Bioengineered
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2022
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IF 6.832
Wenjun Jiang,Xiaoying Wang,Siwei Su,Sen Du,Hongqiang Song
Osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage, which causes loss of joint function and reduce quality of life. Resolvin D1 (RvD1) has shown interesting anti-inflammatory effects; however, the mechanism of action of RvD1 in OA remains unclear. The aim of this study was to investigate the potential mechanism of RvD1 in OA by bioinformatics and partial in vitro mechanisms. Here, 106 shared differentially expressed genes (DEGs) were identified based on the GSE82107, GSE55235, GSE55457 dataset; 700 DEGs were identified based on GSE169077. Enrichment analyses of these genes were then successively conducted. RvD1-targeted genes and KEGG pathways are identified by STITCH. 27 shared KEGG pathways were identified among RvD1-targeted pathways and OA. Furthermore, cell apoptosis assay, western blotting, real-time fluorescent quantitative PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA) were used to confirm the expression levels of the key genes of shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between RvD1-targeted and OA in IL-1β treated rat knee chondrocytes. The results showed that RvD1-targeted pathways and the expression of nuclear p65, p53, and p-JNK were inhibited in the RvD1 group compared with the IL-1β group. Thus, the findings indicate that RvD1 may inhibit the development of OA through NF/kB, p53, MAPK/JNK, PI3K-AKT signaling pathways, and act as a treatment for OA.
研究领域:
生物信息学
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分子生物学
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药理学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shangyou Wen,Xuechun Yuan,Haixing Shi,Yaoyao Luo,Shuangcheng Wang,Zhongshan He,Hu Long,Xiangrong Song
Periodontitis is a chronic inflammatory disease characterized by microbial dysbiosis, oxidative stress, and progressive alveolar bone loss. Macrophage mitochondrial dysfunction and cuproptosis—a copper-dependent form of cell death—are emerging contributors to periodontal immune dysregulation. However, effective therapeutic platforms that simultaneously mitigate oxidative stress, suppress inflammation, and promote tissue regeneration remain lacking. Herein, we developed a reactive oxygen species (ROS)-responsive hydrogel (PVA-TSPBA) integrating PEGylated germanene nanosheets (GeNSs-PEG) and the pro-resolving lipid mediator Resolvin D1 (RvD1) to promote immune modulation and osteoimmune regeneration (GeNSs-PEG@G/R). GeNSs-PEG exhibited high RvD1-loading loading and potent ROS-scavenging ability, while the dynamic boronic ester hydrogel enabled inflammation-responsive degradation and controlled drug release. We demonstrated that GeNSs-PEG@G/R effectively reduced intracellular ROS, restored mitochondrial membrane potential, decreased copper accumulation, and contributed to M2 macrophage polarization. Transcriptomic analyses revealed suppression of TNF and IL-17 signaling and activation of antioxidant pathways. Furthermore, conditioned medium from treated macrophages also enhanced osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). In a rat periodontitis model, GeNS-PEG@G/R attenuated alveolar bone loss and modulated immune cell infiltration via inhibiting cuproptosis and inflammasome related pathways. This multifunctional hydrogel system offers a promising strategy for periodontitis therapy by restoring mitochondrial function and copper homeostasis while promoting immune resolution and tissue repair.
研究领域:
牙科医学
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免疫学
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纳米医学
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再生医学
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炎症生物学
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生物材料
✓ 已验证
产品关联
DOI
高影响因子
Journal of Neuroinflammation
·
2025
·Vol. 22
·期 1
·1-16
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IF 10.1
Ding Peng-Fei,Zhang Jia-Tong,Zhu Xiao-Long,Cui Yue,Chen Chun-Lei,Liu Xun-Zhi,Shen Jun-Da,Zou Le-Xuan,Lu Yue,Zhuang Zong,Hang Chun-Hua,Li Wei
Background
Subarachnoid hemorrhage (SAH) is a common acute condition in neurosurgery, with microglial function playing a crucial role in determining patient outcomes. However, the involved mechanisms are complex and demand thorough investigation. In our study, we combined transcriptomic and metabolomic approaches to identify key regulators of microglial function, offering novel insights for potential therapeutic strategies in SAH treatment.
Methods
The neurological function of SAH mice was evaluated using the open field test, rotarod test, and nissl staining. In an in vitro SAH model, key pathways and genes that regulate microglial function were identified through the integration of transcriptomics and metabolomics. Enzyme-Linked Immunosorbent Assay, Immunofluorescence, Western blot, Real-Time PCR, pHrodo, and Lyso-Tracker were employed to assess lysosomal and microglial function.
Results
In SAH mice, both neurological and microglial functions were significantly impaired on the first day but showed recovery over time. The combined results from transcriptomics and metabolomics identified 5-lipoxygenase (5-LOX) as a key target in regulating microglial function post-SAH. Administering resolvin D1 (RvD1) exogenously to inhibit 5-LOX nuclear translocation or directly supplementing lipoxin A4 (LXA4) to adjust the leukotriene B4 (LTB4)/LXA4 ratio, can improve lysosomal acidification, mitigate impaired lysosomal function, and enhance phagocytosis while reducing the inflammatory response. Protecting microglial function can also be achieved through JNJ or P2X purinoceptor 7 (P2X7) siRNA, which inhibit calcium/calmodulin-dependent protein kinase II (CaMKII) activation, prevent 5-LOX nuclear translocation, and improve lysosomal function. Furthermore, P2X7 siRNA also improved neurological function, lysosomal function and microglial function in SAH mice.
Conclusion
Activation of P2X7-CaMKII after SAH promotes 5-LOX nuclear translocation, increases the LTB4/LXA4 ratio, elevates intracellular Ca2+ concentration, and impairs lysosomal and microglial function.
研究领域:
神经科学
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神经病学
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分子生物学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）