Frontiers in Bioengineering and Biotechnology
·
2022
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IF 6.064
Zhiwei Zha,Qiumeng Chen,Decheng Xiao,Chengjie Pan,Wei Xu,Liangliang Shen,Jianliang Shen,Wei Chen
The inflammatory response mediated by oxidative stress is the main pathogenesis of dry eye, but clinical observations have shown that scavenging oxygen-free radicals alone has limited therapeutic effect. Moreover, the unique anatomy and physiology of the ocular surface result in low bioavailability of drugs, and higher concentration is required to achieve the desired efficacy, which, however, may bring systemic side effects. These problems pose a challenge, but the revelation of the ROS-NLRP3-IL-1β signaling axis opens up new possibilities. In this investigation, an NLRP3 inhibitor was successfully encapsulated in polydopamine-based microgels and used for dry eye treatment. It was demonstrated that the well-designed microgels exhibited good biocompatibility, prolonged drug retention time on the ocular surface, and effective inhibition of corneal epithelial damage and cell apoptosis. In addition, due to the synergistic effect, the NLRP3 inhibitor–loaded microgels could exert enhanced oxygen radical scavenging and inflammation-inhibiting effects at a lower dose than monotherapy. These findings suggest that polydopamine-based microgels have advantages as ocular surface drug delivery platforms and have promising applications in oxidative damage–related inflammatory diseases in synergy with anti-inflammatory drugs.
研究领域:
药学
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眼科
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Pengning Fan,Yuqi Liu,Xingyu Qian,Jinsheng Li,Yin Xu,Xiang Qiu,Lu Tong,Fuqiang Tong,Zhengfeng Fan,Yidan Zheng,Hanshen Luo,Teng Zeng,Yunbing Wang,Li Xu,Fei Li
In situ regeneration of tissue-engineered heart valves (TEHV) is a promising strategy to overcome the limitations of existing heart valve prostheses. Although, decellularized aortic valves (DAVs) are widely regarded as a scaffold in the construction of TEHV, the poor hemocompatibility and adverse immune responses make DAV scaffolds prone to thrombosis and degradation, thus hindering recellularization and in situ regeneration. Our study developed an immune-regulatory strategy involving the use of hydrogel-encapsulated nanoparticles to modify DAV scaffolds. Specifically, folic acid- and hyaluronic acid-modified mesoporous silica nanoparticles (FA-HA-MSNs@CY-09) were engineered to deliver NOD-like receptor family, pyrin domain containing 3 (NLRP3) inhibitor CY-09, thereby targeting macrophages, modulating their polarization and establishing a pro-regenerative immune microenvironment. The reactive oxygen species (ROS)-responsive hydrogel delivering FA-HA-MSNs@CY-09 enabled intelligent nanoparticle release and ROS scavenging. Results demonstrated that the hydrogel-modified DAV scaffold exhibited ROS-responsive release of FA-HA-MSNs@CY-09, which effectively induced macrophage polarization toward the pro-remodeling M2 phenotype. In vitro, the scaffold showed favorable mechanical properties, cytocompatibility, and hemocompatibility. Transcriptome sequencing elucidated the macrophage-reprogramming mechanism of the scaffold. In vivo, the scaffolds promoted significant M2 macrophage infiltration shortly after implantation, facilitating endothelial tissue formation. This resulted in enhanced endothelialization and interstitial cell infiltration under blood flow, without thrombosis or calcification. The novel heart valve overcomes various limitations of conventional heart valve prostheses and demonstrates considerable promise for clinical translation, particularly as an immunomodulatory biomaterial strategy.
研究领域:
生物材料学
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组织工程
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免疫学
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心血管再生医学
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纳米医学
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转化医学
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生物力学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2024
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IF 3.3
Yanyan Heng,Wei Wei,Linzhong Cheng,Feifei Wu,Haoyu Dong,Jingxia Li,Jianing Fu,Bingjie Yang,Xinyue Liang,Chunyan Liu,Haiju Li,Haihua Liu,Pengfei Zhang
Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with progressive senescence in vascular smooth muscle cells (VSMCs). The vascular protective effect of FGF21 has gradually gained increasing attention, but its role in diabetes-induced vascular senescence needs further investigation. In this study, diabetic mice and primary VSMCs are transfected with an FGF21 activation plasmid and treated with a peroxisome proliferator-activated receptor γ (PPARγ) agonist (rosiglitazone), an NLRP3 inhibitor (MCC950), and a spleen tyrosine kinase (SYK)-specific inhibitor, R406, to detect senescence-associated markers. We find that FGF21 overexpression significantly restores the level of catalase (CAT), vascular relaxation, inhibits the intensity of ROSgreen fluorescence and p21 immunofluorescence, and reduces the area of SA-β-gal staining and collagen deposition in the aortas of diabetic mice. FGF21 overexpression restores CAT, inhibits the expression of p21, and limits the area of SA-β-gal staining in VSMCs under high glucose conditions. Mechanistically, FGF21 inhibits SYK phosphorylation, the production of the NLRP3 dimer, the expression of NLRP3, and the colocalization of NLRP3 with PYCARD (ASC), as well as NLRP3 with caspase-1, to reverse the cleavage of PPARγ, preserve CAT levels, suppress ROSgreen density, and reduce the expression of p21 in VSMCs under high glucose conditions. Our results suggest that FGF21 alleviates vascular senescence by regulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway in diabetic mice.
研究领域:
内分泌学
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心血管生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Obesity
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2020
·Vol. 28
·期 7
·1270-1282
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IF 3.742
Tao Zheng,Qibin Wang,Yongcheng Dong,Weidong Ma,Yonghong Zhang,Yan Zhao,Fang Bian,Li Chen
Objective This study aimed to investigate whether the NLRP3 inflammasome in Kupffer cells (KCs) can be activated in response to high glucose (HG) and to evaluate its influence on hepatic insulin sensitivity. Methods Primary KCs and hepatocytes were isolated from mice, and lipid accumulation, glucose output, and insulin sensitivity of hepatocytes were investigated after culturing either alone or with KCs exposed to HG. The influence of HG-induced NLRP3 inflammasome activation in KCs on insulin sensitivity of hepatocytes was examined. Treatment with gadolinium trichloride caused KC depletion, and, subsequently, a streptozotocin-induced hyperglycemic mouse model was used to confirm the influence of KCs on hepatic insulin sensitivity. Results Hepatocytes cocultured with KCs showed enhanced lipid accumulation, glucose output, and impaired insulin sensitivity when exposed to HG. Enhanced NLRP3 inflammasome activation was also evident in both hepatocytes and KCs. Moreover, KCs that were pretreated with caspase-1 inhibitor, NLRP3 inhibitor, and NLRP3 small interfering RNA corrected coculture-induced aberrances in insulin action and NLRP3 inflammasome activation in hepatocytes. KC coculture also increased interleukin-1β (IL-1β)–mediated nuclear factor-κB (NF-κB) activation in hepatocytes. In hyperglycemic mice, KC depletion inhibited NLRP3 inflammasome activation and improved hepatic insulin sensitivity. Conclusions NLRP3 inflammasome activation impaired insulin sensitivity through KC-derived IL-1β–mediated NF-κB activation in hepatocytes exposed to HG.
研究领域:
内分泌学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Structures
·
2024
·
IF 13.9
Yuyao Liu,Jiayin Yan,Luxian Chen,Yuwei Liao,Lijia Huang,Jiali Tan
Alveolar bone resorption caused by bacteria-induced periodontitis remains challenging due to sustained inflammation. Periodontal pathogens like Porphyromonas gingivalis launch the primed signal of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in macrophages; consequent overproduction of proinflammatory cytokines and reactive oxygen species (ROS) leads to tissue destruction. This provides potential targets for a new therapeutic strategy. Herein, a multifunctionalized and dual-crosslinked hydrogel pGM/cPL@NI with NLRP3 inhibitor MCC950 loaded is prepared. Driven by the strategic functionalization of gelatin methacryloyl and ε -poly-lysine with phenylboronic acid and catechol, respectively, pGM/cPL@NI containing dynamic and photo-crosslinking networks demonstrates superior mechanical strength and stimuli-responsive behavior, as well as the overwhelmed performance in bacteria killing and ROS scavenging. Crucially, pGM/cPL@NI restores the compromised osteogenesis by specifically suppressing the proinflammatory cytokine cascade triggered by NLRP3 inflammasome activation and promoting anti-inflammatory polarization of macrophages. Collectively, pGM/cPL@NI presents robust potential as an effective “cocktail therapy” by combining antibacterial, antioxidant, inflammation resolution, and tissue regenerative functions. The present study reveals the underlying mechanism of the bacterial-immune-regeneration cascade and provides an extended approach for periodontal tissue engineering.
研究领域:
生物材料
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组织工程
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炎症
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牙科科学
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再生医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）