Exome-Based Amino Acid Optimization: A Dietary Strategy to Satisfy Human Nutritional Demands and Enhance Muscle Strength in Breast Tumor Mice Undergoing Chemotherapy.

Breast cancer patients undergoing chemotherapy often experience muscle wasting and weakness, which impact their quality of life. A potential solution lies in customizing amino acid compositions based on exome-derived formulations (ExAAs). The study hypothesized that tailoring dietary amino acids using ExAAs could enhance muscle health. Theoretical amino acid requirements were calculated from the genome's exome region, and a breast cancer mouse model undergoing paclitaxel treatment was established. The mice were supplemented with a cancer-specific nutritional formula (QJS), and the effects of QJS and amino acid-adjusted QJS (adjQJS) were compared. Both formulations improved the nutritional status without compromising tumor growth. Notably, adjQJS significantly enhanced muscle strength compared to QJS (1.51 ± 0.25 vs. 1.30 ± 0.08 fold change, p < 0.05). Transcriptome analysis revealed alterations in complement and coagulation cascades, with an observed upregulation of C3 gene expression in adjQJS. Immune regulation also changed, showing a decrease in B cells and an increase in monocytes in skeletal muscle with adjQJS. Importantly, adjQJS resulted in a notable increase in Alistipes abundance compared to QJS (10.19 ± 0.04% vs. 5.03 ± 1.75%). This study highlights the potential of ExAAs as valuable guide for optimizing amino acid composition in diets for breast cancer patients undergoing chemotherapy.

Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds.

Hyperuricemia is a metabolic disease caused by disorders of purine metabolism, the prevalence of which has increased worldwide. Here, a cell model for high uric acid production was established in vitro employing cultured human kidney cells (HK-2 cells), and its molecular basis was analyzed using gene expression profile. High performance liquid chromatography (HPLC) was used to monitor the content of metabolites in cell culture media. Adenosine addition was found to induce HK-2 cells to produce uric acid precursors (inosine and hypoxanthine). Furthermore, the cell model was verified by confirming the antihyperuricemic effect of the widely used antihyperuricemic drugs allopurinol, probenecid, and febuxostat, as well as reported bioactive peptides and amino acids, encompassing glutathione, tryptophan and carnosine, which significantly reduced uric acid production in the HK-2 cells (p < 0.05). RNA-Seq technology was used to perform a wide transcriptome analysis of the hyperuricemic cell model, and the results demonstrated that it has the potential to be used as a rapid and valid in vitro model to screen antihyperuricemic compounds that mimics in vivo cell growth patterns.