. Compared with the control group, the serum hepcidin-25 level and the iron content of kidney tissues in the CKD group were significantly higher, and correlation analysis suggested that both were positively correlated with the renal function of rats (P<0.05). Compared with the control group, the protein and mRNA expression levels of α-SMA, Col-Ⅰ, HAMP, IL-6, TNF-α, NF-κB P65 were higher (P<0.05), while FPN1 expression was lower in CKD group at the end of the second and sixth weeks of modeling (P<0.05). Correlation analysis results showed that HAMP mRNA expression was positively correlated with α-SMA, Col-Ⅰ, IL-6, TNF-α, and NF-κB p65 (P<0.001), which was negatively correlated with FPN1 mRNA expression (P<0.001). FPN1 mRNA expression was significantly negatively correlated with α-SMA, Col-Ⅰ (P<0.001). Conclusions Ferroptosis may be present in the adenine-induced rat model of CKD, and it may be involved in the process of renal fibrosis through the interaction of HAMP-FPN signaling pathway with the inflammatory response. Serum hepcidin-25 is expected to be a serological marker for the early diagnosis of CKD.
ObjectiveTo investigate the pan-cancer expression profile, prognostic value, co-expression networks, immune regulatory roles of BRF1, and its biological functions and molecular mechanisms in esophageal squamous cell carcinoma (ESCC). MethodsIntegrated analysis of TCGA pan-cancer datasets was performed to evaluate BRF1 expression differences between tumor/normal tissues, survival correlations, co-expressed gene-enriched pathways, and immune features (immune checkpoints, cytokines, immune cell infiltration). GEO datasets were used to validate BRF1 expression in ESCC. BRF1 was knocked down using siRNA in ESCC cells, with MTT and Transwell assays assessing proliferation/migration, and Western blot analyzing proliferation- (PCNA) and migration-related proteins (Vimentin, MMP, E-Cadherin). TCGA data were analyzed to explore BRF1-ferroptosis correlations. ResultsBRF1 was significantly upregulated in over 20 cancer types. High BRF1 expression predicted poor prognosis in adrenocortical carcinoma (ACC) and prostate adenocarcinoma (PRAD). BRF1 positively regulated T cell-mediated cell death pathways in ESCA and circadian rhythm pathways in PAAD. BRF1 exhibited cancer-type-specific correlations with immune checkpoints, cytokine networks, and immune cell infiltration. In vitro, BRF1 knockdown suppressed ESCC proliferation (PCNA downregulation) and migration (Vimentin/MMP downregulation, E-Cadherin upregulation). BRF1 expression positively correlated with ferroptosis antagonists (GPX4, HSPA5, SLC7A11). ConclusionBRF1 demonstrates complex pan-cancer expression and functional heterogeneity, modulating tumor progression and immune infiltration. BRF1 promotes ESCC proliferation and migration, potentially via ferroptosis resistance regulation, highlighting its potential as a therapeutic target in ESCC.
ObjectiveTo summarize the mechanism and research progress of ferroptosis in acute liver injury. MethodThe domestic and foreign literatures related of ferroptosis and acute liver injury were searched and reviewed. ResultsFerroptosis was a newly identified form of iron-dependent cell death. The loss of lipid peroxidation repair activity of glutathione peroxidase 4, the presence of redox active iron and the oxidation of phospholipids containing polyunsaturated fatty acids were considered to be distinctive features of ferroptosis. At present, the research on the regulation of ferroptosis genes involved common liver diseases, including drug-induced liver injury, hepatocellular carcinoma, liver fibrosis, liver ischemia-reperfusion injury, liver failure, nonalcoholic fatty liver and so on. Based on the high correlation between ferroptosis and acute liver injury, chemical therapy targeting ferroptosis could provide individualized treatment for patients with acute liver injury in the future. ConclusionsThe ferroptosis plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of acute liver injury through diverse mechanisms. Thoroughly exploring the involvement of the ferroptosis in acute liver injury is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of acute liver injury.
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.
