Iron Loading Research Articles

Metal mobilization from thawing permafrost to aquatic ecosystems is driving rusting of Arctic streams

Climate change in the Arctic is altering watershed hydrologic processes and biogeochemistry. Here, we present an emergent threat to Arctic watersheds based on observations from 75 streams in Alaska’s Brooks Range that recently turned orange, reflecting increased loading of iron and toxic metals. Using remote sensing, we constrain the timing of stream discoloration to the last 10 years, a period of rapid warming and snowfall, suggesting impairment is likely due to permafrost thaw. Thawing permafrost can foster chemical weathering of minerals, microbial reduction of soil iron, and groundwater transport of metals to streams. Compared to clear reference streams, orange streams have lower pH, higher turbidity, and higher sulfate, iron, and trace metal concentrations, supporting sulfide mineral weathering as a primary mobilization process. Stream discoloration was associated with dramatic declines in macroinvertebrate diversity and fish abundance. These findings have considerable implications for drinking water supplies and subsistence fisheries in rural Alaska.

Ceruloplasmin levels in β-thalassaemia major: therapeutic insights and implications for iron homeostasis

Ceruloplasmin (CP) is an enzyme that has ferroxidase activity and is important in maintaining iron homeostasis and serving as a copper-transporter in the bloodstream. Beta-thalassemia major (BTM), a common hereditary disorder in Iraq, can affect CP activity in patients with iron overload resulting from frequent blood transfusions in order to sustain haemoglobin levels. The current study is a single-center observational research. CP activity was measured in 304 patients (120 females and 184 males). Anthropometric indices were recorded and the iron load status was determined by measuring serum ferritin. Ninety-two healthy individuals were also included as a control group. Our findings re¬vealed no relationship between age, body mass index, or plasma ferritin and CP activity in BTM patients. No significant influence of sex on CP activity was observed. The outcomes provide insight into assumed pathways regulating CP, and add to the growing body of research on CP’s contribution to iron metabolism in BTM patients. To our knowledge, this work is the only study of its kind in Iraq, provides the groundwork for upcoming studies and potential therapeutic lines by generating insightful data on the multifaceted relationships between iron homeostasis, CP, and BTM.

In Vivo Silencing of Intestinal DMT1 Mitigates Iron Loading in β-thalassemia Intermedia (Hbbth3/+) Mice

β-thalassemia is an iron-loading anemia caused by homozygous mutations in the hemoglobin subunit beta gene. In β-thalassemia major, frequent blood transfusions and elevated absorption of dietary iron can lead to iron overload, which exacerbates pathological outcomes. Iron absorption is inappropriately high due to blunted expression of the iron-regulatory hormone hepcidin. Low hepcidin potentiates iron export from duodenal enterocytes by ferroportin (FPN); cellular iron depletion then secondarily increases expression of the iron importer, divalent metal-ion transporter 1 (DMT1). High expression of both transporters drives excessive iron absorption and ultimately, iron overload. In non-transfusion-dependent, β-thalassemia intermedia (βTI), hepcidin suppression and high iron absorption are the sole causes of iron loading. In this investigation, two parallel hypotheses were tested in βTI ( Hbbth3/+) mice: 1) Intestinal DMT1 drives elevated iron absorption and precipitates iron overload; and 2) In vivo silencing of intestinal DMT1 mitigates iron loading. Initial experiments revealed that intestine-specific ablation of DMT1 caused a pathophysiological shift from iron overload to an iron-deficiency phenotype with exacerbated anemia, thus proving that intestinal DMT1 is required for iron absorption in Hbbth3/+ mice. Subsequent studies utilized folic acid-coupled, ginger nanoparticle-derived lipid vectors to deliver functional DMT1 siRNAs to the duodenal epithelium of 4-week-old Hbbth3/+ mice daily for 16 days to assess the impact on iron loading. Knockdown of intestinal DMT1 blunted iron loading in Hbbth3/+ mice, thus supporting hypothesis 2. These notable experimental outcomes establish intestinal DMT1 as a plausible therapeutic target to mitigate iron overload in βTI and possibly other non-transfusion dependent, iron-loading anemias. This work was supported by grants R01 DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and R01 DK109717 from NIDDK and the Offce of Dietary Supplements (to JFC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice.

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

A HOMEMADE SEMIAUTOMATIC GRAPHITIZATION DEVICE FOR AMS 14C DATING AT NTUAMS LAB

ABSTRACT A low-cost and computer-controlled graphitization system connected to an elemental analyzer (EA) has been designed and built at the NTUAMS Lab. This semiautomatic system equips 6-unit reactors for the graphitization of CO2 with H2 on the iron catalyst. The entire procedure takes about 7 hours for iron conditioning, sample combustion and loading, and graphitization. The system can produce good-quality graphite for samples containing 0.5–1.6 mg carbon mass, with the pressure yield of graphitization ranging from 57.7% to 87.1%. The average values of OXI and OXII agree well with the consensus value, but the result of ANU sucrose was observed to be slightly higher than the reported one. The background samples of anthracite over ten months yielded an average of 0.38±0.10 pMC (n=21) corresponding to a 14C age of 45 kyr BP. Intercomparison samples L and M of FIRI exhibit that the measured 14C ages are almost identical to the consensus values and have a small spread in these values. The system has been carrying out graphitization for total organic carbon (TOC) of peat samples, and providing a more efficient and convenient way for AMS 14C dating.

Construction of an organic iron phosphate/graphite carbon nitride hybrid system for improved fire safety of epoxy resin

Enhancing the fire safety of epoxy resin (EP) is crucial due to its widespread but inherent flammability, necessitating the integration of additive flame retardants (FRs) that are effective in small quantities and exhibit efficient flame retardancy. This study constructed a novel, efficient FR by synthesizing organic iron phosphate (ATMP-Fe) and loading it on graphitic carbon nitride (g-C3N4). The resulting hybrid flame retardant (ATMP-Fe/g-C3N4) was added to EP in minimal amount to bolster its flame retardancy and safety features. Incorporating a mere 3 wt% of ATMP-Fe/g-C3N4 into EP significantly improved its flame retardancy and thermal stability. This was evidenced by an increase in the limiting oxygen index from 25.5% for EP to 30.1%, achieving a V-1 rating in the UL-94 test, and producing a 22.0 wt% char residue. Moreover, there was a substantial reduction in peak heat release rate, total heat release, and total smoke production by 36.3%, 27.5%, and 39.3%, respectively. The reduction in pyrolysis products, along with the formation of a dense and stable char layer facilitated by the synergistic effects of phosphorus and iron elements, significantly improved the fire safety of EP. Additionally, the enhanced hydrophobicity, mechanical properties, and electrical conductivity of the EP/3ATMP-Fe/g-C3N4 composite suggested potential for wider application of EP in various fields.

The Interplay of Iron and Lipid Homeostasis in Non-Alcoholic Fatty Liver Disease

The liver is essential for numerous metabolic functions and is the primary site of iron storage and regulation in addition to maintaining critical functions in lipid metabolism. Both iron deficiency and overload have been demonstrated as being involved with metabolic dysfunction; hence, tight regulation of iron absorption is essential to maintain health. Approximately one-third of individuals suffering from non-alcoholic fatty liver disease have elevated hepatic iron concentrations, with increased iron associated with increased disease severity, suggesting a convergence in dysregulation between lipid and iron metabolism. Increasingly, the literature is demonstrating, using a myriad of model organisms and iron-loading methods, that iron loading induces dysregulation in multiple aspects of hepatic lipid metabolism. However, the molecular mechanisms involved, and their subsequent effects on human diseases, are unclear. As iron is a fundamental component of many enzymes and proteins involved in lipid metabolism and is involved in the production of free radicals and oxidative stress, the mechanisms are numerous. In this review, we examine and summarise the dysregulation that iron loading elicits on hepatic lipid availability, de novo synthesis, catabolism, and export. We propose that understanding the interplay between iron and lipid metabolism holds the key to unlocking the complexities of disease development and progression, ultimately leading to improved therapeutic avenues.

Superparamagnetic Iron Oxide Nanoparticles Reprogram the Tumor Microenvironment and Reduce Lung Cancer Regrowth after Crizotinib Treatment.

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics. However, they can also be programmed toward a pro-inflammatory tumor suppressive phenotype, which represents a highly active area of therapy development. Iron loading of TAMs can achieve such reprogramming correlating with an improved prognosis in lung cancer patients. We previously showed that superparamagnetic iron oxide nanoparticles containing core-cross-linked polymer micelles (SPION-CCPMs) target macrophages and stimulate pro-inflammatory activation. Here, we show that SPION-CCPMs stimulate TAMs to secrete reactive nitrogen species and cytokines that exert tumoricidal activity. We further show that SPION-CCPMs reshape the immunosuppressive Eml4-Alk lung tumor microenvironment (TME) toward a cytotoxic profile hallmarked by the recruitment of CD8+ T cells, suggesting a multifactorial benefit of SPION-CCPM application. When intratracheally instilled into lung cancer-bearing mice, SPION-CCPMs delay tumor growth and, after first line therapy with a TKI, halt the regrowth of relapsing tumors. These findings identify SPIONs-CCPMs as an adjuvant therapy, which remodels the TME, resulting in a delay in the appearance of resistant tumors.

Cannabidiol induces ERK activation and ROS production to promote autophagy and ferroptosis in glioblastoma cells

Small molecule-driven ERK activation is known to induce autophagy and ferroptosis in cancer cells. Herein the effect of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, on ERK-driven autophagy and ferroptosis has been demonstrated in glioblastoma (GBM) cells (U87 and U373 cells). CBD imparted significant cytotoxicity in GBM cells, induced activation of ERK (not JNK and p38), and increased intracellular reactive oxygen species (ROS) levels. It increased the autophagy-related proteins such as LC3 II, Atg7, and Beclin-1 and modulated the expression of ferroptosis-related proteins such as glutathione peroxidase 4 (GPX4), SLC7A11, and TFRC. CBD significantly elevated the endoplasmic reticulum stress, ROS, and iron load, and decreased GSH levels. Inhibitors of autophagy (3-MA) and ferroptosis (Fer-1) had a marginal effect on CBD-induced autophagy/ferroptosis. Treatment with N-acetyl-cysteine (antioxidant) or PD98059 (ERK inhibitor) partly reverted the CBD-induced autophagy/ferroptosis by decreasing the activation of ERK and the production of ROS. Overall, CBD induced autophagy and ferroptosis through the activation of ERK and generation of ROS in GBM cells.

Sustainable efficient utilization of magnetic porous biochar for adsorption of orange G and tetracycline: Inherent roles of adsorption and mechanisms

Iron-doped biochar has been widely used as an adsorbent to remove contaminants due to the high adsorption performance, but it still suffers from complicated preparation methods, unstable iron loading, unsatisfactory specific surface area, and uneven distribution of active sites. Here, a novel magnetic porous biochar (FeCS800) with nanostructure on surface was synthesized by one-pot pyrolysis method of corn straw with K2FeO4, and used in orange G (OG) and tetracycline (TC) adsorption. FeCS800 exhibited outstanding adsorption capacities for OG and TC after K2FeO4 activation and the adsorption data were fitted satisfactorily to Langmuir isotherm and Pseudo-second-order kinetic model. The maximum adsorption capacities of FeCS800 for OG and TC were around 303.03 mg/g and 322.58 mg/g, respectively, at 25 °C and pH 7.0, which were 16.27 and 24.61 times higher than that before modification. Thermodynamic studies showed that the adsorption of OG/TC by FeCS800 were thermodynamically favorable and highly spontaneous. And the adsorption capacity of OG and TC by FeCS800 remained 77% and 81% after 5 cycles, respectively, indicating that FeCS800 had good stability. The outstanding adsorption properties and remarkable reusability of FeCS800 show its great potential to be an economic and environmental adsorbent in contaminants removal.

Mechanism study of toluene removal using iron/nickel bimetallic catalysts supported on biochar

The present study utilized rice husk biomass as a carrier to synthesize rice husk biochar loaded with iron and nickel. Mono-metallic and bimetallic catalysts were prepared for the removal of toluene as the tar model. The efficiency of the catalysts for the removal of toluene was investigated, and finally, the removal mechanisms of mono-metallic and bimetallic catalysts for toluene were revealed. The experimental results showed that the bimetallic-loaded biochar catalysts had excellent toluene removal performance, which was closely related to the ratio of loaded Fe and Ni. Among them, the catalyst DBC–Fe2.5 %-Ni2.5 % (2.5 wt% iron loading and 2.5 wt% nickel loading) obtained through secondary calcination at 700 °C achieved the highest toluene removal efficiency of 92.76 %. The elements of Fe and Ni in the catalyst were uniformly dispersed on the surface and in the pores of the biochar, and the catalyst had a layered structure with good adsorption. Under the interaction of Fe and Ni, the agglomeration and sintering of Ni were reduced, and the surface acidity of the catalyst was increased, the surface acidity was favorable for toluene removal. The iron‑nickel catalyst did not form significant alloys when calcined at 400 °C, whereas strong metal interactions occurred at 700 °C, resulting in the formation of Fe0.64Ni0.36 alloy and NiFe2O4 alloy. This NiFe alloy had abundant active sites to enhance the catalytic cracking of toluene and provide lattice oxygen for the reaction. Furthermore, the functional groups on the catalyst surface also had an impact on toluene removal. The catalyst prepared in this paper reduces the cost of tar removal, can be applied to the removal of industrial pollutant tars, reduces the pollution of the environment, and provides theoretical guidance and technical reference for the efficient removal of tar.

The relationship between increased iron load and respiratory function tests in patients diagnosed with transfusion dependent thalassemia

Aims: Thalassaemia syndromes are the most common single gene disorders affecting more than 200 million people worldwide. Beta thalassaemia (BT) is the most common cause of transfusion-dependent thalassaemia (TDT). It has been reported in studies that iron accumulation occurs in the lungs, especially in the alveolo-capillary membrane, and the frequency of parenchymal disease increases in patients receiving frequent blood transfusions. In our study, we aimed to investigate whether there is a correlation between iron overload and pulmonary function in patients with TDT.
 Methods: The study included 61 patients aged between 18 and 45 years with a diagnosis of TDT who were followed up in the hematology clinic of our tertiary care center between 2018 and 2023. Based on spirometry measurements, the pattern of respiratory impairment was defined and correlated with serum ferritin levels. 
 Results: The mean age of the 61 patients included in the study was 24.83±6.02 years and 33 were female and 28 were male. The mean ferritin value was 3150.88±2553.51 ng/ml. The annual number of transfusions was 15.39±1.90. According to the PFT results, mean FVC % value was 81.59±9.28, mean FEV1 % value was 82.11±7.6, mean FEV1/FVC % value was 102.55±7.63. Mean ferritin values were found to be significantly higher in patients diagnosed with TDT with restrictive lung pattern (p=0.004). 
 Conclusion: Our study showed that high ferritin levels are related to increased restrictive lung disease in the adult age group.

Effects of iron-alginate ratios and pHs of gelation on characteristics of iron bead encapsulation

Encapsulation is one of the methods to protect iron from oxidation. Among the encapsulation methods, gelation could be the simplest one. This method requires the matrix which could form a gel. Alginate fulfills the requirements as an encapsulant by creating beads. However, performances of the encapsulation are determined by the conditions of the gelation process. The aim of this study was to study the effect of the iron -alginate ratios (0.05-0.5, w/w) and pHs of gelation (5-10) on the properties of alginate beads for iron encapsulation. CaCl2 solution was used as a cross-linked agent to form beads. Solution of iron-alginate was dropped into CaCl2 solution (150 mL, 1 M) using 5- mL unneedled syringe from about 5 cm above the cross-linked solution surfaces. The results showed that the ratio of iron-alginate and pH have a negative correlation with moisture content, diameter beads, and encapsulation efficiency but iron loading. Neutral pH-gelation produced softer bead texture. The highest efficiency encapsulation was found in pH 5 of gelation. Release of iron was higher in pH 6.8 than that in pH 1.2. Increase in iron-alginate ratio led to have more syneresis effect. However, higher pH-gelation tended to have lower syneresis.

Targeting SIRT1, NLRP3 inflammasome, and Nrf2 signaling with chrysin alleviates the iron-triggered hepatotoxicity in rats

Blood transfusion-requiring diseases such as sickle cell anemia and thalassemia are characterized by an imbalance between iron intake and excretion, resulting in an iron overload (IOL) disorder. Hepatotoxicity is prevalent under the IOL disorder because of the associated hepatocellular redox and inflammatory perturbation. The current work was devoted to investigate the potential protection against the IOL-associated hepatotoxicity using chrysin, a naturally-occurring flavone. IOL model was created in male Wistar rats by intraperitoneal injection of 100 mg/kg elemental iron subdivided on five equal injections; one injection was applied every other day over ten days. Chrysin was administered in a daily dose of 50 mg/kg over the ten-day iron treatment period. On day eleven, blood and liver samples were collected and subjected to histopathological, biochemical, and molecular investigations. Chrysin suppressed the IOL-induced hepatocellular damage as revealed by decreased serum activity of the intracellular liver enzymes and improved liver histological picture. Oxidative damage biomarkers, and pro-inflammatory cytokines were significantly suppressed. Mechanistically, the levels of the redox and inflammation-controlling proteins SIRT1 and PPARγ were efficiently up-regulated. The liver iron load, NLRP3 inflammasome activation, and NF-κB acetylation and nuclear shift were significantly suppressed in the iron-intoxicated rats. Equally important, the level of the antioxidant protein Nrf2 and its target HO-1 were up-regulated. In addition, chrysin significantly ameliorated the IOL-induced apoptosis as indicated by reduction in caspase-3 activity and modulation of BAX and Bcl2 protein abundance. Together, these findings highlight the alleviating activity of chrysin against the IOL-associated hepatotoxicity and shed light on the role of SIRT1, NLRP3 inflammasome, and Nrf2 signaling as potential contributing molecular mechanisms.

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19

Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.

Lizhong decoction ameliorates ulcerative colitis by inhibiting ferroptosis of enterocytes via the Nrf2/SLC7A11/GPX4 pathway

Ethnopharmacology relevanceTraditional herbal medicines have been considered as a novel and effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed of Zingiber officinale Rosc., Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., and Glycyrrhiza uralensis Fisch., has been used to treat gastrointestinal disorders in clinical practices for thousands of years. However, the mechanism of LZD in alleviating ulcerative colitis (UC) is still unclear. Aim of the studyThe purpose of this study was to clarify the potential molecular mechanism of LZD in improving UC. Materials and methodsThe amelioration of LZD on dextran sodium sulfate (DSS)-induced UC mice was evaluated by body weight, colon length, pathology of colon tissues, pro-inflammatory cytokines, and intestinal tight junction (TJ) proteins. Moreover, the gene expression profiles of UC patients were extracted to investigate potential pathological mechanisms of UC. The influence of LZD on ferroptosis was analyzed by iron load, malondialdehyde (MDA), and the expression of ferroptosis-associated proteins. Meanwhile, the inhibition of LZD on oxidative stress (OS) was assessed by the superoxide dismutase (SOD) activity, as well as the expression levels of glutathione (GSH) and glutathione disulfide (GSSG). Furthermore, the influence of LZD on ferroptosis was assessed by inhibiting nuclear factor (erythroid-derived-2)-like 2 (Nrf2). ResultsLZD showed significant therapeutic effects in UC mice, including reduction of intestinal injury and inflammation. Moreover, LZD treatment notably upregulated the expression of TJ proteins. Further investigation indicated that LZD significantly inhibited the ferroptosis of enterocytes by decreasing iron load and MDA, and increasing the expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in colon tissues. Furthermore, the decreased activity of SOD, reduced level of GSH, and increased content of GSSG in UC mice were notably reversed by LZD. Consistent with in vivo results, LZD could markedly inhibit ferroptosis and OS in RSL3-induced Caco-2 cells. Mechanistically, LZD alleviated ferroptosis by suppressing OS through the activation of Nrf2 signaling. ConclusionsCollectively, LZD remarkably improved intestinal pathological injury in UC mice, and its potential mechanism was the suppression of ferroptosis in enterocytes by the Nrf2/SLC7A11/GPX4 pathway.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

An iron rheostat controls hematopoietic stem cell fate

Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.

A Deep Insight into Perfluorooctanoic Acid Photodegradation Using Metal Ion-Exchanged Zeolites.

Treating perfluorooctanoic acid (PFOA) in an aqueous environment is problematic due to its low concentration and its high resistance to biological and chemical degradation. To tackle this challenge, combinations of pre-enrichment and photodegradation processes are promising solutions. In this work, we investigated metal ion-exchanged zeolites as adsorbents and photocatalysts for PFOA treatment. Among various transition metal ion-exchanged BEA zeolites, Fe-exchanged BEA (Fe-BEA) zeolites showed significant activity for the photodegradation of PFOA. The isolated iron species in Fe-BEA zeolite are responsible for PFOA photodegradation, whereas other iron species present from excess iron loading in the zeolite will lower its photocatalytic activity. Furthermore, it was proved via size exclusion tests using branched PFOA isomers that the photodegradation of PFOA took place on the internal surface rather than the external surface of Fe-BEA zeolite. Photodegradation of PFOA was also tested to be effective with Fe-exchanged BEA-type zeolites having various SiO2/Al2O3 ratios, but ineffective with FAU-type zeolites. The optimal Fe-BEA zeolite showed a sorption coefficient Kd of 6.0 × 105 L kg-1 at an aqueous phase PFOA concentration of 0.7 μg L-1 and a PFOA half-life of 1.8 h under UV-A irradiation. The presented study offers a deeper understanding of the use of metal ion-exchanged zeolites for photodegradation of PFOA.

Elaborate cooperation of poly(rC)-binding proteins 1/2 and glutathione in ferroptosis induced by plasma-activated Ringer's lactate

Reactive species are involved in various aspects of neoplastic diseases, including carcinogenesis, cancer-specific metabolism and therapeutics. Non-thermal plasma (NTP) can directly provide reactive species, by integrating atmospheric and interjacent molecules as substrates, to represent a handy strategy to load oxidative stress in situ. NTP causes apoptosis and/or ferroptosis specifically in cancer cells of various types. Plasma-activated Ringer's lactate (PAL) is another modality at the preclinical stage as cancer therapeutics, based on more stable reactive species. PAL specifically kills malignant mesothelioma (MM) cells, employing lysosomal ·NO as a switch from autophagy to ferroptosis. However, the entire molecular mechanisms have not been elucidated yet. Here we studied cytosolic iron regulations in MM and other cancer cells in response to PAL exposure. We discovered that cells with higher catalytic Fe(II) are more susceptible to PAL-induced ferroptosis. PAL caused a cytosolic catalytic Fe(II)-associated pathology through iron chaperones, poly (rC)-binding proteins (PCBP)1/2, inducing a disturbance in glutathione-regulated iron homeostasis. PCBP1/NCOA4-mediated ferritinophagy started at a later phase, further increasing cytosolic catalytic Fe(II), ending in ferroptosis. In contrast, PCBP2 after PAL exposure contributed to iron loading to mitochondria, leading to mitochondrial dysfunction. Therapeutic effect of PAL was successfully applied to an orthotopic MM xenograft model in mice. In conclusion, PAL can selectively sensitize MM cells to ferroptosis by remodeling cytoplasmic iron homeostasis, where glutathione and PCBPs play distinct roles, resulting in lethal ferritinophagy and mitochondrial dysfunction. Our findings indicate the clinical application of PAL as a ferroptosis-inducer and the potential of PCBPs as novel targets in cancer therapeutics.