Histidine metabolism drives liver cancer progression via immune microenvironment modulation through metabolic reprogramming

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 4, 2025

Histidine metabolism is crucial in role tumor biology, contributing to progression, immune regulation, and metabolic reprogramming. In hepatocellular carcinoma (HCC), dysregulated histidine may promote growth evasion, although the specific mechanisms remain poorly understood. Using single-cell RNA sequencing, expression patterns of metabolism-related genes were evaluated across different cell types HCC samples. vivo vitro experiments conducted validate how treatment affects macrophage T-cell function. Furthermore, TCGA database was utilized construct a prognostic model identify key gene BUD23 examine its correlation with infiltration. The proportion parenchymal cells exhibiting high significantly increased, accompanied by general reduction stromal Notably, macrophages T demonstrated impaired antitumor functions. group, multiple critical communication pathways (e.g., MIF, CLEC, MHC II) downregulated, shifted toward immunosuppressive subpopulations, exhibited an exhaustion phenotype, CD8 + activation diminished. Further co-culture confirmed that elevated concentrations promoted M2 polarization weakened cytotoxicity, accelerating proliferation. According analyses, upregulated group negatively correlated patient survival Silencing boosted cytotoxic effects, effectively reversing microenvironment. A multivariable Cox regression-based indicated unfavorable outcomes patients metabolism. drives reprogramming reshapes microenvironment through intercellular communication, thereby promoting progression. shows promise as biomarker for prognosis response prediction liver cancer. This study provides new therapeutic targets theoretical support cancer targeting

Language: Английский

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Alterations and mechanistic insights of gut microbiota and its metabolites in type 2 diabetes mellitus and Alzheimer's disease

iMetaOmics., Journal Year: 2025, Volume and Issue: unknown

Published: May 11, 2025

Abstract Epidemiological studies suggest a link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), possibly due to gut microbiota dysbiosis, although the exact mechanisms are unclear. This narrative review uniquely addresses how microbiota‐derived metabolites mediate overlapping pathologies of insulin resistance, neuroinflammation, amyloidogenesis in T2DM AD, proposing framework for dual therapeutic targeting. provides an in‐depth examination roles their context AD. study indicates that dysbiosis significantly impacts pathogenesis progression both diseases by modulating metabolic pathways, immune functions, inflammatory responses. Key bacteria, such as Akkermansia muciniphila (which releases outer membrane vesicles), Lactobacillus , Bifidobacterium well like short‐chain fatty acids (SCFAs), bile (BAs), lipopolysaccharide (LPS), vitamins, Trimethylamine N‐oxide (TMAO) regulate AD through complex mechanisms. Multiple signaling including G‐protein coupled receptor 41/43 (GPR41/43), phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), Toll‐like 4 (TLR4)/nuclear factor kappa‐light‐chain‐enhancer activated cells (NF‐κB), endoplasmic reticulum (ER) stress‐mediated also involved. These findings offer insights into potential targeted therapies

Language: Английский

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Alterations in the Gut Microbiota Composition in Obesity with and without Type 2 Diabetes: A Pilot Study

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2024, Volume and Issue: Volume 17, P. 3965 - 3974

Published: Oct. 1, 2024

Obesity has become a major public health concern worldwide, increasing the risk of T2DM. Growing evidence indicates gut microbiota dysbiosis is related to metabolic disorders. We aimed firstly investigate compositional and functional features microbiome between obesity with without T2DM in Chinese population.

Language: Английский

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Kinetics of imidazole propionate from orally delivered histidine in mice and humans

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 4, 2024

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated type 2 diabetes (T2D). However, the source of histidine role gut microbiota remain unclear. We conducted an intervention study humans, comparing ImP kinetics on high-fat diet with varying levels antibiotics, assessed healthy T2D subjects supplementation. Results show that dietary metabolized to ImP, antibiotic-induced suppression reducing mice. In contrast, oral supplementation resulted increases circulating whereas antibiotic treatment increased levels, which was associated bloom several bacterial genera have been production, such as Lactobacilli. Our findings highlight microbiota's crucial regulating complexity translating mouse models humans.

Language: Английский

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The Gut Microbiota Is Involved in the Regulation of Cognitive Flexibility in Adolescent BALB/c Mice Exposed to Chronic Physical Stress and a High-Fat Diet

Microorganisms, Journal Year: 2024, Volume and Issue: 12(12), P. 2542 - 2542

Published: Dec. 10, 2024

Dysfunction in the prefrontal cortex can lead to cognitive inflexibility due multifactorial causes as included cardiometabolic disorders, stress, inadequate diets, well an imbalance of gut-brain axis microbiota. However, these risk factors have not been evaluated jointly. The purpose this study was evaluate effect physical stress (MS: Male Stress and FS: Female Stress) high-fat diet (MD: Diet FD: Diet) supplementation on gut microbiota flexibility. performed 47 mice, 30 male (M) 17 female (F) BALBc, exposed chronic (S) (D). Cognitive flexibility using Attentional Set-Shifting Test (ASST) composition terms relative abundance (%) alpha-beta diversity. Results showed that S D reduced mice ( Chronic a modify predictive function

Language: Английский

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