Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 289, P. 117452 - 117452
Published: Dec. 6, 2024
Language: Английский
Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 744 - 759.e6
Published: Jan. 23, 2024
Language: Английский
Citations
18
Science Bulletin, Journal Year: 2024, Volume and Issue: unknown
Published: March 1, 2024
Excitatory amino acid transporters (EAATs) are responsible for excitatory transportation and associated with auto-immune diseases in the central nervous system peripheral tissues. However, subcellular location function of EAAT2 macrophages still obscure. In this study, we demonstrated that LPS stimulation increases expression (coded by Slc1a2) via NF-κB signaling. is necessary inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal mediates glutamate aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis mTORC1. We also found mice myeloid depletion Slc1a2 show alleviated responses LPS-induced systemic inflammation high-fat diet induced obesity. Notably, patients type II diabetes (T2D) have a higher level activation blood macrophages. Taken together, our study links fate decision immune cells, provides potential therapeutic targets treatment diseases.
Language: Английский
Citations
12
iMeta, Journal Year: 2024, Volume and Issue: 3(5)
Published: Sept. 14, 2024
Abstract Gut microbiota is an intricate microbial community containing bacteria, fungi, viruses, archaea, and protozoa, each of them contributes to diverse aspects host health. Nevertheless, the influence interaction among gut on health remains uncovered. Here, we showed that between intestinal fungi bacteria shaped lung inflammation during infection. Specifically, antifungal drug‐induced dysbiosis mycobiota enhanced Dysbiosis led Escherichia coli ( E. ) overgrowth translocation infection, which induced accumulation CD45 + F4/80 Ly6G − Ly6C CD11b CD11c macrophages. Clearance macrophages or deletion TLR4 (Toll‐like receptor 4, recognition LPS) rather than Dectin‐1 (recognition beta‐1,3/1,6 glucans fungi) blocked aggravation These findings suggest commensal affects through gut–lung axis, offering a potential therapeutic target for ameliorating
Language: Английский
Citations
9
Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12
Published: Aug. 12, 2024
Cell activation and nutrient dysregulation are common consequences of atherosclerosis its preceding risk factors, such as hypertension, dyslipidemia, diabetes. These diseases may also impact cellular metabolism consequently cell function, the other way around, altered can disease development progression through function. Understanding contribution to how be by co-morbidities factors could support novel strategies lower CVD. Therefore, we briefly review pathogenesis principles metabolic pathways, before detailing changes in context comorbidities. In hypoxic, inflammatory hyperlipidemic milieu atherosclerotic plaque riddled with oxidative stress, shifts increase anaerobic glycolysis, pentose-phosphate pathway amino acid use. We elaborate on for macrophages, neutrophils, vascular endothelial cells, smooth muscle cells lymphocytes Since causal relationships specific key genes a type-specific comorbidity-dependent, cell-specific must thoroughly explored vivo , focus systemic effects. When treatments become feasible, this information will crucial determining best intervention improve interplay co-morbidities.
Language: Английский
Citations
5
Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: Feb. 4, 2025
Abstract Amino acids are pivotal regulators of immune cell metabolism, signaling pathways, and gene expression. In myeloid cells, these processes underlie their functional plasticity, enabling shifts between pro-inflammatory, anti-inflammatory, pro-tumor, anti-tumor activities. Within the tumor microenvironment, amino acid metabolism plays a crucial role in mediating immunosuppressive functions contributing to progression. This review delves into mechanisms by which specific acids—glutamine, serine, arginine, tryptophan—regulate function polarization. Furthermore, we explore therapeutic potential targeting enhance immunity, offering insights novel strategies for cancer treatment.
Language: Английский
Citations
0
Immune Network, Journal Year: 2025, Volume and Issue: 25(1)
Published: Jan. 1, 2025
Aromatic amino acid (AAA) metabolites, derived from tryptophan, phenylalanine, and tyrosine through coordinated host microbial metabolism, have emerged as critical modulators of immune function. We examine the complex journey AAAs dietary intake intestinal absorption metabolic transformation, highlighting crucial role host-microbe networks in generating diverse immunomodulatory compounds. This review provides a unique integrative perspective by mapping molecular mechanisms which these metabolites orchestrate responses. Through detailed analysis metabolite-receptor metabolite-transporter interactions, we reveal how specific recognition drives cell type-specific Our comprehensive examination signaling networks-from membrane receptor engagement to nuclear activation post-translational modifications- demonstrates same metabolite can elicit distinct functional outcomes different populations. The context-dependent nature interactions presents both challenges opportunities for therapeutic development, particularly inflammatory conditions where pathways are dysregulated. Understanding complexity regulatory remaining knowledge gaps is fundamental advancing metabolite-based strategies immune-mediated disorders.
Language: Английский
Citations
0
Cancer & Metabolism, Journal Year: 2025, Volume and Issue: 13(1)
Published: March 20, 2025
Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine tumors, deprivation therapy inhibitors of PA have been developed. Despite some therapeutic advantages, these approaches yielded severe side effects, making it necessary explore an strategy. We previously reported that supplementing sepiapterin (SEP), endogenous precursor tetrahydrobiopterin (BH4, essential NO synthase cofactor), could tumor cells tumor-associated macrophages (TAMs) induce their metabolic phenotypic reprogramming. saw oral SEP treatment effectively suppressed growth HER2-positive mammary animals. also has no dose-dependent toxicity clinical trials for disorders. In present study, we tested our hypothesis a long-term administration individuals susceptible would protect them against occurrence. administered SEP, comparison control DMSO, MMTV-neu mice 8 months starting at pre-pubertal stage. monitored onsets determine rate tumor-free survival. After treatment, grouped animals DMSO with or without tumors. analyzed blood metabolites, PBMC, bone marrow vs. treated found use These SEP-treated had undergone reprogramming systemic immunity, elevating total T cell counts circulation marrow. Given marrow-resident are mostly memory cells, plausible chronic promoted formation, leading potent prevention. findings suggest possible roles SEP/BH4/NO axis promoting formation its potential utility preventing breast cancer.
Language: Английский
Citations
0
Fish & Shellfish Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 110352 - 110352
Published: April 1, 2025
Language: Английский
Citations
0
Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 162 - 162
Published: March 1, 2025
Background: The early nutritional metabolism of piglets is intimately associated with the regulation immune function, and amino acids play a crucial role in modulating fate function porcine cells, especially macrophages. However, metabolic changes upon macrophage activation remain elusive. Methods: We established an vitro model macrophages investigated alterations metabolites involved polyamine tryptophan by various toll-like receptor (TLR) activators. Results: TLR inhibits production spermine alters kynurenine pathway toward kynurenic acid biosynthesis. Specifically, TLR9 redirects synthesis, which subsequently melatonin via protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)/cAMP-responsive element-binding (CREB) signaling pathways. Conclusions: reprograms Knowledge offers valuable insights potential strategies for intervention to enhance piglet immunity.
Language: Английский
Citations
0
Human Reproduction, Journal Year: 2025, Volume and Issue: unknown
Published: March 19, 2025
What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults? Our findings show dysregulation of metabolomic adults endometriosis, revealing systemic elevation fatty acyls ceramides cases compared to controls. Endometriosis is a gynecologic disease often presenting severe pelvic pain impacting around 200 million reproductive-aged women worldwide. However, little known about pathophysiology molecular features diagnosed during adolescence adulthood. We conducted cross-sectional analysis including 190 laparoscopically confirmed 120 controls who participated The Women's Health Study: From Adolescence Adulthood, which enrolled participants from 2012 2018. Control were females without diagnosis same clinics as or recruited general population. Among cases, 81 had blood samples collected before after surgery. Plasma metabolites measured at enrollment using liquid chromatography-tandem mass spectrometry, total 430 evaluated our analysis. used linear regression adjusting for age draw, BMI, hormone use, fasting status draw. Metabolite set enrichment (MSEA) was identify metabolite classes. Number effective tests (NEF) false discovery rate (FDR) multiple testing correction. median 17 years 22 majority rASRM stage I II (>95%). identified 63 (NEF < 0.05). higher levels proinflammatory response [e.g. eicosatrienoic acid (β = 0.61, 95% CI 0.37, 0.86)], increased oxidative stress xanthine 0.64, 0.39, 0.88)], downregulation related apoptosis [glycocholic -0.80, -1.04, -0.56)]. MSEA revealed (FDR 2.3e-4) 6.0e-3) decreased steroids steroid derivatives 1.3e-4) When we examined changes surgery among 55 endometriosis-associated significantly changed 8.1e-4) surgery, while 1.2e-4) Ceramides did not change pre- post-surgery elevated post-surgical 3.9e-3). study population mainly consists self-reported non-Hispanic, white individuals superficial peritoneal lesions only, so generalizability may be limited. Furthermore, despite large sample size limited conduct detailed stratified analyses profiles, especially by outcomes. includes utilization state-of-the-art technology high reproducibility comprehensively investigate that adults. results suggest positive impact endometriosis-related some, but all, on metabolic patients endometriosis. These warrant further investigation whether how persistent treatment lead long-term chronic risk those Financial support establishment data collection within A2A cohort provided J. Willard Alice S. Marriott Foundation, assay costs part Peery family. This project funded Eunice Kennedy Shriver National Institute Child Human Development R21HD107266. S.A.M., A.L.S., K.L.T. supported R01HD094842. S.A.M. received grant funding AbbVie, Institutes Health, Department Defense, Family Foundation; honoraria WERF, Huilun Shanghai, University Kansas Medical Center; travel SRI, ESHRE, FWGBD, Michigan, MIT, ASRM, LIDEA Registry, Taiwan Society, SEUD, Japan NASEM, Foundation America, Gedeon Richter Symposium ESHRE; Board member receiving financial remuneration Roche, Editor Frontiers Reproductive Roundtable participation Abbott; NextGen Jane Statistical Advisory Reproduction; leadership role Society Research, World Research ESHRE. N.S. receive Aspira unrelated this project. remaining authors have no disclosures relevant manuscript. N/A.
Language: Английский
Citations
0