Potassium ferrate's disinfecting ability: a study on human adenovirus, Giardia duodenalis, and microbial indicators under varying pH and water temperature conditions.

Ferrate (Fe(VI): HFeO4- /FeO42-), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of disinfection by-products. In this study, we assessed the disinfecting ability of potassium ferrate against a variety of microorganisms, including waterborne pathogens, under varying pH and water temperature conditions. We presented CT values, a metric of ferrate concentrations (C) and contact time (T), to quantify microbial inactivation rates. Among the tested microorganisms, human adenovirus was the least resistant to ferrate, followed by waterborne bacteria such as Escherichia coli and Vibrio cholerae, and finally, the protozoan parasite Giardia duodenalis. We further investigated the impact of two pH values (7 and 8) and two temperatures (5 and 25 °C) on microbial inactivation rates, observing that inactivation rates increased with lower pH and higher temperature. In addition to showcasing ferrate's capacity to effectively inactivate a range of the tested microorganisms, we offer a ferrate CT table to facilitate the comparison of the effectiveness of various disinfection methods.

Design and Syntheses of New Antibiotics Inspired by Nature's Quest for Iron in an Oxidative Climate.

This Account describes fundamental chemistry that promoted the discovery of new antibiotics. Specifically, the NH acidity of simple hydroxamic acid derivatives facilitated the syntheses of novel ß-lactams (oxamazins and monobactams), siderophore mimics that limit bacterial iron uptake and bacterially targeted sideromycins (siderophore-antibiotic conjugates). The development of resistance to our current limited set of antibiotic scaffolds has created a dire medical situation. As recently stated, "if you weren't taking antibiotic resistance seriously before, now would be a good time to start." A project commissioned by the British government (https://amr-review.org/) has released estimates of the near-future global toll of antibiotic resistance that are jaw-dropping in their seriousness and scale: 10 million deaths per year and at least $100 trillion in sacrificed gross national product. The 2020 COVID pandemic confirmed that infectious disease problems are no longer localized but worldwide. Many classical antibiotics, especially ß-lactams, previously provided economical cures, but the evolution of antibiotic destructive enzymes (i.e., ß-lactamases), efflux pumps, and bacterial cell wall permeability barriers has made many types of bacteria, especially Gram-negative strains, resistant. Still, and in contrast to other therapies, the public expectation is that any new antibiotic must be inexpensive. This creates market limitations that have caused most major pharmaceutical companies to abandon antibiotic research. Much needs to be done to address this significant problem.The critical need for bacteria to sequester essential iron provides an Achilles' heel for new antibiotic development. Although ferric iron is extremely insoluble, bacteria need micromolar intracellular concentrations for growth and virulence. To this end, they biosynthesize siderophores (Gr. iron bearer) and excrete them into their environment, where they bind iron with high affinity. The iron complexes are recognized by specific outer-membrane transporters, and once actively internalized, the iron is released for essential processes. To conserve biosynthetic energy, some bacteria recognize and utilize siderophores made by competing strains. As a counter-revolution in the never-ending fight for survival, bacteria have also evolved sideromycins, which are siderophores conjugated to warheads that are lethal to rogue bacteria. While none are now used therapeutically, natural sideromycins called albomycins have been used clinically, and others have been shown to be well tolerated and active in animal infection models. Herein we describe practical methods to synthesize new antibiotics and artificial sideromycins with the generalized structure shown above (siderophore-linker drug). Utilizing the molecular-recognition-based siderophore/sideromycin bacterial assimilation processes, it is possible to design both broad spectrum and exquisitely narrow spectrum (targeted) sideromycins and even repurpose older or more classical antibiotics. Relevant microbiological assays, in vivo animal infection studies, and the recent FDA approval of cefiderocol demonstrate their effectiveness.

Click ferrocenyl-erlotinib conjugates active against erlotinib-resistant non-small cell lung cancer cells in vitro.

Thanks to development of erlotinib and other target therapy drugs the lung cancer treatment have improved a lot in recent years. However, erlotinib-resistant lung cancer remains an unsolved clinical problem which demands for new therapeutics to be developed. Herein we report the synthesis of a library of 1,4- and 1,5-triazole ferrocenyl derivatives of erlotinib together with their anticancer activity studies against erlotinib-sensitive A549 and H1395 as well as erlotinib-resistant H1650 and H1975 cells. Studies showed that extend of anticancer activity is mainly related to the length of the spacer between the triazole and the ferrocenyl entity. Among the series of investigated compounds two isomers commonly bearing C(O)CH2CH2 spacer have shown superior to erlotinib activity against erlotinib-resistant H1650 and H1975 cells whereas compound with short methylene spacer devoid of any activity. In-depth biological studies for the most active compound showed differences in its mechanism of action in compare to erlotinib. The latter is known EGFR inhibitor whereas their ferrocenyl congener exerts anticancer activity mainly as ROS-inducer which activates mitochondrial pathway of apoptosis in cancer cells. However, docking studies suggested that the most active compound can also binds to the active site of EGFR TK in a similar way as erlotinib.

Criticality of Surface Characteristics of Intravenous Iron-Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics.

Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron-carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron-carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron-carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.

Novel Type of Tetranitrosyl Iron Salt: Synthesis, Structure and Antibacterial Activity of Complex [FeL'2(NO)2][FeL'L"(NO)2] with L'-thiobenzamide and L"-thiosulfate.

In this work a new donor of nitric oxide (NO) with antibacterial properties, namely nitrosyl iron complex of [Fe(C6H5C-SNH2)2(NO)2][Fe(C6H5C-SNH2)(S2O3)(NO)2] composition (complex I), has been synthesized and studied. Complex I was produced by the reduction of the aqueous solution of [Fe2(S2O3)2(NO)2]2- dianion by the thiosulfate, with the further treatment of the mixture by the acidified alcohol solution of thiobenzamide. Based on the structural study of I (X-ray analysis, quantum chemical calculations by NBO and QTAIM methods in the frame of DFT), the data were obtained on the presence of the NO…NO interactions, which stabilize the DNIC dimer in the solid phase. The conformation properties, electronic structure and free energies of complex I hydration were studied using B3LYP functional and the set of 6-31 + G(d,p) basis functions. The effect of an aquatic surrounding was taken into account in the frame of a polarized continuous model (PCM). The NO-donating activity of complex I was studied by the amperometry method using an "amiNO-700" sensor electrode of the "inNO Nitric Oxide Measuring System". The antibacterial activity of I was studied on gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria. Cytotoxicity was studied using Vero cells. Complex I was found to exhibit antibacterial activity comparable to that of antibiotics, and moderate toxicity to Vero cells.

N-Heterocyclic Carbene Iron Complexes as Anticancer Agents: In Vitro and In Vivo Biological Studies.

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.

Targeted cancer cell delivery of arsenate as a reductively activated prodrug.

Nanoformulations, prodrugs, and targeted therapies are among the most intensively investigated approaches to new cancer therapeutics. Human ferritin has been used extensively as a nanocarrier for the delivery of drugs and imaging agents to cancerous tumor cells both in vitro and in vivo. We report exploitation of the native properties of ferritin, which can be co-loaded with simple forms of iron (FeOOH) and arsenic (arsenate) in place of the native phosphate. The As(III) form arsenic trioxide has been successfully used to treat one blood cancer, but has so far proven too systemically toxic for use on solid tumors in the clinic. The As(V) form, arsenate, on the other hand, while much less systemically toxic upon bolus injection has also proven ineffective for cancer therapy. We extended the C-terminal ends of the human ferritin subunits with a tumor cell receptor targeting peptide and loaded this modified ferritin with ~ 800 arsenates and ~ 1100 irons. Our results demonstrate targeting and uptake of the iron, arsenate-loaded modified human ferritin by breast cancer cells. At the same arsenic levels, the cytotoxicity of the iron, arsenate-loaded human ferritin was equivalent to that of free arsenic trioxide and much greater than that of free arsenate. The iron-only loaded human ferritin was not cytotoxic at the highest achievable doses. The results are consistent with the receptor-targeted human ferritin delivering arsenate as a reductively activated 'prodrug'. This targeted delivery could be readily adapted to treat other types of solid tumor cancers.

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity.

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron µ-vinyliminium precursors [Fe2Cp2(CO)( µ-CO){ µ-η1: η3-C3(R')C2HC1N(Me)(R)}]CF3SO3 (R = R' = Me, 1a; R = 2,6-C6H3Me2 = Xyl, R' = Ph, 1b; R = Xyl, R' = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a-d, 5a-b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

Exosome-Mimetic Supramolecular Vesicles with Reversible and Controllable Fusion and Fission*.

The fusion and fission behaviors of exosomes are essential for the cell-to-cell communication. Developing exosome-mimetic vesicles with such behaviors is of vital importance, but still remains a big challenge. Presented herein is an artificial supramolecular vesicle that exhibits redox-modulated reversible fusion-fission functions. These vesicles tend to fuse together and form large-sized vesicles upon oxidation, undergo a fission process and then return to small-sized vesicles through reduction. Noteworthy, the aggregation-induced emission (AIE) characteristics of the supramolecular building blocks enable the molecular configuration during vesicular transformation to be monitored by fluorescence technology. Moreover, the presented vesicles are excellent nanocarrier candidates to transfer siRNA into cancer cells.

Simultaneous hyperthermia-chemotherapy effect by arterial injection of Fe(Salen) for femur tumor.

We previously identified a novel nanomagnetic particle, N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet-guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra-arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra-arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra-arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra-arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia-chemotherapy in the future.

Protective effects of carbonyl iron against multiple low-dose streptozotocin-induced diabetes in rodents.

Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ-specific autoimmune disease-type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+ CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down-regulated the number of inflammatory CD4+ IFN-γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas-infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+ IL17+ cells. The regulatory arm of the immune system represented by CD3+ NK1.1+ (NKT) and CD4+ CD25+ FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down-regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen-presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells.

Distinct in vitro Complement Activation by Various Intravenous Iron Preparations.

BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. RESULTS: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. CONCLUSION: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

The biomedical piglet: establishing reference intervals for haematology and clinical chemistry parameters of two age groups with and without iron supplementation.

BACKGROUND: The similarities between swine and humans in physiological and genomic patterns, and the great correlation in size and anatomy, make pigs extremely useful in preclinical studies. New-born piglets can represent a model for congenital and genetic diseases in new-born children. It is known that piglets may have significant differences in clinicopathological results compared to adult pigs. Therefore, adult laboratory reference intervals cannot be applied to piglets. The aim of this study was to compare haematological and chemical variables in piglets of two ages and determinate age-related reference intervals for commercial hybrid young pigs. Blood samples were collected under general anaesthesia from 130 animals divided into five- (P5) and 30- (P30) day-old piglets. Only P30 animals were treated with parenteral iron after birth. Samples were analysed using automated haematology (ADVIA 2120) and chemistry analysers, and age-related reference intervals were calculated. RESULTS: Significant higher values of RBC, Hb and HCT were observed in P30 animals when compared to P5, with an opposite trend for MCV. These results were associated with a reduction of the RBC regeneration process and the thrombopoietic response. The TSAT and TIBC were significantly higher in P30 compared to P5; however, piglets remained iron deficient compared to adult reference intervals reported previously. CONCLUSIONS: In conclusion, this paper emphasises the high variability occurring in clinicopathological variables between new-born and 30-day-old pigs, and between piglets and adult pigs. This study provides valuable reference data for piglets at precise ages and could be used in the future as historical control improving the Reduction in animal experiments, as suggested by the 3Rs principle.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

Importance: Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. Objective: To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants: Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions: Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Main Outcomes and Measures: Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 µg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Results: Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 µg/dL (ferrous sulfate) vs 506 to 417 µg/dL (iron complex) (a greater difference of -50 µg/dL [95% CI, -86 to -14 µg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04). Conclusions and Relevance: Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia. Trial Registration: clinicaltrials.gov Identifier: NCT01904864.

Removal of Chromium from Soils Cultivated with Maize (Zea Mays) After the Addition of Natural Minerals as Soil Amendments.

The efficiency of natural minerals, i.e. zeolite, bentonite and goethite, regarding the retention of chromium, from maize was examined. Specifically, 1.0 kg of soil, 1.0 g of soil amendment and either 50 mg L-1 Cr(III) or 1 mg L-1 Cr(VI) were added in plant pots. Then, seeds of maize were cultivated. Each treatment was repeated three times. The statistical results of the experiments were analyzed by LSD test. Cr(III) addition in soil has shown that zeolite was the only amendment that increased the dry weight. Zeolite and bentonite reduced significantly the total chromium in plants after the addition of 50 mg L-1 Cr(III). The addition of Cr(VI) in soil has shown that bentonite was the only amendment that increased the dry weight of biomass and the plants' height. All soil amendments reduced to zero the total chromium concentration measured to plants after the addition of 1 mg L-1 Cr(VI).

Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells.

BACKGROUND: Treatment of iron deficiency with intravenous (i.v.) iron is a first-line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs. METHODS: Via flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM. RESULTS: Phenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen-activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not. CONCLUSIONS: This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.

A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv⁻/⁻ mice.

Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice.

Interfacial interaction between methyl parathion-degrading bacteria and minerals is important in biodegradation.

In the present study, the influence of kaolinite and goethite on microbial degradation of methyl parathion was investigated. We observed that the biodegradation process was improved by kaolinite and depressed by goethite. Calorimetric data further showed that the metabolic activities of degrading cells (Pseudomonas putida) were enhanced by the presence of kaolinite and depressed by the presence of goethite. A semipermeable membrane experiment was performed and results supported the above observations: the promotive effect of kaolinite and the inhibition of goethite for microbial degradation was not found when the bacteria was enclosed by semipermeable membrane and had no direct contact with these minerals, suggesting the important function of the contact of cellular surfaces with mineral particles. The relative larger particles of kaolinite were loosely attached to the bacteria. This attachment made the cells easy to use the sorbed substrate and then stimulated biodegradation. For goethite, small particles were tightly bound to bacterial cells and limited the acquisition of substrate and nutrients, thereby inhibiting biodegradation. These results indicated that interfacial interaction between bacterial cells and minerals significantly affected the biodegradation of pesticides.

Bioevaluation of novel anti-biofilm coatings based on PVP/Fe3O4 nanostructures and 2-((4-ethylphenoxy)methyl)-N- (arylcarbamothioyl)benzamides.

Novel derivatives were prepared by reaction of aromatic amines with 2-(4-ethylphenoxymethyl)benzoyl isothiocyanate, affording the N-[2-(4-ethylphenoxymethyl) benzoyl]-Nꞌ-(substituted phenyl)thiourea. Structural elucidation of these compounds was performed by IR, NMR spectroscopy and elemental analysis. The new compounds were used in combination with Fe3O4 and polyvinylpyrrolidone (PVP) for the coating of medical surfaces. In our experiments, catheter pieces were coated by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The microbial adherence ability was investigated in 6 multi-well plates by using culture based methods. The obtained surfaces were also assessed for their cytotoxicity with respect to osteoblast cells, by using fluorescence microscopy and MTT assay. The prepared surfaces by advanced laser processing inhibited the adherence and biofilm development ability of Staphylococcus aureus and Pseudomonas aeruginosa tested strains while cytotoxic effects on the 3T3-E1 preosteoblasts embedded in layer shaped alginate hydrogels were not observed. These results suggest that the obtained medical surfaces, based on the novel thiourea derivatives and magnetic nanoparticles with a polymeric shell could represent a promising alternative for the development of new and effective anti-infective strategies.

Inactivation of bacteriophage MS2 with potassium ferrate(VI).

Ferrate [Fe(VI); FeO(4)(2-)] is an emerging oxidizing agent capable of controlling chemical and microbial water contaminants. Here, inactivation of MS2 coliphage by Fe(VI) was examined. The inactivation kinetics observed in individual batch experiments was well described by a Chick-Watson model with first-order dependences on disinfectant and infective phage concentrations. The inactivation rate constant k(i) at a Fe(VI) dose of 1.23 mgFe/L (pH 7.0, 25 °C) was 2.27(±0.05) L/(mgFe × min), corresponding to 99.99% inactivation at a Ct of ~4 (mgFe × min)/L. Measured k(i) values were found to increase with increasing applied Fe(VI) dose (0.56-2.24 mgFe/L), increasing temperature (5-30 °C), and decreasing pH conditions (pH 6-11). The Fe(VI) dose effect suggested that an unidentified Fe byproduct also contributed to inactivation. Temperature dependence was characterized by an activation energy of 39(±6) kJ mol(-1), and k(i) increased >50-fold when pH decreased from 11 to 6. The pH effect was quantitatively described by parallel reactions with HFeO(4)(-) and FeO(4)(2-). Mass spectrometry and qRT-PCR analyses demonstrated that both capsid protein and genome damage increased with the extent of inactivation, suggesting that both may contribute to phage inactivation. Capsid protein damage, localized in the two regions containing oxidant-sensitive cysteine residues, and protein cleavage in one of the two regions may facilitate genome damage by increasing Fe(VI) access to the interior of the virion.