Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Colorectal cancer (CRC) ranks among the leading causes of cancer‐related dea ths worldwide, and rising incidence mortality CRC underscores urgent need for better understanding management strategies. Icaritin (ICA) is metabolites icariin, a natural flavonoid glycoside compound derived from stems leaves Epimedium . It has broad spectrum antitumor activity inhibits proliferation, migration, invasion cells, S phase cell cycle arrest. exerts its effects against through repressing autophagy to promote apoptosis via interfering HSP90‐TXNDC9 interactions. The safety efficacy ICA are also affirmed in mouse xenograft model. Additionally, test whether synergistic with low‐temperature photothermal therapy (LTPTT), novel nanodrug delivery system, employing SiO 2 nanocarriers, designed aiming load materials polydopamine (PDA), folic acid (FA). This /Ica‐PDA‐FA multifunctional nanocomposite actively targets tumor tissues high affinity FA cells. Once internalized, acidic intracellular environment triggers controlled release ICA, inhibiting By LTPTT drug under near‐infrared illumination, dual effect achieved, holding promise enhancing therapeutic outcomes treatment.

Language: Английский

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Exposure to PFOS, PFBS, PFOA and PFBA impairs cell cycle progression in bovine brain (Bos taurus) endothelial cells

Research in Veterinary Science, Journal Year: 2025, Volume and Issue: 187, P. 105585 - 105585

Published: Feb. 26, 2025

Language: Английский

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Exploring the neurodegenerative potential of per- and polyfluoroalkyl substances through an adverse outcome pathway network

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 969, P. 178972 - 178972

Published: Feb. 28, 2025

While emerging evidence links per- and polyfluoroalkyl substances (PFAS) to neurotoxicity, their potential role in neurodegeneration remains poorly understood. Moreover, existing neurodegeneration-related adverse outcome pathways (AOPs) available on AOP-Wiki have not yet been integrated into a unified network. To address these gaps, this study aims develop the first AOP network utilize it explore possible contributions of long-chain legacy PFAS neurodegeneration, specifically concerning Alzheimer's Parkinson's diseases. A total 74 AOPs were screened from AOP-Wiki, which 13 met eligibility criteria incorporated We analyzed resulting using topological parameters such as in-degree, out-degree, eccentricity, betweenness centrality. elucidate mechanistic exposure neurodegenerative pathways, we linking key events (KEs) within The results highlighted increased intracellular calcium hub with highest connectivity followed by critical KEs neuronal apoptosis, oxidative stress, N-methyl-d-aspartate receptor (NMDA-R) overactivation, mitochondrial dysfunction. Consistent toxicological evidence, indicate that may adversely affect neurotransmitter systems, particularly through NMDA-R leading excitotoxicity. This result dyshomeostasis, dysfunction, inflammatory-oxidative cascades, neuroinflammation, cell death. By providing basis for understanding PFAS, offers crucial framework assessing risks associated chemicals inform future regulatory measures public health strategies. Further experimental validation is needed confirm animal models or human populations.

Language: Английский

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Perfluorooctane sulfonate mediates GSH degradation leading to oral keratinocytes ferroptosis and mucositis through activation of the ER stress-ATF4-CHAC1 axis

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 292, P. 117964 - 117964

Published: March 1, 2025

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that induces inflammatory response and oxidative stress in oral mucosa. Ferroptosis, form of cell death characterized by iron-dependent lipid peroxidation (the degradation lipids), was believed to play crucial role pathogenesis mucositis; however, the involvement PFOS-induced ferroptosis remained unclear. Our findings demonstrated PFOS inhibited proliferation induced pro-apoptotic effects cells, with most pronounced observed human keratinocytes (HOK). significantly increased reactive oxygen species (ROS) peroxidation, depleted glutathione (GSH) HOK cells. Notably, decreased peroxidase 4 (GPX4) expression elevated Fe2 + levels, suggesting potential induction ferroptosis. Ferroptosis inhibitors mitigated GSH depletion, subsequently enhancing viability. Mechanistically, endoplasmic reticulum (ER) contributed nuclear translocation (from cytoplasm into nucleus) activating transcription factor (ATF4) up-regulated its downstream target gene Chac1. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) catalyzed conversion cysteinylglycine 5-oxoproline, resulting depletion-a critical Knocking down CHAC1 attenuated Tauroursodeoxycholic acid (TUDCA), classical ER inhibitor, mucositis inhibiting ATF4/CHAC1 pathway activation. These elucidated toxicological mechanisms proposed therapeutic strategies counteract exposure mucositis.

Language: Английский

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Dissection of the potential mechanism of polystyrene microplastic exposure on cardiomyocytes

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 973, P. 179048 - 179048

Published: March 18, 2025

Language: Английский

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Perfluorooctane sulfonic acid: a possible risk factor of endothelial dysfunction based on in silico and in vitro studies

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

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Perfluorooctane sulfonate causes DNA damage and apoptosis via oxidative stress in umbilical cord fibroblast cells of Yangtze finless porpoise

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 958, P. 178030 - 178030

Published: Dec. 10, 2024

Language: Английский

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