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BackgroundGastric 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 the effectiveness of tumor treatment when combined with immune checkpoint inhibitors.MethodsGene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.ResultsGC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells.ConclusionThis is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

Aspects of manganese metabolism during normal and acidogenic growth of Aspergillus niger were explored. Arginase from this fungus was a Mn[II]-enzyme. The contribution of the arginase protein towards A. niger manganese metabolism was investigated using arginase knockout (D-42) and arginase over-expressing (ΔXCA-29) strains of A. niger NCIM 565. The Mn[II] contents of various mycelial fractions were found in the order: D-42 strain < parent strain < ΔXCA-29 strain. While the soluble fraction forms 60 % of the total mycelial Mn[II] content, arginase accounted for a significant fraction of this soluble Mn[II] pool. Changes in the arginase levels affected the absolute mycelial Mn[II] content but not its distribution in the various mycelial fractions. The A. niger mycelia harvested from acidogenic growth media contain substantially less Mn[II] as compared to those from normal growth media. Nevertheless, acidogenic mycelia harbor considerable Mn[II] levels and a functional arginase. Altered levels of mycelial arginase protein did not significantly influence citric acid production. The relevance of arginase to cellular Mn[II] pool and homeostasis was evaluated and the results suggest that arginase regulation could occur via manganese availability. [ABSTRACT FROM AUTHOR]

This article examines the evolution of nutritional iron deficiency and the possible interactions with other minerals, such as manganese, in control and iron-deficient rats. The evolution of iron deficiency was studied at 0, 10, 20, 30 and 40 days of providing the animals with an iron-free diet (diet 0). It was found that the critical period in the development of nutritional iron deficiency occurs after 30–40 days without iron, at which moment the organism is unable to maintain hemoglobin levels without endangering the iron-dependent enzymatic groups which, in turn, are essential for life. It was also demonstrated that in a situation of iron deficiency, there occurs a greater absorption of manganese. It should be noted that this greater absorption of manganese is not reflected in the concentration of the mineral in the organs. Therefore, it is evident that the interactions of iron with manganese take place at the digestive level with no apparent consequences being observed at the metabolic level. [ABSTRACT FROM AUTHOR]

The effects of acute manganese (Mn) toxicity on tissue manganese concentrations and on plasma glucose levels were investigated in adult male Sprague-Dawley rats. Manganese injection in all tissues analyzed was reflected by a significant increase in Mn concentration that was transitory. Changes in the molecular localization of Mn in liver following injection include both increases in protein-bound Mn and low molecular weight Mn complexes. A rapid, dose-responsive rise in blood glucose followed Mn injection, whereas circulating insulin levels decreased after injection. These data show that acute changes in tissue Mn levels can have a pronounced effect on carbohydrate metabolism. [ABSTRACT FROM AUTHOR]