Chelating Agents

Intercropping has the potential to improve plant nutrition as well as crop yield. However, the exact mechanism promoting improved nutrient acquisition and the role the rhizosphere microbiome may play in this process remains poorly understood. Here, we use a peanut/maize intercropping system to investigate the role of root-associated microbiota in iron nutrition in these crops, combining microbiome profiling, strain and substance isolation and functional validation. We find that intercropping increases iron nutrition in peanut but not in maize plants and that the microbiota composition changes and converges between the two plants tested in intercropping experiments. We identify a Pseudomonas secreted siderophore, pyoverdine, that improves iron nutrition in glasshouse and field experiments. Our results suggest that the presence of siderophore-secreting Pseudomonas in peanut and maize intercropped plays an important role in iron nutrition. These findings could be used to envision future intercropping practices aiming to improve plant nutrition.

BackgroundVascular calcification (VC) is an independent risk factor for cardiovascular diseases. Recently, ferroptosis has been recognised as a novel therapeutic target for cardiovascular diseases. Although an association between ferroptosis and vascular calcification has been reported, the role and mechanism of iron overload in vascular calcification are still poorly understood. Specifically, further in-depth research is required on whether metalloproteins SLC39a14 and SLC39a8 are involved in ferroptosis induced by iron overload.MethodsR language was employed for the differential analysis of the dataset, revealing the correlation between ferroptosis and calcification. The experimental approaches encompassed both in vitro and in vivo studies, incorporating the use of iron chelators and models of iron overload. Additionally, gain- and loss-of-function experiments were conducted to investigate iron's effects on vascular calcification comprehensively. Electron microscopy, immunofluorescence, western blotting, and real-time polymerase chain reaction were used to elucidate how Slc39a14 and Slc39a8 mediate iron overload and promote calcification.ResultsFerroptosis was observed in conjunction with vascular calcification (VC); the association was consistently confirmed by in vitro and in vivo studies. Our results showed a positive correlation between iron overload in VSMCs and calcification. Iron chelators are effective in reversing VC and iron overload exacerbates this process. The expression levels of the metal transport proteins Slc39a14 and Slc39a8 were significantly upregulated during calcification; the inhibition of their expression alleviated VC. Conversely, Slc39a14 overexpression exacerbates calcification and promotes intracellular iron accumulation in VSMCs.ConclusionsOur research demonstrates that iron overload occurs during VC, and that inhibition of Slc39a14 and Slc39a8 significantly relieves VC by intercepting iron overload-induced ferroptosis in VSMCs, providing new insights into the VC treatment.

Myocardial infarction (MI), a consequence of coronary artery occlusion, triggers the degradation of ferritin, resulting in elevated levels of free iron in the heart and thereby inducing ferroptosis. Targeting myocardial ferroptosis through the chelation of excess iron has therapeutic potential for MI treatment. However, iron chelation in post ischemic injury areas using conventional iron-specific chelators is hindered by ineffective myocardial intracellular chelation, rapid clearance, and high systemic toxicity. A chitosan-desferrioxamine nanosponge (CDNS) is designed by co-crosslinking chitosan and deferoxamine through noncovalent gelation to address these challenges. This architecture facilitates direct iron chelation regardless of deferoxamine (DFO) release due to its sponge-like porous hydrogel structure. Upon cellular internalization, CDNS can effectively chelate cellular iron and facilitate the efflux of captured iron, thereby inhibiting ferroptosis and associated oxidative stress and lipid peroxidation. In MI mouse models, myocardial injection of CDNS promotes sustainable retention and the suppression of ferroptosis in the infarcted heart. This intervention improves cardiac function and alleviates adverse cardiac remodeling post-MI, leading to decreased oxidative stress and the promotion of angiogenesis due to ferroptosis inhibition by CDNS in the infarcted heart. This study reveals a nanosponge-based nanomedicine targeting myocardial ferroptosis with efficient iron chelation and efflux, offering a promising MI treatment.

Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic weapon in oncology and their inhibition for neuroprotection. We synthesize evidence ranging from small-molecule synergy to advanced nanomedicine, examining how the interplay between iron and copper governs cellular fate in resistant malignancies and neurodegenerative diseases such as Parkinson's disease and Multiple Sclerosis. In oncology, bimetallic nanoplatforms and CRISPR-Cas9 nano-ionophores exploit "iron addiction" and metabolic vulnerabilities to induce fatal lipid peroxidation and FDX1-mediated proteotoxic stress, often by circumventing efflux transporters like ATP7A/B. Conversely, neuroprotective strategies focus on site-specific chelation, utilizing brain-penetrant molecules like SK4 (targeting the LAT1 transporter) and radical trapping antioxidants like CuII(atsm). Importantly, we elucidate the "iron trap" mechanism, where copper deficiency inactivates multicopper ferroxidases-including ceruloplasmin and hephaestin-thereby triggering iron-dependent ferroptosis. Our analysis reveals a self-amplifying cycle of oxidative damage driven by metal-induced ATP depletion and glutathione exhaustion. By delineating the molecular machinery of iron and copper metabolism, this article provides a roadmap for leveraging regulated cell death to overcome apoptosis resistance in cancer and preserve neural integrity in chronic degeneration.