Establishing chronic models of age-related macular degeneration via long-term iron ion overload.

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Regulating Interlayer-Spacing of Vanadium Phosphates for High-Capacity and Long-Life Aqueous Iron-Ion Batteries.

Although the research on aqueous batteries employing metal as the anode is still mainly focused on the aqueous zinc-ion battery, aqueous iron-ion batteries are considered as promising aqueous batteries owing to the lower cost, higher specific capacity, and better stability. However, the sluggish Fe2+ (de)intercalation leads to unsatisfactory specific capacity and poor electrochemical stability, which makes it difficult to find cathode materials with excellent electrochemical properties. Herein, phenylamine (PA)-intercalated VOPO4 materials with expanded interlayer spacing are synthesized and applied successfully in aqueous iron-ion batteries. Owing to enough diffusion space from the expanded interlayer, which can boost fast Fe2+ diffusion, the aqueous iron-ion battery shows a high specific capacity of 170 mAh g-1 at 0.2 A g-1 , excellent rate performance, and cycle stability (96.2% capacity retention after 2200 cycles). This work provides a new direction for cathode material design in the development of aqueous iron-ion batteries.

Novel Bis-pyrazoline Fluorescent Probe for Cu2+ and Fe3+ Detection and Application in Cell Imaging.

A fluorescent probe Y((1,1'-([1,1'-biphenyl]-4,4'-diylbis(3-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazole-5,1-diyl)) bis(ethan-1-one))) was designed and synthesized, which could be used to Cu2+ and Fe3+ sensors. Through the study of optical properties, the probe Y shows good selectivity and sensitivity to Cu2+ and Fe3+ in aqueous tetrahydrofuran solution [10.0 mM HEPES, pH 7.4, THF-H2O = 9:1(v/v)] with has excellent anti-interference performance, and its detection limits were 0.931 uΜ for Cu2+ and 0.401uΜ for Fe3+. The coordination mechanism of probe Y with Cu2+ and Fe3+ was speculated and verified at DFT level and HRNM. By Hela cytotoxicity and imaging tests, probe Y not only has good biocompatibility, but also can be used for sensing Cu2+ in cells.

A smart paper-based electrochemical sensor for reliable detection of iron ions in serum.

The fast-growing healthcare demand for user-friendly and affordable analytical tools is driving the efforts to develop reliable platforms for the customization of therapy based on individual health conditions. In this overall scenario, we developed a paper-based electrochemical sensor for the quantification of iron ions in serum as a cost-effective sensing tool for the correct supplement administration. In detail, the working electrode of the screen-printed device has been modified with a nanocomposite constituted of carbon black and gold nanoparticles with a drop-casting procedure. Square wave voltammetry has been adopted as an electrochemical technique. This sensor was further modified with Nafion for iron quantification in serum after sample treatment with trifluoroacetic acid. Under optimized conditions, iron ions have been detected with a LOD down to 0.05 mg/L and a linearity up to 10 mg/L in standard solution. The obtained results have been compared with reference methods namely commercial colorimetric assay and atomic absorption spectroscopy, obtaining a good correlation within the experimental errors. These results demonstrated the suitability of the developed paper-based sensor for future applications in precision medicine of iron-deficiency diseases.

Fe3+-cysteine enhanced persulfate fenton-like process for quinclorac degradation: A wide pH tolerance and reaction mechanism.

A green, high-efficiency, and wide pH tolerance water remediation process has been urgently acquired for the increasingly exacerbating contaminated water. In this study, a Fe3+/persulfate (Fe3+/PS) system was employed and enhanced with a green natural ligand cysteine (Cys) for the degradation of quinclorac (QNC). The introduction of Cys into the Fe3+/PS system widened the effective pH range to 9 with a superior removal rate for QNC. The mechanism revealed that the Fe3+/Cys/PS system can enhance the ability of degrading QNC by accelerating the Fe3+/Fe2+ redox cycle, maintaining Fe2+ concentration and thereby generating more HO• and SO4•-. The impact factors (i.e., pH, concentrations of PS, Fe3+ and Cys) were optimized as well. This work provides a promising strategy with high catalytic activity and wide pH tolerance for organic contaminated water remediation.

Functionalized activated carbon as support for trypsin immobilization and its application in casein hydrolysis.

This study aimed to immobilize trypsin on activated carbon submitted to different surface modifications and its application in casein hydrolysis. With the aim of determining which support can promote better maintenance of the immobilized enzyme. Results showed that pH 5.0 was obtained as optimal for immobilization and pH 9.0 for the casein hydrolysis reaction for activated carbon and glutaraldehyde functionalized carbon. Among the supports used, activated carbon modified with iron ions in the presence of a chelating agent was the one that showed best results, under the conditions evaluated in this study. Presenting an immobilization yield of 95.15% and a hydrolytic activity of 4.11 U, same as soluble enzyme (3.76 U). This derivative kept its activity stable at temperatures above 40 °C for1 h and when stored for 30 days at 5 °C. Furthermore, it was effective for more than 6 reuse cycles (under the same conditions as the 1st cycle). In general, immobilization of trypsin on metallized activated carbon can be an alternative to biocatalysis, highlighting the advantages of protease immobilization.

Regulation of Iron-Ion Transporter SLC11A2 by Three Identical miRNAs.

Here, we searched for microRNAs (miRNAs) in silico that could interact with SLC11A2 mRNA, a solute carrier (SLC) iron-ion transporter, and investigated their effects on SLC11A2 gene expression using the cultured human colon carcinoma cell line, Caco-2. In silico analysis using the miRWalk2.0 database revealed that several types of miRNAs interact with the human SLC11A2 gene; we focused on three miRNAs, miR-149-5p, miR-362-5p, and miR-539-5p as candidates in this study. We first revealed that the three miRNAs interact with the SLC11A2 3'-untranslated region (3'-UTR) using a luciferase assay in a Caco-2 cell line. We then examined whether the expression of each miRNA affected the expression of SLC11A2 mRNAs and their transcribed transporter proteins. We found transiently expressed miRNAs significantly reduced the reporter activity of the SLC11A2 3'-UTR site in Caco-2 cells by significantly decreasing the SLC11A2 gene and protein expression in the miRNA-transfected Caco-2 cells. Subsequently, we investigated the effects of these miRNAs on SLC11A2's iron-ion transporting activity by measuring iron-ion concentration in Caco-2 cells. Administration of ammonium iron (II) sulfate hexahydrate to Caco-2 cells significantly increased the intracellular iron-ion concentration. However, in iron-ion-pretreated cells, overexpression of each of the three miRNAs resulted in decreased intracellular iron-ion concentration. This indicated that overexpressed miRNAs inhibited iron-ion influx into Caco-2 cells by attenuating SLC11A2 transporting activity. Using in silico analysis, we predicted that three studied miRNAs could bind to the iron-ion influx transporter SLC11A2 and revealed that they regulate SLC11A2 gene expression and iron-ion transporting function in an in vitro system.

Non-clinical studies indicating lack of interactions between iron/calcium ions and linzagolix, an orally available GnRH antagonist.

Linzagolix is an orally available gonadotropin-releasing hormone antagonist used to treat sex-hormone-dependent diseases in women. This study aimed to investigate drug-drug interactions between linzagolix and iron/calcium ions in the intended clinical setting by conducting pharmacokinetic studies in vitro and in rats.Insoluble precipitate formation with metal ions was evaluated by measuring linzagolix concentrations in four types of bio-relevant dissolution media (fasted/fed state simulated gastric fluid and fasted/fed state simulated gastric fluid version 2), and chelate complex formation with metal ions was evaluated by release of linzagolix from a cellulose membrane sac. In these in vitro studies, linzagolix showed no potential for insoluble precipitate formation under fasted/fed conditions and no chelate complex formation in the presence of metal ions.In rats, the plasma concentration-time profiles of linzagolix and iron ion were similar regardless of whether they were administered with or without ferrous sulphate and linzagolix choline at clinically relevant doses. Thus, linzagolix and iron ion had no effect on each other's absorption in vivo.In conclusion, linzagolix is unlikely to cause clinically relevant drug-drug interactions by chelating metal ions according to the results of in vitro and in vivo studies.

Design, synthesis and biological evaluation of potential anti-AD hybrids with monoamine oxidase B inhibitory and iron-chelating effects.

A series of active hybrids combining 3-hydroxypyridin-4(1H)-one and coumarin pharmacophores were designed and synthesized as potential agents for the treatment of Alzheimer's disease (AD). All the compounds exhibited excellent iron-chelating activities (pFe3+ = 14.8-19.2) and showed favorable monoamine oxidase B (MAO-B) inhibitory effects compared to the reference drug Pargyline (IC50 = 86.9 nM). Among them, compound 11 g displayed the best MAO-B inhibitory activity with an IC50 value of 99.3 nM. Molecular docking analysis showed that compound 11 g could enter the entrance cavity and substrate cavity of MAO-B. Furthermore, the compound 11 g had an excellent antioxidant effect and was capable of protecting from the amyloid-ß1-42 (Aß1-42) induced PC12 cell damage. In silico tools were applied for predicting the blood-brain barrier (BBB) penetration and compound 11 g was proved to overcome the brain exposure challenge. In the mice behavioral study, compound 11 g significantly ameliorated cognitive impairment induced by Scopolamine. More importantly, compound 11 g displayed favorable pharmacokinetic profiles in a rat model. In summary, compound 11 g, with both anti-MAO-B and iron-chelating ability, was proved to be a promising potential anti-AD agent for further optimization.

Analysis of the mechanism for enhanced pyrene biodegradation based on the interactions between iron-ions and Rhodococcus ruber strain L9.

A slow degradation rate and low transformation efficiency are the main problems in the biodegradation of polycyclic aromatic hydrocarbons (PAHs). This study selected pyrene as the target PAH to investigate the effect of ferrous ion and ferric ion on pyrene degradation. The driving effect and mechanism, including the interaction between pyrene and iron ions and the bacterial physiological response during the biodegradation process by Rhodococcus ruber strain L9, were investigated. The results showed that iron ions did not enhance bacterial growth but improved bacteria's pyrene removal capacity, contributing to the total efficiency of pyrene biodegradation. The process started with an initial formation of "cation-π" between Fe (III) and pyrene, which subsequently drove the pyrene removal process and accelerated the bacterial metabolic process. Moreover, a significant increase in the protein concentration, catechol dioxygenase (C12O and C23O) activities, and intracellular protein regulation in crude enzyme solution indicate a positive response of the bacteria during the iron ion-enhanced pyrene degradation process.

Expression and functional analysis of Nile tilapia transferrin receptors (TfRs) in host resistance to pathogenic bacteria and iron ion metabolism.

Transferrin receptors (TfRs) play an essential role in iron-withholding strategy, and are involved in immune response against bacterial infection. In this study, the transferrin receptor 1 (OnTfR1) and transferrin receptor 2 (OnTfR2) genes are identified and characterized in Nile tilapia (Oreochromis niloticus). The open reading frames of OnTfR1 and OnTfR2 are 2220 and 2343 bp of nucleotide sequence, encoding 739 and 780 amino acids, respectively. The deduced proteins of OnTfR1 and OnTfR2 are highly homologous to those of other species, containing three conserved TfR superfamily domains (PA TfR domain, M28 TfR domain and TfR dimer domain). Expression analyses of OnTfRs in the healthy tilapia reveal that the OnTfR1 and OnTfR2 transcripts are the most abundant in the liver. The in vivo studies show that the expressions of OnTfRs are significantly up-regulate in liver and spleen, following infections of Streptococcus agalactiae and Aeromonas hydrophila. In addition, the in vitro studies reveal that the up-regulations of OnTfR expressions are also significant in monocytes/macrophages and hepatocytes upon the stimulations of S. agalactiae and A. hydrophila. Moreover, the iron ion (Fe3+) could significantly increase the expressions of OnTfRs in monocytes/macrophages and hepatocytes. Taken together, the present study indicates that OnTfRs may be involved in host defense against bacterial infection and possess the function of combining or transporting iron ions in Nile tilapia.

Determination of iron(II) and iron(III) via static quenching of the fluorescence of tryptophan-protected copper nanoclusters.

"Tryptophan-coated blue fluorescent copper nanocluster (CuNC@Trp) was prepared by a strategy where Trp acts as both the reducing and capping agent. The fluorescence of the CuNC, with excitation/emission peaks at 340/405 nm, is selectively quenched by iron(II) and iron(III) ions. Studying the mechanism of this interaction revealed that Fe2+ and Fe3+ ions can make a ground state complex with the protecting ligand which can result in quenching of the cluster emission. Structural and optical properties of the modified CuNC were investigated by ESI-MS, DLS, TEM, UV-vis and photoluminescence. The effects of pH value and temperature, time of interaction, and cluster volume were optimized. Under optimized conditions, the probe response is linear in concentration range of 10-1000 µM for Fe(II) and Fe(III) with the relative standard deviations of 0.13 and 0.14% (n = 5) respectively. The respective limits of detection are 3.0 and 2.2 µM. The method was successfully used for determination of trace amount of both ions in spiked water, blood and iron supplement tablets. The results were in good agreement with those obtained by the ICP-AES method." Graphical abstractThe scheme represents the synthesis of CuNC@Trp at basic conditions and at elevated temperature. The emission of the cluster decreases due to static quenching of fluorescence by iron ions.

Dual-target anti-Alzheimer's disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity.

MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds displayed excellent iron ion chelating activity and moderate to good anti-MAO-B activity. Compounds 27b and 27j exhibited the most potent MAO-B inhibitory activity, with IC50 values of 0.68 and 0.86 µM, respectively. In summary, these dual-target compounds have the potential anti-AD activity.

A Schiff Base Fluorescence Enhancement Probe for Fe(III) and Its Sensing Applications in Cancer Cells.

We report a new Schiff base fluorescent probe which senses ferric ion, Fe(III), with a significant fluorescence enhancement response. The probe showed high sensitivity (0.8 ppb), and fast response time (<10 s) of Fe(III) in aqueous media. In addition, the probe showed the ability to sense Fe(III) in a HeLa cancer cell line, with very low cytotoxicity. As a new bio-imaging probe for Fe(III), it gave bright fluorescent images in confocal laser scanning microscopy (CLSM).

[The role of DFO in Al (mal) (3)-induced ferroptosis in PC12 cells].

Objective: To investigate the mechanism of Al (mal) (3)-induced ferroptosis in rat adrenal pheochromocytoma cells (PC12), to explore the effect of deferoxamine (DFO) . Methods: Taken PC12 cells growing at logarithmic phase and divided into 6 groups: control group, 200 µmol/L Al (mal) (3) group, 0.5% DMSO group, 200 µmol/L DFO group, Al (mal) (3)+DMSO group, Al (mal) (3)+DFO group. DMSO and DFO were added to the DMSO group and the Al (mal) (3)+DMSO group, the DFO group and the Al (mal) (3)+DFO group for 2 h, respectively, Al (mal) (3) was then added to the Al (mal) (3) group, Al (mal) (3)+DMSO group, and the Al (mal) (3)+DFO group to a final concentration of 200 µmol/L. The cell viability was detected by CCK8, the morphology and ROS levels of PC12 cells was observed by inverted microscope, the cell proliferation toxicity and intracellular iron ion content were detected by colorimetry, the GSH content and GSH-PX activity were detected by biochemical method. Results: Al (mal) (3) exposure significantly inhibited the growth of PC12 cells and destroyed the cell morphological structure, resulting in increased LDH activity and intracellular iron ion content in PC12 cells, decreased GSH content and GSH-PX activity, increased ROS levels; the combined treatment of Al (mal) (3)+DFO can significantly improve the cell viability of PC12 cells, improved cell morphology, decreased cell LDH activity and intracellular iron ion content (P>0.05), increased GSH content and GSH-PX activity, decreased ROS levels. Conclusion: Al (mal) (3) can induce ferroptosis in PC12 cells, DFO may inhibit ferroptosis by reducing intracellular iron levels and reducing oxidative damage.

Dual-Functional Fluorescein-Based Chemosensor for Chromogenic Detection of Fe3+ and Fluorgenic Detection of HOCl.

A novel fluorescein-based dual probe was designed and synthesized. The probe exhibited highly sensitive and selective colormetric response to Fe3+ and turn-on fluorescence response towards OCl- with very low detection limits of 100 and 50 nM, respectively. It was successfully applied for quantitative detection of Fe3+ and OCl- in real water samples. Moreover, probe 1 was expected to be a potentially powerful tool for studying and providing further insights into OCl- and Fe3+ chemistry in the near future.

Highly Selective and Sensitive Detection of Nitroaromatic Compounds and Metal Ions by Supramolecular Assemblies of 3,3',5,5'-Azobenzenetetracarboxylic Acid and 4,4'-Bipyridine.

A supramolecular compound, (H4L)(4,4'-bpy)2 (1) (H4L = 1,2-bis(3,5-dicarboxyphenyl)diazene oxide, 4,4'-bpy = 4,4'-bipyridine) with 2D + 2D â†’ 2D 3-fold parallel interpenetrated layer feature, has been prepared which was investigated as selective sensing material for detection of nitroaromatic compounds (NACs) and metal ions, and exhibits significant fluorescence quenching toward NACs and high selectivity for detection of Fe3+ ion. The result indicates that 1 is a promising multi-functional fluorescence probe for detecting and recognizing NACs and metal ions with high sensitivity and selectivity.

2,6-Bis(2-Benzimidazolyl)Pyridine Fluorescent Red-Shifted Sensor for Recognition of Zinc(II) and a Calorimetric Sensor for Iron Ions.

The ability of 2,6-bis(2-benzimidazolyl)pyridine (bbp) as an optical sensor was studied by fluorescence spectroscopy, colorimetric and UV-visible techniques. The fluorescence spectra of bbp demonstrated a red-shifted upon addition of Zn(2+) ion, whereas rest of the cations did not induce any shift. Selectivity of the sensor was examined toward Zn(2+) in the presence of a wide range of cations, as interfering agents, that showed no disruption in its function. In addition, the pH effect was tested on the fluorescence response of bbp; which showed the efficiency of the sensor in a wide pH range. The limit of detection for Zn(2+) was estimated as 2.1 µM. Furthermore, the colorimetric studies were carried out and the observations showed a color change from colorless to purple by the addition of Fe(2+) ion and from colorless to yellow by the addition of Fe(3+). The UV-visible studies were carried out to confirm the colorimetric observations. The color changes occurred when Fe(2+) and Fe(3+) were added to the sensors solution, respectively. The detection limits were calculated as 2.8 × 10(-7) M and 3.5 × 10(-6) M for Fe(2+) and Fe(3+), respectively. Hence, bbp can be used as a dual mode optical sensor for detection of Zn(2+) by fluorescence and discriminately detection of Fe(2+) and Fe(3+) visually.

A novel hybrid lanthanide metal-organic frameworks based on porphyrin for rapid detection of iron ions.

BACKGROUND: Iron ion (Fe3+) is essential for the environment and human health. Detecting Fe3+ in water is crucial, making high-performance detection a key objective. Lanthanide metal-organic frameworks with abundant functional sites have been deemed a promising fluorescence sensor for Fe3+ detection. Currently, most metal-organic framework-based sensors for Fe3+ detection have cumbersome and time-consuming synthesis procedures and long detection times, which greatly limits their practical application. This study aims to construct a hybrid lanthanide metal-organic frameworks-based fluorescence sensor for Fe3+ detection that promises simple and rapid iron ion quantification in water. RESULTS: A novel hybrid lanthanide metal-organic frameworks (ECTMNs) was synthesized in one step using a solvothermal method with only 4 h. The frameworks comprise two metal ions, cerium and europium, serving as metal centers, and 4,4,4,4-(Porphine-5,10,15,20-tetrayl) tetrakis (TCPP) as an organic ligand. With the addition of Fe3+, the host-guest reaction occurred between Fe3+ and ECTMNs probe, leading to the gradual fluorescence burst of ECTMNs probe. A strong linear correlation between ECTMNs fluorescence intensity and Fe3+ concentration (1-90 µM) makes it a reliable sensor for Fe3+ monitoring with a detection limit of 0.3 µM. Moreover, the method was used to analyze real samples (tap water and river water), showing good recoveries (92-98 %) and low relative standard deviations (3.96-6.11 %), making it a promising option for rapidly detecting Fe3+. SIGNIFICANCE AND NOVELTY: A rapid synthesis protocol for hybrid lanthanide metal-organic frameworks is proposed in this study. The obtained ECTMNs exhibits good water solubility, high stability, and specificity for Fe3+. Based on ECTMNs, an innovative fluorescence sensor is established for selectively detecting Fe3+ in water, which is a simple operation method with a low detection limit and short sensing time. It provides a novel method for accurately and rapidly detecting Fe3+ in environmental pollution and water safety monitoring.