Bioengineering-Basel
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2026
·Vol. 13
·期 8
·908
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IF 4.4
Dandan Zhang,Zhigang Zhang,Dingxing Huang,Zhuoran Sun,Jiamin Huang,Chi Zhang,Qingyang Zeng,Qiling Liu,Wenzhuo Chen
Osteoarthritis is an irreversible degenerative joint disease driven by sustained NF-κB-mediated inflammatory responses, and conventional intra-articular hyaluronic acid or small-molecule NF-κB inhibitors cannot achieve targeted on-demand treatment due to poor solubility, rapid clearance and lack of lesion microenvironment responsiveness. OA with inherent anti-chondrolytic activity can self-assemble into nanocarriers in water, yet it lacks stimuli-responsive capacity. Herein, we rationally designed and synthesized an OA-Der by covalently conjugating o-phenylenediamine fragments to the OA backbone.1H NMR and HRESI-MS spectra fully verified the accurate chemical structures of intermediate and final OA-Der. Blank OA-Der micelles exhibited uniform spherical core–shell nanostructures (50–150 nm) under TEM and AFM, while pathological high NO triggered complete disassembly of micellar assemblies. We further co-assembled OA-Der with NF-κB inhibitor BAY 11-7082 to construct NO-responsive BAY@OA-Der supramolecular micelles. In vitro experiments using human C28/I2 chondrocytes with LPS-induced inflammatory injury demonstrated that BAY@OA-Der significantly improved cell viability and reduced apoptotic chondrocyte proportion. At mRNA and protein levels, the supramolecular micelle formulation remarkably suppressed NF-κB p65 phosphorylation, downregulated cartilage-degrading ADAMTS5, and upregulated ACAN compared with free BAY or blank OA-Der. Collectively, this natural bioactive self-assembled NO-responsive delivery platform achieves synergistic anti-inflammatory and matrix-protective effects by precisely releasing drugs at NO-overexpressed osteoarthritis inflammatory sites and offers an in vitro design strategy for osteoarthritis responsive delivery systems.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2016
·
IF 5.091
Shan Liu,Lingxin Zhu,Jie Zhang,Jingjing Yu,Xue Cheng,Bin Peng
Previous studies, including those from our laboratory, have demonstrated that the natural flavonoid isoliquiritigenin (ISL) is a promising agent for bone destructive diseases. However, the mechanisms underlying its anti-osteoclastogenic effects are still far from clear. Here, we evaluated the potential alterations of autophagy and nuclear factor-κB (NF-κB) during anti-osteoclastogenic effects by ISL in vitro and in vivo . We observed that ISL inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed autophagic microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 accumulation. ISL treatment resulted in the interruption of several specific features for autophagy in osteoclast precursors, including acidic vesicular organelle formation, LC3-II accumulation, and appearance of autophagic vacuoles. The RANKL-stimulated expression levels of autophagy-related genes and proteins also diminished in ISL-treated osteoclast precursors. The reactivation of autophagy by rapamycin almost reversed the ISL-elicited anti-osteoclastogenic effects. Interestingly, ISL inhibited the RANKL-stimulated NF-κB expression and nuclear translocation, whereas the NF-κB inhibitor Bay 11-7082 markedly suppressed the RANKL-induced autophagic activation. Consistent with the in vitro results, the administration of ISL could attenuate osteoclastogenic cathepsin K , autophagic LC3, and NF-κB expression to protect against inflammatory calvarial bone erosion in vivo . Our findings highlight the inhibition of NF-κB-dependent autophagy as an important mechanism of ISL-mediated anti-osteoclastogenic activity.
研究领域:
药理学
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免疫学
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骨骼生物学
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DOI
PubMed
高影响因子
STEM CELLS
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2014
·Vol. 32
·期 7
·1943-1955
·
IF 7.133
Sun Hualing,Wu Yanru,Fu Dongjie,Liu Yinchen,Huang Cui
Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase involved in lifespan regulation. To evaluate the effect of SIRT6 on osteogenesis, rat bone marrow mesenchymal stem cells (rBMSCs) with enhanced or reduced SIRT6 function were developed. We observed that SIRT6 knockdown significantly reduced the mRNA levels of several key osteogenic markers in vitro, including alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin, while overexpression of SIRT6 enhanced their expression. Additionally, SIRT6 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of acetyl-NF-κB p65 (Lys310). The decreased osteogenic differentiation ability of rBMSCs could be partially rescued by the addition of NF-κB inhibitor BAY 11–7082. Furthermore, SIRT6 overexpression in rBMSCs combined with the use of collagen/chitosan/hydroxyapatite scaffold could significantly boost new bone formation in rat cranial critical-sized defects, as determined by microcomputed tomography and histological examination. These data confirm that SIRT6 is mainly located in the nuclei of rBMSCs and plays an essential role in their normal osteogenic differentiation, partly by suppressing NF-κB signaling. Stem Cells 2014;32:1943–1955
研究领域:
干细胞生物学
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骨再生
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分子生物学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Jinzhao Zhou,Yanwei Zhang,Ling Zeng,Xiaofei Wang,Wenpei Xiang,Ping Su
Cadmium (Cd) is a harmful metal that seriously affects the male reproductive system, but the mechanism of how Cd exposure damages Sertoli cells is not fully understood. This study used TM4 cells to explore the mechanism of Cd damage to Sertoli cells. We found that Cd was concentration- and time-dependent on TM4 cell viability. Cd exposure increased intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH), and Interleukin-1β (IL-1β) release in TM4 cells, decreased mitochondrial function, and increased pyroptosis. N-acetylcysteine (NAC), MCC950 and BAY 11–7082 (BAY) alleviate the release of IL-1β and LDH induced by Cd. NAC reduced Cd induced increases in ROS, NLRP3, Caspase-1, Heme oxygenase-1(HO-1), superoxide dismutase (SOD2), and increased mitochondrial function. The activation of GSDMD is the main causes of pyroptosis, and NAC significantly inhibit its activation and formation. Our results suggest that Cd exposure induces a toxic mechanism of GSDMD-mediated pyroptosis in TM4 cells by increasing ROS levels and activating the inflammasome.
研究领域:
毒理学
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细胞生物学
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生殖健康
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DOI
PubMed
高影响因子
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