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Diabetic kidney disease (DKD) progression can be predicted by abnormalities in the tubulointerstitial lining, and their treatment may be useful for preventing the disease. DKD is a progressive disease that contributes to renal tubular cell death, but its underlying mechanisms remain unclear. Ferroptosis is a novel term linked to lipid hydroperoxidation, and it plays an important role in the pathogenesis of DKD. Overexpression of cyclooxygenase-2 (COX2), an enzyme of the proximal tubule, causes cellular redox damage in DKD. It remains unknown whether COX2 exacerbates tubular damage by accelerating ferroptosis in the kidneys of diabetic mice. HK-2 cells cultured in high glucose exhibited ferroptosis, which was inhibited by ferroptosis inhibitors. Additionally, alterations in the sensors of ferroptosis metabolism, such as glutathione peroxidase 4 (GPX4) activity, lipid hydroperoxidation, reduced glutathione (GSH) levels and changes in mitochondrial morphology, were observed in high glucose-cultured HK-2 cells. Diabetic mice manifested tubular injury and deranged renal physiological indices, which were mitigated by ferrostatin-1 (Fer-1). Importantly, these perturbations were ameliorated by downregulating COX2. In addition, the increased COX2 was observed to be elevated in the daibetic kindney. To explore the relevance of COX2 to ferroptosis, HK-2 cells that knocked down from COX2 exhibited decreased ferroptosis sensitivity under high glucose conditions. In RSL-3-treated HK-2 cells, ferroptosis was improved by downregulating COX2 by treatment with aspirin, which was confirmed in high glucose-cultured HK-2 cells. Furthermore, the ferroptosis changes were also suppressed by decreasing COX2 in diabetic mice treated with aspirin, which retarded DKD progression. In conclusion, our results demonstrated that ferroptosis in renal tubular cells contributes to DKD development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD. Our findings support a renoprotective mechanism by which aspirin inhibits COX2 activation, identify COX2 as a potential target of ferroptosis, and establish that ferroptosis in renal tubular cells is an integral process in the pathogenesis of DKD regulated by COX2 expression profiles. [ABSTRACT FROM AUTHOR]

Global changes in precipitation and atmospheric N deposition affect the geochemical cycle of the element and its hydrological cycle in the ecosystem. It may also affect the relationship between plant water use efficiency (WUE) and nutrients, as well as the relationship between plant nutrients. Desert ecosystems are vulnerable to global changes. Haloxylon ammodendron is the dominant species in the Asian desert. Revealing the variations in these relationships in H. ammodendron with precipitation and N deposition will enhance our understanding of the responses of plants to global change in terms of trade-off strategies of nutrient absorption, water and element geochemical cycles in desert ecosystems. Thus, we conducted field experiments with different amounts of water and N. This study showed that WUE of H. ammodendron was not correlated with nitrogen content (N), phosphorus content (P), and potassium content (K) when water and N supply were varied (p > 0.05 for WUE vs. N, P, and K), suggesting lack of coupling between water use and nutrient economics. This result was associated with the lack of correlation between plant nutrients and gas exchang in H. ammodendron. However, water addition, N addition and the interaction between both of them all played a role in the correlation between plant N, P and K owing to their different responses to water and N supplies. This indicates that global changes in precipitation and N deposition will affect N, P and K geochemical cycles in the Asian deserts dominated by H. ammodendron, and drive changes in the relationships between plant nutrients, resulting in changes in the trade-off strategy of plant absorption of N, P, and K. [ABSTRACT FROM AUTHOR]