BIOMATERIALS
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2025
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IF 12.9
Yuanyuan Fu,Ting Wang,Xinyue Ge,Hong Wen,Yang Fei,Menghuan Li,Zhong Luo
Probiotics emerges as a promising option for ulcerative colitis (UC) treatment, but its application remains challenging due to insufficient colon-targeted delivery efficiency and survival against the inflammation-associated intestinal oxidative stress. To address these issues, here we report a supramolecular liposome-microgel complex (SLMC) incorporated with Bacillus subtilis spores (BSSs) and dexamethasone (DEX) for orally-deliverable probiotic UC therapy. Specifically, BSSs and cholesterols were conjugated with gelatin via diselenide ligation to prepare microgels, followed by supramolecular complexation with UC-targeted DEX-loaded liposome via microfluidic engineering. The orally-administered SLMC efficiently accumulated in UC-affected colonic sites to release BSSs and DEX. DEX elicited rapid anti-inflammatory effect to reduce ROS generation, which cooperated with the ROS consumption by spore germination and diselenide cleavage to orchestrate an anaerobic intestinal microenvironment, thus promoting Bacillus subtilis colonization to restore gut homeostasis and initiate anti-inflammatory microbiota-macrophage metabolic crosstalk. Indeed, in vivo analysis showed that the SLMC treatment markedly inhibited pro-inflammatory TLR4-NF-κB signaling activities in mucosal macrophages through localized DEX delivery and boosting tryptophan metabolite production, leading to robust and durable UC abolishment. This study offers a practical approach for improving UC treatment in the clinic.
研究领域:
生物医学工程
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消化病学
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药剂学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2023
·
IF 3.5
Wenbin Wang,Shiyang Zhou,Wenming Jiang,Guangying Chen
A series of 1-(2-oxocyclohexyl)butane-1, 3-dione derivatives were designed and synthesized as TLR4 inhibitors by modifying the core structure of the lead compound ((6, 8-dioxo-1, 2, 3, 4, 6, 7, 8, 8a-octahydronaphthalen-2-yl) carbamate)). In vitro , compound 3p significantly inhibited the proliferation of rat synovial cells, inhibited the proliferation of LPS-induced RAW264.7 cells, and inhibited TLR4 activity, with IC 50 values of 1.21 ± 0.09 μM, 0.73 ± 0.05 μM and 0.43 ± 0.03 μM, respectively, which was superior to the positive control methotrexate. In vivo anti-rheumatoid arthritis evaluation, compound 3p can significantly inhibit the inflammatory factors TNF-α, IL-1β and IL-6, so as to achieve the therapeutic purpose. In the preliminary mechanism study, compound 3p has obvious regulatory effects on the abnormal increase of TLR4, JAK2 and STAT3 protein and gene expression related to inflammatory signaling pathway in RAW264.7 cells. In summary, this study aims to develop more effective candidates for rheumatoid arthritis.
研究领域:
免疫学
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药理学
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医学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
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IF 10.8
Qing Xia,Yuan Wei,Long-ji Hu,Fan-mei Zeng,Yu-wei Chen,Dan Xu,Yuan Sun,Lu-wei Zhao,Yi-fei Li,Guan-hua Pang,Wen Peng,Miao He
Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.
研究领域:
环境科学
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免疫学
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毒理学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
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