Ferric Research Articles

The successive reduction of iodate to iodide driven by iron redox cycling

Ferrous iron (Fe(II)) produced by microbial Fe(III) reduction and reactive oxygen species (ROS) generated from aerobic Fe(II) oxidation can mediate iodate (IO3−) reduction and iodide (I−) oxidation, respectively. Nevertheless, how Fe redox cycling under redox fluctuating conditions drives transformation of iodine species remain unclear. In this study, Shewanella oneidensis MR-1 wildtype (WT) and its mutant △dmsEFAB, which lost the ability to enzymatically reduce IO3−, were chosen to conduct ferrihydrite/goethite/nontronite culture experiments under consecutive cycles of anoxic reduction of Fe(III) and re-oxidation of Fe(II) by O2 to reveal the role of Fe redox cycling in the transformation of iodine species. The results showed that both surface-adsorbed and mineral structural Fe(II) chemically reduced IO3−. Chemical IO3− reduction by biogenic Fe(II) was slower than enzymatic IO3− reduction by WT. Compared to △dmsEFAB cultures, WT cultures all showed higher Fe(II) concentrations under anoxic conditions but lower cumulative •OH under oxic conditions, which imply the chemical reaction between I− and ROS. I− oxidation by ROS, however, did not lead to a significant production of IO3− compared with I− formed under anoxic conditions. Consequently, Fe redox cycling successively reduced IO3− to I−, which highlights vital roles of Fe(III)-reducing bacteria in I− formation and mobilization in environments.

Iron deficiency anemia and anemia of chronic disease – what is known?

Anemia is the most common disease in the world, affecting about 30–40% of people. Children, adolescents, and women are most often affected by anemia. The main causes of true iron deficiency (ID and IDA) are insufficient iron intake, increased iron loss (chronic bleeding), increased iron requirement, and impaired iron absorption (gastrointestinal diseases). Chronic diseases, inflammatory conditions, autoimmune diseases, obesity cause an increase in the synthesis of hepcidin in the liver and block the entry of iron into the bloodstream, leading to functional iron deficiency. Anemia of chronic diseases (ACD) or anemia of chronic inflammation (the second most common anemia) is associated with the fact that iron is present in the body, but the absorption of iron in various areas is limited. Until recently, it was believed that treatment with iron supplements in the absence of iron deficiency does not bring benefit to patients with ACD. The opinion has been repeatedly expressed about the harm of iron therapy, since iron is necessary for the growth of some pathogenic microorganisms and tumor cells. However, the real clinical significance of these mainly theoretical provisions is unknown. Therefore, the prescription of iron preparations for anemia is justified and logical. Ferrous sulfate (ferrous iron) is most often prescribed orally due to its low cost, high bioavailability and effectiveness. The drug Tardiferon, containing iron sulphate 247.25 mg (in terms of iron (II) 80.00 mg), is widely used in patients with IDA and ID, since divalent iron has a high ability to overcome the intestinal barrier by “passive” transport and quickly create high concentrations in the blood, restoring the level of hemoglobin and iron stores in the body. The drug Tardiferon has a relatively low dose of iron – 80 mg with slow-release technology to avoid irritating effects on the intestine, contributing to good tolerability. A number of studies confirmed a high safety profile – patients did not refuse to take the drug due to side effects. Timely examination and identification of patients with anemia allows you to prescribe an effective correction. The drug Tardiferon promotes rapid restoration of hemoglobin and iron stores in the body and has good tolerability.

5-Aminolevulinic acid combined with ferrous iron ameliorates myocardial ischemia/reperfusion injury by increasing heme oxygenase-1.

5-Aminolevulinic acid (5-ALA) is a naturally occurring metabolic precursor of heme, and 5-ALA combined with ferrous iron can induce heme oxygenase-1 (HO-1) in various cells. In this study, we investigated the cardioprotective effect of 5-ALA after myocardial ischemia/reperfusion (I/R) injury using a murine model. Male C57BL/6J mice (10-12weeks of age and weighing 21-26g) were pretreated with 100mg/kg of 5-ALA hydrochloride and 157mg/kg of sodium ferrous citrate (SFC) or vehicle 48h, 24h, and 1h before I/R, and underwent 50min of left coronary artery occlusion followed by reperfusion. Infarct area (IA) and area at risk (AAR) were determined by Evans blue and triphenyltetrazolium chloride double staining after reocclusion. Pre-administration with 5-ALA/SFC significantly reduced IA/AAR compared with placebo (34.0% vs. 51.7%, respectively; p = 0.001). Real-time PCR assay after reperfusion showed that mRNA expressions of TNF-α, IL-1β, and BNP were significantly lower, and that of HO-1 was significantly higher in the 5-ALA/SFC group than in the vehicle group in ischemic sites. An inhibition experiment revealed that zinc protoporphyrin IX, an inhibitor of HO-1, inhibited the cardioprotective effects of 5-ALA/SFC. These results suggest that 5-ALA/SFC might play a cardioprotective role in myocardial I/R injury by attenuating the inflammatory reaction by increasing the expression of HO-1.

GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.

Synovial over-proliferation is a key event in the progression of rheumatoid arthritis (RA) disease. Ferroptosis may be essential for maintaining the balance between synovial proliferation and death. This study aimed to investigate the molecular mechanisms mediating the activation and ferroptosis of collagen-induced arthritis(CIA)-synovial fibroblasts (SFs). Differentially expressed genes (DEGs) in the synovial tissues of CIA rats and normal rats were screened through sequencing. The GSE115662 dataset from the GEO database was analyzed and screened for DEGs. The viability, proliferation, migration, invasion, cell cycle, and apoptosis of CIA-SFs were analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell migration, and invasion assays. The ferroptosis of CIA-SFs was assessed using matching reagent kits to detect indicators like reactive oxygen species, ferrous iron, malondialdehyde, glutathione, and superoxide dismutase. The interaction between Granzyme K (GZMK) and C-C motif chemokine 5 (CCL5) was determined by coimmunoprecipitation assay. We found abnormal GZMK expression in the GSE115662 database and mRNA sequencing data. GZMK was overexpressed in CIA-SFs, and GZMK promoted cell proliferation, migration, invasion, inflammation, and decreased cell apoptosis and ferroptosis in CIA-SFs. GZMK could interact with CCL5 to activate the ERK signaling. GZMK and CCL5 knockdown improved by reducing arthritis scores, redness and swelling of paws, and pathological changes in joint synovium of CIA rats. CCL5 overexpression reversed the effects of GZMK silencing on CIA-SFs cell proliferation, migration, invasion, apoptosis, and ferroptosis. We confirmed that GZMK accelerated experimental rheumatoid arthritis progression by interacting with CCL5 and activating the ERK signaling.

Comparative analysis of ferric carboxymaltose and iron sucrose in treating iron deficiency anemia in perimenopausal women with heavy menstrual bleeding: a randomized controlled trial.

To evaluate the impact of intravenous ferric carboxymaltose (FCM) compared to iron sucrose (ISC) in perimenopausal women with heavy menstrual bleeding (HMB) and anemia. This prospective, open-label, randomized controlled trial enrolled perimenopausal women (40-50 years) with HMB and hemoglobin levels between 6-10 g/dL, intolerant or non-compliant to oral iron therapy. The study compared FCM and ISC by assessing hematological parameters, including hemoglobin, ferritin, and iron levels, over a 12-week period. The patients were followed up at 3, 6, and 12 weeks after initiation. The adverse effects were also evaluated. The study included 60 perimenopausal women, with 30 in each group. The baseline patient characteristics were comparable. FCM demonstrated a statistically significant higher mean increase in hemoglobin (4.97 g/dL) than ISC (4.63 g/dL) over 12 weeks. The proportion of patients achieving correction of anemia (Hb ≥12%) was higher in the FCM group (75.9% vs. 65.5%). Serum ferritin levels were significantly higher in the FCM group after 3 weeks. Adverse effects were minimal and comparable between the groups. Although the direct cost of FCM is high, its ability to be administered in larger doses may result in lower total costs. In perimenopausal women with heavy menstrual bleeding and iron deficiency anemia, FCM and ISC show comparable efficacy in increasing hemoglobin levels with similar side effect profiles. This study highlights the potential benefits of FCM and calls for further exploration of these therapies in diverse patient populations.

Cost-Effective Strategy and Feasibility for Amylase Production from Okara by Bacillus subtilis J12

Low-cost enzyme production is considered a feasibility factor in enzyme commercialization. Okara, a high-nutritional agro-industrial residue from soybean processing, was performed as a medium for bacterial amylase production to save costs and increase productivity. This study aimed to produce, characterize, activate amylase, and evaluate the material cost for media from okara. Under solid-state fermentation (SSF) of okara without pretreatment, Bacillus subtilis J12 could produce 983 U/g of amylase within 24 h. Bacillus subtilis J12 amylase had optimal activity at pH 6.0 and 50 °C and was stable at a moderate temperature for up to 120 min. Identified as a metalloenzyme, the activity was improved by ferric ions. The purification of amylase resulted in two fractions which contained at least two types of amylases. Compared with other producers, the production was evaluated using low-cost media without additional supplementations. Based on the productivity, characteristics, and evaluation, Bacillus subtilis J12 amylase was potentially commercialized, had economic value, possessed energy-saving features, and could be applied for industrial use.

KARAKTERISTIK TANAH SULFAT MASAM DAN PENGELOLAANNYA UNTUK LAHAN PERTANIAN

Acid sulfate soils are quite abundant in Indonesia, and some have been used for agricultural land. The main problem with this soil is the presence of pyrite compounds (FeS2). The oxidation of these compounds causes the soil to become acidic, metals and bases dissolve so that the soil becomes poor and the life of aquatic biota affected by the drainage water is disturbed. The oxidized soil, if flooded again, causes an increase in ferrous iron ions and hydrogen sulfide which can poison plants, therefore management of acid sulfate soils needs to be carried out so that the soil has characteristics that can support plant growth. Some soil management actions that can be taken are controlling the activity of microorganisms in the oxidation and reduction processes of pyrite, providing amelioration materials and fertilization, land management and water management.

Determination of Biological Activity and Biochemical Content of Ethanol Extract from Fruiting Body of Tricholoma bufonium (Pers.) Gillet

The current study investigates the biochemical composition and biological activities of ethanol extract from the fruit body of Tricholoma bufonium, marking the first detailed examination of this species. The primary goal was to assess the antimicrobial, anti-biofilm, and antioxidant properties of ethanol extract from the fruit body of T. bufonium against a range of bacterial strains. Conventional microbiological and biochemical techniques were employed to assess the antimicrobial efficacy of the extract and to determine its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Furthermore, a GC-MS analysis identified bioactive compounds, such as palmitic acid and oleic acid, which are likely contributors to the observed antimicrobial activity. The anti-biofilm activity was tested using glucose monohydrate-modified environments for biofilm formation, while the antioxidant potential was measured using the DPPH radical scavenging assay, CUPRAC (cupric ion reducing antioxidant capacity) assay, and FRAP (ferric ion reducing antioxidant power) assay. The ethanol extract exhibited potent antimicrobial activity, particularly against Enterococcus faecium, Bacillus subtilis, and Staphylococcus aureus MRSA, with MIC values as low as 0.0338 mg/mL for several pathogens. Additionally, the extract exhibited significant anti-biofilm activity against Bacillus cereus and antioxidant activity with an EC50 value of 11.745 mg/mL. These results suggest that ethanol extract from the fruit body of T. bufonium may be a potent candidate for developing novel antimicrobial agents, particularly against resistant strains such as MRSA, while also providing antioxidant benefits.

Ferric ions crosslinked hyaluronic acid beads: potentials for drug delivery use

Introduction and purpose Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads. Methods The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead’s morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated. Results The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model. Conclusions This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Relationship Between Aquatic Factors and Sulfide and Ferrous Iron in Black Bloom in Lakes: A Case Study of a Eutrophic Lake in Eastern China

Black bloom is a very serious water pollution phenomenon in eutrophic lakes, with Fe(II) and S(−II) being the key limiting factors for this problem. In this paper, three different machine learning methods, namely, Random Forest (RF), Gaussian Mixture Model (GMM), and Bayesian Network (BN), were used to explore the complex interactions among Fe(II), S(−II), and other aquatic factors in the estuary of Chaohu Lake to better characterize and monitor water degradation by black bloom. The results of RF showed that total nitrogen (TN), ammonia, total phosphorous (TP), suspended sediment concentration (SSC), and oxidation–reduction potential (ORP), which were chosen from 11 factors, had the most important relationships with Fe(II) and S(−II). The 69 sampling sites were divided in three groups identified as worst, worse, and bad according to the observed values of seven factors using the GMM. Then, the BN model was applied to three observation groups. The results showed that the structures of the interaction networks were different between the groups. S(−II) controlled only SSC production in the bad and worse group sites, while SSC was determined by both S(−II) and Fe(II) in the worst group. Ammonia and TN exhibited the most direct importance for S(−II) and Fe(II) production in all observation groups. According to the indications from the BNs, potential management strategies for different water pollution conditions were developed. Finally, the threshold values of Fe(II), S(−II), TP, ammonia, TN, SSC, and ORP, which were 0.80 mg/L, 0.04 mg/L, 0.45 mg/L, 3.44 mg/L, 4.15 mg/L, 55 mg/L, and 135 mv, respectively, were determined on the basis of the BN models. These values will be helpful to develop accurate strategies of oxygenation to quickly eliminate black bloom in the lake.

Activation of peroxymonosulfate by Fe based metal organic framework for selective degradation of phenol in water

Phenol is a common pollutant in various wastewater, which is required to be removed to a certain standard before the wastewater can be discharged. Persulfate-based advanced oxidation processes (PS-AOPs) are an effective technology for phenol removal, with efficacy contingent upon the activation methods and materials employed. In this study, Fe-based metal-organic frameworks (Fe-MOFs) constructed with carboxylic acid as a ligand were synthesized by a solvothermal method, which can form chelates with ferrous ions. Fe-MOFs showed the activity similar to the homogeneous catalyst thus improving their activation efficiency, and can be used to activate peroxymonosulfate (PMS) for phenol degradation in water. The effects of catalyst dosage, PMS and phenol concentration, temperature, and pH on the degradation efficiency were investigated. Under the optimum reaction conditions, the 96 % of phenol can be rapidly removed in 5 min. SO4·− was determined as the primary radical. Fe species on Fe-MOFs acted as the key active sites. Density functional theory (DFT) analysis suggested enhanced charge redistribution, fostering electron-rich sites that facilitate electron transfer in AOPs, thus boosting phenol degradation. The Fe-MOFs/PMS system enables iron recycling and efficient phenol degradation in water, indicating the potential for phenol-contaminated water treatment.

Commodity Market Downturn: Systemic Risk and Spillovers during Left Tail Events

We investigate systemic risk and spillovers in the commodity network during left-tail events using state-of-the-art methodologies: the Component Exponent Shortfall (CES), Quantile-Vector Autoregression (QVAR) and Causality-in-Risk. Our analysis focuses on five commodity groups: Energy (Crude Oil, Heating Oil, Natural Gas, Coal), Base Metals (Aluminum, Copper, Nickel, Zinc), Ferrous Metals (Iron, Steel), Precious Metals (Gold, Palladium, Platinum, Silver), and Others (Rubber). Across the models utilized, we consistently find that energy commodities and precious metals, along with copper as a standalone commodity, represent the most systemically risky group. Thus, portfolios incorporating these commodities are advised to implement more careful diversification to mitigate risks stemming from systemic factors. This may require additional attention to precious metals, as they are often considered safe-haven assets. Expediting the implementation of regulations that promote the replacement of fossil energy sources with green alternatives could be instrumental in managing systemic risk in the commodity market while also facilitating global sustainability. Finally, the results show that the impact of the Israeli-Palestinian conflict on both systemic risk and spillovers has been limited compared to the effects of COVID-19 and the Russia-Ukraine war.

Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro

The emerging antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV–visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays. Both chloroxine and its structural analogues exhibited increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosted chloroxine’s antibacterial efficacy against Gram-negative bacteria, including the notorious ESKAPE pathogens. However, the enhanced antibacterial activity induced by zinc ions could be negated in the presence of copper or ferrous iron ions, as well as changes in oxygen availability, highlighting the involvement of proton motive force, oxidative and antioxidative systems. Notably, chloroxine effectively inhibited the enzymatic activity of superoxide dismutase (SOD). In addition, chloroxine could reverse polymyxin and carbapenem resistance in E. coli in vitro. Therefore, these results suggested that chloroxine with zinc ions are promising therapeutics and antibiotics potentiator to combat multidrug-resistant ESKAPE pathogens

Marked microcytosis and increased transferrin saturation: Think about variants in SLC11A2 (DMT1)

Congenital microcytic anemias are rare diseases associated with decreased hemoglobin synthesis and red blood cells of low corpuscular volume. DMT1/NRAMP2 is a highly conserved divalent cation transporter encoded by the SLC11A2 gene, expressed at the membrane of various cells. It ensures ferrous iron absorption from the apical membrane of enterocytes, iron recovery from urine by renal tubules, and acidified endosome uptake after transferrin internalization. Pathogenic DMT1 variants have been described in 10 individuals to date, associated with recessive hypochromic anemia and iron overload. Herein, we report a new variant of SLC11A2 (c.469A>G, p.Ile157Val) compound with known p.Arg416Cys associated with a frankly microcytic anemia and increased transferrin saturation. The clinical picture observed in the patient was exceptionally mild, extending the field of the DMT1 phenotypes to borderline anemias.

High lead-tolerant mutant Bacillus tropicus AT31-1 from rhizosphere soil of Pu-erh and its remediation mechanism

In this study, we successfully generated the mutant strain Bacillus tropicus AT31-1 from AT31 through atmospheric room-temperature plasma mutagenesis. This mutant strain AT31-1 demonstrated an impressive 48.6 % removal efficiency in 400 mg/L lead medium. Comparative genomic analysis showed that the mutant strain AT31-1 had three mutation sites, which affect the efflux RND transporter permease subunit, the response regulator transcription factor, and a gene with unknown function. The transcriptional analysis showed a notable upregulation in the expression of 283 genes in AT31-1 as lead concentrations increased from 0 to 200 mg/L and then to 400 mg/L, which include zinc-transporting ATPase, ferrous iron transport protein B, NADH dehydrogenase, and others. The Gene ontology function of the peptide metabolic process, along with the KEGG pathway of carbon metabolism were identified as closely linked to the extreme lead tolerance of AT31-1. This study presents novel insights into the lead tolerance mechanisms of bacteria.

Diammonium glycyrrhizinate alleviates iron overload-induced liver injury in mice via regulating the gut-liver axis

BackgroundEvidence indicates a close association between iron overload (IO) and the pathogenesis of chronic liver diseases, highlighting the potential for interventions targeted at IO to impede or decelerate the progression of chronic liver diseases. Diammonium glycyrrhizinate (DG), the medicinal form of glycyrrhizic acid, a principal constituent of licorice, has been clinically employed as a hepatoprotective agent; however, its protective effect against IO-induced liver injury and underlying molecular mechanisms remain elusive. PurposeThe aim of the present study is to investigate the hepatoprotective effect of DG against IO-induced liver injury with a focus on the gut-liver axis. Study design and methodsAnimal models of IO-induced liver injury and DG treatment have been established in vivo. Iron deposition, liver injury, intestinal barrier damage, and liver inflammation were assessed in mice treated with iron dextran or DG. The microbiome composition in feces was analyzed using 16S rRNA full-length sequencing. Bile acids (BAs) profiles in feces were detected by UPLC-Q-TOF-MS technique, and the expression levels of receptors, enzymes or transporters involved in BAs metabolism were also determined. ResultsDG partially reduced the iron deposition and the levels of ferrous ion in the livers of mice with IO, thereby mitigating oxidative damage. DG also improved gut microbiota dysbiosis, repaired intestinal barrier damage, inhibited endotoxin translocation to the liver, and subsequently suppressed TLR4/NF-κB/NLRP3 pathway-mediated liver inflammation caused by IO. Moreover, DG modulated BAs metabolism disorder in IO mice, reducing the accumulation of BAs in the liver. ConclusionDG alleviates IO-induced liver injury in mice by regulating the gut-liver axis. This study provides novel insights into the underlying mechanisms through which DG ameliorates liver injury caused by IO.

Revealing the catalytic behavior of different types ZVI (powder Fe0, sponge Fe1, foam Fe2) in US/Fex/PDS and its effect on the dewaterability of waste activated sludge

The ultrasound (US) irradiation-coupled zero-valent iron (ZVI) activated persulfate system could improve dewatering performance, reduce WAS volume, decrease transport and final disposal costs. However, there are huge differences between various types of ZVI on activation efficiency, reaction mechanism, and application potential in WAS conditioning process. In this study, three ZVI (Fex) catalysts (Fe0 powder iron, Fe1 sponge iron and Fe2 foam iron) were used in the US/PDS system, whose catalytic performance and the fundamentals of the WAS conditioning were explored and compared. The results showed that the capillary suction time (CST) reduction rates were 89 %, 85 %, and 87 % in US/Fe0/PDS, US/Fe1/PDS, and US/Fe2/PDS, respectively, which indicated that the US/Fex/PDS system had an outstanding conditioning performance. The WAS reduction rate was US/Fe1/PDS > US/Fe2/PDS > US/Fe0/PDS attributed to Fe1 surface activate sites. Similarly, the organic matters characterization showed soluble protein content (PN), polysaccharide content (PS), and microbial by-products were significantly reduced in the US/Fe1/PDS system. Further examination of the thermodynamic parameters revealed that the WAS cohesive interfacial energy (ΔGslscoh) was minimally reduced to promote release of bound water in the system due to the effective regulation of intermolecular forces. In addition, examination of the trivalent iron/divalent iron ratio (Fe3+/Fe2+) to assess the efficacy of ferric ion recycling showed a significant advantage for US/Fe1/PDS system. On the basis of improving catalyst utilization, PDS produced SO4·- that dominated free radicals to condition WAS, improve dewaterability and achieve WAS reduction. Finally, evaluating laboratory WAS conditioning results and costs, US/Fe1/PDS system has potential applications value.

Structure-Guided Discovery of a Potent Inhibitor of the Ferric Citrate Binding Protein FecB in Vibrio Bacteria.

Infections caused by Gram-negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug-resistant bacteria. Here, we report a new approach to combat infections by targeting iron-binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe3+-(citrate)2 complex. Based on these results, a structure-based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.

Structure‐Guided Discovery of a Potent Inhibitor of the Ferric Citrate Binding Protein FecB in Vibrio Bacteria

AbstractInfections caused by Gram‐negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug‐resistant bacteria. Here, we report a new approach to combat infections by targeting iron‐binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe3+‐(citrate)2 complex. Based on these results, a structure‐based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.

Antioxidant, cytotoxic, anti-migratory, and pro-apoptotic effects of Bolanthus turcicus extracts on head and neck cancer cells.

Investigation of various plant extracts using in-vitro/in-vivo assays has emerged as a promising avenue for identifying potential pharmacophores that can be developed into therapeutic drugs. This study aims to assess the bioactive compounds and antioxidant capacity of the Bolanthus turcicus (B. turcicus) and to investigate the effects on head and neck cancer (HNC) cell lines. Methanol (MeOH), ethyl acetate (EA) and aqueous (Aq) extracts were prepared from B. turcicus, and the amount of total phenolic content (TPC) and total flavonoid content (TFC) in the extracts were analyzed by the Folin-Ciocalteu and Aluminum chloride method, respectively. In addition, the total antioxidant capacity and iron reducing potential of B. turcicus extracts were determined by the Phosphomolybdenum and Ferric ion reducing antioxidant power (FRAP) method. The effect of B. turcicus on HEp-2, SCC-90, SCC-9, FaDu HNC cell viability, motility, and cell-nuclear morphology was evaluated by MTT, scratch-wound healing assay, and Pllalloidin-DAPI staining, respectively. The effect of B. turcicus on the expression of CASP-3, BAX, and BCL-2 genes at the mRNA, protein, and intracellular level was evaluated by quantitative PCR (qPCR), western blot, and immunofluorescence staining. Moreover, Annexin V-FITC/PI, was used in flow cytometry to investigate the effect of B. turcicus on apoptosis. The MeOH extract exhibited the highest phenolic content, flavonoid content and antioxidant activity (p < 0.05 for all). HNC cells treated with extracts indicated delayed wound healing and decreased motility (p < 0.05 for all). Analysis of annexin V-PI staining indicated that the B. turcicus extracts induced apoptosis but not viability and necrosis in the HNC cell (p < 0.05 for all). Moreover, qPCR data regarding the apoptotic mechanism showed that the extracts could induce apoptosis by upregulation of pro-apoptotic CASP-3 and BAX genes and downregulation of anti-apoptotic BCL-2 gene (p < 0.05 for all). The expression of protein and intracellular levels of CASP-3 and BAX were increased, while the BCL-2 was decreased in cells treated with the extracts (p < 0.05 for all). In addition, diffuse pycnosis and DNA condensation in HNC cell nuclei, confirming apoptotic cell death (p < 0.05 for all). This study data indicated that B. turcicus extracts have antioxidant, cytotoxic, anti-migratory and pro-apoptotic activity. In conclusion, it has been shown that B. turcicus can be used as a potential therapeutic agent against HNC.