Peripheral injury reprograms metabolism in spinal cord oligodendrocytes, initiating a molecular cascade that drives chronic pain via neuronal β-amyloid (Aβ) release. After injury, mouse spinal oligode Show more
Peripheral injury reprograms metabolism in spinal cord oligodendrocytes, initiating a molecular cascade that drives chronic pain via neuronal β-amyloid (Aβ) release. After injury, mouse spinal oligodendrocytes downregulate myelin protein synthesis and upregulate lipid biosynthesis-but reroute lipids toward neuroplastic remodeling and away from myelin maintenance. This metabolic reallocation disrupts myelin integrity and axonal function, causing neuronal accumulation of amyloid precursor protein, enhanced expression of its processing β-secretase BACE1, and local release of Aβ peptides. Blocking Aβ production or clearing Aβ deposits stops the transition to pain chronicity. Deleting the lysosomal lipid hydrolase NAAA in oligodendrocytes prevents both injury-induced Aβ production and chronic pain development. The findings identify an unexpected mechanistic link between chronic pain and Alzheimer's-like neurodegeneration, positioning Aβ as a target for therapeutic intervention. Show less
Sedum species are reported to possess diverse pharmacological activities in various solid tumors. However, the anticancer functions of Sedum orizyfolium and its constituents have never been determined Show more
Sedum species are reported to possess diverse pharmacological activities in various solid tumors. However, the anticancer functions of Sedum orizyfolium and its constituents have never been determined in human cancers. The present study focused on addressing the inhibition efficacy of the methanol extract of S. orizyfolium (MESO) and its constituents and the molecular mechanism underlying invasion and epithelial-to-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) cell lines. After MESO treatment, a wound-healing assay, an invasion assay, and immunocytochemistry were performed in OSCC cell lines, coupled with in silico analysis and immunohistochemistry in OSCC patient samples, to investigate the role of the EMT transcription factor Slug. Trehalose, an active component of MESO, was identified through gas chromatography-mass spectrometry. Among the methanol extracts of 18 various wild plants from South Korea, MESO exhibited the highest anticancer functionality in OSCC cells by downregulating Slug expression. In silico analysis and immunohistochemistry indicated that elevated Slug levels are remarkably associated with tumor progression and invasion in patients with OSCC, suggesting that changes in Slug expression alter EMT progression and invasion in OSCC. Notably, treatment with trehalose, a sugar component of MESO, inhibited invasiveness and Slug expression in OSCC cells. Cumulatively, this study highlighted the beneficial role of MESO and trehalose in the inhibition of invasiveness of OSCC cells via suppression of Slug expression and suggested a new design for potential chemotherapeutic drugs against OSCC. Show less