ABSTRACT
Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. However, the current lack of effective biomarkers for PC could contribute to the insufficiency of existing treatments. These findings underscore the urgent need to develop novel strategies to fight this disease. This study utilized multiple comprehensive bioinformatic analyses to identify potential therapeutic target genes in PC, focusing on histone lysine demethylases (KDMs). We found that high expression levels of KDM family genes, particularly KDM1A, KDM5A and KDM5B, were associated with improved overall survival in the cohort. Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8+ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/ß-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.
Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Jumonji Domain-Containing Histone Demethylases , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Computational Biology , F-Box Proteins/metabolism , F-Box Proteins/genetics , Histone Demethylases/metabolism , Histone Demethylases/genetics , Molecular Targeted Therapy/methods , Retinoblastoma-Binding Protein 2/metabolism , Retinoblastoma-Binding Protein 2/genetics , Wnt Signaling Pathway/genetics , Cell Proliferation/genetics , Nuclear Proteins , Repressor ProteinsABSTRACT
To understand the mechanism(s) of age-dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age-related HBV mouse model in which 6-week-old (N6W) C3H/HeN mice exhibited virus tolerance whereas 12-week-old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C-C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C)+ monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF-α-secreting Ly6C+ monocytes and fewer IL-10-secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon-γ+ TNF-α+ CD8+ T cells at D7 was only seen in the older cohort. The enhanced Ly6C+ monocyte induction in N12W mice resulted from elevated C-C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C+ monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C+ monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C+ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV-related liver diseases.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Hepatitis B Surface Antigens/blood , Hepatitis B virus/genetics , Hepatitis B/immunology , Immunotherapy/methods , Monocytes/immunology , Animals , Cells, Cultured , Chemokines/metabolism , Cytokines/metabolism , Disease Models, Animal , Hepatitis B/physiopathology , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatocytes/immunology , Humans , Kupffer Cells/immunology , Male , Mice , Mice, Inbred C3H , Random Allocation , Reference Values , TransfectionABSTRACT
PURPOSE: This study explored the relationship between adolescents' emotional intelligence and the tendency to develop an eating disorder. METHODS: Senior high school students in Taiwan were recruited for the study. A 3- part anonymous questionnaire measured demographic information, body weight satisfaction, and expectation of body weight. Students also completed the Adolescent Emotional Intelligence Scale and the Eating Disorders Attitude- 26 Test (EAT-26). Height and weight were also measured. RESULTS: The mean of EAT-26 score was 8.66 ± 7.36, and 8.6% students were at high risk to develop eating disorders. Gender, body weight, body dissatisfaction and the expected body shape were significantly related to disturbed eating attitudes and behaviours. Scores of EAT-26 were positively correlated with emotional perception, emotional expression, and emotional application. CONCLUSIONS: Disturbed eating behaviours exist among adolescents in Taiwan, and these behaviours may be related to emotional intelligence. However further studies with larger samples are needed.