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Background: Amino acid metabolism is essential for tumor cell proliferation and regulation of immune cell function. However, the clinical significance of free amino acids (plasma-free amino acids (PFAAs)) and tryptophan-related metabolites in plasma has not been fully understood in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors.
Methods: We conducted a single cohort observational study. Peripheral blood samples were collected from 53 patients with NSCLC before treatment with PD-1 (Programmed cell death-1) inhibitors. The plasma concentrations of 21 PFAAs, 14 metabolites, and neopterin were measured by liquid chromatography-mass spectrometry. Using Cox hazard analysis with these variables, a multivariate model was established to stratify patient overall survival (OS). Gene expression in peripheral blood mononuclear cells (PBMCs) was compared between the high-risk and low-risk patients by this multivariate model.
Results: On Cox proportional hazard analysis, higher concentrations of seven PFAAs (glycine, histidine, threonine, alanine, citrulline, arginine, and tryptophan) as well as lower concentrations of three metabolites (3h-kynurenine, anthranilic acid, and quinolinic acid) and neopterin in plasma were significantly correlated with better OS (p<0.05). In particular, the multivariate model, composed of a combination of serine, glycine, arginine, and quinolinic acid, could most efficiently stratify patient OS (concordance index=0.775, HR=3.23, 95% CI 2.04 to 5.26). From the transcriptome analysis in PBMCs, this multivariate model was significantly correlated with the gene signatures related to immune responses, such as CD8 T-cell activation/proliferation and proinflammatory immune responses, and 12 amino acid-related genes were differentially expressed between the high-risk and low-risk groups.
Conclusions: The multivariate model with PFAAs and metabolites in plasma might be useful for stratifying patients who will benefit from PD-1 inhibitors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109096 | PMC |
http://dx.doi.org/10.1136/jitc-2021-004420 | DOI Listing |
Mar Biotechnol (NY)
September 2025
Department of Marine Life Science, Jeju National University, Jeju, 63243, South Korea.
This study assessed the optimum dietary vitamin B requirement of Pacific white shrimp, Penaeus vannamei, for growth, feed efficiency, hemocyte counts, innate immunity, and ammonia stress resistance. Semi-purified experimental diets were prepared by adding vitamin B at 0.0, 0.
View Article and Find Full Text PDFOrg Lett
September 2025
State Key Laboratory of Chemistry for NBC Hazards Protection, Beijing 102205, China.
Optically active α-aminophosphonic acids are unique analogues of α-amino acids, and numerous synthetic methods have been developed. Herein, we present a highly diastereoselective α-azidation approach to the CAMDOL-derived phosphonates, enabling ready access to 27 diverse α-azidophosphonates with defined chirality in up to 85% yield and more than 99:1 dr. Late-stage transformations through the Staudinger reaction or click reaction efficiently delivered the related pharmacological α-aminophosphonic acids or the unique α-triazolylphosphonate derivative, respectively.
View Article and Find Full Text PDFElife
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Innate immune cells can acquire a memory phenotype, termed trained immunity, but the mechanism underlying the regulation of trained immunity remains largely elusive. Here, we demonstrate that inhibition of Aurora kinase A (AurA) dampens trained immunity induced by β-glucan. ATAC-seq and RNA-seq analysis reveal that AurA inhibition restricts chromatin accessibility of genes associated with inflammatory pathways such as JAK-STAT, TNF, and NF-κB pathways.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
PhyMedExp - Inserm U1046 - CNRS UMR 9214, CHU Arnaud de Villeneuve Bâtiment Crastes de Paulet, 371 avenue du Doyen Gaston Giraud, Montpellier Cedex 05 34295, France.
Different precursors of volatile sulfur compounds (VSCs) are present in fermented beverages, such as wine and beer. Carbon-sulfur (CS) lyases are enzymes that play a crucial role in releasing aromas from these varietal thiol precursors. These enzymes are expressed by various organisms, including yeasts and bacteria, involved in fermentation processes during brewing and winemaking.
View Article and Find Full Text PDFmSystems
September 2025
Department of Biological Sciences and BioDiscovery Institute, University of North Texas, Denton, Texas, USA.
is a human fungal pathogen that survives and proliferates within phagocytic immune cells. To sustain growth in the nutrient-limited phagosome environment, the pathogenic yeast scavenges available carbon sources, which must be metabolized through central carbon metabolism for respiration and biomass synthesis. However, carbon metabolic pathways operating in the pathogenic yeast phase have not been extensively mapped.
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