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Anti-Inflammatory Mechanisms of Selenium Nanosheets in Ulcerative Colitis: Protein Corona, GP130 Interaction, and
Dingyi Shen1, Li Gong2, Wei Yang1
1Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agriculture University, Guangzhou, Guangdong, 510642, China.
Abstract:
Ulcerative colitis (UC) is a complex inflammatory bowel disease characterized by multiple factors. Alleviating inflammation is the primary therapeutic approach. However, currently employed anti-inflammatory treatments have limited efficacy and cause side effects. Safer, more effective therapies are needed. Selenium nanosheets (SeNSs) are biocompatible, anti-inflammatory, and low-toxicity nanomaterials with high surface areas and abundant active sites, making them potential therapeutic agents for UC. This study indicates that SeNSs can interact with macrophages and adhere to their cell membranes, significantly increasing their internalization into cells. Proteomic analysis reveals that the main components of the SeNS protein corona are proteins involved in cell proliferation and migration, including those associated with the AKT/PI3K and NF-κB signaling pathways. SeNSs hydrophobically interact with GP130, inhibiting its expression. This interaction downregulates the proteins involved in the aforementioned pathways. In addition, a transcriptomic analysis confirms that SeNSs inhibit apoptosis, cytokine-cytokine receptor interactions, and the chemokine and TNF signaling pathways. In dextran sulfate sodium (DSS)-induced UC model mice, SeNSs significantly decrease IL-1β, IL-6, and TNF-α levels, alleviate tissue damage, and lower the disease activity index. These findings suggest that SeNSs can be a safe and effective treatment strategy for UC, offering a novel approach for managing inflammatory diseases.
Insights
Selenium nanosheets (SeNSs) show promise for treating ulcerative colitis (UC) by reducing inflammation and tissue damage. These nanomaterials offer a safer, more effective therapeutic strategy for inflammatory bowel disease.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Immunology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
- Current anti-inflammatory therapies for UC have suboptimal efficacy and adverse effects.
- There is a critical need for safer and more effective therapeutic agents for UC.
Purpose of the Study:
- To investigate the potential of selenium nanosheets (SeNSs) as a novel therapeutic agent for ulcerative colitis.
- To elucidate the underlying mechanisms of SeNSs' anti-inflammatory effects in UC.
Main Methods:
- Proteomic and transcriptomic analyses were performed to understand SeNS-macrophage interactions and signaling pathway modulation.
- A dextran sulfate sodium (DSS)-induced mouse model of UC was used to evaluate SeNS efficacy in vivo.
- Key inflammatory markers (IL-1β, IL-6, TNF-α) and disease activity were assessed.
Main Results:
- SeNSs were internalized by macrophages, modulating proteins in the AKT/PI3K and NF-κB signaling pathways.
- SeNSs inhibited GP130 expression, downregulating key inflammatory signaling cascades.
- In vivo studies demonstrated that SeNSs reduced inflammatory cytokine levels, alleviated colon tissue damage, and lowered the disease activity index in DSS-induced UC mice.
Conclusions:
- Selenium nanosheets (SeNSs) exhibit significant anti-inflammatory properties and therapeutic potential for ulcerative colitis.
- SeNSs modulate macrophage behavior and key inflammatory pathways, offering a promising new strategy for managing inflammatory diseases.
- The biocompatibility and low toxicity of SeNSs position them as a safe and effective alternative for UC treatment.
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