Figure - available from: Frontiers in Immunology
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Development of nomograms based on clinical features and risk scores. (A, D) The nomograms predicting the 1-, 2- and 3-year survival rate of patients with GC in the TCGA cohort (A) and in the GEO cohort (D). (B, E) Calibration curves for nomograms in the TCGA cohort (B) and in the GEO cohort (E). (C, F) ROC curves assessing the prognostic accuracy of nomogram and other clinical features in the TCGA cohort (C) and in the GEO cohort (F).
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Background
Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body’s anti-tumor immune response, has the potential to enhance...
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Background
Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on sampl...
Citations
... In a univariate analysis, the risk score and TNM stage emerged as significant predictors of survival in gastric cancer patients (P < 0.001) (Fig. 6F); furthermore, multivariate analysis indicated a statistically significant correlation (P < 0.001) between the risk score, age, and survival, even after controlling for other variables (Fig. 6G). We compared our own model to 14 other published GC models to better highlight its predictive capability [18][19][20][21][22][23][24][25][26][27][28][29][30][31]. When compared to other models, ours has a higher C-index (Fig. 6H). ...
Gastric cancer (GC) has a poor prognosis, considerable cellular heterogeneity, and ranks fifth among malignant tumours. Understanding the tumour microenvironment (TME) and intra-tumor heterogeneity (ITH) may lead to the development of novel GC treatments.
The single-cell RNA sequencing (scRNA-seq) dataset was obtained from the Gene Expression Omnibus (GEO) database, where diverse immune cells were isolated and re-annotated based on cell markers established in the original study to ascertain their individual characteristics. We conducted a weighted gene co-expression network analysis (WGCNA) to identify genes with a significant correlation to GC. Utilising bulk RNA sequencing data, we employed machine learning integration methods to train specific biomarkers for the development of novel diagnostic combinations. A two-sample Mendelian randomisation study was performed to investigate the causal effect of biomarkers on gastric cancer (GC). Ultimately, we utilised the DSigDB database to acquire associations between signature genes and pharmaceuticals.
The 18 genes that made up the signature were as follows: ZFAND2A, PBX4, RAMP2, NNMT, RNASE1, CD93, CDH5, NFKBIE, VWF, DAB2, FAAH2, VAT1, MRAS, TSPAN4, EPAS1, AFAP1L1, DNM3. Patients were categorised into high-risk and low-risk groups according to their risk scores. Individuals in the high-risk cohort exhibited a dismal outlook. The Mendelian randomisation study demonstrated that individuals with a genetic predisposition for elevated NFKBIE levels exhibited a heightened likelihood of acquiring GC. Molecular docking indicates that gemcitabine and chloropyramine may serve as effective therapeutics against NFKBIE.
We developed and validated a signature utilising scRNA-seq and bulk sequencing data from gastric cancer patients. NFKBIE may function as a novel biomarker and therapeutic target for GC.
Introduction
The study aimed to determine the effect of manganese (Mn) exclusion from the mineral mixture added to the rat diet and replacing the recommended level of MnCO3 (65 mg Mn/kg diet) with Mn2O3 nanoparticles (Mn2O3NPs) in the diet on blood hematology and selected immunological indices of the blood, jejunum, and brain.
Methods
The experiment was conducted on twenty-four, Wistar rats divided into 3 equal groups. The control (K) group received a diet containing 65 mg/kg of additional Mn originating from the mineral mixture), group B (negative control) was fed a diet deprived of Mn from the mineral mixture, and group N was fed a diet containing 65 mg/kg Mn from Mn2O3NPs preparation. All rats received the experimental diets for 12 weeks. At the end of the experiment, samples of blood, jejunum, and brain were collected from all rats from each group.
Results
Mn exclusion from the rat diet led to anemia, worsened the body’s immune response, and caused systemic and local inflammation as indicated e.g. by decreased RBC, HCT, and the level of HGB, and CRP in blood, CRP and IgA in the jejunum, and IgG in the brain as well as an increased level of IL-2, IgG and TNF-α in blood, and IL-6 in jejunum. In turn, replacing the recommended level of MnCO3 with Mn2O3NPs in the rat diet worsened the immune response and caused local inflammation in the brain as indicated by an increase in TNF-α level and Cp activity, as well as decreased levels of IgG. Analogical changes were not observed in the jejunum or systemic level.
Discussion
The obtained results may suggest that the body has activated adaptive mechanisms that efficiently limit the spread of immune system disorders throughout the body.
