Nanocapsules loaded with iron-saturated bovine lactoferrin have antimicrobial therapeutic potential and maintain calcium, zinc and iron metabolism

Aim: This study aimed to evaluate the potential antimicrobial efficacy of alginate gel-encapsulated ceramic nanocarriers loaded with iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (AEC-CP-Fe-bLf NCs). Materials & methods: The antimicrobial activities of non-nanoformulated apo (iron free), Fe-bLf and native forms of Australian bLf against pathogenic Salmonella typhimurium (wild strain) were studied in vitro. The efficacy of AEC-CP-Fe-bLf NCs were checked in vivo using Balb/c mice model. Results: The study revealed that native bLf is more effective in combating infection than the conventional drug ciprofloxacin (0.4 mg/ml). The efficacy of the drug was also revealed in vivo when BALB/c mice that, after being challenged with S. typhimurium (200 μl of 10(8) CFU/ml suspension), were fed orally with a nanoformulated bLf diet and the infection was observed to be eliminated. However, chronic infection developed in the group of infected mice that did not receive any drug treatment, as well as the mice treated with ciprofloxacin. The immune response to bacterial infection and to various drug treatments thereafter was studied in the mice. Conclusion: The study concludes that bLf and nanoformulated Fe-bLf are more effective in the treatment of Salmonella-infected mice than ciprofloxacin.

Molecular dynamics modelling of diffusional formation of titanium carbide clusters in iron matrix

Molecular dynamics simulation was employed to study the atomic interactions in titanium carbides and iron matrix containing carbon and titanium, which are significant for understanding the formation of titanium carbide cluster during precipitate process. The atoms trajectory and diffusion coefficients of carbon in titanium carbide were analyzed to provide a vacancy-exchanging mechanism and clarify the carbon concentration dependence of carbon diffusion in titanium carbide. The dependence of the formation of titanium carbide cluster in iron matrix on carbon was determined from the study of atoms diffusivity, cluster formation and formation energy of titanium carbide cluster. The simulation results provided insight into the carbon diffusion process and improved the understanding of the formation of titanium carbide cluster.

Associations between dietary iron and zinc intakes, and between biochemical iron and zinc status in women

Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18–50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12–38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort.

Recent advances in machining of Austempered Ductile Iron to avoid machining induced microstructural phase transformation reaction

Austempered Ductile Iron (ADI) is a type of nodular, ductile cast iron subjected to heat treatments-austenitising and austempering. Whilst machining is conducted prior to heat treatment and offers no significant difficulty, machining post heat treatment is demanding and often avoided. Phase transformation of retained austenite to martensite leading to poor machinability characteristics is a common problem experienced during machining. Study of phase transformations is an investigative study on the factors-plastic strain (εp) and thermal energy (Q) which effect phase transformations during machining. The experimental design consists of face milling grade 1200 at variable Depth of Cut (DoC) range from 1 to 4 mm, coolant on/off, at constant speed, 1992 rpm and feed rate, 0.1 mm/tooth. Plastic strain (εp) and martensite content (M) at fracture point for each grade was evaluated by tensile testing. The effect of thermal energy (Q) on phase transformations was also verified through temperature measurements at DoC 3 and 1 mm using thermocouples embedded into the workpiece. Finally, the amount of plastic strain (εp) and thermal energy (Q) responsible for a given martensite increase (M) during milling was related and calculated using a mathematical function, M=f (εp, Q). The future work of the thesis involves an in-depth study on the new link discovered through this research: mathematical model relating the role of plastic strain and thermal energy in martensite formation.

Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.

Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer

BACKGROUND: Iron binding, naturally occurring protein bovine lactoferrin (bLf) has attracted attention as a safe anti-cancer agent capable of inducing apoptosis. Naturally, bLf exists partially saturated (15-20%) with Fe(3+) however, it has been demonstrated that manipulating the saturation state can enhance bLf's anti-cancer activities. METHODS: Apo-bLf (Fe(3+) free) and Fe-bLf (>90% Fe(3+) Saturated) were therefore, tested in MDA-MB-231 and MCF-7 human breast cancer cells in terms of cytotoxicity, proliferation, migration and invasion. Annexin-V Fluos staining was also employed in addition to apoptotic protein arrays and Western blotting to determine the specific mechanism of bLf-induced apoptosis with a key focus on p53 and inhibitor of apoptosis proteins (IAP), specifically survivin. RESULTS: Apo-bLf induced significantly greater cytotoxicity and reduction in cell proliferation in both cancer cells showing a time and dose dependent effect. Importantly, no cytotoxicity was detected in normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP members and their inhibitors were significantly modulated by both forms of bLf, though differentially in each cell line. Most interestingly, both Apo-bLf and Fe-bLf completely inhibited the expression of survivin protein (key IAP), after 48 h at 30 and 40 nM in cancer cells. CONCLUSIONS: The capacity of these forms of bLf to target survivin expression and modulation of apoptosis demonstrates an exciting potential for bLf as an anti-cancer therapeutic in the existing void of survivin inhibitors, with a lack of successful inhibitors in the clinical management of cancer.

Warm deformation and annealing behaviour of iron-silicon-(carbon) steel sheets

Single pass warm rolling and compression experiments were carried out from ambient to 800°C for ultra-low carbon (ULC) steel with ∼100 ppm carbon and interstitial free (IF) steels, both with two levels of silicon. Subsequently, annealing was done in order to recrystallize the deformed specimens. The main purpose of this study was to understand the effects of rolling temperature and silicon on stress responses and textures. This study comprises two main themes: flow stress and strain rate sensitivity during compression and shear banding and textures in warm rolled specimens. The effects of deformation temperature on in-grain shear bands were different between ULC-Si and IF-Si steels. As in previous work with more conventional steels, in-grain shear bands in the IF grade had low sensitivity to rolling temperature, while those in the ULC grade depended significantly on the deformation temperature. However, the temperature profile of shear banding in the ULC grade was approximately 150°C higher than in previous work. Deformation and recrystallisation textures for both IF and ULC grades depended on their rolling temperatures. The variation of both grain size and texture after annealing can be explained by the rise and fall of in-grain shear banding activity which is related to the strain rate sensitivity.

Chip formation mechanism and machinability of wrought duplex stainless steel alloys

This paper investigates the chip formation mechanism and machinability of two-phase materials, such as, wrought duplex stainless steel alloys SAF 2205 and SAF 2507. SEM and optical microscopic details of the frozen cutting zone and chips revealed that the harder austenite phase dissipates in the advancement of the cutting tool, being effectively squeezed out of the softer ferrite phase. Microhardness profiles reveal correlation in hardness from the workpiece material transitioning to the chip. The tool wear (TiAIN + TiN coated solid carbide twist drill) and machining forces were investigated. Tool wear, was dominantly due to the adhesion process which developed from built-up edge formation, is highly detrimental to the flank face. Flute damage was also observed as a major issue in the drilling of duplex alloys leading to premature tool failure. Duplex 2507 shows higher sensitivity to cutting speed during machining and strain hardening at higher velocity and less machinability due to presence of higher percentage of Ni, Mo and Cr.

Mobile phone app aimed at improving iron intake and bioavailability in premenopausal women: a qualitative evaluation

BACKGROUND: Low iron intake can lead to iron deficiency, which can result in impaired health and iron-deficiency anemia. A mobile phone app, combining successful dietary strategies to increase bioavailable iron with strategies for behavior change, such as goal setting, monitoring, feedback, and resources for knowledge acquisition, was developed with the aim to increase bioavailable iron intake in premenopausal women.

OBJECTIVE: To evaluate the content, usability, and acceptability of a mobile phone app designed to improve intake of bioavailable dietary iron.

METHODS: Women aged 18-50 years with an Android mobile phone were invited to participate. Over a 2-week period women were asked to interact with the app. Following this period, semistructured focus groups with participants were conducted. Focus groups were audio recorded and analyzed via an inductive open-coding method using the qualitative analysis software NVivo 10. Themes were identified and frequency of code occurrence was calculated.

RESULTS: Four focus groups (n=26) were conducted (age range 19-36 years, mean 24.7, SD 5.2). Two themes about the app's functionality were identified (frequency of occurrence in brackets): interface and design (134) and usability (86). Four themes about the app's components were identified: goal tracker (121), facts (78), photo diary (40), and games (46). A number of suggestions to improve the interface and design of the app were provided and will inform the ongoing development of the app.

CONCLUSIONS: This research indicates that participants are interested in iron and their health and are willing to use an app utilizing behavior change strategies to increase intake of bioavailable iron. The inclusion of information about the link between diet and health, monitoring and tracking of the achievement of dietary goals, and weekly reviews of goals were also seen as valuable components of the app and should be considered in mobile health apps aimed at adult women.

Iron intakes of Australian infants and toddlers: findings from the Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program

Fe deficiency remains the most common nutritional deficiency worldwide and young children are at particular risk. Preventative food-based strategies require knowledge of current intakes, sources of Fe, and factors associated with low Fe intakes; yet few data are available for Australian children under 2 years. This study’s objectives were to determine intakes and food sources of Fe for Australian infants and toddlers and identify non-dietary factors associated with Fe intake. Dietary, anthropometric and socio-demographic data from the Melbourne Infant Feeding, Activity and Nutrition Trial Program were analysed for 485 infants (mean age: 9·1 (sd 1·2) months) and 423 toddlers (mean age: 19·6 (sd 2·6) months) and their mothers. Dietary intakes were assessed via 24-h recalls over 3 non-consecutive days. Prevalence of inadequate Fe intake was estimated using the full probability approach. Associations between potential non-dietary predictors (sex, breast-feeding status, age when introduced to solid foods, maternal age, maternal education, maternal employment status and mother’s country of birth) and Fe intakes were assessed using linear regression. Mean Fe intakes were 9·1 (sd 4·3) mg/d for infants and 6·6 (sd 2·4) mg/d for toddlers. Our results showed that 32·6 % of infants and 18·6 % of toddlers had inadequate Fe intake. Main food sources of Fe were Fe-fortified infant formula and cereals for infants and toddlers, respectively. Female sex and current breast-feeding were negatively associated with infant Fe intakes. Introduction to solid foods at or later than 6 months was negatively associated with Fe intake in toddlers. These data may facilitate food-based interventions to improve Australian children’s Fe intake levels.

The reduction of oxygen on iron(II) oxide/poly(3,4-ethylenedioxythiophene) composite thin film electrodes

© 2014 Elsevier Ltd. All rights reserved. Conducting polymers (CPs) are currently being investigated for use in many applications owing to their abilities to catalyze a wide range of electrochemical reactions and act as an effective electrode support for various inorganic and organic electrocatalyst materials. Here, we have found that the deposition of poly(3,4-ethylenedioxythiophene) (PEDOT) through the use of an established base-inhibited chemical vapor-phase polymerization (VPP) procedure using an iron(III) tosylate oxidant results in the co-deposition of electrocatalytic iron(II) oxide species within the film. The presence of these species accounts for the 2-electron reduction of hydrogen peroxide that occurs on these electrodes during the series 4-electron oxygen reduction reaction. Furthermore, this realization leads to the possibility of fabricating thin film inorganic/CP composites of various compositions through careful choice of oxidant in a facile, one-step process. A combination of in situ Raman (487.77 nm laser) and in situ UV-Vis spectroscopy was used to probe the oxidation state of PEDOT in the thin film composite electrodes while reducing oxygen in alkaline conditions. These measurements show that the 2-electron electroreduction of hydrogen peroxide (or HO2 -) occurs only on the iron(II) oxide species in a reaction that is facilitated by an effective electron transfer from the delocalized electron orbitals of the PEDOT matrix. This approach could potentially be used in situ to monitor the electrocatalyst/electrode interface quality of conducting polymer-supported electrocatalysts.

Microstructure and mechanical properties of wrought and additive manufactured Ti-6Al-4V cylindrical bars

Titanium alloys are widely used in various engineering design application due to its superior material properties. The traditional manufacturing of titanium products is always difficult, time consuming, high material wastage and manufacturing costs. Selective laser melting (SLM), an additive manufacturing technology has widely gained attention due to its capability to produce near net shape components with less production time. In this technical paper,microstructure,chemical composition,tensile properties and hardness are studied for the wrought and additive manufactured SLM cylindrical bar. Microstructure,mechanical properties and hardness were studied in both the longitudinal and transverse directions of the bar to study the effect of orientation. It was found that additive manufactured bar have higher yield strength, ultimate tensile strength and hardness than the wrought bar. For both conventional and SLM test samples, the yield strength, ultimate tensile strength and hardness was found to be high in the transverse direction. The difference in the properties can be attributed to the difference in microstructure as a result of processing conditions. The tensile fracture area was quantified by careful examination of the fracture surfaces in the scanning electron microscope.

Relationships of nicotianamine and other amino acids with nickel, zinc and iron in Thlaspi hyperaccumulators

Experimental evidence suggests that nicotianamine (NA) is involved in the complexation of metal ions in some metal-hyperaccumulating plants. Closely-related nickel (Ni)- and zinc (Zn)-hyperaccumulating species were studied to determine whether a correlation exists between the Ni and Zn concentrations and NA in foliar tissues. A liquid chromatography–mass spectrometry (LC-MS) procedure was developed to quantify the NA and amino acid contents using the derivatizing agent 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. A strong correlation emerged between Ni and NA, but not between Zn and NA. Concentrations of NA and l-histidine (His) also increased in response to higher Ni concentrations in the hydroponic solution supplied to a serpentine population of Thlaspi caerulescens. An inversely proportional correlation was found between the iron (Fe) and Ni concentrations in the leaves. Correlations were also found between Zn and asparagine. The results obtained in this study suggest that NA is involved in hyperaccumulation of Ni but not Zn. The inverse proportionality between the Ni and Fe concentrations in the leaf may suggest that Ni and Fe compete for complexation to NA.