Fe Increase Research Articles

Crocin Protects the 661W Murine Photoreceptor Cell Line against the Toxic Effects of All-Trans-Retinal.

Age-related macular degeneration (AMD) is a common disease contributing to vision loss in the elderly. All-trans-retinal (atRAL) is a retinoid in the retina, and its abnormal accumulation exhibits toxicity to the retina and promotes oxidative stress-induced photoreceptor degeneration, which plays a crucial role in AMD progression. Crocin is a natural product extracted from saffron, which displays significant antioxidant and anti-inflammatory effects. The present study elucidates the protective effects of crocin on photoreceptor cell damage by atRAL and its potential mechanisms. The results revealed that crocin significantly attenuated cytotoxicity by repressing oxidative stress, mitochondrial injury, and DNA damage in atRAL-loaded photoreceptor cells. Moreover, crocin visibly inhibited DNA damage-induced apoptosis and gasdermin E (GSDME)-mediated pyroptosis in photoreceptor cells after exposure to atRAL. It was also observed that crocin distinctly prevented an increase in Fe2+ levels and lipid peroxidation caused by atRAL via suppressing the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway, thereby ameliorating photoreceptor cell ferroptosis. In short, these findings provide new insights that crocin mitigates atRAL-induced toxicity to photoreceptor cells by inhibiting oxidative stress, apoptosis, pyroptosis, and ferroptosis.

Inhibition of Phosphodiesterase 4 Suppresses Neuronal Ferroptosis After Cerebral Ischemia/Reperfusion.

We have previously shown that inhibition of phosphodiesterase 4 (PDE4) protects against cerebral ischemia/reperfusion injury. However, it remains unclear whether and how PDE4 affects ferroptosis under cerebral ischemia/reperfusion conditions. In this study, we found that overexpression of PDE4B in HT-22 cells exacerbated the detrimental effects of oxygen-glucose deprivation/reoxygenation (OGD/R), including a decrease in cell viability and glutathione (GSH) levels and an increase in Fe2+ content. PDE4B knockdown mitigated the effects of OGD/R, as evidenced by decreased oxidative stress, lactate dehydrogenase (LDH) release, Fe2+ content, and nuclear receptor coactivator 4 (NCOA4) expression. PDE4B knockdown also enhanced the levels of GSH, ferroportin (FPN), and ferritin heavy chain 1 (FTH1). Consistently, inhibition of PDE4 by roflumilast (Roflu) produced similar effects as PDE4B knockdown. Roflu also ameliorated the morphology and membrane potential of the mitochondria. Glutathione peroxidase 4 (GPX4) knockdown blocked the effects of Roflu on cell viability and lipid peroxidation. Moreover, we found that nuclear factor erythroid 2-related factor 2 (Nrf-2) knockdown decreased GPX4 expression. In addition, Nrf-2 knockdown led to enhanced lipid peroxidation, LDH release, and iron levels, while the GSH and FPN levels decreased. More crucially, PDE4 inhibition decreased infarct volume, alleviated oxidative stress, and restored the expression levels of ferroptosis-associated proteins in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Interestingly, the GPX4 inhibitor RSL3 blocked the neuroprotective effects of Roflu in rats subjected to MCAO/R. Thus, PDE4 inhibition significantly inhibits neuronal ferroptosis by activating the Nrf-2/GPX4 pathway. These data indicate the existence of a novel mechanism underlying the neuroprotective effects of PDE4 inhibition.

Experimental constraints on iron and sulfur redox equilibria and kinetics in basaltic melt inclusions

The oxidation states of dissolved iron (Fe) and sulfur (S) in silicate melts were studied experimentally by heating Hawaiian olivines containing S-bearing melt inclusions (MIs) in a 1 atm gas-mixing furnace. The MIs are closed with respect to S and C, but equilibrate with the oxygen fugacity (ƒO2) and water fugacity (ƒH2O) of the furnace. We also conducted experiments using a S-free synthetic Hawaiian MI composition held on Pt-loops. Experiments were run at 1225 °C for 8–96 hr in H2-CO2 gas mixtures corresponding to ƒO2 values that varied over seven orders of magnitude and then drop-quenched into water. Time-series experiments show that MI Fe3+/Fe2+ and S6+/S2− ratios reached constant values within ∼24 hr. The H2O contents of the Pt-loop glasses and the dehydrated MIs overlap and are proportional to the fH2O in the furnace gas. The slope of log10(Fe3+/Fe2+) vs. log10ƒO2 is 0.25±0.02(2σ) for the Pt-loop glasses and 0.23±0.01(2σ) for the quenched MIs; the slopes of the two sets of experiments are consistent with equilibrium having been reached via the reaction FeO + ¼ O2 = FeO1.5. S-bearing quenched MI glasses have Fe3+/Fe2+ ratios that are systematically low compared to ratios measured in the S-free Pt-loop glasses run at the same T and ƒO2; this may reflect an effect of S on Fe3+/Fe2+, although further experiments are needed to explore this possibility. S6+/S2− ratios in the experimental melt inclusions vary systematically as a function of ƒO2, and the measured ratios agree with independent calculations of S oxidation state in basaltic melts.After being held at 1225 °C for 24 or 48 hr, a subset of olivine-hosted MIs were cooled at rates of 1700–40,000 °C/hr and quenched at temperatures between 900 °C and 1150 °C to explore whether Fe and S speciation are modified during cooling. Fe and S speciation in isothermal and cooled MIs held initially at the same ƒO2 overlap within uncertainty, suggesting that the T dependence of the homogeneous reaction 8Fe3+ + S2− = 8Fe2+ + S6+ is small and/or its kinetics are sluggish relative to cooling rates required to quench basaltic liquids to glasses. The centers of unheated, naturally quenched MIs from Papakōlea, Hawaii with syneruptive cooling rates ranging from ∼50 to 12,000 °C/hr were also measured for Fe and S speciation. MIs that experienced the lowest cooling rates have higher Fe3+/Fe2+ and S6+/S2− ratios relative to rapidly cooled inclusions of comparable size. The increase in Fe3+/Fe2+ is due to olivine crystallization on the inclusion walls during cooling and diffusion of the resulting oxidized boundary layer into MI interiors. Diffusive modification is minimized in MIs that have been rapidly cooled and/or are sufficiently large such that the oxidized boundary layer is restricted to a narrow region adjacent to the inclusion walls. Our experiments and their comparison to naturally quenched MIs show that measurements of Fe3+/Fe2+ and S6+/S2− ratios in quenched basaltic glasses and in the centers of rapidly cooled and/or large MIs are likely to be representative of the redox state in the melt at magmatic temperatures prior to quenching to glass.

Biogeochemical changes during supercritical CO2–H2O-coal-microorganism interaction

A 100-day scCO2-H2O-coal-microorganism interaction experiment was conducted in this study to explore the biogeochemical changes during the supercritical CO2 (scCO2) storage in deep water-bearing coal seams. Compared to a control experiment without microorganisms, the presence of microorganisms resulted in a slightly increase in pH but a marked reduction in oxidation-reduction potential (ORP). An increase in Fe2+ ions and decrease in SO42− ions in the experimental group were found to be closely related to microbial mediation, potentially leading to an increase in secondary pyrite. Networked biofilms and N-acetyl-L-leucine as a leucine derivative were only appeared in the experimental group, indicating microbial growth and metabolism. Microbial activities increased the dissolved organic carbon (DOC), accelerated the accumulation of aromatic organic compounds, and diminished macromolecular organic compounds. After scCO2 injection, microbial number and diversity exhibited a sharp decline and gradual recovery. The dominant Clostridium sensu stricto 13 (>50%), Desulfohalotomaculum (>20%) and norank Desulfallas-Sporotomaculum (>9%) may play important roles in the biogeochemical processes of Fe and S through cooperative relationships. Microbial communities resisted scCO2-H2O stress through diversified defense strategies such as spore formation, enhanced leucine metabolism level, and extracellular polymeric substances (EPS) secretion. The recovery of the number and activity of methanogens indicated potential for the biomethanation of sequestered CO2.

The effect of trace Fe3+ on the magneto-optical properties of Tb3+ doped B2O3-GeO2-Al2O3-ZnO-BaO glass

Magnetic particles of BaFe12O19 were synthesized using a high-temperature solid-phase method. Magneto-optical glass samples were prepared by incorporating different concentrations of Fe3+ ions (ranging from 0 to 0.25 mol%) into the glass matrix with a constant doping of Tb2O3 (30 mol%) using a high-temperature melting method. The glasses are composed of B2O3-GeO2-Al2O3-ZnO-BaO-Tb2O3 (BGAZBa-T30-xFe). The effects of varying Fe3+ ion concentrations on the structure, physical properties, and magneto-optical performance of BGAZBa-T30 glass were investigated. The study reveals that the density and magneto-optical properties of the glass are enhanced with the increase of Fe3+ ion concentration. When the Fe3+ ion concentration reaches 0.20 mol%, the Verdet constant of BGAZBa-T30 glass increases from −82.51 rad/(T·m) to −91.90 rad/(T·m) at an incident light wavelength of 633 nm. Meanwhile, the density rises from 4.93 g/cm3 to 4.98 g/cm3. Notably, the BGAZBa-T30-0.20Fe glass sample exhibits excellent magneto-optical performance, with a Verdet constant value of −142.50 rad/(T⋅m) at an incident light wavelength of 515 nm, which is 1.2 times that of the glass matrix main body (−118.28 rad/(T·m)). This presents potential research value in the field of optoelectronic functionality.

Study on the repair behavior of passive film of iron-based amorphous coatings by eco-friendly phosphate inhibitors

The passivation ability of the coating can be improved by adjusting the elements proportion in the Iron-based Amorphous Coating and the spraying process, but the process is complicated and costly. In this study, it was found for the first time that Iron-based Amorphous Coatings can quickly form passive films in phosphate atmosphere, which simplifies the coating strengthening process. Electrochemical measurements, XPS, AFM, FTIR, and SEM-EDS were used to investigate the inhibition mechanism of eco-friendly phosphates on the dynamic dissolution of passive film of Fe-based amorphous coating. When the coating was soaked in 3.5 wt% NaCl + 0.1 M solution, the iron phosphate compound on the coating surface promoted the repair and growth of the passive film, and the film thickness increased by more than 32.9 %. The increase of Fe2+/Fe3+ and (O2-+H2O)/OH- in the passive film means that more insoluble Fe-Cr compound growth significantly reduces the donor density (Nd) in the passive film and inhibits the degradation rate of the passive film in the corrosive environment.

Application of green tea residue-derived carbon dots in the detection of Fe3+ ions and imaging of Caco-2 cells

In this study, we successfully synthesized green luminescent carbon dots by using green tea residue as the precursor of carbon source. Based on the internal filter effect (IFE), the fluorescence emission intensity of the probe decreased significantly with the increase of Fe3 + concentration. Based on this, a linear relationship between Fe3 + concentration and the fluorescence emission intensity of the probe was established to semi-quantitatively detect Fe3 +. The results showed that the linear range was 1–400 μM, and the detection limit was 3.58 μM. In addition, the probe was further applied to actual samples, and it was found that the recovery rate was between 97.75% and 104.59%, and the relative standard deviation was below 1.81%. These findings underscore the considerable potential of the carbon dots for practical Fe3+ detection applications. In a further application, the fluorescent carbon dots were diluted and directly employed to stain Caco-2 cells. Remarkably, even after 10 and 20-fold dilutions, the Caco-2 cells displayed vivid fluorescence at the green excitation wavelength. This outcome suggests a promising avenue for the application of fluorescent carbon dots in the field of biology.

Shape Memory Polyurethane Composite With Fast Response to Near-Infrared Light Based on Tannic Acid-Iron and Dynamic Phenol-Carbamate Network.

Intelligent materials derived from green and renewable bio-based materials garner widespread attention recently. Herein, shape memory polyurethane composite (PUTA/Fe) with fast response to near-infrared (NIR) light is successfully prepared by introducing Fe3+ into the tannic acid-based polyurethane (PUTA) matrix through coordination between Fe3+ and tannic acid. The results show that the excellent NIR light response ability is due to the even distribution of Fe3+ filler with good photo-thermal conversion ability. With the increase of Fe3+ content, the NIR light response shape recovery rate of PUTA/Fe composite films is significantly improved, and the shape recovery time is reduced from over 60 s to 40s. In addition, the mechanical properties of PUTA/Fe composite film are also improved. Importantly, owing to the dynamic phenol-carbamate network within the polymer matrix, the PUTA/Fe composite film can reshape its permanent shape through topological rearrangement and show its good NIR light response shape memory performance. Therefore, PUTA/Fe composites with high content of bio-based material (TA content of 15.1-19.4%) demonstrate the shape memory characteristics of fast response to NIR light; so, it will have great potential in the application of new intelligent materials including efficient and environmentally friendly smart photothermal responder.

DMSO-mediated ag lateral coated Au nanobipyramids: Ultrafast colormetric detection platform for Fe3+ with uniform etching

Colorimetric detection by etching based on metal nanoparticles is one of the most commonly portable detection methods, but there are problems such as poor particle controllability and irregular etching. In this paper, a novel Ag lateral coated Au nanobipyramids nanostructure (Au@Ag LCNBPs) for multi-colorimetric detection of Fe3+ is prepared through the mediation of dimethyl sulfoxide (DMSO). When DMSO is used to cover the surface of Au nanobipyramids (Au NBPs), it greatly affects the way Ag coated Au NBPs. When the volume ratio of DMSO is 25%, Ag is no longer deposited at the tip, but gradually deposited on the side of the Au NBPs to form the Au@Ag LCNBPs. The long axis cross-section of the Au@Ag LCNBPs takes the shape of a hexagon. As the Ag content increases, the width of the Ag layer gradually increases, the cross-section gradually converts to a positive hexagonal shape, and the aspect ratio of the whole structure decreases, leading to the blueshift of the longitudinal LSPR peak. This mode of deposition is different from the longitudinal deposition reported in the previous literature. A multi-colorimetric detection method for Fe3+ using the etching of the Ag layer by Au@Ag LCNBPs has been developed. This method exhibits a good exponential correlation in the concentration range of 1–210 μM with the detection limit of 200 nM. With the increase of Fe3+, the colloid color shows the change of yellow, orange, red, purple, blue, green and colorless. The etching process can be completed in about 30 s. This nanostructure achieves two etching modes of the Ag layer by Fe3+, uniform etching and concave etching. Moreover, it demonstrates that the enormous potential of Au@Ag LCNBPs in colorimetric etching detection.

Butylated hydroxyanisole induces vascular endothelial injury via TFEB-mediated degradation of GPX4 and FTH1

Butylated hydroxyanisole (BHA) is one of the most commonly used antioxidants and is widely used in food, but whether it causes vascular damage has not been clearly studied. The present study demonstrated for the first time that BHA reduced the viability of human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (BEND3) in a dose- and time-dependent manner. Moreover, BHA inhibited the migration and proliferation of vascular endothelial cells (ECs). Further analysis revealed that in ECs, the ferroptosis inhibitor ferrostatin-1 (Fer-1) reversed the BHA-induced increase in Fe2+ and malonaldehyde (MDA) levels. Acridine orange staining demonstrated that BHA increased lysosomal permeability. At the protein level, BHA increased the expression of transcription factor EB (TFEB) and decreased the expression of glutathione peroxidase (GPX4), solute carrier family 7 member 11 (SLC7A11, xCT), and ferritin heavy chain 1 (FTH1). Moreover, these effects of BHA could be reversed by knocking down TFEB. In vivo experiments confirmed that BHA caused elevated pulse wave velocity (PWV) and reduced acetylcholine-dependent vascular endothelial diastole. In conclusion, BHA degrades GPX4, xCT, and FTH1 through activation of the TFEB-mediated lysosomal pathway and promotes ferroptosis, ultimately leading to vascular endothelial cell injury.

Metasomatic ijolite, glimmerite, silicocarbonatite, and antiskarn formation: carbonatite and silicate phase equilibria in the system Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–O2–CO2

Silicocarbonatites are carbonatite rocks containing > 20% silicate minerals. Their formation is not well understood due to low silica solubility in carbonatite melts and negligible amounts of silicate minerals on carbonatite melt cotectics at upper crustal conditions. We explore whether silicocarbonatites can be thought of as antiskarns: rocks formed by leaching of SiO2 from siliceous wall rocks by carbonatite melts, and its deposition as solid silicate minerals by reaction with chemical components already present in the carbonatite melt. Solid state thermodynamic modelling at 1–5 kbar and 500–800 °C predicts that calcite–dolomite–magnetite assemblages will transform to dolomite-free silicocarbonatites with an increase in silica contents. In sodic systems, the formation of aegirine and alkali amphiboles suppresses silica activity despite elevated silica contents. Therefore, dolomite remains stable, but Fe3+ is consumed, firstly from magnetite breakdown, and secondly by coupled Fe oxidation and reduction of CO2 to CO, CH4, and graphite, particularly at higher pressures. Despite a net increase in Fe3+/Fe2+, the system evolves to increasingly lower oxygen fugacity. In aluminous systems, nepheline indicates high temperatures whereas alkali feldspars form at lower temperatures. Modelling of potassic systems demonstrates stability of mostly phlogopite-rich biotites, leading to Fe2+ increase in all other carbonate and silicate phases. We find that perthites are expected in high pressures whereas two feldspars are more likely in lower pressures.Aspects of the clinopyroxene natural compositional trend (diopside to hedenbergite to aegirine) of carbonatite systems can be explained by silica contamination. Ferrous clinopyroxenes typically require low alumina and are predicted in potassic or low temperature sodic systems, primarily at mid to high pressures. Silica contamination permits the formation of silicocarbonatite-like assemblages in a way that is not limited by SiO2 solubility in carbonatite melts. Glimmerites and clinopyroxene-rich rocks (such as the ijolite series) that often occur around carbonatite rocks at the contact with silica-oversaturated wall rocks can be explained as the extreme end of silica contamination of carbonatite melts. Therefore, these clinopyroxenites and glimmerites can form solely via metasomatic processes without the presence of a silicate melt.

Fluorescent Paper Based on CQDs/Rhodamine B: A Ratio and Sensitive Detection Platform for On-Site Fe3+ Sensing.

Fluorescent sensors with single reading are generally subject to unpredictable disturbs from environmental and artificial factors. In order to overcome this barrier of detection reliability, a paper-based optical sensor with proportional fluorescence was established and further combined with a smartphone for visual, on-site and quantitative detection of Fe3+, which affects the color, smell and taste of water, and endangers the health of plants and animals. The ratio fluorescent probe was fabricated by rhodamine B and carbon quantum dots derived from xylan. The red fluorescence of rhodamine B was inert to Fe3+, which was referred to as background. And blue emitting carbon quantum dots functioned as signal report units, which would be quenched by Fe3+ and make the fluorescence of the ratio probe change from purple to red. The quantitative detection of Fe3+ was conducted by investigating the RGB value of fluorescent images with a smartphone. With the increase of Fe3+ concentration, the R/B (red/blue) value of the fluorescent paper gradually increased. The linear detection range was 10-180 μM, and the limit of detection was 198.2 nM. The application of ratio fluorescent paper with a smartphone provides a facile method for the rapid detection of ions.

Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc--GSH-GPX4 signaling pathway in ferroptosis response.

Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc--GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity.

Icariin‑curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO‑1 signaling.

Ferroptosis is a form of regulatory cell death that relies on iron and reactive oxygen species (ROS) to inhibit tumors. The present study aimed to investigate whether icariin-curcumol could be a novel ferroptosis inducer in tumor inhibition. Various concentrations of icariin-curcumol were used to stimulate prostate cell lines (RWPE-2, PC-3, VCAP and DU145). Small interfering negative control (si-NC) and si-nuclear factor erythroid 2-related factor 2 (Nrf2) were used to transfect DU145 cells. Cell viability was determined by using cell counting kit-8. Ferroptosis-related factor levels were analyzed using western blotting and reverse transcription-quantitative PCR. Enzyme-linked immunosorbent assays were used to assess the ferrous (Fe2+), glutathione and malondialdehyde (MDA) content. The ROS fluorescence intensity was assessed using flow cytometry. DU145 cells were most sensitive to icariin-curcumol concentration. The Fe2+ content, ROS fluorescence intensity and MDA level gradually increased, while solute carrier family 7 member 11 (SLC7A11) level, glutathione peroxidase 4 (GPX4) level, GSH content, Nrf2 and heme oxygenase-1 (HO-1) decreased with icariin-curcumol in a dose-dependent manner. After si-Nrf2 was transfected, the cell proliferation ability, SLC7A11 and GPX4 levels declined compared with the si-NC group. In contrast to the control group, the icariin + curcumol group showed reductions in Nrf2 and HO-1 levels, cell proliferation, SLC7A11 and GPX4 levels, with an increase in Fe2+ content and ROS fluorescence intensity. Overexpression of Nrf2 reversed the regulation observed in the icariin + curcumol group. Icariin-curcumol induced ferroptosis in PCa cells, mechanistically by inhibiting the Nrf2/HO-1 signaling pathway. Icariin-curcumol could be used as a new type of ferroptosis inducer to treat PCa effectively.

The relationship between iron redox states and H2O contents in back-arc basin basaltic glasses from the North Fiji Basin

Island-arc basalts (IAB) from convergent plate margins tend to have both higher iron oxidation states (higher Fe3+/Fe2+) and higher H2O contents than the mid-ocean ridge basalts (MORB) produced by seafloor spreading, which raises the question of whether these two characteristics are causally related. Back-arc basin basalts (BABB) may help with this question, in that they are products of seafloor spreading, like MORB, but sourced from supra-subduction mantle, like IAB. Here we examine the relationship between Fe3+/Fe2+ (determined by XANES spectroscopy) and H2O contents in BABB glasses from the North Fiji Basin (NFB). The glasses cover a range of compositions from 6.1 to 8.5 wt% MgO, and from 0.16 to 1.6 wt% H2O, and have also been analysed for trace elements and Sr-Nd-Pb-isotopes. Measured Fe3+/Fe2+ range from MORB-like to slightly higher values and are positively correlated with H2O and heavy-halogen contents (Cl, Br and I). The correlation is due to lower Fe2+ rather than higher Fe3+ compared to the MORB array. This suite of BABBs is not significantly enriched in trace elements other than H2O and the heavy halogens, with MORB-like Ba/Th and other incompatible-element ratios, suggesting that the H2O and halogens may have come from dehydration of subducted lithospheric serpentinites under subsolidus conditions. Na2O is unusually variable for a suite of samples from such a limited area, and is not correlated with H2O, precluding a relationship between H2O and degree of melting. The link between H2O and low Fe2+ may be explained by H2O-rich fluids entering the transcrustal magma plumbing system, where they increase the proportion of olivine and augite to plagioclase crystallizing during the crustal evolution of the magmas. In this situation, relatively small additions of H2O can have an enhanced effect on major-element chemistry if the crustal evolution proceeds by cycles of replenish-mix-tap-crystallize (RMTX) rather than by simple fractional crystallization without repeated replenishment and tapping. The absence of any increase in Fe3+ with H2O, together with the lack of any correlation between H2O and Fe3+/Fe2+ in MORB glasses generally, suggest that various mechanisms, including more extensive olivine fractionation, were responsible for elevating Fe3+/Fe2+ in H2O-rich basalts from convergent margin settings. Proxy methods based on concentrations of elements with redox-variable partition coefficients (V, Eu) are not sensitive enough to record the subtle variations in Fe3+/Fe2+ observable by XANES spectroscopy.

Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy

Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mechanism is not clear. Ferroptosis is involved in the pathgenesis of many diseases, including IPF. Ferritinophagy is a form of cellular autophagy which regulates intracellular iron homeostasis. The function of DHA on myofibroblasts differentiation of pulmonary and whether related with ferroptosis and ferritinophagy are unknown now. Using human fetal lung fibroblast 1(HFL1) cell line and the qRT-PCR, immunofluorescent and Western blotting techniques, we found that after TGF-β1 treatment, the levels of ɑ-SMA expression and ROS increased; the mRNA and protein levels of FTH1 and NCOA4, the content of Fe2+ and 4-HNE increased significantly at 6h, then gradually reduced with time. After DHA treatment, FHL1 cells appeared ferroptosis; the levels of α-SMA mRNA and protein reduced and the levels of ROS and 4-HNE increased; the Fe2+ levels decreased sharply at 6h, then increased with time, and were higher than normal since 24h; the mRNA and protein levels of FTH1 and NCOA4 decreased, exhibited a downward trend. These results show that Fe2+, ROS and lipid peroxidation are involved in and ferritinophagy is inhibited during fibroblast-to-myofibroblast differentiation; The depletion of Fe2+ at early stage induced by DHA treatment triggers the ferritinophagy in HFL1 cells, leading to degradation of FTH1 and NCOA4 and following increase of Fe2+ levels. DHA may inhibit the fibroblast-to-myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy.

Role of circPSEN1 in carbon black and cadmium co-exposure induced autophagy-dependent ferroptosis in respiratory epithelial cells

Carbon black and cadmium (Cd) are important components of atmospheric particulate matter and cigarette smoke that are closely associated with the occurrence and development of lung diseases. Carbon black, particularly carbon black nanoparticles (CBNPs), can easily adsorbs metals and cause severe lung damage and even cell death. Therefore, this study aimed to explore the mechanisms underlying the combined toxicity of CBNPs and Cd. We found that the combined exposure to CBNPs and Cd promoted significantly greater autophagosome formation and ferroptosis (increased malonaldehyde (MDA), reactive oxygen species (ROS), and divalent iron ions (Fe2+) levels and altered ferroptosis-related proteins) compared with single exposure in both 16HBE cells (human bronchial epithelioid cells) and mouse lung tissues. The levels of ferroptosis proteins, transferrin receptor protein 1 (TFRC) and glutathione peroxidase 4 (GPX4), were restored by CBNPs-Cd exposure following treatment with a 3-MA inhibitor. Additionally, under CBNPs-Cd exposure, circPSEN1 overexpression inhibited increases in the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3II/I) and sequestosome-1 (P62). Moreover, increases in TFRC and Fe2+, and decreases in GPX4were inhibited. Knockdown of circPSEN1 reversed these effects. circPSEN1 interacts with autophagy-related gene 5 (ATG5) protein and upregulates nuclear receptor coactivator 4 (NCOA4), the co-interacting protein of ATG5, thereby degrading ferritin heavy chain 1 (FTH1) and increasing Fe2+ in 16HBE cells. These results indicated that the combined exposure to CBNPs and Cd promoted the binding of circPSEN1 to ATG5, thereby increasing autophagosome synthesis and ATG5-NCOA4-FTH1 axis activation, ultimately inducing autophagy-dependent ferroptosis in 16HBE cells and mouse lung tissues. This study provides novel insights into the toxic effects of CBNPs and Cd in mixed pollutants.

Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells.

Epidermal growth factor receptor substrate 15 (EPS15) is part of the EGFR pathway and has been implicated in various tumorigenesis. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an essential role in liver hepatocellular carcinoma (LIHC) by regulating the expression of proteins and genes. Through analysis of the cancer genome atlas (TCGA) database, we found that EPS15 is highly expressed in LIHC tissue, and lncRNA EPS15-antisense1 (EPS15-AS1) decreased in LIHC cell lines. However, the function of EPS15-AS1 in LIHC is still unknown. When EPS15-AS1 was overexpressed in HepG2 cell lines, the expression of EPS15 was reduced and cell activity and invasiveness were inhibited. In addition, we observed an increase in Fe2+ ion and lipid peroxidation after overexpression of EPS15-AS1, and further analysis showed that the susceptibility to ferroptosis increased. Aldo-keto reductase family 1 member B 1 (AKR1B1) belongs to the aldo/keto reductase superfamily and is involved in maintaining the cellular redox balance. Survival analysis revealed that patients with a higher level of AKR1B1 have a lower survival rate in the TCGA database. We also found that EPS15 enhanced the AKR1B1 expression in LIHC, and AKR1B1 had the ability to promote cell invasiveness. Moreover, overexpression of AKR1B1 alleviated the promoting effect of EPS15-AS1 on ferroptosis. Therefore, EPS15-AS1 can induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of EPS15 and AKR1B1 and disrupting the redox balance. EPS15 and AKR1B1 may serve as biomarkers for diagnosis and lncRNA EPS15-AS1 potential drug for LIHC.

Preparation of whey protein isolate-iron-curcumin ternary composite nanoparticles and investigation of formation mechanism

Whey protein isolate (WPI) exhibits mineral binding and acts as a potentially versatile carrier of the nutritional properties of curcumin. This study aimed to investigate the synthesis of WPI-Fe-Curcumin by combining iron and curcumin with WPI, to determine whether the antioxidant capacity of curcumin can protect the high-quality iron source Fe2+ when it binds to divalent iron ions, to describe the mechanism of WPI-Fe-Curcumin complex formation and to investigate the solubility stability of the complex. The results showed that (i) The iron content was 3.561 mg/g protein, and the encapsulation efficiency for curcumin was 99.98% efficiency. (ii) After dehydration, the high solubility of the WPI-Fe-Curcumin dry powder was 85.41% at 0 day and 82.84% at day 30. (iii) The addition of curcumin resulted in a 6.04% increase in Fe2+ content, indicating that curcumin provided an antioxidant reducing environment for the iron ions. (iv) The introduction of iron reduced the particle size and promoted the formation of β-sheet structures of whey protein. These results suggest that WPI-Fe-Curcumin can facilitate the development of effective nutrient delivery systems for applications in food, iron supplement, and pharmaceutical industries.