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Synthesis of Multi-walled Carbon Nanotubes Modified with Silver Nanoparticles and Evaluation of Their Antibacterial Activities and Cytotoxic Properties
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Cytotoxic Mechanism for Silver Nanoparticles Based High-Content Cellomics and Transcriptome Sequencing.

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    Silver nanoparticles (SNPs) induce cytotoxicity in human dermal fibroblasts (HDFs) by down-regulating SOS1 and CDC25B via the MAPK signaling pathway, impacting cell cycle and apoptosis.

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    Area of Science:

    • Nanotechnology
    • Toxicology
    • Cell Biology

    Background:

    • Silver nanoparticles (SNPs) are increasingly used, necessitating an understanding of their toxicological mechanisms.
    • The impact of SNP size on cellular responses in human dermal fibroblasts (HDFs) requires detailed investigation.

    Purpose of the Study:

    • To elucidate the toxic mechanism of differently sized SNPs on HDFs.
    • To identify key molecular pathways and genes involved in SNP-induced cytotoxicity.

    Main Methods:

    • Combined high-content cellomics, transcriptome sequencing, and qRT-PCR.
    • Assessed SNP effects on reactive oxygen species (ROS), focal adhesion, cytoskeleton, and ATP content.
    • Analyzed differentially expressed genes and biological pathways, focusing on the MAPK signaling pathway.

    Main Results:

    • SNP-5 exhibited the strongest cytotoxic effects, while SNP-20 showed the least.
    • Transcriptome analysis revealed significant gene expression changes, with the MAPK signaling pathway identified as crucial.
    • SOS1 and CDC25B were identified as key genes in SNP-induced cytotoxicity, regulated by miR-424-5p.

    Conclusions:

    • SNP-induced cytotoxicity in HDFs involves the down-regulation of SOS1 and CDC25B through miR-424-5p within the MAPK pathway.
    • This mechanism leads to cell cycle arrest and apoptosis, ultimately causing cytotoxicity.
    • Understanding this pathway is critical for assessing the safety of silver nanoparticles.