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Clavibacter michiganensis subsp. michiganensis (Cmm) and C. michiganensis subsp. capsici (Cmc) are phytopathogenic bacteria that cause bacterial canker disease in tomatoes and peppers, respectively. Bacterial canker disease poses serious challenges to solanaceous crops, causing significant yield losses and economic costs. Effective management necessitates the development of sustainable control strategies employing nanobiotechnology. In this study, the antibacterial effects of four Aspergillus sojae-mediated nanoformulations, including cobalt oxide nanoparticles (Co 3 O 4 NPs), zinc oxide nanoparticles (ZnO NPs), cobalt ferrite nanoparticles (CoFe 2 O 4 NPs), and CoFe 2 O 4 /functionalized multi-walled carbon nanotube (fMWCNT) bionanocomposite, were evaluated against Cmm and Cmc. The diameters of the zone of inhibition of A. sojae-mediated Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmm and Cmc were 23.60 mm, 22.09 mm, 27.65 mm, 22.51 mm, and 19.33 mm, 17.66 mm, 21.64 mm, 18.77 mm, respectively. The broth microdilution assay was conducted to determine the minimal inhibitory and bactericidal concentrations. The MICs of Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmm were 2.50 mg/mL, 1.25 mg/mL, 2.50 mg/mL, and 2.50 mg/mL, respectively. While, their respective MBCs against Cmm were 5.00 mg/mL, 2.50 mg/mL, 5.00 mg/mL, and 5.00 mg/mL. The respective MICs of Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmc were 2.50 mg/mL, 1.25 mg/mL, 5.00 mg/mL, and 5.00 mg/mL. While, their respective MBCs against Cmc were 5.00 mg/mL, 2.50 mg/mL, 10.00 mg/mL, and 10.00 mg/mL. The morphological and ultrastructural changes of Cmm and Cmc cells were observed using field-emission scanning and transmission electron microscopy before and after treatment with sub-minimal inhibitory concentrations of the nanoformulations. Nanoformulation-treated bacterial cells became deformed and disrupted, displaying pits, deep cavities, and groove-like structures. The cell membrane detached from the bacterial cell wall, electron-dense particles accumulated in the cytoplasm, cellular components disintegrated, and the cells were lysed. Direct physical interactions between the prepared nanoformulations with Cmm and Cmc cells might be the major mechanism for their antibacterial potency. Further research is required for the in vivo application of the mycosynthesized nanoformulations as countermeasures to combat bacterial phytopathogens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) represents an aggressive brain tumor, characterized by intra- and inter-tumoral heterogeneity and therapy resistance, leading to unfavourable prognosis. An increasing number of studies pays attention on the regulation of ferroptosis, an iron-dependent cell death, as a strategy to reverse drug resistance in cancer. However, the debate on whether this strategy may have important implications for the treatment of GBM is still ongoing. In the present study, we used ferric ammonium citrate and erastin to evaluate ferroptosis induction effects on two human GBM cell lines, U-251 MG, with proneural characteristics, and T98-G, with a mesenchymal profile. The response to ferroptosis induction was markedly different between cell lines, indeed T98-G cells showed an enhanced antioxidant defence, with increased glutathione levels, as compared to U-251 MG cells. Moreover, using bioinformatic approaches and analysing publicly available datasets from patients' biopsies, we found that GBM with a mesenchymal phenotype showed an up-regulation of several genes involved in antioxidant mechanisms as compared to proneural subtype. Thus, our results suggest that GBM subtypes differently respond to ferroptosis induction, emphasizing the significance of further molecular studies on GBM to better discriminate between various tumor subtypes and progressively move towards personalized therapy., (© 2024. The Author(s).)

Objective: Nowadays, the prevalence of cognitive impairment in women has gradually increased, especially in postmenopausal women. There were few studies on the mechanistic effects of iron exposure on neurotoxicity in postmenopausal women. The aim of this study is to investigate the effect of iron accumulation on cognitive ability in ovariectomized mice and its possible mechanism and to provide a scientific basis for the prevention of cognitive dysfunction in postmenopausal women., Methods: Female C57BL/6N ovariectomized model mice were induced with ferric citrate (FAC). The mice were randomly divided into 5 groups: control, sham, ovariectomized (Ovx), Ovx + 50 mg/kg FAC (Ovx + l), and Ovx + 100 mg/kg FAC (Ovx + h). The impact of motor and cognitive function was verified by a series of behavioral tests. The levels of serum iron parameters, malondialdehyde, and superoxide dismutase were measured. The ultrastructure of mice hippocampal microglia was imaged by transmission electron microscopy. The differential expression of hippocampal proteins was analyzed by Tandem Mass Tag labeling., Results: Movement and cognitive function in Ovx + l/Ovx + h mice were significantly decreased compared to control and Sham mice. Then, iron exposure caused histopathological changes in the hippocampus of mice. In addition, proteomic analysis revealed that 29/27/41 proteins were differentially expressed in the hippocampus when compared by Ovx vs. Sham, Ovx + l vs. Ovx, as well as Ovx + h vs. Ovx + l groups, respectively. Moreover, transferrin receptor protein (TFR1) and divalent metal transporter 1 (DMT1) protein expression were significantly increased in the iron accumulation mice model with ovariectomy., Conclusion: Iron exposure could cause histopathological damage in the hippocampus of ovariectomised mice and, by altering hippocampal proteomics, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Iron(III) complexes based on N,N´-bis(salicylidene)ethylenediamine (salene) scaffolds have demonstrated promising anticancer features like induction of ferroptosis, an iron dependent cell death. Since poor cellular uptake limits their therapeutical potential, this study aimed to enhance the lipophilic character of chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes by introducing lipophilicity improving ligands such as fluorine (X1), chlorine (X2) and bromine (X3) in 5-position in the salicylidene moieties. After detailed characterization the binding to nucleophiles, logP values and cellular uptake were determined. The complexes were further evaluated regarding their biological activity on MDA-MB 231 mammary carcinoma, the non-tumorous SV-80 fibroblast, HS-5 stroma and MCF-10A mammary gland cell lines. Stability of the complexes in aqueous and biological environments was proven by the lack of interactions with amino acids and glutathione. Cellular uptake was positively correlated with the logP values, indicating that higher lipophilicity enhanced cellular uptake. The complexes induced strong antiproliferative and antimetabolic effects on MDA-MB 231 cells, but were inactive on all non-malignant cells tested. Generation of mitochondrial reactive oxygen species, increase of lipid peroxidation and induction of both ferroptosis and necroptosis were identified as mechanisms of action. In conclusion, halogenation of chlorido[N,N'-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes raises their lipophilic character resulting in improved cellular uptake., (© 2024. The Author(s).)

Three carboxamide-based ligands and their iron(III) complexes were prepared and structurally characterized. Analytical, thermal and mass spectra measurements showed a 1:1 stoichiometric (M:L) of the synthesized iron(III) complexes. The distorted octahedral geometry of the present iron(III) complexes was assigned based on the results of spectroscopy and magnetometry. Processing of X-ray diffraction data for powder samples by the software Expo 2014 confirmed the octahedral geometry of the three iron(III) complexes. Electrochemical properties of the present iron(III) complexes were studied by cyclic voltammetric measurements. The present iron(III) complexes exhibit SOD like activity with IC 50 values of 16.45, 15.24 and 9.70 μM. The drive forces (-λ or Δ G °) controlling these biocatalytic reactions were determined and correlated with catalytic activity. The proposed catalytic mechanistic implications for the conversion of O 2 •- to H 2 O 2 and H 2 O were discussed. The antimicrobial activity has been studied in vitro against G(+) and G(-) pathogenic bacteria. The in vitro anticancer activity of the carboxamide-based ligands and their iron(III) complexes against human Hepatocellular carcinoma (HepG-2) cell lines was examined. The obtained results demonstrated the potent anticancer activity of iron(III) complexes with increased safety on normal cells compared to cisplatin. Molecular docking calculations confirmed the experimental findings of the antibacterial and anticancer activities of both free ligands and their iron(III) chelates.Communicated by Ramaswamy H. Sarma.

Reactive oxygen species (ROS)-mediated therapeutic strategies, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H 2 O 2 in tumors into O 2 required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe Fe 2 O 3 /CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert Fe 2 O 3 to Fe 2+ . After modified by MgO 2 and photosensitizer Ce6, MgO 2 -Fe 2 O 3 /CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H 2 O 2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14 %. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yan Chen reports financial support was provided by Anhui Provincial Department of Education. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, using pharmacological ascorbic acid has emerged as a promising therapeutic approach in cancer treatment, owing to its capacity to induce extracellular hydrogen peroxide (H 2 O 2 ) production in solid tumors. The H 2 O 2 is then converted into cytotoxic hydroxyl free radicals (HO˙) by redox-active Fe 2+ inside cells. However, the high dosage of ascorbic acid required for efficacy is hampered by adverse effects such as kidney stone formation. In a recent study, we demonstrated the efficient catalytic conversion of H 2 O 2 to HO˙ by wüstite (Fe 1- x O) nanoparticles (WNPs) through a heterogenous Fenton reaction. Here, we explore whether WNPs can enhance the therapeutic potential of ascorbic acid, thus mitigating its dose-related limitations. Our findings reveal distinct pH dependencies for WNPs and ascorbic acid in the Fenton reaction and H 2 O 2 generation, respectively. Importantly, WNPs exhibit the capability to either impede or enhance the cytotoxic effect of ascorbic acid, depending on the spatial segregation of the two reagents by cellular compartments. Furthermore, our study demonstrates that treatment with ascorbic acid promotes the polarization of WNP-loaded macrophages toward a pro-inflammatory M1 phenotype, significantly suppressing the growth of 4T1 breast cancer cells. This study highlights the importance of orchestrating the interplay between ascorbic acid and nanozymes in cancer therapy and presents a novel macrophage-based cell therapy approach.

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe 2 O 4 -PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe 2 O 4 , denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Magnetic drug delivery systems using nanoparticles present a promising opportunity for clinical treatment. This study explored the potential anti-inflammatory properties of RosA- CrFe2O4 nanoparticles. These nanoparticles were developed through rosmarinic acid (RosA) co-precipitation via a photo-mediated extraction technique. XRD, FTIR, and TEM techniques were employed to characterize the nanoparticles, and the results indicated that they had a cubic spinel ferrite (FCC) structure with an average particle size of 25nm. The anti-inflammatory and antioxidant properties of RosA- CrFe2O4 nanoparticles were evaluated by using LPS-induced raw 264.7 macrophages and a hydrogen peroxide scavenging assay, respectively. The results showed that RosA- CrFe2O4 nanoparticles had moderate DPPH scavenging effects with an IC50 value of 59.61±4.52μg/ml. Notably, these nanoparticles effectively suppressed the expression of pro-inflammatory genes (IL-1β, TNF-α, IL-6, and iNOS) in LPS-stimulated cells. Additionally, the anti-inflammatory activity of RosA- CrFe2O4 nanoparticles was confirmed by reducing the release of secretory pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated macrophages. This investigation highlights the promising potential of Phyto-mediated CrFe2O4-RosA as an anti-inflammatory and antioxidant agent in biomedical applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al-Hunaiti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Preservation of primary teeth in children is highly important. Pulpotomy is a commonly performed treatment procedure for primary teeth with extensive caries. Thus, biocompatibility of pulpotomy agents is highly important. Biodentine, calcium enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) Angelus are commonly used for this purpose. Thus, this study aimed to assess the apoptotic effects of Biodentine, CEM cement, ferric sulfate, and MTA on stem cells isolated from the human pulp of exfoliated deciduous teeth., Methods: In this in-vitro, experimental study, stem cells isolated from the human pulp of exfoliated deciduous teeth were exposed to three different concentrations of Biodentine, CEM cement, ferric sulfate, and MTA for different time periods. The cytotoxicity of the materials was evaluated by flow cytometry using the annexin propidium iodide (PI) kit. Data were analyzed by ANOVA and Tukey's test at P<0.05 level of significance., Results: All four tested materials induced significantly greater apoptosis compared with the control group. The difference in cell apoptosis caused by the first concentration of ferric sulfate and MTA was not significant at 24 hours. In other comparisons, the cytotoxicity of ferric sulfate was significantly lower than that of other materials. Biodentine showed higher cytotoxicity than MTA at first; but this difference faded over time. The cytotoxicity of CEM cement was comparable to that of MTA. The highest cell viability was noted at 24 hours in presence of the minimum concentration of ferric sulfate. The lowest cell viability was noted at 72 hours in presence of the maximum concentration of CEM cement., Conclusions: In comparison with other materials, ferric sulfate showed minimum cytotoxicity; the cytotoxicity of the three cements was comparable. It appears that the concentration of ferric sulfate and the composition of cements are responsible for different levels of cytotoxicity.

Combining a biocompatible hydrogel scaffold with the cell-supportive properties of silk fibroin (SF) and the unique functionalities of ZnFe 2 O 4 nanoparticles creates a promising platform for advanced nanobiomaterials. The research is centered on synthesizing a natural hydrogel using cellulose (Cellul) and sodium alginate (SA) combined with SF and zinc ferrite nanoparticles. A range of analytical and biological assays were conducted to determine the biological and physicochemical properties of the nanobiocomposite. The hemolysis and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assays indicated that the SA-Cellul hydrogel/SF/ZnFe 2 O 4 nanobiocomposite was a biocompatible against human dermal fibroblasts (Hu02) and red blood cells (RBC). In addition, aside from demonstrating outstanding anti-biofilm activity, the nanobiocomposite also promotes the Hu02 cells adhesion, showcasing the synergistic effect of incorporating SF and ZnFe 2 O 4 nanoparticle. These promising results show that this nanobiocomposite has potential applications in various biomedical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nickel ferrite nanoparticles (NiFe 2 O 4 NPs) were synthesized using the medicinally important plant Aloe vera leaf extract, and their structural, morphological, and magnetic properties were characterized by x-ray diffraction (XRD), fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized NPs were soft ferromagnetic and spinel in nature, with an average particle size of 22.2 nm. To the best of our understanding, this is the first comprehensive investigation into the antibacterial, anticandidal, antibiofilm, and antihyphal properties of NiFe 2 O 4 NPs against C. albicans as well as drug-resistant gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative multidrug resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) bacteria. NiFe 2 O 4 NPs showed potent antimicrobial activity (MIC 1.6-2 mg/mL) against the test pathogens. NiFe 2 O 4 NPs at 0.5 mg/mL suppressed biofilm formation by 49.5-53.1 % in test pathogens. The study found that the NPs not only prevent the formation of biofilm, but also eliminate existing mature biofilms by 50.5-75.79 % at 0.5 mg/mL, which was further validated by SEM. SEM examination revealed a reduction in the number of cells that form biofilms and adhere to the surface. Additionally, it considerably impeded the colonization and aggregation of the biofilm strains on the glass surface. Light microscopic examination demonstrated that NPs effectively prevent the expansion of hyphae, filaments, and yeast-to-hyphae transformation in C. albicans, resulting in a substantial decrease in their ability to cause infection. Moreover, SEM images of the treated cells exhibited the presence of wrinkles, deformities, and impaired cell walls, which suggests an alteration and instability of the membrane. This study demonstrated the efficacy of the greenly manufactured NPs in suppressing the proliferation of candida, drug-resistant bacteria, and their preexisting biofilms, as well as yeast-to-hyphae transformation. Therefore, these NPs with broad spectrum applications could be utilized in health settings to mitigate biofilm-related health conditions caused by pathogenic microbial strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Polyferric sulfate (PFS), an economical coagulant widely used for removing heavy metal contaminants from water, is susceptible to reduction and transformation by iron-reducing bacteria prevalent in sediments. However, the effect of heavy metal ions adsorbed in PFS flocs on this biological process remains unclear. According to our results, compared with other heavy metal cations (e.g., Cu 2+ , Cd 2+ , Zn 2+ , Ni 2+ , Pb 2+ , and Co 2+ ), Cu 2+ had a stronger inhibitory effect on PFS floc reduction by Shewanella putrefaciens CN32, a typical dissimilatory iron-reducing bacterium. The presence of Cu 2+ remarkably influenced the global transcription of CN32, resulting in 782 upregulated genes and 713 downregulated genes that are mainly annotated in energy production, amino acid metabolism, protein biosynthesis, and oxidation‒reduction processes. The anaerobic TCA cycle for energy (electron) production was significantly activated in the presence of Cu 2+ , while the transcription of many genes related to the extracellular electron transfer pathway was downregulated, which is responsible for the decreased Fe 3+ reduction. Moreover, the pathways of assimilatory sulfate reduction and subsequent cysteine biosynthesis were significantly enriched, which is hypothesized to result in the consumption of abundant energy produced from the enhanced anaerobic TCA cycle, revealing a strategy to address the oxidative stress caused by Cu 2+ . This work elucidates the unusual suppressive effects of Cu 2+ on the microbial reduction of PFS flocs, which reveals the high resistance of PFS flocs to microbial destruction when used to treat Cu 2+ pollution in water, thus demonstrating their tremendous practical prospects., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The clinical treatment of human acute myeloid leukemia (AML) is rapidly progressing from chemotherapy to targeted therapies led by the BCL-2 inhibitor venetoclax (VEN). Despite its unprecedented success, VEN still encounters clinical resistance. Thus, uncovering the biological vulnerability of VEN-resistant AML disease and identifying effective therapies to treat them are urgently needed. We have previously demonstrated that iron oxide nanozymes (IONE) are capable of overcoming chemoresistance in AML. The current study reports a new activity of IONE in overcoming VEN resistance. Specifically, we revealed an aberrant redox balance with excessive intracellular reactive oxygen species (ROS) in VEN-resistant monocytic AML. Treatment with IONE potently induced ROS-dependent cell death in monocytic AML in both cell lines and primary AML models. In primary AML with developmental heterogeneity containing primitive and monocytic subpopulations, IONE selectively eradicated the VEN-resistant ROS-high monocytic subpopulation, successfully resolving the challenge of developmental heterogeneity faced by VEN. Overall, our study revealed an aberrant redox balance as a therapeutic target for monocytic AML and identified a candidate IONE that could selectively and potently eradicate VEN-resistant monocytic disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe 3 O 4 ) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe 3 O 4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe 3 O 4 scaffolds containing different Fe 3 O 4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe 3 O 4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10 F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe 3 O 4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe 3 O 4 composite oriented scaffolds have potential applications in neural tissue engineering., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The strategic integration of multi-functionalities within a singular nanoplatform has received growing attention for enhancing treatment efficacy, particularly in chemo-photothermal therapy. This study introduces a comprehensive concept of Janus nanoparticles (JNPs) composed of Au and Fe 3 O 4 nanostructures intricately bonded with β-cyclodextrins (β-CD) to encapsulate 5-Fluorouracil (5-FU) and Ibuprofen (IBU). This strategic structure is engineered to exploit the synergistic effects of chemo-photothermal therapy, underscored by their exceptional biocompatibility and photothermal conversion efficiency (∼32.88 %). Furthermore, these β-CD-conjugated JNPs enhance photodynamic therapy by generating singlet oxygen ( 1 O 2 ) species, offering a multi-modality approach to cancer eradication. Computer simulation results were in good agreement with in vitro and in vivo assays. Through these studies, we were able to prove the improved tumor ablation ability of the drug-loaded β-CD-conjugated JNPs, without inducing adverse effects in tumor-bearing nude mice. The findings underscore a formidable tumor ablation potency of β-CD-conjugated Au-Fe 3 O 4 JNPs, heralding a new era in achieving nuanced, highly effective, and side-effect-free cancer treatment modalities. STATEMENT OF SIGNIFICANCE: The emergence of multifunctional nanoparticles marks a pivotal stride in cancer therapy research. This investigation unveils Janus nanoparticles (JNPs) amalgamating gold (Au), iron oxide (Fe 3 O 4 ), and β-cyclodextrins (β-CD), encapsulating 5-Fluorouracil (5-FU) and Ibuprofen (IBU) for synergistic chemo-photothermal therapy. Demonstrating both biocompatibility and potent photothermal properties (∼32.88 %), these JNPs present a promising avenue for cancer treatment. Noteworthy is their heightened photodynamic efficiency and remarkable tumor ablation capabilities observed in vitro and in vivo, devoid of adverse effects. Furthermore, computational simulations validate their interactions with cancer cells, bolstering their utility as an emerging therapeutic modality. This endeavor pioneers a secure and efficacious strategy for cancer therapy, underscoring the significance of β-CD-conjugated Au-Fe 3 O 4 JNPs as innovative nanoplatforms with profound implications for the advancement of cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe 3 O 4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe 3 O 4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe 3 O 4 , and co-treatment with nano-Fe 3 O 4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe 3 O 4 . The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe 3 O 4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe 3 O 4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe 3 O 4 ., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xuebing Yan reports financial support was provided by National Natural Science Foundation of China. Zhao Chen reports financial support was provided by National Natural Science Foundation of China. Zhao Chen reports financial support was provided by Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Many microbes produce siderophores, which are extremely potent weapons capable of stealing iron ions from human tissues, fluids and cells and transferring them into bacteria through their appropriate porins. We have recently designed a multi-block molecule, each block having a dedicated role. The first component is an antimicrobial peptide, whose good effectiveness against some bacterial strains was gradually improved through interactive sequence modifications. Connected to this block is a flexible bio-band, also optimized in length, which terminates in a hydroxyamide unit, a strong metal binder. Thus, the whole molecule brings together two pieces that work synergistically to fight infection. To understand if the peptide unit, although modified with a long tail, preserves the structure and therefore the antimicrobial activity, and to characterize the mechanism of interaction with bio-membrane models mimicking Gram-negative membranes, we performed a set of fluorescence-based experiments and circular dichroism studies, which further supported our design of a combination of two different entities working synergistically. The chelating activity and iron(III) binding of the peptide was confirmed by iron(III) paramagnetic NMR analyses, and through a competitive assay with ethylenediamine-tetra acetic acid by ultraviolet-visible spectroscopy. The complexation parameters, the Michaelis constant K, and the number of sites n, evaluated with spectrophotometric techniques are confirmed by Fe(III) paramagnetic NMR analyses here reported. In conclusion, we showed that the coupling of antimicrobial capabilities with iron-trapping capabilities works well in the treatment of infectious diseases caused by Gram-negative pathogens., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, photodynamic therapy (PDT) is restricted by the laser penetration depth. Except for PDT at 1064 nm wavelength excitation, the development of other NIR-II-activated nanomaterials with a higher response depth is still hindered and rarely reported in the literature. To overcome these problems, we fabricated a nanoplatform with heterostructures that generate reactive oxygen species (ROS) and ferrite nanoparticles under a high concentration of zinc doping (Zn x Fe 3- x O 4 NPs), which can achieve oxidative damage of tumor cells under near-infrared (NIR) illumination. The recombination of photoelectrons and holes has been markedly inhibited due to the formation of heterostructures in the interfaces, thus greatly enhancing the capability for ROS and oxygen production by modulating the single-component doping content. The efficiency of PDT was verified by in vivo and in vitro assays under NIR light. Our results revealed that NIR-II (1208 nm) light irradiation of Zn x Fe 3- x O 4 NPs exerted a remarkable antitumor activity, superior to NIR-I light (808 nm). More importantly, the reported Zn x Fe 3- x O 4 NPs strategy provides an opportunity for the success of comparison with light in the first and second near-infrared regions.

The nuclear receptor-related factor 1 (Nurr1), an orphan nuclear receptor in microglia, has been recognized as a major player in attenuating the transcription of the pro-inflammatory genes to maintain CNS homeostasis. In this study, we investigate Nurr1 trans-repression activity by targeting this receptor with one of the indole derivatives 3-Indole acetic acid hydrazide (IAAH) loaded onto zinc iron oxide (ZnFe 2 O 4 ) NPs coated with PEG. XRD, SEM, FTIR, UV-Vis spectroscopy, and DLS were used to characterize the synthesized IAAH-NPs. The anti-inflammatory properties of IAAH-NPs on LPS-stimulated SimA9 microglia were assayed by measuring pro-inflammatory cytokine gene expressions and protein levels using RT-PCR and ELISA, respectively. As a result, IAAH-NPs showed an ability to suppress pro-inflammatory genes, including IL-6, IL-1β, and TNF-α in LPS-stimulated SimA9 via targeting Nurr1. The current study suggests that ZnFe 2 O 4 NPs as a delivery system can increase the efficiency of cellular uptake and enhance the IAAH ability to inhibit the pro-inflammatory cytokines. Collectively, we demonstrate that IAAH-NPs is a potential modulator of Nurr1 that combines nanotechnology as a delivery system to suppress neuroinflammation in CNS which opens a window for possible ambitious neuroprotective therapeutic approaches to neuro disorders., (© 2024. The Author(s).)

Goals of the investigation: This work aimed to evaluate the neuroprotective effects of zinc oxide (ZnO) nanoparticles in an experimental mouse model of rotenone-induced PD and investigate the therapeutic effects of ZnO, cobalt ferrite nanoparticles, and their combination. Methods: The levels of dopamine, norepinephrine, epinephrine, and serotonin were assessed using ELISA in the control and experimental model of PD mice. The dopa-decarboxylase expression level was assayed by real-time PCR. The expression level of tyrosine hydroxylase (TH) was assessed by western blot analysis. Results: Our data showed that levels of dopamine decreased in PD mice compared to normal. ZnO NP increased dopamine levels in normal and PD mice (37.5% and 29.5%; respectively, compared to untreated mice). However, ZnO NP did not cause any change in norepinephrine and epinephrine levels either in normal or in PD mice. Levels of serotonin decreased by 64.0%, and 51.1% in PD mice treated with cobalt ferrite and dual ZnO- cobalt ferrite NPs; respectively, when compared to PD untreated mice. The mRNA levels of dopa-decarboxylase increased in both normal and PD mice treated with ZnO NP. Its level decreased when using cobalt ferrite NP and the dual ZnO-cobalt ferrite NP when compared to untreated PD mice. A significant decrease in TH expression by 0.25, 0.68, and 0.62 folds was observed in normal mice treated with ZnO, cobalt ferrite, and the dual ZnO-cobalt ferrite NP as compared to normal untreated mice. In PD mice, ZnO administration caused a non-significant 0.15-fold decrease in TH levels while both cobalt ferrite and the dual ZnO-cobalt ferrite NP administration caused a significant 0.3 and 0.4-fold decrease respectively when compared to untreated PD mice. Principal conclusion : This study reveals that ZnO NPs may be utilized as a potential intervention to elevate dopamine levels to aid in PD treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This study reports the antibacterial and antibiofilm activities of Magnesium ferrite nanoparticles (MgFe 2 O 4 ) against gram-positive and gram-negative bacteria. The photocatalytic degradation of Carbol Fuchsin (CF) dye (a class of dyestuffs that are resistant to biodegradation) under the influence of UV-light irradiation is also studied. The crystalline magnesium ferrite (MgFe 2 O 4 ) nanoparticles were synthesized using the co-precipitation method. The morphology of the resulting nanocomposite was examined using scanning electron microscopy (SEM), while transmission electron microscopy (TEM) was employed for further characterization of particle morphology and size. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were utilized to analyze the crystalline structure, chemical composition, and surface area, respectively. Optical properties were evaluated using UV-Vis spectroscopy. The UV-assisted photocatalytic performance of MgFe 2 O 4 nanoparticles was assessed by studying the decolorization of Carbol fuchsin (CF) azo dye. The crystallite size of the MgFe 2 O 4 nanoparticles at the (311) plane, the most prominent peak, was determined to be 28.5 nm. The photocatalytic degradation of 10 ppm CF using 15 mg of MgFe 2 O 4 nanoparticles resulted in a significant 96% reduction after 135 min at ambient temperature (25 °C) and a pH value of 9. Additionally, MgFe 2 O 4 nanoparticles exhibited potent antibacterial activity against E. coli and S. aureus in a dose dependent manner with maximum utilized concentration of 30 µg/ml. Specifically, MgFe 2 O 4 nanoparticles demonstrated substantial antibacterial activity via disk diffusion and microbroth dilution tests with zones of inhibition and minimum inhibitory concentrations (MIC) for E. coli (26.0 mm, 1.25 µg/ml) and S. aureus (23.0 mm, 2.5 µg/ml), respectively. Moreover, 10.0 µg/ml of MgFe 2 O 4 nanoparticles elicited marked percent reduction in biofilm formation by E. coli (89%) followed by S. aureus (78.5%) after treatment. In conclusion, MgFe 2 O 4 nanoparticles demonstrated efficient dye removal capabilities along with significant antimicrobial and antibiofilm activity against gram-positive and gram-negative bacterial strains suggesting their potential as promising antimicrobial and detoxifying agents., (© 2024. The Author(s).)

New tranexamic acid (TXA) complexes of ferric(III), cobalt(II), nickel(II), copper(II) and zirconium(IV) were synthesized and characterized by elemental analysis (CHN), conductimetric (Λ), magnetic susceptibility investigations (μeff), Fourier transform infrared (FT-IR), proton nuclear magnetic resonance ( 1 H-NMR), ultraviolet visible (UV-vis.), optical band gap energy (E g ) and thermal studies (TG/DTG and DTA). TXA complexes were established in 1 : 2 (metal: ligand) stoichiometric ratio according to CHN data. Based on FT-IR and 1 H-NMR data the disappeared of the carboxylic proton supported the deprotonating of TXA and linked to metal ions via the carboxylate group's oxygen atom as a bidentate ligand. UV-visible spectra and magnetic moment demonstrated that all chelates have geometric octahedral structures. E g values indicated that our complexes are more electro conductive. DTA revealed presence of water molecules in inner and outer spheres of the complexes. DTA results showed that endothermic and exothermic peaks were identified in the degradation mechanisms. The ligand and metal complexes were investigated for their antimicrobial and herbicidal efficacy. The Co(II) and Ni(II) complexes showed antimicrobial activity against some tested species. The obtained results showed a promising herbicidal effect of TXA ligand and its metal complexes particularly copper and zirconium against the three tested plants., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: An iron overload status induces ferroptosis, an iron-dependent nonapoptotic cell death, in various pathological conditions. We previously reported that hemin (heme), protoporphyrin-IX with ferric iron, activates platelets via C-type lectin-like receptor-2 (CLEC-2) and glycoprotein VI/FcRγ, but protoporphyrin-IX alone blocks CLEC-2-dependent platelet activation. Therefore, we hypothesized that free iron has the ability to activate platelets., Objectives: This study aimed to elucidate platelet activation mechanisms of iron (ferric chloride), including the identification of signaling pathways and receptors, and to examine whether platelets regulate ferroptosis., Methods: Platelet aggregometry, platelet activation marker expression, and protein phosphorylation were examined in ferric chloride-stimulated human and murine platelets. Inhibitors of platelet activation signaling pathways and receptor-deleted platelets were utilized to identify the responsible signaling pathway and receptor. The effect of platelets on ferroptosis of endothelial cells was investigated in vitro., Results: Ferric chloride induced platelet activation dependent on Src family kinase pathways in humans and mice. Ferric chloride-induced platelet aggregation was almost lost in CLEC-2-depleted murine platelets and wild-type platelets preincubated with recombinant CLEC-2 proteins. Furthermore, coculture of wild-type platelets, but not CLEC-2-deficient platelets, attenuated ferroptosis of endothelial cells in vitro., Conclusion: Ferric chloride activates platelets via CLEC-2 and Src family kinase pathways, and platelets have a protective role in the ferroptosis of endothelial cells dependent on CLEC-2., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

One of the global challenges for living things is to provide pollution and harmful microbes-free environment. In this study, magnetically retrievable spinel-structured manganese zinc ferrite (Mn 0.5 Zn 0.5 Fe 2 O 4 ) (MZF) was synthesized by a facile solvothermal method. Further, the MZF with different weight percentages (10 wt%, 50 wt%, and 80 wt%) were supported on reduced graphene oxide (rGO). The phase purity and morphology of MZF and MZF/rGO nanocomposite were confirmed by x-ray diffraction technique and scanning electron microscopy, respectively. The Fourier transform infrared spectroscopy, Raman, UV-visible spectroscopy, and thermogravimetric analyses of the as-synthesized nanocomposites were examined for the detection of various chemical groups, band gap, and thermal properties, respectively. The MZF/rGO nanocomposite exhibited significant antibacterial and antifungal activity against Eggerthella lenta, Enterococcus faecalis, Klebsiella pneumonia, Pseudomonas aeruginosa, and Candida albicans compared to bare MZF and rGO. The high surface area of rGO plays a crucible role in antimicrobial analysis. Additionally, the antibacterial and antifungal activity is compared by synthesizing various metal ferrites such as MnFe 2 O 4 , ZnFe 2 O 4 , and Fe 3 O 4 . The 50 wt% MZF/rGO nanocomposite exhibits significantly high antibacterial activity. However, 10 wt% MZF/rGO nanocomposite shows good antifungal activity than Fe 3 O 4 , MnFe 2 O 4 , ZnFe 2 O 4 , MnZnFe 2 O 4 , 50 wt%, and 80 wt% MZF/rGO nanocomposites. These findings suggest that the prepared ferrite nanocomposites hold promise for microbial inhibition., (© 2024 IOP Publishing Ltd.)

Objective: To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis., Methods: We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared., Results: There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose., Conclusions: Administration of IV iron at various high doses appears safe in our rat model of cirrhosis., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Teeth exemplify architectures comprising an interplay of inorganic and organic constituents, resulting in sophisticated natural composites. Rodents (Rodentia) showcase extraordinary adaptations, with their continuously growing incisors surpassing human teeth in functional and structural optimizations. In this study, employing state-of-the-art direct atomic-scale imaging and nanoscale spectroscopies, we present compelling evidence that the release of material from ameloblasts and the subsequent formation of iron-rich enamel and surface layers in the constantly growing incisors of rodents are complex orchestrated processes, intricately regulated and independent of environmental factors. The synergistic fusion of three-dimensional tomography and imaging techniques of etched rodent́s enamel unveils a direct correlation between the presence of pockets infused with ferrihydrite-like material and the acid resistant properties exhibited by the iron-rich enamel, fortifying it as an efficient protective shield. Moreover, observations using optical microscopy shed light on the role of iron-rich enamel as a microstructural element that acts as a path for color transmission, although the native color remains indistinguishable from that of regular enamel, challenging the prevailing paradigms. The redefinition of "pigmented enamel" to encompass ferrihydrite-like infusion in rodent incisors reshapes our perception of incisor microstructure and color generation. The functional significance of acid-resistant iron-rich enamel and the understanding of the underlying coloration mechanism in rodent incisors have far-reaching implications for human health, development of potentially groundbreaking dental materials, and restorative dentistry. These findings enable the creation of an entirely different class of dental biomaterials with enhanced properties, inspired by the ingenious designs found in nature.

In search of materials with superior capability of light-to-heat (photothermal) conversion, biocompatibility, and confinement of active photothermal materials within the cells, novel magnetic MXene-based nanocomposites are found to possess all of these criteria. The CoF@Ti 3 C 2 composite is fabricated by a simple two-step method, including an exfoliation strategy followed by sonochemical method. MXene composite has been modified with polyvinylpyrrolidone (PVP) to improve the stability in physiological conditions. The synthesized composite was characterized with multiple analytical tools. In vitro photothermal conversion efficiency of composite was determined by the time constant method and achieved η = 34.2% with an NIR 808 nm laser. In vitro, cytotoxicity studies conducted on human malignant melanoma (Ht144) and cells validated the photothermal property of the CoF@Ti 3 C 2 -PVP composite in the presence of an NIR laser (808 nm, 1.0 W cm -2 ), with significantly increased cytotoxicity. Calculated IC 50 values were 86 μg/mL with laser, compared to 226 μg/mL without the presence of NIR laser. Microscopic results demonstrated increased apoptosis in the presence of NIR laser. Additionally, hemolysis assay confirmed biocompatibility of CoF@Ti 3 C 2 -PVP composite for intravenous applications at the IC 50 concentration. The research described in this work expands the potential applications of MXene-based nanoplatforms in the biomedical field, particularly in photothermal therapy (PTT). Furthermore, the addition of cobalt ferrite serves as a magnetic nanocomposite, which eventually helps to confine therapeutic photothermal materials inside the cells, provides enhanced photothermal conversion efficiency, and creates externally controlled theranostic nanoplatforms for cancer therapy.

The surface modification of magnetite nanoparticles (Fe 3 O 4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe 3 O 4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe 3 O 4 NPs in situ coated by dextran (Fe 3 O 4 @Dex) and glucosamine-based amorphous carbon coating (Fe 3 O 4 @aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe 3 O 4 @aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe 3 O 4 @aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe 3 O 4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.

Prostate cancer is the second most frequent type of cancer death in men. This study refers to the novel hyperthermia application of poloxamer-coated cobalt ferrite as a new approach for thermal eradication of DU-145 human prostate cancerous cells under a radio frequency magnetic field (RF-MF). The hydrothermal method was applied for the synthesis of cobalt ferrite nanoparticles. Then, the structure, size, and morphology of nanoparticle were characterized. The cytotoxicity of the synthesized nanoparticles and RF-MF exposure on DU-145 prostate cancer cells was investigated separately or in combination with colony formation methods and MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. Transmission electron microscopy (TEM) confirmed the spherical morphology of nanoparticles with a size of 5.5 ± 2.6 nm. The temperature of cells treated with nanoparticles under RF-MF reached 42.73 ± 0.2°C after 15 min. RF-MF treatment or nanoparticles have not affected cell viability significantly. However, the combination of them eradicated 53% ± 4% of cancerous cells. In-vitro hyperthermia was performed on human prostate cancer cells (DU-145) with cobalt ferrite nanoparticles at specific concentrations that demonstrated a decrease in survival fraction based on colony formation assay compared to cells that were treated alone with nanoparticles or with RF-MF., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Nazanin Oroskhani et al.)

Nanozyme has been proven to be an attractive and promising candidate to alleviate the current pressing medical problems. However, the unknown clinical safety and limited function beyond the catalysis of the most reported nanozymes cannot promise an ideal therapeutic outcome in further clinical application. Herein, we find that ferric maltol (FM), a clinically approved iron supplement synthesized through a facile scalable method, exhibits excellent peroxidase-like activity than natural horseradish peroxidase-like (HRP) and commonly reported Fe-based nanozymes, and also shows high antibacterial performance for methicillin-resistant Staphylococcus aureus (MRSA) elimination (100%) and wound disinfection. In addition, with added effects inherited from contained maltol, FM can accelerate skin barrier recovery. Therefore, the exploration of FM as a safe and desired nanozyme provides a timely alternative to current antibiotic therapy against drug-resistant bacteria.

Background: Bioreductive processes are quite potent, effective and affordable for the synthesis of green nanoparticles (NPs), as compared to the physical and chemical methods. The present study aimed to evaluate the bactericidal, antioxidative and anticancer activity of turmeric rhizome-iron oxide nanoparticles (FeONPs) derived from the turmeric rhizome (Curcuma amada) using ferric chloride as a precursor., Methods: With focusing on the manufacture of FeONPs via green approach, we characterized the NPs using FTIR, FT-Vis, DLS, and UV-Vis spectroscopy. The produced particles were tested for antibacterial, antioxidant, and anticancer properties. The synthesized NPs were also examined using the MDA-MB-231 human epithelial breast cancer cell line and NCI-60 cancer cell lines., Results: The antioxidant activity of TR-FeONPs was concentration-dependent. The scavenging activity of TR-FeONPs was 76.09% at a concentration of 140 µg/ml. Using different concentrations of TR-FeONPs in the MTT assay against the MDA-MB-231 cell line indicated a reduction of less than 50% in cell viability at 125 µg/ml. Moreover, TR-FeONPs exhibited an effective bactericidal property. The gTR-FeONPs synthesized bioreductively were found to be effective in renal cancer, UO-31 cell line, with GI50 value of 66.64%., Conclusion: Our study showcases a sustainable method based on green chemistry principles to produce FeONPs utilizing turmeric rhizome. We anticipate that the FeONPs produced through this biosynthesis process could serve as a promising drug delivery system in cancer treatment and as an effective antimicrobial agent against various diseases.

There is a growing interest in eco-friendly and cost-effective organic-inorganic nanocomposites due to their alignment with the principles of "green" chemistry, as well as their biocompatibility and non-toxicity. This study focused on producing Chitosan-PEG-Fe 2 O 3 @NiO nanomagnetic composites to improve the stability, dielectric properties, and antimicrobial effectiveness of these nanocomposite materials. The process involved synthesizing Fe 2 O 3 @NiO via sol-gel and polymerizing chitosan-PEG. The nanocomposites were characterized by XRD, TEM, FTIR, optical, dielectric, and VSM. Incorporating Fe 2 O 3 @NiO significantly improved stability, and the interaction with Fe2O3 during the sol-gel process facilitated the formation of NiFe 2 O 4 with an increase in the crystallinity within the chitosan-PEG matrix. The study examined optical and dielectric properties, highlighting that the 3 NiO-doped chitosan-PEG-Fe 2 O 3 composites had high electrical conductivity (1.8 ∗ 10 -3  S/cm) and a significant dielectric constant (10 6 at low frequencies). As the ratio of NiO NPs within the chitosan-PEG-Fe 2 O 3 increases, the energy band gap of chitosan-PEG-Fe 2 O 3 films decreases up to 3.7 eV. This decrease is owing to the quantum confinement effect. These composites also demonstrated improved antimicrobial activity against E. coli and S. aureus and higher activity in the presence of nanomagnetic particles. The minimum inhibitory concentrations of CS-PEG-Fe 2 O 3 /NiO NPs against (Bacillus cereus, M. luteus, S. aureus and (S. enterica, H. pylori, E. coli) were (22-35 mm) and (21-34 mm), respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Iron deficiency correction with ferric carboxymaltose improves symptoms and reduces rehospitalization in patients with reduced left ventricular ejection fraction. The mechanisms underlying these improvements are poorly understood. This study aimed to determine changes in left ventricular contractility after iron treatment as reflected in global longitudinal strain., Methods: Prospective single-center study including 43 adults with reduced ejection fraction, non-anemic iron deficiency, and functional class II-III heart failure despite optimal medical treatment. Global longitudinal strain through speckle-tracking echocardiography was measured at baseline and 4 weeks after ferric carboxymaltose., Results: A significant improvement in global longitudinal strain was detected (from -12.3% ± 4.0% at baseline to -15.6% ± 4.1%, p < .001); ferritin and transferrin saturation index had increased, but ejection fraction presented no significant changes (baseline 35.7% ± 4.6%, follow-up 37.2% ± 6.6%, p = .073)., Conclusions: In patients with heart failure and reduced ejection fraction, the correction of iron deficiency with ferric carboxymaltose is associated with an early improvement in global longitudinal strain, possibly suggesting a direct effect of iron correction on myocardial contractility., (© 2023 Wiley Periodicals LLC.)

A lot of nanomaterials have been applied to various nano-biotechnological fields, such as contrast agents, drug or gene delivery systems, cosmetics, and so on. Despite the expanding usage of nanomaterials, concerns persist regarding their potential toxicity. To address this issue, many scientists have tried to develop biocompatible nanomaterials containing phytochemicals as a promising solution. In this study, we synthesized biocompatible nanomaterials by using gallic acid (GA), which is a phytochemical, and coating it onto the surface of iron oxide nanoparticles (IONPs). Importantly, the GA-modified iron oxide nanoparticles (GA-IONPs) were successfully prepared through environmentally friendly methods, avoiding the use of harmful reagents and extreme conditions. The presence of GA on the surface of IONPs improved their stability and bioactive properties. In addition, cell viability assays proved that GA-IONPs possessed excellent biocompatibility in human dermal papilla cells (HDPCs). Additionally, GA-IONPs showed antioxidant activity, which reduced intracellular reactive oxygen species (ROS) levels in an oxidative stress model induced by hydrogen peroxide (H 2 O 2 ). To investigate the impact of GA-IONPs on exosome secretions from oxidative stress-induced cells, we analyzed the number and characteristics of exosomes in the culture media of HDPCs after H 2 O 2 stimulation or GA-IONP treatment. Our analysis revealed that both the number and proportions of tetraspanins (CD9, CD81, and CD63) in exosomes were similar in the control group and the GA-IONP-treated groups. In contrast, exosome secretion was increased, and the proportion of tetraspanin was changed in the H 2 O 2 -treated group compared to the control group. It demonstrated that treatment with GA-IONPs effectively attenuated exosome secretion induced by H 2 O 2 -induced oxidative stress. Therefore, this GA-IONP exhibited outstanding promise for applications in the field of nanobiotechnology.

Gallium has a long history as a chemotherapeutic agent. The mechanisms of action of Ga(III)-based anti-infectives are different from conventional antibiotics, which primarily result from the chemical similarities of Ga(III) with Fe(III) and substitution of gallium into iron-dependent biological pathways. However, more aspects of the molecular mechanisms of Ga(III) against human pathogens, especially the effects on bacterial metabolic processes, remain to be understood. Herein, by using conventional quantitative proteomics, we identified the protein changes of Pseudomonas aeruginosa (P. aeruginosa) in response to Ga(NO 3 ) 3 treatment. We show that Ga(III) exhibits bacteriostatic mode of action against P. aeruginosa through affecting the expressions of a number of key enzymes in the main metabolic pathways, including glycolysis, TCA cycle, amino acid metabolism, and protein and nucleic acid biosynthesis. In addition, decreased expressions of proteins associated with pathogenesis and virulence of P. aeruginosa were also identified. Moreover, the correlations between protein expressions and metabolome changes in P. aeruginosa upon Ga(III) treatment were identified and discussed. Our findings thus expand the understanding on the antimicrobial mechanisms of Ga(III) that shed light on enhanced therapeutic strategies. BIOLOGICAL SIGNIFICANCE: Mounting evidence suggest that the efficacy and resistance of clinical antibiotics are closely related to the metabolic homeostasis in bacterial pathogens. Ga(III)-based compounds have been repurposed as antibacterial therapeutic candidates against antibiotics resistant pathogens, and represent a safe and promising treatment for clinical human infections, while more thorough understandings of how bacteria respond to Ga(III) treatment are needed. In the present study, we provide evidences at the proteome level that indicate Ga(III)-induced metabolic perturbations in P. aeruginosa. We identified and discussed the interference of Ga(III) on the expressions and activities of enzymes in the main metabolic pathways in P. aeruginosa. In view of our previous report that the antimicrobial efficacy of Ga(III) could be modulated according to Ga(III)-induced metabolome changes in P. aeruginosa, our current analyses may provide theoretical basis at the proteome level for the development of efficient gallium-based therapies by exploiting bacterial metabolic mechanisms., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Optimizing photosynthesis is imperative for providing energy and organics for all life on the earth. Here, carbon dots doped with pyridinic nitrogen (named lev-CDs) are synthesized by the one-pot hydrothermal method, and the structure-function relationship between functional groups on lev-CDs and photosynthesis of Chlorella pyrenoidosa (C. pyrenoidosa) is proposed. Pyridinic nitrogen plays a key role in the positive effect on photosynthesis caused by lev-CDs. In detail, lev-CDs act as electron donors to supply photo-induced electrons to P680 + and QA + , causing electron transfer from lev-CDs to the photosynthetic electron transport chain in the photosystems. In return, the recombination efficiency of electron-hole pairs on lev-CDs decreases. As a result, the electron transfer rate in the electron transport chain, the activity of photosystem II, and the Calvin cycle are enhanced. Moreover, the electron transfer rate between C. pyrenoidosa and external circumstances enhanced by lev-CDs is about 50%, and electrons exported from C. pyrenoidosa can be used to reduce iron(III). This study is of great significance for engineering nanomaterials to improve photosynthesis., (© 2023 Wiley-VCH GmbH.)

Herien, three new Fe(III) (FeAZD), Ni(II) (NiAZD), and Cu(II) (CuAZD) complexes were synthesized and characterized using various physicochemical and spectroscopic approaches. The H 2 AZD ligand acted as a bi-basic bi-dentate NO ligand in a 1:1 molar ratio. The results revealed that the FeAZD and CuAZD complexes had octahedral geometry, while the NiAZD had a tetrahedral geometry. The optimized geometry, HOMO and LUMO analysis of the ligand and its metal complexes was determined via Density functional theory (DFT) using the B3LYP with 6-311 G(d,p), and LanL2DZ level of theory. The FeAZD, NiAZD and CuAZD had lower energy gap, 7.40, 7.93 and 7.06 eV, respectively, than the free ligand (9.58 eV), which proposed that CuAZD was more active one. The free ligand and its metal complexes were in vitro investigated for their antibacterial and antifungal activity. The results illustrated that the metal complexes had higher antibacterial and antifungal activity than the free ligand. More specifically, the CuAZD demonstrated good antibacterial activity against E. coli, P. aeruginosa, S. aureus, B. cereus, and A. flavus, T. rubrum, and C. albicans, with activity indexes of 72.22%, 65.01%, 77.78%, and 72.22%, 63.16%, 59.09%, and 61.90%, respectively. Also, the metal complexes showed lower MIC (6.25-3.125 ppm) compared to the free ligand (about 50 ppm). Finally, molecular docking was utilized to investigate the ability of the free ligand and its metal complexes to inhibit the growth of E. coli (PDB ID: 5iq9). The results showed that the CuAZD had the highest binding affinity to the receptor, with a more negative docking score of - 7.05 Kcal/mol, and lower inhibition constant (Ki) of 6.90 µM. That is indicating that it may be the most effective at inhibiting the growth of E. coli (PDB ID: 5iq9)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Implant-associated infections (IAIs) significantly impair the integration between titanium (Ti) implants and bone tissues. Bacteria colonized on the surface of the implant can induce innate immune suppression of the host to resist clearance. Herein, an interfacial functionalization strategy is employed to introduce Fe III TA nanoparticles (NPs) and acetyl Bletilla striata polysaccharide (acBSP) on the Ti substrate to obtain the Ti-TF-acBSP system. Under near-infrared (NIR) irradiation, the hyperthermal effect induced by Fe III TA NPs directly killed bacteria. Meanwhile, macrophages are induced by acBSP to polarize into pro-inflammatory M1 phenotype, which enhanced the phagocytosis ability of macrophages and activated host innate immunity. Moreover, the asBSP instructed macrophages to secrete pro-osteogenic cytokine, which promoted osteogenic differentiation of MSCs. The results of the animal experiment in vivo confirmed that the Ti-TF-acBSP implant effectively eliminated bacterial infection under NIR irradiation, enhanced the expression of pro-inflammatory cytokine, and induced the production of bone-forming related factors. In a word, the functionalized Ti implant not only have a direct bactericidal effect but also regulate macrophage polarization as well as macrophage-mediated bactericidal and osteogenic effect. The strategy of combining photothermal therapy with immunoregulation will present a potential candidate for the development of novel antibacterial orthopedic devices., (© 2023 Wiley-VCH GmbH.)

Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok) 3 (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC 50 = 2.05 ± 0.90 μM or 1.20 μg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC 50 = 0.92 ± 0.73 μM or 0.50 μg/mL), ovarian cancer cells (SKOV-3; IC 50 = 1.23 ± 0.01 μM or 0.67 μg/mL), breast cancer cells (MDA-MB-231; IC 50 = 3.83 ± 0.12 μM or 2.0 μg/mL) and lung cancer cells (A549; IC 50 = 1.50 ± 0.32 μM or 0.82 μg/mL). Of great significance is that Fe(hinok) 3 exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.

Planting rice (Oryza sativa L.) in As-contaminated paddy soils can lead to accumulation of arsenic (As) in rice grains, while the application of phosphorus (P) fertilizers during rice growth may aggravate the accumulation effect. However, remediating flooding As-contaminated paddy soils with conventional Fe(III) oxides/hydroxides can hardly achieve the goals of effectively reducing grain As and maintaining the utilization efficiency of phosphate (Pi) fertilizers simultaneously. In the present study, schwertmannite was proposed to remediate flooding As-contaminated paddy soil because of its strong sorption capacity for soil As, and its effect on the utilization efficiency of Pi fertilizer was investigated. Results of a pot experiment showed that Pi fertilization along with schwertmannite amendment was effective to reduce the mobility of As in the contaminated paddy soil and meanwhile increase soil P availability. The schwertmannite amendment along with Pi fertilization reduced the content of P in Fe plaque on rice roots, compared with the corresponding amount of Pi fertilizer alone, which can be attributed to the change in mineral composition of Fe plaque mainly induced by schwertmannite amendment. Such reduction in P retention on Fe plaque was beneficial for improving the utilization efficiency of Pi fertilizer. In particular, amending flooding As-contaminated paddy soil with schwertmannite and Pi fertilizer together has reduced the content of As in rice grains from 1.06 to 1.47 mg/kg to only 0.38-0.63 mg/kg and significantly increased the shoot biomass of rice plants. Therefore, using schwertmannite to remediate flooding As-contaminated paddy soils can achieve the dual goals of effectively reducing grain As and maintaining the utilization efficiency of P fertilizers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Herein, we use two exemplary superparamagnetic iron oxide multicore nanoparticles (SPIONs) to illustrate the significant influence of slightly different physicochemical properties on the cellular and molecular processes that define SPION interplay with primary neural cells. Particularly, we have designed two different SPION structures, NFA (i.e., a denser multicore structure accompanied by a slightly less negative surface charge and a higher magnetic response) and NFD (i.e., a larger surface area and more negatively charged), and identified specific biological responses dependent on SPION type, concentration, exposure time, and magnetic actuation. Interestingly, NFA SPIONs display a higher cell uptake, likely driven by their less negative surface and smaller protein corona, more significantly impacting cell viability and complexity. The tight contact of both SPIONs with neural cell membranes results in the significant augmentation of phosphatidylcholine, phosphatidylserine, and sphingomyelin and the reduction of free fatty acids and triacylglycerides for both SPIONs. Nonetheless, NFD induces greater effects on lipids, especially under magnetic actuation, likely indicating a preferential membranal location and/or a tighter interaction with membrane lipids than NFA, in agreement with their lower cell uptake. From a functional perspective, these lipid changes correlate with an increase in plasma membrane fluidity, again larger for more negatively charged nanoparticles (NFD). Finally, the mRNA expression of iron-related genes such as Ireb-2 and Fth-1 remains unaltered, while TfR-1 is only detected in SPION-treated cells. Taken together, these results demonstrate the substantial impact that minor physicochemical differences of nanomaterials may exert in the specific targeting of cellular and molecular processes. A denser multicore structure generated by autoclave-based production is accompanied by a slight difference in surface charge and magnetic properties that become decisive for the biological impact of these SPIONs. Their capacity to markedly modify the lipidic cell content makes them attractive as lipid-targetable nanomedicines.

Aim: To assess the efficacy of intravenous ferric carboxymaltose (IV FCM) for the treatment of iron deficiency anemia (IDA) diagnosed de novo in the third trimester of pregnancy., Methods: Case-control study conducted in pregnant women with IDA newly diagnosed in the third trimester of pregnancy. Women treated with a single IV FCM injection were included as cases and those who received daily 210 g of oral ferrous sulphate (FS) as controls. Controls were matched to cases in a 2:1 ratio by basal hemoglobin (Hb) concentration (±0.5 g/dl)., Results: A total of 35 cases and 70 controls were included in the study. The mean Hb concentration level significantly increased after iron treatment in both cases (from 9.3 ± 0.8 to 11.1 ± 0.8 g/dl, p < 0.0001) and controls (from 9.6 ± 0.9 to 10.9 ± 1 g/dl, p < 0.0001). The rate of women who exceeded the recommended threshold of 11 g/dl after treatment did not significantly differ between cases (63% (95%CI, 45%-79%)) and controls (56% (95%CI, 44%-68%)) (p = 0.48). Comparison of maternal and neonatal outcomes and adverse effects did not show any significant difference between groups., Conclusions: Our results suggest that IV FCM and oral FS can be considered equally effective in the treatment of IDA newly detected in the third trimester of pregnancy., (© 2023 Japan Society of Obstetrics and Gynecology.)

We previously showed that two iron compounds that are orally ingested by humans, namely ferric EDTA and ferric citrate, can induce an oncogenic growth factor (amphiregulin) in human intestinal epithelial adenocarcinoma cell lines. Here, we further screened these iron compounds, plus four other iron chelates and six iron salts (i.e., 12 oral iron compounds in total), for their effects on biomarkers of cancer and inflammation. Ferric pyrophosphate and ferric EDTA were the main inducers of amphiregulin and its receptor monomer, IGFr1. Moreover, at the maximum iron concentrations investigated (500 µM), the highest levels of amphiregulin were induced by the six iron chelates, while four of these also increased IGfr1. In addition, we observed that ferric pyrophosphate promoted signaling via the JAK/STAT pathway by up-regulating the cytokine receptor subunit IFN-γr1 and IL-6. For pro-inflammatory cyclooxygenase-2 (COX-2), ferric pyrophosphate but not ferric EDTA elevated intracellular levels. This, however, did not drive the other biomarkers based on COX-2 inhibition studies and was probably downstream of IL-6. We conclude that of all oral iron compounds, iron chelates may particularly elevate intracellular amphiregulin. Ferric pyrophosphate additionally induced COX-2, probably because of the high IL-6 induction that was observed with this compound.

Saussurea costus is from medicinal plants and have therapeutic properties that were recorded in a variety of medical functions. The usage of biomaterials in the synthesis of nanoparticles is an essential strategy in green nanotechnology. Iron oxide nanoparticles (IONPs) were composed in the stage of (2:1, FeCl2: FeCl3) solution by using the aqueous extract of Saussurea costus peel in an eco-friendly method to evaluate their antimicrobial property. The properties of the obtained IONPs were evaluated using a scanning (SEM) and transmission (TEM) electron microscope. The mean size of IONPs discovered by Zetasizer varies between 100 and 300 nm, with a mean particle size of 295 nm. The morphology of IONPs (γ-Fe2O3) was determined to be nearly spherical and prismatic-curved. Moreover, the antimicrobial property of IONPs was assessed with nine pathogenic microbes, revealing that the nanoparticles have antimicrobial activities with Pseudomonas aeruginosa, Escherichia coli, Shigella sp., Staphylococcus sp. and Aspergillus niger, with possible applications in the therapeutic and biomedical fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jehan S. Al-brahim. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Perioperative anemia is common in cardiac surgery. Few studies investigated the effect of postoperative intravenous (IV) iron supplementation and were mostly inconclusive., Methods: Design: A randomized single-center, double-blind, placebo-controlled, parallel-group trial., Participants: 195 non-anemic patients were recruited from December 2018 to December 2020: 97 patients received 1 g of ferric carboxymaltose (FCM) and 98 patients received 100 mL of physiological serum on postoperative day 1., Measurements: hemoglobin levels, reticulocyte count, serum iron, serum ferritin, and transferrin saturation were measured at induction of anesthesia, postoperative days 1, 5, and 30. Transfusion rate, duration of mechanical ventilation, critical care unit length of stay, and side effects associated with IV iron administration were measured. The primary outcome was hemoglobin level on day 30. Secondary outcomes included iron balance, transfused red cell packs, and critical care unit length of stay., Results: At day 30, the hemoglobine level was higher in the FCM group than in the placebo group (mean 12.9 ± 1.2 vs. 12.1 ± 1.3 g/dL (95%CI 0.41-1.23, p-value <0.001)). Patients in the FCM group received fewer blood units (median 1[0-2] unit vs. 2 [0-3] units, p-value = 0.037) and had significant improvement in iron balance compared to the control group. No side effects associated with FCM administration were reported., Conclusion: In this randomized controlled trial, administration of FCM on postoperative day 1 in non-anemic patients undergoing cardiac surgery increased hemoglobin levels by 0.8 g/dL on postoperative day 30, leading to reduced transfusion rate, and improved iron levels on postoperative day 5 and 30., Clinical Trial Registry Number: NCT03759964., (Copyright © 2022 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Modern intravenous iron compounds (e.g., ferric carboxymaltose [FCM] and ferric derisomaltose [FDI]) are utilized in the treatment of iron deficiency anemia in non-dialysis-dependent chronic kidney disease (ND-CKD). Product-specific alterations in the metabolism of fibroblast growth factor 23 (FGF-23) leading to hypophosphatemia have been described for certain intravenous iron compounds, such as FCM, with potential effects on bone and cardiovascular health and quality of life. No prior head-to-head comparison between FCM and FDI exists in ND-CKD. This single-center exploratory double-blind randomized controlled trial primarily aimed to investigate the differential impact of FCM and FDI on FGF-23 and phosphate in patients with iron deficiency +/- anemia and ND-CKD (stages 3a-5 - serum ferritin &lt;200 μg/L or serum ferritin 200-299 μg/L and transferrin saturation &lt;20%). Patients were randomized (1:1) to receive either FCM or FDI over two infusions (1 month apart). Follow-up was 3 months. Measurements of serum intact FGF-23, phosphate, vitamin D metabolites, parathyroid hormone, other bone metabolism, cardiovascular, and quality of life markers were monitored. 168 patients were prescreened. Thirty-five patients were screened; 26 patients were randomized. The mean (standard deviation) age was 67.9 (12.4) years and 17 participants were male. Most participants had stage 4 CKD (median [interquartile range] estimated glomerular filtration rate [eGFR]: 18.0 [11.3] mL/min/1.73 m2). A higher than normal median (interquartile range) level of intact FGF-23 (212.1 [116.4] pg/mL) was noted. Serum phosphate was within normal range, while parathyroid hormone was higher and 1,25 (OH)2 vitamin D lower than the normal range. The "Iron and Phosphaturia - ExplorIRON-CKD" trial will provide important information regarding the differential effect of intravenous iron products in terms of FGF-23, phosphate, and other markers of bone and cardiovascular metabolism, alongside patient-reported outcome measures in patients with ND-CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)