Dynamic Proteome and Phosphoproteome Profiling Reveals Regulatory Mechanisms in LPS-Stimulated Macrophage Inflammatory Responses

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151341 - 151341

Published: Jan. 1, 2025

Language: Английский

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Fucoxanthin Mitigates High-Fat-Induced Lipid Deposition and Insulin Resistance in Skeletal Muscle through Inhibiting PKM1 Activity

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(32), P. 18013 - 18026

Published: Aug. 1, 2024

Glucose and lipid metabolism dysregulation in skeletal muscle contributes to the development of metabolic disorders. The efficacy fucoxanthin alleviating disorders remains poorly understood. In this study, we systematically investigated impact on mitigating deposition insulin resistance employing palmitic acid-induced C2C12 cells ob/ob mice. Fucoxanthin significantly alleviated PA-induced resistance. addition, prominently upregulated expression metabolism-related genes (Pparα Cpt-1), promoting fatty acid β-oxidation metabolism. Additionally, increased Pgc-1α Tfam, elevated mtDNA/nDNA ratio, reduced ROS levels. Further, identified pyruvate kinase isozyme 1 (PKM1) as a high-affinity protein for by drug affinity-responsive target stability LC–MS confirmed their robust interaction CETSA, microscale thermophoresis, circular dichroism. Supplementation with pyruvate, product PKM1, attenuated beneficial effects Mechanistically, glucose glycolysis rate enhanced mitochondrial biosynthesis through inhibiting PKM1 activity, thereby stress. These findings present novel clinical strategy treating diseases using fucoxanthin.

Language: Английский

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Mechanism of Yinxu Weitong Capsule in the treatment of precancerous lesions of gastric cancer based on network pharmacology and experimental validation

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: 341, P. 119303 - 119303

Published: Jan. 5, 2025

Language: Английский

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Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 123 - 123

Published: Jan. 17, 2025

Background/Objectives: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by colorectal immune infiltration and significant microbiota compositional changes. Gut homeostasis necessary to maintain the healthy state of humans. MR2938, quinazolin-4(3H)-one derivative derived from marine natural product penipanoid C, alleviated DSS-induced in dose-dependent manner. Herein, we aimed investigate impact MR2938 on gut dextran sodium sulfate (DSS)-induced mice elucidate role therapeutic mechanism for alleviating colitis. Methods: Acute was induced with DSS mice. Mice were administered 100 mg/kg or 50 MR2938. Cecal content also preserved liquid nitrogen subsequently analyzed following 16S RNA sequencing. Antibiotic cocktail-induced microbiome depletion performed further relationship between microbiota. The factor levels quantitative polymerase chain reaction (qPCR) enzyme-linked immunosorbent assay (ELISA). Alcian blue staining immunofluorescence used estimate intestinal barrier. Results: rRNA sequencing revealed modulation Compared model group, group associated higher abundances Entercoccus lower abundance Staphylococcus, while Lactobacillus Staphylococcus. antibiotic-mediated experiments demonstrated that primarily contributed barrier function protection, little during treatment. Conclusions: These findings suggest flora play crucial MR2938's

Language: Английский

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Fucoxanthin Targets β1 Integrin to Disrupt Adhesion and Migration in Human Glioma Cells

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Glioblastoma, the most aggressive type of primary brain tumor, is marked by high invasiveness and metastasis, posing significant challenges in treatment. Fucoxanthin, a carotenoid derived from brown macroalgae, has demonstrated therapeutic potential cancer therapy; however, its precise mechanisms action remain unclear. In this study, we explored inhibitory effects fucoxanthin on integrin-mediated adhesion migration human glioma U-87 MG cells, shedding light antimetastatic properties. Our data indicated that at 1 μM did not affect cell viability but inhibited cells to fibronectin, key extracellular matrix (ECM) ligand for integrins, without affecting poly-l-lysine, nonintegrin ligand, indicating selective impact adhesion. Fucoxanthin treatment significantly reduced size number focal adhesions (FA), which play central role migration. addition, impaired migratory capacity, including accumulated distance velocity, determined time-lapse videomicroscopy. Further, remarkably integrin engagement-mediated actin polymerization, Vav3 phosphorylation, downstream activation Rac1, FAK, paxillin, further supporting disrupting signaling cytoskeletal remodeling. Additionally, complementary experiments utilizing protein binding assays, competitive ELISA, CETSA, DARTS, MST collectively confirmed direct interaction between β1 as well affinity fibronectin. The theoretical model molecular docking dynamics simulation align with our experimental findings, providing plausible mechanism competitively inhibits summary, study highlights promising agent impairs glioblastoma directly targeting pathways. These findings offer valuable insights into an

Language: Английский

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Puerarin exerts an inhibitory effect on inflammatory infiltration in the cardiac tissue of EAM mice by regulation of the TNF-α/CCL2/CCR2 signal pathway

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 157, P. 114721 - 114721

Published: April 28, 2025

Language: Английский

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Biological Characteristics of a Novel Bibenzyl Synthase (DoBS1) Gene from Dendrobium officinale Catalyzing Dihydroresveratrol Synthesis

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5320 - 5320

Published: Nov. 12, 2024

Bibenzyl compounds are one of the most important bioactive components natural medicine. However,

Language: Английский

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