CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Zihan Liu,Jiale Miao,Weiqing Ni,Ting Yang,Wenjing Dong,Junjiang Yu,Jiayu Yang,Yanhua Liu
An inflammation-responsive and endothelial cell-targeting R/HTM prodrug micelle nanotherapeutic system was developed for the effective management of rheumatoid arthritis. • R/HTM micelles realized dual modulation of neutrophil recruitment and survival via blocking P-selectin/PSGL-1-mediated adhesion cascade and ROS-triggered site-specific co-release of R-rsc and methylprednisolone. • R/HTM micelles comprehensively regulated the pathological synovial microenvironment, including clearing excess ROS, and inhibiting fibroblast-like synoviocyte invasion. • R/HTM micelles markedly mitigated synovial inflammation, cartilage damage and bone erosion in AIA rat models, holding broad translational potential for neutrophil-dominated inflammatory diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction, wherein aberrant neutrophil infiltration and prolonged neutrophil survival drive the amplification of inflammatory cascades. To disrupt these pathological processes, an inflammation-responsive, endothelial cell-targeting nanotherapeutic platform was constructed for dual modulation of neutrophil recruitment and survival. This system is composed of a heparin-thioketal-methylprednisolone (HTM) prodrug that self-assembles into HTM micelles, and it is loaded with the cyclin-dependent kinase inhibitor R-roscovitine (R-rsc) to produce R/HTM (R-rsc/HTM micelles). R/HTM micelle treatment effectively inhibited neutrophil recruitment in vitro by blocking P-selectin/PSGL-1-mediated adhesion to inflamed vascular endothelial cells. In the reactive oxygen species-enriched joint synovial microenvironment of the adjuvant-induced arthritis rat model, R/HTM micelle disassembly enabled co-release of R-rsc and methylprednisolone, which synergistically induced neutrophil apoptosis through Bcl-2 downregulation and Bax/Caspase-3 upregulation. This dual-phase strategy also suppressed neutrophil extracellular trap formation, reprogrammed macrophage polarization (toward an anti-inflammatory M2 phenotype), inhibited fibroblast-like synoviocyte invasion, and cleared excess ROS. Moreover, R/HTM treatment significantly alleviated joint inflammation, repaired cartilage damage, ameliorated bone erosion, and suppressed the levels of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α). Collectively, these findings establish R/HTM micelles as a potent nanotherapeutic system with a dual-phase mechanism that targets the key pathological checkpoints of neutrophil-mediated inflammation, offering a promising approach for the effective management of RA.
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高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·
IF 2.9
Yuan Liang,Zhuolin Li,Jie Zhang,Tiezhu Li,Chengyu Lv
Over the past decades, the synthetic glucocorticoids (GCs) have been widely used in clinical practice and animal husbandry. Given the health hazard of these toxic residues in food, it is necessary to explore the detailed interaction mechanisms of typical GCs and their main target glucocorticoid receptor (GR). Hence, this work compared the GR binding and agonist activities of typical GCs. Fluorescence polarization assay showed that these GCs were potent ligands of GR. Their GR binding affinities were in the order of methylprednisolone>betamethasone≈prednisolone>dexamethasone, with IC 50 values of 1.67, 2.94, 2.95, and 5.58 nM. Additionally, the limits of detection of dexamethasone, betamethasone, prednisolone, and methylprednisolone were 0.32, 0.14, 0.19, and 0.09 μg/kg in fluorescence polarization assay. Reporter gene assay showed that these GCs induced GR transactivation in a dose-dependent manner, confirming their GR agonist activities. Among which, dexamethasone at the concentration of 100 nM produced a maximal induction of more than 11-fold over the blank control. Molecular docking and molecular dynamics simulations suggested that hydrogen-bonding and hydrophobic interactions played an important role in stabilizing the GC-GR-LBD complexes. In summary, this work might help to understand the GR-mediated endocrine disrupting effects of typical GCs. Graphical
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PubMed
高影响因子
Small
·
2024
·
IF 13
Taoyang Yuan,Weijie Liu,Tianyou Wang,Feng Ye,Jianhua Zhang,Zhipeng Gu,Jianguo Xu,Yiwen Li
The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 2
·1-11
·
IF 5.3
Huang Suiyuan,Sun Xuehua,Xin Jianwei,Ma Panpan,Zhang Yuqi,Cai Zhongyu,Wang Ji-Jiang
Dexamethasone sodium phosphate (DSP) and betamethasone sodium phosphate (BSP) imprinted hydrogels embedded with two-dimensional photonic crystals (2DPC) were developed as hormones-sensitive photonic hydrogel sensors with highly sensitive, selective, anti-interference and reproducible recognition capability. The DSP/BSP molecularly imprinted photonic hydrogels (denoted as DSP-MIPH and BSP-MIPH) can specifically recognize DSP/BSP by rebinding the DSP/BET molecules to nanocavities in the hydrogel network. This recognition is enabled by the similar shape, size, and binding sites of the nanocavities to the target molecules. The rebinding of hormones molecules causes the hydrogel to swell, resulting in a particle spacing increase of the embedded 2DPC of the hydrogel. The particle spacing increase can be used as sensing signal and can be acquired by simply measuring the Debye diffraction diameters of the photonic hydrogel sensor before and after exposure with a laser pointer and a ruler. The particle spacing increments of the DSP-MIPH and BSP-MIPH sensors linearly change when DSP and BSP concentrations changes within the ranges 0.025–1 μM, 10–100 μM, and 100–500 μM, and the limits of detection (LoD) are 21.8 nM for DSP and 12.6 nM for BSP, respectively. These photonic hydrogel sensors were successfully applied to the determination of DSP/BSP contents in the real pharmaceutical injections, providing an ideal strategy for the development of portable hormones sensors. Graphical
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PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Fan Xinyu,Zhang Ying,Li Xinyu,Ding Junhui,Huang Jiaolong,Lian Kai,Duan Peng,Hu Chunhui,Xu Junchang
In this study, the effects of Ginsenoside Rg1 (Rg1), the primary bioactive constituent of Panax ginseng roots, on glucocorticoid-induced osteoporosis (GIOP) were examined using a zebrafish model, with a focus on elucidating its underlying mechanisms. Our findings demonstrated that Rg1 treatment inhibited osteoporosis induced by methylprednisolone (PN), as evidenced by increased mineralisation area and integrated optical density in the spine and skull of zebrafish larvae. Rg1 reduced the expression of bglap (an osteogenic marker gene) and increased the expression of traf (an osteoclast marker gene) compared with the PN group. Behavioural analysis revealed that Rg1 alleviated PN-induced hypoactivity, resulting in enhanced motion speed. Furthermore, transcriptome analysis identified 383 genes reversed by Rg1 treatment, with significant enrichment in skeletal system development. KEGG analysis indicated that Rg1 influenced several signalling pathways primarily involved in retinol, fat, protein and lipid metabolism. Several genes related to skeletal system development and retinol metabolism were validated by qRT-PCR. In summary, this study provides scientific evidence for the potential mechanisms of Rg1 in the therapeutic intervention of GIOP, highlighting its promise as a potential pharmacological agent for the prevention and treatment of osteoporosis.
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PubMed
高影响因子
Advanced Materials Technologies
·
2025
·
IF 6.2
Mingyu Cui,Suiyuan Huang,Jianwei Xin,Panpan Ma,Liping Heng,Yuqi Zhang,Ji-Jiang Wang
Dexamethasone sodium phosphate (DSP) and betamethasone sodium phosphate (BSP) are synthetic corticosteroids used for anti-inflammatory and immunosuppressive purposes. However, prolonged use may cause severe side effects, necessitating sensitive detection methods. Conventional techniques often suffer from complexity, signal interference, and a lack of real-time capability. This study develops molecularly imprinted 2D photonic hydrogels (DSP/BSP-MIPH) for selective, sensitive, and regenerable detection of DSP and BSP. The DSP-MIPH sensor exhibits swelling in DSP solution, enabling linear detection in three ranges (0.1–9, 10–100, and 100–1000 µ M ) with a limit of detection (LoD) of 41 nM. BSP-MIPH shows shrinkage upon binding, with linear responses in 0.05–1 and 5–1000 µ M ranges and a LoD of 28 n M . The limits of quantitation are 1.2 µ M and 146 n M for DSP and BSP, respectively. The opposite volume changes stem from distinct hydrogen bonding interactions between drug functional groups and the hydrogel network. The sensors successfully quantify DSP and BSP in commercial injections, achieving recovery rates of 96.7%–109.5% for DSP and 97.9%–104.8% for BSP, with RSDs 3.91%–6.21% for DSP and 3.57%–5.76% for BSP. These results demonstrate that the MIPH sensors provide accurate, reliable, and straightforward detection for DSP and BSP in real samples, giving a promising strategy for precise hormone drug monitoring.
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高影响因子
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