JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-23
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IF 12.6
Yang Yang,Lv Mingzhu,Liu Ruihong,Yu Peilu,Shen Ziyi,Bai Dazhang,Zhao Peilin,Yang Jin,Tang Xiaoping,Yang Hanfeng,Yong Yuan,Jiang Guohui
Background Intracerebral haemorrhage (ICH) is a devastating neurological disorder with high morbidity and mortality rates, largely owing to the lack of effective therapeutic strategies. Growing evidence has underscored the pivotal role of ferroptosis in intracerebral haemorrhage, and its contribution to neuronal death and exacerbation of brain injury, thus establishing it as a crucial target for therapeutic intervention. In recent years, polyoxometalate nanoclusters (NCs) have been applied in various neurodegenerative diseases, demonstrating neuroprotective effects. However, their impact on brain iron content and neurological function following ICH has yet to be reported. Here, we explored the potential of tungsten-based polyoxometalate (W-POM) NCs as ferroptosis inhibitors targeting the iron metabolic pathway mediated by S100A8/A9 for the treatment of ICH. Results We successfully synthesized ultra-small reduced W-POM NCs that can rapidly cross the blood-brain barrier and are cleared through the kidney. In vitro experiments demonstrated that W-POM NCs exhibit significant and stable ROS scavenging activity while effectively alleviating iron overload and associated neuronal damage. In vivo, W-POM NCs treatment restored iron metabolism homeostasis, suppressed neuroinflammation and oxidative stress, ultimately alleviating severe neurological damage and motor deficits in ICH mice. Proteomic combined with bioinformatic analyses identified two core genes, S100A8 and S100A9, most associated with W-POM NCs intervention in ICH. Further experiments confirmed that W-POM NCs act by modulating the toll-like receptor 4/hepcidin/ferroportin signaling pathway, thereby regulating iron metabolism and reducing secondary brain injury. Conclusions This study pioneers the application of polyoxometalates in intracerebral haemorrhage, offering a novel and promising therapeutic approach for the management of ferroptosis-related brain injuries.
研究领域:
神经病学
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药理学
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纳米技术
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生物化学
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DOI
PubMed
高影响因子
Theranostics
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2025
·Vol. 15
·期 16
·8587
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IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
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DOI
PubMed
高影响因子
Mucosal Immunology
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2019
·Vol. 12
·期 4
·945-957
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IF 7.352
Qiu Miao,Huang Keqing,Liu Yanzhuo,Yang Yuqing,Tang Honglin,Liu Xiaoxiao,Wang Chenlong,Chen Honglei,Xiong Yu,Zhang Jing,Yang Jing
High-fat diet (HFD) promotes lung pre-metastatic niche formation and metastasis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrate that glycyrrhizic acid (GA) prevents HFD-enhanced pre-metastatic niche formation and metastasis through gut microbiota. GA reduced HFD-enhanced myeloid-derived suppressor cell recruitment, pro-metastatic protein S100A8/A9 expression and metastasis burden of 4T1 breast cancer and B16F10 melanoma, accompanied by gut microbiota alteration and colonic macrophage polarization far away the M1-like phenotype. These parameters were greatly decreased by treatment with antibiotics, recolonization of Desulfovibrio vulgaris and Clostridium sordellii , and administration of lipopolysaccharide or deoxycholic acid. Macrophage depletion attenuated HFD-enhanced pre-metastatic niche formation and metastasis, but failed to further affect the effects of GA. Mechanistically, counteraction of HFD-enhanced gut microbiota dysbiosis by GA inhibited Gr-1 + myeloid cell migration and S100A8/A9 expression through decreasing the proportion of M1-like macrophages and their production of CCL2 and TNF-α in the colons via LPS/HMGB1/NF-κB signaling inactivation. Together, targeting the gut microbiota by GA to modulate colonic macrophages could be a novel strategy for the prevention of HFD-enhanced pre-metastatic niche formation and metastasis.
研究领域:
肿瘤学
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微生物学
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免疫学
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营养学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-17
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IF 14.7
Zhou Xianchi,Lu Zhouyu,Cao Wenzhong,Zhu Zihao,Chen Yifeng,Ni Yanwen,Liu Zuolong,Jia Fan,Ye Yang,Han Haijie,Yao Ke,Liu Weifeng,Wang Youxiang,Ji Jian,Zhang Peng
Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.
研究领域:
生物材料
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生物医学工程
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免疫学
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组织工程
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产品关联
DOI
PubMed
高影响因子
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