Wang Yuanlin, Han Qingqing, Liu Lingling, Wang Shuai, Li Yongfa, Qian Zhanying, Jiang Yi, Yu Yonghao
Department of Anesthesiology, Tianjin Medical University General Hospital, 300052, Tianjin, China.
The Graduate School, Tianjin Medical University, 300070, Tianjin, China.
Mater Today Bio. 2024 Sep 14;28:101247. doi: 10.1016/j.mtbio.2024.101247. eCollection 2024 Oct.
Hydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis.
Phosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes' co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability.
As a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = -22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice.
Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics.
氢气和微藻均存在于自然环境中。我们旨在将氢气与生物纳米微藻整合在一起，以拓展脓毒症的治疗选择。
从接受盲肠结扎和穿刺（CLP）并吸入氢气的小鼠中获取磷酸化蛋白质组学、代谢组学和蛋白质组学数据。所有组学分析程序均符合标准。在单细胞和空间转录组学分析中使用多个R包来鉴定表达靶向基因的原代细胞，以及脓毒症相关肺组织中基因的共表达关系。然后，采用网络药理学方法鉴定候选药物。我们使用疏水作用力驱动自组装方法构建二氢槲皮素（DQ）纳米颗粒。为了与分子氢协同作用，将氨硼烷（B）添加到DQ表面。然后，使用（C）作为生物载体来改进自组装纳米颗粒。进行体内和体外实验以评估抗炎、抗铁死亡、抗感染和器官保护能力。
结果，我们确定Esam和Zo-1是肺部分子氢治疗的靶向磷酸化蛋白。铁死亡和谷胱甘肽代谢是两个靶标途径。改善了DQB的分散性并重建了DQB的形态特征，形成了DQB@C纳米系统（尺寸 = 307.3 nm，zeta电位 = -22mv），具有良好的感染响应性氢气释放能力和生物安全性。此外，DQB@C能够减少肺细胞中氧化应激和炎症因子的积累。通过提高Slc7a11/xCT的表达水平并降低Cox2水平来参与铁死亡的调节。此外，DQB@C对CLP小鼠发挥肺和多器官保护及抗炎作用。
我们的研究提出DQB@C作为一种新型生物纳米系统，在治疗脓毒症相关急性肺损伤方面具有巨大潜力，以解决临床中氢气利用的局限性。
