Materials Today Bio
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2025
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IF 10.2
Yanhui Cui,Xueqin Wang,Caiyang Lu,Liling Ran,Zirui Guo,Jiayu Yao,Tian Yu,Xuanxi Liu,Fang Li,Changqi Li,Yingcai Meng,Wenhu Zhou
Acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition marked by severe inflammatory responses and disruption of the alveolar-capillary barrier, leading to high mortality rates and lack of effective treatments. Recent research has underscored the crucial role of programmed cell death pathways-pyroptosis, apoptosis, and necroptosis-in exacerbating inflammation and barrier dysfunction in ALI/ARDS. However, effective therapeutic agents targeting this process remain scarce. In this study, we reveal that PANoptosis, which integrates these cell death pathways through the PANoptosome complex, plays a central role in the pathogenesis and progression of ALI/ ARDS. The levels of PANoptosis-related molecules were significantly elevated in both the ALI mice and the clinical ARDS patient samples, highlighting it as a novel therapeutic target. Building on this insight, we developed a multifunctional nanomedicine, TPNs/Sal B, which integrates tea polyphenol-based nanoparticles (TPNs), a bioactive nanomaterial with anti-pyroptotic and anti-necroptotic properties, with salvianolic acid B (Sal B), known for its anti-apoptotic effects. Our results demonstrate that the nanomedcine TPNs/Sal B effectively inhibit PANoptosis, thereby attenuating lung tissue pathological damage, reducing inflammation, and improving lung epithelial barrier function in ALI models. Moreover, we identified LIM and SH3 protein 1 (LASP1) which may play an critical role in modulating alveolar epithelial barrier function during ALI/ARDS progression, and treatment with TPNs/Sal B effectively restored LASP1 levels. Our findings underscore the therapeutic potential of TPNs/Sal B as a targeted treatment for ALI/ARDS, offering a promising strategy for modulating PANoptosis and preserving lung function.
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Quanwei Li,Pan Guo,Shaofeng Wang,Luna Su,Tingyu Liang,Wenlan Yu,Jianying Guo,Qingwen Yang,Zhaoxin Tang,Jianzhao Liao
Terbuthylazine (TBA) is a widely prevalent pesticide pollutant, which is a global concern due to its environmental residual. However, the toxic mechanism of TBA have not been fully solved. Here, we explored that TBA exposure disrupts the intestinal flora and aggravated disturbance of mitochondrial quality control and PANapoptosis in hepatocytes via gut-liver axis. Our findings demonstrated that TBA exposure induced significant damage to the jejunum barrier, evidenced by a marked decrease in the expression of Occludin and ZO-1. Moreover. TBA led to intestinal microflora disorder, manifested as the decreased abundance of Firmicutes , and increased abundance of the Nitrospirota , Chloroflexi , Desulfobacterota , Crenarchaeota , Myxococcota , and Planctomycetota . Meanwhile, intestinal microflora disorder affected the biological processes of lipid metabolism and cell growth and death of hepatocytes by RNA-Seq analysis. Furthermore, TBA could induced mitochondrial quality control imbalance, including mitochondrial redox disorders, lower activity of mitochondrial fusion and biogenesis decrease, and increasing level of mitophagy. Subsequently, TBA significantly increased expression levels of pyroptosis, apoptosis and necroptosis-related proteins. In general, these results demonstrated the underlying mechanisms of TBA-induced hepatotoxicity induced via the gut–liver axis, which provides a theoretical basis for further research of ecotoxicology of TBA.
研究领域:
毒理学
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环境科学
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分子生物学
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胃肠病学
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肝病学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Huiyue Zhao,Jingjing Chen,Qing Lin,Sile Shen,Yuanfeng Ye,Da Huo
Organelle-precision photothermal therapy (OPTT) is widely used for disease treatment with fewer side effects, but its potential to manipulate organelle dynamics is not fully understood. This study investigates how OPTT-induced PANoptotic cell death regulates inter-mitochondrial behaviors using gold nanorods. We show that localized heat stress prompts initial mitochondrial network fusion followed by hyper-fission, disrupting homeostasis and increasing sensitivity to chemotherapeutics. Both non-specific and mitochondria-targeted OPTT were analyzed, revealing the importance of mitochondrial dynamics in determining cell fate. Our results indicate that modulating these dynamics can control cell death and immune responses, highlighting the promise of nanotherapeutic approaches for enhancing cancer therapies.
研究领域:
纳米医学
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癌症生物学
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光热治疗
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细胞生物学
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线粒体动力学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Yiqiong Wang,Yi Tao,Shujing Zhang,Qiuru Wang,Zheting Liu,Shudong Lin,Yaoting Wang,Yunchao Huang,Ting Zhang,Henry Anselmo Mayala,Wenming He,Hui Shen,Ling Zhang,Hui Chai
Background Diabetes mellitus (DM) and its complications pose a significant threat to human health. Diabetes-related lower limb ischemia (DLLI), as a severe complication of diabetic macrovascular disease, presents substantial challenges in clinical management. Purpose The pharmacodynamic profile and mode of action of Pseudostellaria heterophylla polysaccharides (PHP) in DLLI treatment constitute the core investigative objectives herein. Study Design Using complementary in vivo (DLLI murine model) and in vitro (high glucose (HG)-exposed human umbilical vein endothelial cells (HUVECs)) systems, PHP's bioactivity was systematically profiled. Methods In vivo: The effects of PHP on blood perfusion, microvessel density, and PANoptosome assembly in the ischemic limbs of DLLI mice were evaluated. In vitro: HUVECs treated with HG were used to assess PHP’s regulatory effects on angiogenesis functions (cell migration, proliferation, tube formation), PANoptosome/inflammasome formation, key components of the PANoptotic pathway, reactive oxygen species (ROS/mtROS), mitochondrial homeostasis, and autophagy. Transcriptomic analysis was conducted to identify potential target genes. Results In vivo: PHP significantly improved blood perfusion, increased microvessel density, and modulated PANoptosome assembly in ischemic limbs. In vitro: PHP reversed HG-induced angiogenesis dysfunction, inhibited PANoptosis and oxidative stress, restored mitochondrial function, and enhanced autophagic activity. Mechanism: PHP exerted its effects by targeting cytochrome P450 enzyme CYP2E1 through downregulating its expression, thereby alleviating mitochondrial damage and PANoptosis. Additionally, CYP2E1 downregulation promoted endothelial cell migration. Conclusion We pioneered a PANoptosome-centric framework for DLLI, proving that PHP targets CYP2E1 to restore mitochondrial homeostasis, inhibit PANoptosis, and drive angiogenesis, thereby offering a novel natural product-derived therapeutic strategy. Collectively, this work establishes PHP as a promising candidate for DLLI treatment through CYP2E1-mediated restoration of mitochondrial homeostasis and PANoptosis suppression.
研究领域:
药理学
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内分泌学
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心血管研究
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分子生物学
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天然产物
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线粒体生物学
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细胞死亡机制
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）