Search Results (89)

Iron overload disrupts cellular homeostasis and drives ferroptosis through dysregulated iron metabolism. Non-coding RNAs (ncRNAs) are considered as key regulators of various biological functions and targets for a new generation of RNA therapeutics and biomarkers. However, few studies have investigated the regulatory roles of ncRNAs, particularly competitive endogenous RNAs (ceRNAs) in iron overload. This study performed whole-transcriptome sequencing to characterize the ceRNA network in ferric ammonium citrate (FAC)-induced iron-overloaded HT-1080 fibrosarcoma cells. A total of 208 differentially expressed mRNAs, 83 lncRNAs, and 170 circRNAs (q < 0.05) were identified, with hierarchical clustering revealing distinct expression patterns between control and iron-treated groups. KEGG enrichment implicated vitamin B6 metabolism (q < 0.001) and lysine degradation (q < 0.001) as key disrupted pathways. ceRNA network was conducted and further demonstrated lncRNA/circRNA-mediated regulation of ferroptosis genes via shared miRNA response elements. Notably, LINC-PINT-232 was implicated in the regulation of both ferritin heavy chain (FTH) and sequestosome 1 (SQSTM1), two ferroptosis-associated mRNAs. FTH upregulation mitigates iron toxicity through ferroxidase activity, while SQSTM1 modulates lipid peroxidation in ferroptosis. These findings provide a preliminary transcriptomic landscape for hypothesis generation regarding ncRNA-mediated regulatory mechanisms in iron overload-induced ferroptosis and offer a computational foundation for future functional and therapeutic investigations. Full article

Retinal pigment epithelium (RPE) degeneration remains a formidable challenge in dry age-related macular degeneration (AMD) research, primarily due to the toxic interplay between iron overload and ferroptosis. We investigated whether EPO-R76E, a non-erythropoietic modified variant of erythropoietin, could effectively interrupt this destructive cycle. Using ARPE-19 cells challenged with ferric ammonium citrate (FAC) to model iron-induced toxicity, we show that EPO-R76E confers protection against ferroptosis. Our results demonstrate that this variant significantly reduces the intracellular labile iron pool, directly quenching the lipid peroxidation that drives ferroptotic cell death. This resilience is fueled by a robust upregulation of Glutathione Peroxidase 4 (GPX4) and the broad transcriptional activation of the NRF2 (Nuclear factor erythroid 2-related factor 2) NRF2 antioxidant axis. Furthermore, we found that EPO-R76E enhances autophagic flux, ensuring that cells maintain essential proteostasis and “housekeeping” functions even under metabolic crisis. By integrating iron sequestration with reinforced antioxidant signaling and cellular clearing mechanisms, EPO-R76E stands out as a potent candidate for preserving RPE health. These findings uncover a novel molecular framework for protecting the retina against iron-mediated injury, positioning EPO-R76E as a versatile and targeted gene-based therapeutic for addressing the fundamental causes of retinal degeneration. Full article

Females with iron overload suffer from follicular dysplasia, and effective therapeutic strategies for preserving fertility remain lacking. As a natural aliphatic polyamine, spermidine exerts antioxidant activity and plays an anti-ferroptosis role in the pathogenesis of various diseases. However, the role and underlying mechanism of spermidine in iron overload-induced ovarian ferroptosis remain largely elusive. This study aimed to investigate the therapeutic potential of spermidine against iron overload-induced ferroptosis in ovarian granulosa cells and elucidate its molecular mechanism. As a result, iron overload models were established in female mice (in vivo, ferrous sulfate) and porcine ovarian granulosa cells (in vitro, ferric ammonium citrate), with spermidine administered at 3 mM (in vivo) or 150 μM (in vitro). Ferritin heavy chain (FHC) and solute carrier family 7 member 11 (SLC7A11) silencing were performed via siRNA transfection, and relevant controls were set. In vivo studies showed that spermidine elevated serum estradiol and progesterone levels, enhanced ovarian catalase (CAT) and superoxide dismutase (SOD) activities, improved granulosa cell mitochondrial morphology, and increased estrous cycle regularity from 35.6% (high-iron group) to 63.1%. In vitro, spermidine improved ferric ammonium citrate (FAC)-impaired cell viability; attenuated reactive oxygen species (ROS) accumulation; upregulated FHC, Nrf2/p-Nrf2/GPX4, SLC7A11 and anti-müllerian hormone (AMH) expression; and inhibited excessive autophagy (decreased LC3BII/I ratio). Mechanistically, spermidine activated AKT-mediated autophagy, modulated iron homeostasis and glutathione (GSH) synthesis via FHC, alleviated ferroptosis-related Nrf2/p-Nrf2/HO-1 pathway overactivation, reduced lipid peroxidation and DNA damage, and restored mitochondrial function. SLC7A11 silencing disrupted glutathione metabolism, induced mitochondrial ROS accumulation, and inhibited autophagy. Proteomic analysis identified microsomal glutathione S-transferase 3 (MGST3) as a potential key downstream target of spermidine in suppressing SLC7A11-mediated ferroptosis. This study reveals a novel therapeutic strategy wherein spermidine protects against ovarian ferroptosis and preserves ovarian function by regulating iron homeostasis through the FHC/SLC7A11 axis. Full article

Iron is an essential nutrient for piglets, but iron sources vary greatly in bioavailability, and their effects on intestinal health remain unclear. In this study, 21-day-old weaned piglets were used to compare the effects of different iron sources (ferrous sulfate (FeSO₄), ferric ammonium citrate (FAC), and ferrous glycinate (Fe-Gly)) on growth performance, intestinal inflammation, and gut microbiota. Compared to the FeSO₄ group, the Fe-Gly group significantly increased the body weight of piglets at 35 days (p < 0.05), promoted the average daily feed intake (ADFI) and average daily gain (ADG) of piglets from day 21 to 35 (p < 0.01), and also markedly reduced the diarrhea rate of piglets (p < 0.01). Meanwhile, although FAC increased growth performance-related indicators (ADG, ADFI) in piglets, there was no significant statistical difference compared with FeSO₄ (p > 0.10). Moreover, Fe-Gly supplementation significantly elevated serum iron levels and total iron-binding capacity (p < 0.01), while significantly reducing the iron content in colonic chyme (p < 0.0001). Both the Fe-Gly and FAC significantly improved the anti-inflammatory and antioxidant capacities of the piglets (p < 0.01). Interestingly, Fe-Gly primarily increased the abundance of Lactobacillus, thereby reducing the abundance of harmful bacteria such as Escherichia coli. Functional prediction using PICRUSt2 revealed that Fe-Gly supplementation tended to elevate the relative abundance of gut bacteria capable of carbohydrate metabolism and amino acid synthesis. In conclusion, this study demonstrated that dietary Fe-Gly supplementation improved systemic iron status, effectively reduce residual iron in the intestine, inhibit the proliferation of pathogenic bacteria in the gut, promote the growth performance and intestinal health of piglets, and reduce the diarrhea rate. Full article

Capacitive deionization (CDI) technology represents an emerging and energy-efficient solution for seawater desalination and wastewater treatment. To further enhance its sustainability and economic viability, it is very important to develop high-performance electrodes made from low-cost and renewable raw materials. Herein, a new electrode material is introduced; the material was derived from wheat straw and modified via a simple and green process using ammonium ferric citrate (AFC) as a synergistic activator and modifier. The modification of AFC significantly enhanced the physicochemical properties of biochar. At the optimal AFC concentration of 1 mol·L⁻¹, the specific surface area reached 321.27 m²·g⁻¹, with a specific capacitance of 208.19 F·g⁻¹. In the NaCl desalination experiment, the MWC-1.0 electrode exhibited a desalination capacity of 13.62 mg g⁻¹ under the conditions of 1.2 V voltage and 2 mm electrode spacing in an initial solution concentration of 500 mg L⁻¹. After 20 cycles of adsorption/desorption, the deionization capacity of the material was still retained at 90.5% of its initial capacity, demonstrating excellent regeneration performance. This work provides a sustainable method for preparing efficient and stable biochar electrodes, further highlighting its potential application in energy-saving seawater desalination technology. Full article

Lipid peroxide (LPO) accumulation and a depletion of intracellular antioxidants are hallmarks of ferroptosis, a controlled iron-dependent form of cell death. Iron chelators and radical scavengers can stop it, while erastin or iron overload can cause it. The main catechin in green tea extract (GTE), epigallocatechin-3-gallate (EGCG), has iron-chelating and antioxidant activities. Herein, we investigated the effects of EGCG-rich GTE on ferroptosis in iron-loaded hepatocytes. The contents of EGCG, total phenolics (TPC), and flavonoids (TFC), as well as ABTS^•+-scavenging activity and cytotoxicity, were determined. Human hepatoma (Huh7) cells were treated with ferric ammonium citrate (FAC) to induce ferroptosis and were co-treated with various concentrations of GTE. Labile iron pool (LIP), reactive oxygen species (ROS), LPO, glutathione (GSH), and glutathione peroxidase 4 (GPX-4) activity were then measured in the cells. One gram of GTE contained 26 mg of EGCG, with a TPC of 172.2 mg gallic acid equivalents and a TFC of 32.9 mg quercetin equivalents. GTE displayed concentration-dependent ABTS^•+-scavenging activity (IC₅₀ = 1.03 mg) that was equivalent to 0.29 mg of Trolox, reporting a Trolox-equivalent antioxidant capacity (TEAC) value of 0.29 mg. High-dose GTE (>100 µM EGCG equivalent) reduced cell viability below 80% (p < 0.05). Intracellular LIP, ROS, and LPO levels were markedly elevated, whereas GSH and GPX-4 activity levels were decreased (p < 0.05) in iron-loaded Huh7 cells. GTE treatment mitigated these alterations in a dose-dependent manner (p < 0.05). These cell-based in vitro findings indicate that EGCG-rich GTE can attenuate ferroptosis-associated oxidative stress in hepatocytes under iron-loading conditions. GTE may serve as a potential dietary antioxidant candidate; further mechanistic studies and in vivo experiments are required to determine its physiological relevance and translational applicability. Full article

Toxicant-associated steatohepatitis (TASH) is caused by environmental toxicants rather than metabolic factors; however, its pathogenic mechanisms remain poorly understood. Polychlorinated biphenyl 138 (PCB138), a persistent lipophilic contaminant that bioaccumulates in adipose tissue, may promote TASH through unclear mechanisms. In this study, we investigated whether PCB138 induces liver injury via hepatic iron dysregulation and adipose-liver inflammatory signaling. Male C57BL/6 mice received intraperitoneal PCB138 (1, 5, 10, or 50 mg/kg, four injections over six weeks). HepG2 hepatocytes were treated with PCB138 with or without ferric ammonium citrate (FAC), and PCB138-exposed 3T3-L1 adipocytes were co-cultured with HepG2 cells using a Transwell system. PCB138 dose-dependently increased serum transaminase and hepatic non-heme iron levels, with Hamp upregulation, macrophage infiltration, and fibrosis. In HepG2 cells, PCB138 synergized with FAC to elevate intracellular Fe²⁺, induced Hamp, suppressed Slc40a1, and upregulated inflammatory/profibrotic genes. In Transwell co-cultures, TNF-α, IL-6, and IL-1β from PCB138-exposed adipocytes amplified hepatic iron dysregulation and fibrotic responses. These findings demonstrated that PCB138 induced TASH through hepatic iron dysregulation and adipose-derived inflammatory signaling, independent of steatosis. These results highlighted the iron–adipose axis as a novel mechanistic link between PCB138 exposure and liver injury, offering potential therapeutic targets. Full article

Objectives: This study utilized IPEC-J2, a neonatal pig jejunum-derived cell line, to assess how iron deficiency (ID) and excess (IE) alter enterocyte metabolism and the transcription of inflammatory markers. Methods: Cells were treated with deferiprone (DFP) or ferric ammonium citrate (FAC) to induce ID or IE, respectively. The study evaluated: (1) transcriptional changes in iron-regulatory genes over 96 h under ID or IE; (2) the interaction between iron imbalance and lipopolysaccharide (LPS) exposure on mRNA expression of inflammation markers and iron transporters; and (3) cellular metabolic responses to ID, IE, and iron repletion using untargeted metabolomics. Results: ID triggered dynamic transcriptional changes in iron regulatory genes and suppressed cellular proliferation via impaired DNA replication. IE resulted in a persistent reduction in TFRC expression. LPS increased CYBRD1 (p < 0.001) and IL8 (p = 0.004) and tended to elevate TLR4 and TNF expression (p ≤ 0.07), while iron deficiency upregulated IL8 expression (p < 0.001). ID disrupted the TCA cycle, reduced glucuronic acid synthesis, and elevated glycolysis for energy production, whereas IE increased cholesterol biosynthesis and decreased alpha-tocopherol levels. Repletion of iron partially reversed ID-induced metabolic changes. Conclusions: ID impaired enterocyte proliferation and profoundly disrupted cellular metabolism, whereas IE enhanced cholesterol synthesis and depleted alpha-tocopherol levels. Restoration of cellular metabolism following iron repletion was observed, highlighting the resilience of enterocytes. Full article

The presence of impurities such as Ca, Mg, and Al during the precipitation of rare earths (REs) using ammonium bicarbonate directly affects product purity. It is necessary to optimize precipitation methods and conditions to improve the separation efficiency between REs and impurities. In this study, RE (La and Ce) ions were precipitated using ammonium bicarbonate solution, and the separation efficiency of REs from Al, Fe, Ca, and Mg ions was investigated with or without the addition of triammonium citrate (TAC). The results showed that as long as the precipitation yield of REs was controlled below 94%, Ca and Mg ions would not enter the precipitation in the absence of other impurities, and the purity of the obtained rare earth oxides (RE₂O₃) was close to 100%. The presence of Al and Fe impurities would reduce the separation efficiency of REs from Ca and Mg. Therefore, Al and Fe must be separated before the precipitation of REs. First, Fe was completely precipitated by controlling the pH value to 4.12. Then, by filtering out the isolation and adjusting the pH value to 4.6, approximately 84% of Al³⁺ was precipitated, with a loss of REs of about 6%. Finally, the pH value was increased to 6.43, and REs were completely precipitated, yielding rare earth carbonate. The RE₂O₃ purity of its calcination product was 97.8% with Al and Mg contents of 1.05% and 0.21%, respectively, and no Ca or Fe was detected. This indicated that Mg can enter the product by co-precipitation with Al. To address this, a small amount of TAC was added during the pre-removal of Fe and Al to facilitate the complete removal of Al. By controlling the precipitation yield of REs at 94%, the purity of the final RE₂O₃ reached 99.6% with an Al content of 0.09%. Furthermore, using a continuous precipitation crystallization method, RE₂O₃ purity can be achieved at 99.8% with an Al content of 0.06%. Full article

The fermentation performance of Lactobacillus acidophilus is constrained by factors such as low cell density and fastidious nutritional and environmental requirements, which greatly limit its industrial-scale applications. This study aimed to develop an efficient fermentation condition for L. acidophilus CCFM137 through systematic optimization of both culture medium and environmental parameters, thereby enabling high-yield industrial-scale production of this strain. An optimized medium was developed, consisting of glucose (30 g/L), YEP FM503 (35 g/L), sodium acetate (5 g/L), ammonium citrate (2 g/L), K₂HPO₄ (2 g/L), MgSO₄·7H₂O (0.1 g/L), MnSO₄·H₂O (0.05 g/L), L-cysteine hydrochloride (0.5 g/L), and Tween 80 (1 mL/L), to achieve a viable cell count of 1.95 × 10⁹ CFU/mL, representing a 9.42-fold increase over that of standard MRS broth. Subsequent pH-stat fermentation trials in a 100 L fermenter using the optimized medium revealed morphological and growth characteristics of the strain in variable pH-stat environments. Optimal performance was observed under pH-stat 4.5 rather than the more commonly used 5.7, achieving maximum viable cell counts of 3.37 × 10⁹ CFU/mL, accompanied by a transformation of cell morphology toward shorter rod-shaped structures, as well as an increase in substrate utilization rate, cell recovery rate and lyophilization survival rate. The fermentation performance and cellular morphology of L. acidophilus CCFM137 were enhanced by both nutrient composition and pH environment. These results showed that this strategy has potential for application in high cell density fermentation of L. acidophilus CCFM137. Full article

Secondary iron overload exacerbates osteoporosis by elevating reactive oxygen species (ROS), which suppress osteoblast function and enhance osteoclast activity, disrupting bone remodeling. Reducing iron overload and oxidative stress may improve bone health. Epigallocatechin-3-gallate (EGCG), the main bioactive compound in green tea extract (GTE), is recognized for its antioxidant and iron-chelating properties. This study examined the effect of GTE on bone formation and mineralization in iron-overloaded human osteoblast-like MG-63 cells. An iron-overloaded model was established using ferric ammonium citrate (FAC), followed by treatment with GTE, deferiprone (DFP), or their combination. GTE significantly reduced intracellular iron, ROS levels, and lipid peroxidation while upregulating the osteogenic marker BGLAP, the anti-resorptive marker OPG, and osteogenic mineralization, indicating restored bone health. These results suggest that EGCG-containing GTE mitigates iron-induced oxidative stress and promotes osteogenesis, highlighting its potential as a natural therapeutic supplement for managing iron-overload-associated osteoporosis. Full article

Harmful Raphidiopsis raciborskii blooms threaten aquatic ecosystems via toxin production, hypoxia induction, and biodiversity loss. To elucidate the synergistic regulatory mechanisms of Fe³⁺ and phosphorus (P) in cyanobacterial growth, we used a sterile pure culture system under laboratory conditions. We set different phosphorus sources (organic phosphorus and inorganic phosphorus) and low phosphorus concentration of R. raciborskii culture medium for culture, and set different Fe³⁺ addition amount to determine the basic growth index of cyanobacteria cells and the phosphorus content of different components. The results revealed that under conditions of sufficient inorganic phosphorus, there was a logarithmic relationship between ferric ammonium citrate (Fe³⁺) and the specific growth rate of R. raciborskii. Fe³⁺ > 2 mg/L enhanced IPS enrichment and biomass accumulation. However, in oligotrophic or mesotrophic environments with low inorganic phosphorus concentrations, the effect of Fe³⁺ on the growth of R. raciborskii contrasted with that observed in high-IP (eutrophic) environments, exhibiting a pattern of ‘low promotion and high inhibition’. Under organic phosphorus conditions, R. raciborskii converted phosphorus by increasing alkaline phosphatase activity (APA), but this metabolic compensation failed to restore physiological functions, resulting in growth suppression and enhanced cellular phosphorus reserves. Our results establish quantitative linkages between Fe³⁺-P co-limitation thresholds and algal adaptive responses, providing mechanistic insights for controlling bloom dynamics through targeted manipulation of Fe-P bioavailability. Full article

N-Nitrosodimethylamine (NDMA) is a widely recognized disinfection by-product that poses significant carcinogenic risks in drinking water. Conventional methods for NDMA removal, such as nanofiltration and reverse osmosis membranes, have limited efficacy due to NDMA’s small molecular weight and polar properties. Advanced oxidation processes (AOPs) have shown promise, but traditional Fenton processes often fall short due to the chemical structure of nitrosamines in NDMA. This study proposes a novel, cost-effective approach using a one-step carbonization method to synthesize a catalyst from ferric ammonium citrate (FAC). The resulting FAC-600 integrates zero-valent iron and iron carbide with carbon-based functional groups, enhancing catalytic and electron transport activities. Our experiments demonstrated that the FAC-600/persulfate (PS) AOP system achieves over 90% NDMA removal across a wide concentration range (50 μg L⁻¹ to 1000 μg L ⁻¹) with a limited dosage of 0.5 g L⁻¹. Mechanistic insights revealed that superoxide and hydroxyl radicals dominate NDMA degradation, facilitated by the presence of dissolved oxygen and PS. This study underscores the potential of the FAC-600/PS AOP system as a robust and efficient solution for NDMA removal, promising safer drinking water through practical application. Full article

Phosphorus is essential for crop growth, but excessive use of chemical fertilizers can lead to environmental issues. The incorporation of organic materials has the potential to enhance phosphorus availability and promote soil phosphorus cycling. This study investigated the effects of chemical fertilizer co-application with two organic materials on soil properties and functions. Four treatments were established: (1) chemical fertilizer alone (SC, consisting of urea, ammonium phosphate, and potassium sulfate), (2) chemical fertilizer with corn-straw-derived biochar (SCB), (3) chemical fertilizer with composted manure-based organic fertilizer (SCF), and (4) chemical fertilizer with both biochar and organic fertilizer (SCBF). This study focused on changes in soil properties, bioavailable phosphorus, phosphorus cycling functional genes, and related microbial communities. Compared to SC, the combined application of organic materials significantly increased available phosphorus (AP), alkaline hydrolysis nitrogen (AN), and available potassium (AK), with the SCBF exhibiting the highest increases of 78.76%, 47.47%, and 336.61%, respectively. However, applying organic materials reduced alkaline phosphatase (ALP) and acid phosphatase (ACP) activities, except for the increase in ACP in SCBF. Additionally, bioavailable phosphorus increased by up to 157.00% in SCBF. Adding organic materials significantly decreased organic phosphorus mineralization genes (phoA, phoD, phnP) and phosphate degradation genes (ppk2), while increasing inorganic phosphorus solubilization genes (pqqC, gcd), which subsequently increased CaCl₂-P and Citrate-P contents in SCB and in SCBF. In summary, organic material application significantly enhances phosphorus bioavailability by improving soil physicochemical properties and phosphorus-related gene abundance. These findings provide new insights into sustainable soil fertility management and highlight the potential of integrating organic materials with chemical fertilizers to improve soil nutrient availability, thereby contributing to increased soybean yield. Moreover, this study advances our understanding of the underlying mechanisms driving phosphorus cycling under combined fertilization strategies, offering a scientific basis for optimizing fertilization practices in agroecosystems. Full article

Iron overload contributes to proliferative vascular diseases, yet its interplay with hydrogen sulfide (H₂S) in vascular smooth muscle cell (VSMC) proliferation remains poorly understood. This study elucidates H₂S’s role in mitigating iron-overload-induced oxidative stress and cellular damage. Using aortic VSMCs from wildtype (WT) and cystathionine γ-lyase-knockout (CSE-KO) mice treated with ferric ammonium citrate (FAC) at concentrations equivalent to serum levels of iron and citrate, we demonstrate that FAC triggers the integrated stress response (ISR) in WT cells, upregulating CSE to enhance H₂S production. The ISR mediator ATF4 activates caspases but simultaneously induces CSE, which inhibits caspase activity and promotes autophagy via AMPK signaling. In CSE-KO cells, iron overload leads to diminished Ferritin upregulation, unchecked Caspase activation, and impaired autophagy compared to WT cells. Exogenous H₂S restored iron homeostasis by enhancing Ferritin expression, activating NRF2 antioxidant pathways, and restoring apoptosis–autophagy equilibrium in both WT and KO cells. These findings establish H₂S as a critical regulator of iron-induced VSMC dysfunction, highlighting its therapeutic potential in managing vascular pathologies linked to iron dysregulation. Full article