Huang Chunlian, Liao Jiaqi, Cen Xufeng, Jiao Changwei, Chen Sijia, Liu Dong, Qu Hang-Shuai, Zhu Jiansheng, He Sailing
Department of Infectious Diseases, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, 317000, China; MedEnglnfo Collaborative Research Center, Zhejiang Engineering Research Center for Intelligent Medical Imaging, Sensing and Non-invasive Rapid Testing, Taizhou Hospital, Zhejiang University, Taizhou, China.
Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, Zhejiang University, Hangzhou, 310058, China; MedEnglnfo Collaborative Research Center, Zhejiang Engineering Research Center for Intelligent Medical Imaging, Sensing and Non-invasive Rapid Testing, Taizhou Hospital, Zhejiang University, Taizhou, China; National Engineering Research Center for Optical Instruments, Zhejiang University, Hangzhou, 310058, China.
Redox Biol. 2025 Jun;83:103654. doi: 10.1016/j.redox.2025.103654. Epub 2025 Apr 29.
Impaired mitophagy underlies the pathophysiology of acute liver failure (ALF) and is closely associated with tissue damage and dysfunction. A novel mitophagy inducer, TJ0113, was used for treatment during ALF pathogenesis. In this study, we used a novel mitophagy inducer, TJ0113, to investigate the effects and mechanisms of TAA-induced ALF mice. The results showed that TJ0113 could enhance mitophagy through Parkin/PINK1 and ATG5 pathways, which in turn attenuated mitochondrial damage, hepatocyte apoptosis, nuclear factor (NF)-κB/NLRP3 signaling activation and inflammatory responses after TAA. Metabolomics results showed that TJ0113 mainly regulated lipid metabolism, amino acid metabolism and nucleotide metabolism in the livers of ALF mice. RNA sequencing (RNA-seq) analysis yielded that TJ0113 was involved in the development of ALF by regulating the P13K/AKT signaling pathway. The key highlight of this work is the use of an aberration-free line-scanning confocal Raman imager (AFLSCRI) to study the molecular changes in blood, liver tissue, gastrocnemius muscle, and mitochondrial extracts in ALF mice after TJ0113 treatment. Compared to the measurement with conventional assays, Raman microspectroscopy (micro-Raman) offers the benefits of being rapid, non-invasive, label-free and real-time. Our results found good agreement between Raman signals and histopathologic findings. The system has good performance with a spatial resolution of 2 μm, a spectral resolution of 4 cm and a fast detection speed improved by 2 orders. Innovations in this test contribute to clinical diagnosis of disease, personalized treatment, effective intraoperative guidance and accurate prognosis. The data may help in the development of a non-invasive clinical device for mitochondrial damage using bedside micro-Raman.
线粒体自噬功能受损是急性肝衰竭（ALF）病理生理学的基础，且与组织损伤和功能障碍密切相关。一种新型线粒体自噬诱导剂TJ0113在ALF发病过程中用于治疗。在本研究中，我们使用新型线粒体自噬诱导剂TJ0113来研究其对TAA诱导的ALF小鼠的影响及机制。结果表明，TJ0113可通过Parkin/PINK1和ATG5途径增强线粒体自噬，进而减轻TAA诱导后的线粒体损伤、肝细胞凋亡、核因子（NF）-κB/NLRP3信号激活及炎症反应。代谢组学结果显示，TJ0113主要调节ALF小鼠肝脏中的脂质代谢、氨基酸代谢和核苷酸代谢。RNA测序（RNA-seq）分析表明，TJ0113通过调节P13K/AKT信号通路参与ALF的发展。本研究的关键亮点在于使用无像差线扫描共聚焦拉曼成像仪（AFLSCRI）来研究TJ0113治疗后ALF小鼠血液、肝组织、腓肠肌和线粒体提取物中的分子变化。与传统检测方法相比，拉曼光谱（显微拉曼）具有快速、无创、无标记和实时的优点。我们的结果发现拉曼信号与组织病理学结果具有良好的一致性。该系统性能良好，空间分辨率为2μm，光谱分辨率为4cm，检测速度提高了2个数量级。本检测方法的创新有助于疾病的临床诊断、个性化治疗、有效的术中指导和准确的预后评估。这些数据可能有助于开发一种使用床边显微拉曼技术检测线粒体损伤的无创临床设备。
