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Keywords = iron binding

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15 pages, 2134 KiB  
Article
Integrated Characterization of Sediments Contaminated by Acid Mine Drainage: Mineralogical, Magnetic, and Geochemical Properties
by Patrícia Gomes, Teresa Valente and Eric Font
Minerals 2025, 15(8), 786; https://doi.org/10.3390/min15080786 - 26 Jul 2025
Viewed by 116
Abstract
Acid mine drainage, a consequence of exposure of sulfide mining waste to weathering processes, results in significant water, sediment, and soil contamination. This contamination results in acidophilic ecosystems, with low pH values and elevated concentrations of sulfate and potentially toxic elements. The São [...] Read more.
Acid mine drainage, a consequence of exposure of sulfide mining waste to weathering processes, results in significant water, sediment, and soil contamination. This contamination results in acidophilic ecosystems, with low pH values and elevated concentrations of sulfate and potentially toxic elements. The São Domingos mine, an abandoned site in the Iberian Pyrite Belt, lacks remediation measures and has numerous waste dumps, which are a major source of contamination to local water systems. Therefore, this study examines sediment accumulation in five mine dams along the São Domingos stream that traverses the entire mine complex. Decades of sediment and waste transport since mine closure have resulted in dam-clogging processes. The geochemical, mineralogical, and magnetic properties of the sediments were analyzed to evaluate the mineralogical controls on the mobilization of potentially toxic elements. The sediments are dominated by iron oxides, oxyhydroxides, and hydroxysulfates, with jarosite playing a key role in binding high concentrations of iron and toxic elements. However, no considerable correlation was found between potentially toxic elements and magnetic parameters, highlighting the complex behavior of these contaminants in acid mine drainage-affected systems. Full article
(This article belongs to the Section Environmental Mineralogy and Biogeochemistry)
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16 pages, 5637 KiB  
Article
Optimizing High-Al2O3 Limonite Pellet Performance: The Critical Role of Basicity in Consolidation and Reduction
by Yufeng Guo, Yixi Zhang, Feng Chen, Shuai Wang, Lingzhi Yang, Yanqin Xie and Xinyao Xia
Metals 2025, 15(7), 801; https://doi.org/10.3390/met15070801 - 16 Jul 2025
Viewed by 211
Abstract
With the gradual depletion of high-quality iron ore resources, global steel enterprises have shifted their focus to low-grade, high-impurity iron ores. Using low-grade iron ore to produce pellets for blast furnaces is crucial for companies to control production costs and diversify raw material [...] Read more.
With the gradual depletion of high-quality iron ore resources, global steel enterprises have shifted their focus to low-grade, high-impurity iron ores. Using low-grade iron ore to produce pellets for blast furnaces is crucial for companies to control production costs and diversify raw material sources. However, producing qualified pellets from limonite and other low-grade iron ores remains highly challenging. This study investigates the mechanism by which basicity affects the consolidation and reduction behavior of high-Al2O3 limonite pellets from a thermodynamic perspective. As the binary basicity of the pellets increased from 0.01 under natural conditions to 1.2, the compressive strength of the roasted pellets increased from 1100 N/P to 5200 N/P. The enhancement in basicity led to an increase in the amount of low-melting-point calcium ferrite in the binding phase, which increased the liquid phase in the pellets, thereby strengthening the consolidation. CaO infiltrated into large-sized iron particles and reacted with Al and Si elements, segregating the contiguous large-sized iron particles and encapsulating them with liquid-phase calcium ferrite. Calcium oxide reacts with the Al and Si elements in large hematite particles, segmenting them and forming liquid calcium ferrite that encapsulates the particles. Additionally, this study used thermodynamic analysis to characterize the influence of CaO on aluminum elements in high-aluminum iron ore pellets. Adding CaO boosted the liquid phase’s ability to incorporate aluminum, lessening the inhibition by high-melting-point aluminum elements of hematite recrystallization. During the reduction process, pellets with high basicity exhibited superior reduction performance. Full article
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17 pages, 2681 KiB  
Article
Magnetically Retrievable Nanoparticles with Tailored Surface Ligands for Investigating the Interaction and Removal of Water-Soluble PFASs in Natural Water Matrices
by Yunfei Zhang, Jacqueline Ortiz, Shi He, Xianzhi Li, Bableen Kaur, Bing Cao, Zachariah Seiden, Shuo Wu and He Wei
Sensors 2025, 25(14), 4353; https://doi.org/10.3390/s25144353 - 11 Jul 2025
Viewed by 310
Abstract
Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industrial applications and have become persistent environmental contaminants due to their chemical stability. Water-soluble PFASs with fewer than ten carbon atoms, such as perfluorooctanoic acid (PFOA), are particularly concerning because of their [...] Read more.
Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industrial applications and have become persistent environmental contaminants due to their chemical stability. Water-soluble PFASs with fewer than ten carbon atoms, such as perfluorooctanoic acid (PFOA), are particularly concerning because of their high solubility in water, environmental mobility, and resistance to degradation. In this work, we present an eco-friendly Fe3O4 magnetic nanoparticle (MNP)-based platform for the detection and removal of PFOA from water. The synthesized iron oxide MNPs exhibit rapid and strong magnetic responsiveness, enabling efficient magnetic separation for both PFOA detection and removal. To optimize surface affinity for PFOA, we functionalized the MNPs with distinctive ligands, including polyethylene glycol (PEG), β-cyclodextrin (βCD), and dopamine (DA). Among these, PEG and DA showed notable binding affinity toward PFOA, as confirmed by infrared spectroscopy and colorimetric assays. After incubation with the functionalized MNPs followed by magnetic retrieval, we achieved over 90% PFOA removal efficiencies, demonstrating the potential for future research in PFAS remediation technologies. Importantly, the system was validated using deionized, tap, and lake water, all of which yielded comparable and promising results. This study provides a promising, eco-friendly, and recyclable nanomaterial platform for investigating the crucial role of surface chemistry in nanoparticle–PFAS interactions through ligand-mediated magnetic separation. Full article
(This article belongs to the Special Issue Chemical Sensors for Toxic Chemical Detection: 2nd Edition)
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14 pages, 2208 KiB  
Review
The Relationship Between Non-Transferrin-Bound Iron (NTBI), Labile Plasma Iron (LPI), and Iron Toxicity
by Lorena Duca, Elena Di Pierro, Natalia Scaramellini, Francesca Granata and Giovanna Graziadei
Int. J. Mol. Sci. 2025, 26(13), 6433; https://doi.org/10.3390/ijms26136433 - 3 Jul 2025
Viewed by 368
Abstract
Plasma non-transferrin-bound iron (NTBI) comprises multiple subspecies, classified by their composition, chemical reactivity, and susceptibility to chelation. The redox-active and chelatable fraction of NTBI is referred to as labile plasma iron (LPI). The pathophysiological significance of NTBI and LPI lies in their ability [...] Read more.
Plasma non-transferrin-bound iron (NTBI) comprises multiple subspecies, classified by their composition, chemical reactivity, and susceptibility to chelation. The redox-active and chelatable fraction of NTBI is referred to as labile plasma iron (LPI). The pathophysiological significance of NTBI and LPI lies in their ability to enter cells via alternative transport pathways that are not regulated by the transferrin receptor system or by cellular iron levels. Several mechanisms have been proposed for their cellular entry, including the hijacking of divalent metal transporters and passive diffusion. This unregulated uptake can lead to iron accumulation in vulnerable tissues such as the liver and the heart. NTBI and LPI bypassing normal cellular control mechanisms can rapidly exceed the cell’s capacity to safely store excess iron, leading to toxicity. Both NTBI and LPI contribute to oxidative stress by participating in free-radical-generating reactions. However, LPI concentration in the bloodstream may be differentially affected by the mode and extent of iron overload, the presence of residual serum iron-binding activity, and the antioxidant capacity of individual sera. In summary, both NTBI and LPI contribute to iron-mediated toxicity but differ in terms of reactivity, availability, and pathogenic potential depending on the pathophysiological conditions that influence the degree of toxicity. Full article
(This article belongs to the Special Issue Iron Dyshomeostasis)
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10 pages, 807 KiB  
Communication
The Siderophore Phymabactin Facilitates the Growth of the Legume Symbiont Paraburkholderia phymatum in Aluminium-Rich Martian Soil
by Daphné Golaz, Luca Bürgi, Marcel Egli, Laurent Bigler and Gabriella Pessi
Life 2025, 15(7), 1044; https://doi.org/10.3390/life15071044 - 30 Jun 2025
Viewed by 297
Abstract
Beneficial interactions between nitrogen-fixing soil bacteria and legumes offer a solution to increase crop yield on Earth and potentially in future Martian colonies. Paraburkholderia phymatum is a nitrogen-fixing beta-rhizobium, which enters symbiosis with more than 50 legumes and can survive in acidic or [...] Read more.
Beneficial interactions between nitrogen-fixing soil bacteria and legumes offer a solution to increase crop yield on Earth and potentially in future Martian colonies. Paraburkholderia phymatum is a nitrogen-fixing beta-rhizobium, which enters symbiosis with more than 50 legumes and can survive in acidic or aluminium-rich soils. In a previous RNA-sequencing study, we showed that the beta-rhizobium P. phymatum grows well in simulated microgravity and identified phymabactin as the only siderophore produced by this strain. Here, the growth of the beta-rhizobium P. phymatum was assessed in Martian simulant soil using Enhanced Mojave Mars Simulant 2 (MMS-2), which contains a high amount of iron (18.4 percent by weight) and aluminium (13.1 percent by weight). While P. phymatum wild-type’s growth was not affected by exposure to MMS-2, a mutant strain impaired in siderophore biosynthesis (ΔphmJK) grew less than P. phymatum wild-type on gradient plates in the presence of a high concentration of MMS-2 or aluminium. This result suggests that the P. phymatum siderophore phymabactin alleviates aluminium-induced heavy metal stress. Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) showed that phymabactin can bind to aluminium more efficiently than iron. These results not only deepen our understanding of the behaviour of rhizobia in simulated extraterrestrial environments but also provide new insights into the potential use of P. phymatum for bioremediation of aluminium-rich soils and the multiple roles of the siderophore phymabactin. Full article
(This article belongs to the Section Plant Science)
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18 pages, 2333 KiB  
Article
Molecular Structure and Biosynthesis of Pyoverdines Produced by Pseudomonas fulva
by Eri Ochiai, Takeru Kawabe, Masafumi Shionyu and Makoto Hasegawa
Microorganisms 2025, 13(6), 1409; https://doi.org/10.3390/microorganisms13061409 - 17 Jun 2025
Viewed by 374
Abstract
This study explored the biosynthetic mechanisms and structural diversity of pyoverdines (PVDs) produced by Pseudomonas fulva. Genomic analysis using antiSMASH identified the PVD biosynthetic gene cluster, although the C-terminal peptide sequence could not be predicted. Subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) [...] Read more.
This study explored the biosynthetic mechanisms and structural diversity of pyoverdines (PVDs) produced by Pseudomonas fulva. Genomic analysis using antiSMASH identified the PVD biosynthetic gene cluster, although the C-terminal peptide sequence could not be predicted. Subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed the full peptide structure, including modified residues, such as N-acetylhydroxyornithine and cyclohydroxyornithine, and confirmed the presence of several PVD isoforms with different chromophore side chains. Comparative LC-MS analysis across Pseudomonas species demonstrated that P. fulva produces unique PVD molecular mass patterns. The bioinformatic and structural modeling of non-ribosomal peptide synthetase PvdL open reading frame 3 revealed that the A2 and A3 adenylation domains are lysine selective. Although their sequences differ from known lysine-specific signatures, AlphaFold3-based structural prediction revealed conserved substrate-binding configurations, suggesting that similar substrate-binding features may have arisen independently. Notably, Thr297, a unique residue in the non-ribosomal code, likely plays a key role in lysine recognition. The high degree of sequence similarity between the A2 and A3 domains may reflect domain duplication and could be involved in the diversification of the PVD structure. Further functional and ecological studies are required to assess the physiological significance of P. fulva PVDs in microbial iron acquisition. Full article
(This article belongs to the Section Environmental Microbiology)
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51 pages, 1310 KiB  
Review
Ferritin in Acute Myeloid Leukemia: Not Only a Marker of Inflammation and Iron Overload, but Also a Regulator of Cellular Iron Metabolism, Signaling and Communication
by Håkon Reikvam, Magnus Gramstad Rolfsnes, Linn Rolsdorph, Miriam Sandnes, Frode Selheim, Maria Hernandez-Valladares and Øystein Bruserud
Int. J. Mol. Sci. 2025, 26(12), 5744; https://doi.org/10.3390/ijms26125744 - 15 Jun 2025
Viewed by 1303
Abstract
Ferritin is important for cellular iron storage and metabolism. It consists of 24 ferritin heavy- or light-chain subunits surrounding an iron-containing core, but it is also released as an extracellular molecule that shows increased systemic levels during acute-phase reactions. Furthermore, acute myeloid leukemia [...] Read more.
Ferritin is important for cellular iron storage and metabolism. It consists of 24 ferritin heavy- or light-chain subunits surrounding an iron-containing core, but it is also released as an extracellular molecule that shows increased systemic levels during acute-phase reactions. Furthermore, acute myeloid leukemia (AML) is an aggressive bone marrow malignancy that can be associated with increased ferritin levels both at the time of first diagnosis but also during/following anti-AML treatment due to an iron overload. Such high systemic ferritin levels at diagnosis or later allogeneic stem cell transplantation are associated with decreased long-term survival. Extracellular ferritin binds to several receptors expressed by AML cells (e.g., the transferrin receptor and CXCR4 chemokine receptor) and AML-supporting non-leukemic bone marrow cells (e.g., endothelial, mesenchymal or immunocompetent cells). Ferritin can thereby affect the AML cells directly as well as indirectly via AML-supporting neighboring cells. Finally, ferritin should be regarded as a regulator of the dysfunctional iron metabolism that causes increased iron levels in AML cells, and it is important for cell survival through its function during the initial steps of ferroptosis. Thus, ferritin is not only an adverse prognostic biomarker, but also an important regulator of AML cell proliferation, survival and chemosensitivity and the targeting of iron metabolism/ferroptosis is, therefore, a possible strategy in AML therapy. Full article
(This article belongs to the Special Issue Molecular Mechanism of Acute Myeloid Leukemia)
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26 pages, 3646 KiB  
Article
Application of Chelex-100 and SPR-IDA Resin in Combination with the Optimized Beam Deflection Spectrometry for High-Sensitivity Determination of Iron Species in Sediment Porewater
by Hanna Budasheva, Mohanachandran Nair Sindhu Swapna, Arne Bratkič and Dorota Korte
Sensors 2025, 25(12), 3643; https://doi.org/10.3390/s25123643 - 10 Jun 2025
Viewed by 409
Abstract
In this work, photothermal beam deflection spectrometry (BDS), combined with a passive sampling technique of diffusive gradients in thin film (DGT), is optimized to improve the method’s sensitivity. The limit of detection (LOD) is then reduced by a factor of 2 (to the [...] Read more.
In this work, photothermal beam deflection spectrometry (BDS), combined with a passive sampling technique of diffusive gradients in thin film (DGT), is optimized to improve the method’s sensitivity. The limit of detection (LOD) is then reduced by a factor of 2 (to the value of 20 nM). The functionality of the technique is compared for Chelex-100 (Ch-100) and suspended particulate reagent–iminodiacetate resin (SPR-IDA), used as binding resins in passive samplers. The absorption capacity of SPR-IDA resin is found to be less than 1 μM and far below that one of Chelex-100 resin (around 6 μM). The BDS technique is applied for determination of iron redox species concentration in sediment porewater. It is found that Fe in sediment porewater occurs both in Fe2+ (0.073 μM) and Fe3+ (0.095 μM) forms. The validation of the presented method reveals that the BDS technique ensures good repeatability, reproducibility, and reliability. Full article
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21 pages, 3980 KiB  
Article
Binding Capacity and Adsorption Stability of Uremic Metabolites to Albumin-Modified Magnetic Nanoparticles
by Indu Sharma, Agatha Milley, Lun Zhang, Jiamin Zheng, Ethan Lockwood, David S. Wishart, Marcello Tonelli and Larry D. Unsworth
Int. J. Mol. Sci. 2025, 26(11), 5366; https://doi.org/10.3390/ijms26115366 - 3 Jun 2025
Viewed by 375
Abstract
Kidney disease causes the retention of uremic metabolites in blood, which is associated with many comorbidities. Hemodialysis does not properly clear many metabolites, including large, middle-sized, and small protein-bound uremic toxins (PBUTs). Adsorption strategies for metabolite removal require the development of engineered adsorbents [...] Read more.
Kidney disease causes the retention of uremic metabolites in blood, which is associated with many comorbidities. Hemodialysis does not properly clear many metabolites, including large, middle-sized, and small protein-bound uremic toxins (PBUTs). Adsorption strategies for metabolite removal require the development of engineered adsorbents with tailored surfaces to increase the binding of desired metabolites. Albumin is uniquely positioned for modifying blood-contacting surfaces to absorb uremic metabolites, as it (i) minimizes non-specific protein adsorption and (ii) binds a range of molecules at Sudlow Sites I and II with different affinities. It is unknown if albumin-modified surfaces retain the adsorption qualities of solution-free albumin, namely, adsorption stability or specificity. Herein, albumin was covalently attached to iron oxide nanoparticles and characterized using multiple methods. Metabolite adsorption was conducted by incubating particles in a model solution of thirty-three uremic metabolites associated with kidney failure. Adsorption efficiency, selectivity, and stability were affected by albumin concentration and incubation time. Metabolite adsorption was found to change with time, and it was more effective on albumin-modified particles than unmodified controls. The findings outlined in this paper are crucial for the design of next-generation advanced blood-contacting materials to enhance dialysis and blood purification for patients with kidney disease. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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28 pages, 3280 KiB  
Article
Structural, Computational, and Biomolecular Interaction Study of Europium(III) and Iron(III) Complexes with Pyridoxal-Semicarbazone Ligand
by Violeta Jevtovic, Stefan Perendija, Aljazi Abdullah Alrashidi, Maha Awjan Alreshidi, Elham A. Alzahrani, Odeh A. O. Alshammari, Mostafa Aly Hussien, Jasmina Dimitrić Marković and Dušan Dimić
Int. J. Mol. Sci. 2025, 26(11), 5289; https://doi.org/10.3390/ijms26115289 - 30 May 2025
Viewed by 491
Abstract
The coordination chemistry, structural characterization, and biomolecular interactions of europium(III) and iron(III) complexes with the pyridoxal-semicarbazone (PLSC) ligand were thoroughly examined using experimental and computational approaches. Single-crystal X-ray diffraction revealed that the europium complex exhibits a nine-coordinate geometry with one protonated and one [...] Read more.
The coordination chemistry, structural characterization, and biomolecular interactions of europium(III) and iron(III) complexes with the pyridoxal-semicarbazone (PLSC) ligand were thoroughly examined using experimental and computational approaches. Single-crystal X-ray diffraction revealed that the europium complex exhibits a nine-coordinate geometry with one protonated and one deprotonated PLSC ligand and nitrato and aqua ligands. In contrast, the iron complex adopts a six-coordinate structure featuring a monoprotonated PLSC, two chlorido, and an aqua ligand. Hirshfeld surface analysis confirmed the significance of intermolecular contacts in stabilizing the crystal lattice. Theoretical geometry optimizations using DFT methods demonstrated excellent agreement with experimental bond lengths and angles, thereby validating the reliability of the chosen computational levels for subsequent quantum chemical analyses. Quantum Theory of Atoms in Molecules (QTAIM) analysis was employed to investigate the nature of metal–ligand interactions, with variations based on the identity of the donor atom and the ligand’s protonation state. The biological potential of the complexes was evaluated through spectrofluorimetric titration and molecular docking. Eu-PLSC displayed stronger binding to human serum albumin (HSA), while Fe-PLSC showed higher affinity for calf thymus DNA (CT-DNA), driven by intercalation. Thermodynamic data confirmed spontaneous and enthalpy-driven interactions. These findings support using PLSC-based metal complexes as promising candidates for future biomedical applications, particularly in drug delivery and DNA targeting. Full article
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23 pages, 1158 KiB  
Article
Iron(III) Complexes with Substituted Salicylaldehydes: Synthesis, Interaction with DNA and Serum Albumins, and Antioxidant Activity
by Zisis Papadopoulos, Antonios G. Hatzidimitriou and George Psomas
Molecules 2025, 30(11), 2383; https://doi.org/10.3390/molecules30112383 - 29 May 2025
Viewed by 699
Abstract
Metal complexes of endogenous metals, such as iron, copper, and zinc, offer a biocompatible, cost-effective, and eco-friendly alternative to heavy metals for drug design. This study presents the synthesis, structural characterization, and evaluation of the biological activity of eight novel iron(III) complexes with [...] Read more.
Metal complexes of endogenous metals, such as iron, copper, and zinc, offer a biocompatible, cost-effective, and eco-friendly alternative to heavy metals for drug design. This study presents the synthesis, structural characterization, and evaluation of the biological activity of eight novel iron(III) complexes with substituted salicylaldehydes as ligands. The characterization of the complexes involved spectroscopic and physicochemical methods. The structures of two complexes were determined using single-crystal X-ray crystallography. The biological studies of the complexes focused on the interaction of calf-thymus DNA, the (photo)cleavage of pBR322 plasmid DNA (pDNA), the affinity for bovine and human serum albumins, and the antioxidant activity. The complexes interacted with calf-thymus DNA via intercalation with high DNA-binding constants. The complexes exhibited high pDNA-cleavage ability, which is significantly enhanced upon exposure to UVA or UVB irradiation. The complexes can bind tightly and reversibly to both serum albumins, and their binding locations were identified. Finally, the complexes showed moderate ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals with a high ability to reduce hydrogen peroxide. Full article
(This article belongs to the Special Issue Synthesis and Biological Evaluation of Coordination Compounds)
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11 pages, 1830 KiB  
Article
Lactoferrin Solution as a New Natural Photosensitizer in Photodynamic Therapy Against Oral Candida spp. Multidrug-Resistant Isolates: A Preliminary In Vitro Study
by Cinzia Casu, Andrea Butera, Alice Piga, Andrea Scribante, Sara Fais and Germano Orrù
Microorganisms 2025, 13(6), 1255; https://doi.org/10.3390/microorganisms13061255 - 29 May 2025
Viewed by 561
Abstract
Serious oral infections are frequently caused by Candida species, which have lately demonstrated resistance to antifungal medications. As a result, new therapeutic strategies, like photodynamic therapy (PDT), are desperately needed. Lactoferrin (LF), a salivary enzyme, is a natural protein that binds iron and [...] Read more.
Serious oral infections are frequently caused by Candida species, which have lately demonstrated resistance to antifungal medications. As a result, new therapeutic strategies, like photodynamic therapy (PDT), are desperately needed. Lactoferrin (LF), a salivary enzyme, is a natural protein that binds iron and has antifungal properties. Given its chemical structure and light absorption at 310–350 nm, LF appears to be a good photosensitizer in a PDT process for treating oral candidiasis. The purpose of this work was to assess the effectiveness of lactoferrin (LF) as a photosensitizer (PS) in photodynamic treatment (PDT) against oral multidrug-resistant (MDR) isolates of Candida spp. using an in vitro investigation. For this in vitro investigation, oral MDR isolates of Candida albicans, Candida kruseii, and Candida glabrata were employed. Using a Kirby–Bauer test (Eucast protocol), a solution of 20 mg of bovine lactoferrin dissolved in 1 mL of Sabouraud’s broth was tested in four different experimental combinations: (i) the solution as it is; (ii) the solution activated with 3% H2O2; (iii) the solution activated by light at 310–350 nm; and (iv) the solution activated with both 3% H2O2 and light at 310–350 nm. A control group and one with only H2O2 were also tested. After that, the Petri plates were incubated for 48 h at 37 °C. With inhibitory halos ranging from 30 to 40 mm for all Candida spp. MDR analyzed, group (iv) displayed the greatest results. H2O2 + lactoferrin-based solutions are thought to be potential PS in PDT for MDR Candida spp. eradication. Full article
(This article belongs to the Special Issue Oral Microbes and Human Health, Second Edition)
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23 pages, 2393 KiB  
Article
Salutary Effects of Overexpression of Rsm22, an Assembly Factor for the Mitochondrial Ribosome, on Frataxin/Yfh1 Depletion Phenotypes in Saccharomyces cerevisiae
by Ashutosh K. Pandey, Pratibha Singh, Jayashree Pain, Andrew Dancis and Debkumar Pain
Biomolecules 2025, 15(6), 785; https://doi.org/10.3390/biom15060785 - 28 May 2025
Viewed by 360
Abstract
Frataxin is a component of the iron–sulfur (Fe-S) cluster assembly complex in mitochondria, and deficiency is associated with Friedreich ataxia (FA). The yeast homolog Yfh1 resembles and cross-complements with its human equivalent, and frataxin bypass scenarios are of particular interest because they may [...] Read more.
Frataxin is a component of the iron–sulfur (Fe-S) cluster assembly complex in mitochondria, and deficiency is associated with Friedreich ataxia (FA). The yeast homolog Yfh1 resembles and cross-complements with its human equivalent, and frataxin bypass scenarios are of particular interest because they may point to strategies for treating FA. Here, we describe frataxin/Yfh1 bypass by overexpression of Rsm22, an assembly factor for the mitochondrial ribosome. Rsm22 overexpression in Yfh1-depleted yeast cells restored critical processes in mitochondria, including Fe-S cluster assembly, lipoic acid synthesis, iron homeostasis, and heme synthesis, to a significant extent. Formation of cytoplasmic Fe-S proteins was also restored, suggesting recovery of the mitochondrial ability to generate the (Fe-S)int intermediate that is exported from mitochondria and is utilized for cytoplasmic Fe-S cluster assembly. Importantly, an essential component of the mitochondrial iron–sulfur cluster machinery, namely ferredoxin, was virtually absent in mitochondria lacking Yfh1, but it was recovered with Rsm22 overexpression. Interestingly, ferredoxin overexpression could offset some of the effects of Yfh1 depletion. Ferredoxin has recently been shown to bind to the cysteine desulfurase protein Nfs1 at the same site as Yfh1, in a conserved arginine patch on Nfs1, such that ferredoxin binding at this site may confer frataxin-bypass activity. Full article
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24 pages, 21945 KiB  
Article
Drug Pair of Astragali Radix–Ligustri Lucidi Fructus Alleviates Acute Kidney Injury in Mice Induced by Ischemia–Reperfusion Through Inhibiting Ferroptosis
by Xuanhe Liu, Dan Zhang, Yuting Xie, Mengdan Wang, Xiaochun Chen, Weijie Yu, Yuming Ma, Jia Zeng, Qixuan Long, Guangrui Huang, Jie Geng and Anlong Xu
Pharmaceuticals 2025, 18(6), 789; https://doi.org/10.3390/ph18060789 - 25 May 2025
Viewed by 710
Abstract
Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise [...] Read more.
Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise in renal diseases, but its protective effects against RIRI and associated molecular pathways via ferroptosis inhibition are unknown. This study aimed to investigate DAL’s therapeutic effects on RIRI and its mechanisms. Methods: A mouse model of bilateral renal ischemia–reperfusion was established. Renal function (serum creatinine, Scr; blood urea nitrogen, BUN), inflammatory cytokines (TNF-α, IFN-γ, IL-6), ferroptosis markers (GPX4, MDA, GSH, tissue iron), and pathological damage were evaluated. Transcriptomic sequencing and electron microscopy analyzed gene pathways and mitochondrial structure. In HK-2 cells, oxygen–glucose deprivation/reoxygenation (OGD/R) and RSL3-induced ferroptosis models were used to assess DAL-containing serum effects via cell viability, GPX4 expression, and mitochondrial morphology. LC-MS analyzed DAL’s chemical components, and network pharmacology predicted ferroptosis-related targets. Results: DAL significantly reduced Scr/BUN levels, alleviated tubular injury, fibrosis, and apoptosis, and downregulated inflammatory cytokines and damage markers. It inhibited ferroptosis by upregulating GPX4, decreasing MDA/tissue iron, and increasing GSH. Transcriptomics revealed enrichment in lipid metabolism pathways. DAL restored the mitochondrial cristae structure; DAL-containing serum improved cell viability, blocked RSL3-induced GPX4 downregulation, and mitigated mitochondrial dysfunction. Network pharmacology identified DAL’s potential active components and targets. Molecular docking validated binding affinity and interaction patterns of active components with targets. Conclusions: DAL protects against RIRI by upregulating GPX4, preserving the mitochondrial structure, and inhibiting ferroptosis, highlighting its therapeutic potential for AKI prevention and treatment. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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15 pages, 1596 KiB  
Review
Ovotransferrin as a Multifunctional Bioactive Protein: Unlocking Its Potential in Animal Health and Wellness
by Sahdeo Prasad, Bhaumik Patel, Prafulla Kumar, Jeffrey Kaufman and Rajiv Lall
Vet. Sci. 2025, 12(6), 514; https://doi.org/10.3390/vetsci12060514 - 24 May 2025
Viewed by 752
Abstract
Ovotransferrin (OVT) is one of the major proteins of egg white and is known to bind and transport irons in animals. OVT exerts bacteriostatic and bactericidal activities due to its iron-binding capacity. OVT effectively controls the growth of various pathogenic microorganisms, including Pseudomonas, [...] Read more.
Ovotransferrin (OVT) is one of the major proteins of egg white and is known to bind and transport irons in animals. OVT exerts bacteriostatic and bactericidal activities due to its iron-binding capacity. OVT effectively controls the growth of various pathogenic microorganisms, including Pseudomonas, E. coli, Staphylococcus, Proteus, and Klebsiella species, as well as inhibiting the replication of viruses. OVT also has antioxidant, anti-inflammatory, anti-hypertensive, anticancer, and immuno-stimulating properties. For instances, OVT quenches free radicals, induces antioxidant enzymes, suppresses pro-inflammatory cytokines, increases immune cells, reduces angiotensin-converting enzymes, and inhibits the proliferation of cancer cells. In this review, the beneficial effects of OVT in both in vitro and in vivo, particularly livestock, are described. Because of its antimicrobial properties, OVT supplementation in livestock feed would be an excellent alternative to antibiotics, which reducing the development of antibiotic-resistant pathogenic microorganisms. Thus, OVT could be a game-changing protein for the growth, performance, and healthy life of animals. Full article
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