Ferroptosis is a new form of regulated cell death, which is characterized by the iron-dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self-preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those-tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis-based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context.
Background: In western countries and China, back and neck pain has become a common problem that bothers daily life and severely influences the quality of our daily life. Among all factors that lead to chronic neck and back pain, IDD is the one that couldn’t be easily neglected. Methods: This study aims to figure out the critical genes and pathways involved in the development of IDD and provide a new aspect of following investigations on the etiology of IDD. We firstly systemically searched the GEO database and identified the differentially expressed genes (DEGs) from the expression profile dataset we selected. We secondly constructed the protein-protein interaction (PPI) network for DEGs, identified the top ten hub genes from the whole PPI network and found two statically and medically significant modules from the network, we then performed the GO and KEGG analysis on the DEGs, top ten hub genes, the PPI network and the two statically and medically modules. In the end, we provided the primers of the mRNAs of all DEGs, which will be useful for the validation experiment of this study. Results: FN1, MMP2, POSTN, COL3A1, TIMP3, FBN1, GJA1, TGFBI, EFEMP1 and ID1 were top ten hub genes identified from this study, and they may play a vital role in the development of IDD. Angiogenesis and integrin binging are crucial biological process and molecular function defined in this study, which are worthy of being intensely investigated.Conclusion: More studies on the top ten hub genes, the role of angiogenesis and integrin binding in IDD are urgently needed, which will benefit the prevention, screening, diagnosis and prognosis of IDD.
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