Duodenal atresia (DA) is a common neonatal digestive tract obstruction, with unclear prenatal diagnostic specificity and optimal intervention timing. tRNA-derived small RNAs (tsRNAs), stable and enriched in blood, are promising biomarkers for disease diagnosis. Therefore, identifying tsRNA biomarkers, elucidating DA pathogenesis, and exploring potential intrauterine interventions is urgently needed. This study conducts tsRNA profiling via sequencing on plasma samples from pregnant women carrying fetuses with DA and matched healthy controls. Validation was performed in 147 pregnant women, including cohorts with fetal gastrointestinal atresia, normal pregnancies, and post-delivery cases. Functional analyses in cellular models and Adriamycin rat models with DA explored the role of key tsRNAs in DA pathogenesis and intrauterine therapy. It is found that tsRNAs, including tRF-61:78-chrM. Leu-TAA, tRF-60:77-Ile-AAT-1-M4, tRF-57:76-Arg-ACG-1-M2, and tRF-58:76-Tyr-GTA-2-M3, were significantly downregulated in DA cases. tRF-58:76-Tyr-GTA-2-M3 is further implicated in DA development, with knockdown inducing excessive apoptosis via upregulation of SUFU and suppression of GLI1, a hedgehog pathway transcription factor. Intraperitoneal microinjection of tRF-58:76-Tyr-GTA-2-M3 agomir in DA rat models reduce apoptosis and mitigates DA formation by modulating SUFU and GLI1 expression. Taken together, this study identifies novel tsRNA biomarkers for DA, with tRF-58:76-Tyr-GTA-2-M3 playing a pivotal role in its pathogenesis. These findings offer insights into DA mechanisms and suggest potential therapeutic targets, advancing strategies for early diagnosis and intervention.
Annulus fibrosus (AF) injury is a significant cause of NP protrusion and intervertebral disc degeneration (IDD). Currently, the molecular mechanisms of IDD remain unclear, and there is a lack of methods for early diagnosis and targeted drug delivery through the circulatory system. This study focuses on the mitochondria-derived tsRNA, IDDMT (IDD-related mitochondrial-derived tsRNA, mt-TRF3-24-AspGTC), which is significantly upregulated in degenerated AF tissues of intervertebral discs. Mechanistically, IDDMT overexpression interacts with IMPDH2, activating the NF-κB signaling pathway and leading to mitochondrial dysfunction, ROS production, and apoptosis in AF cells. To address this issue, a nanocarrier system, UCNP (NaGdF 4 @NaErF 4 @NaLuF 4 @MSN@ZIF-8@IN-IDDMT@Suc-(GfO) 9 ), capable of dual-modal imaging with MRI and NIR II, for targeted delivery of IDDMT inhibitors to repair AF damage and slow the progression of IDD is developed. In vitro and in vivo experiments have confirmed the effectiveness of UMZG in restoring mitochondrial dynamics, reducing ROS production, inflammation, and cell apoptosis. This innovative therapeutic approach, which integrates dual-modal imaging capabilities, offers a new avenue for the early treatment of IDD.
危险品化学品经营许可证（带存储）