The evaluation of oxidative stress parameters in breast and colon cancer.

ABSTRACT: Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.

Subsequent monitoring of ferric ion and ascorbic acid using graphdiyne quantum dots-based optical sensors.

Graphdiyne (GDY) as an emerging carbon nanomaterial has attracted increasing attention because of its uniformly distributed pores, highly π-conjugated, and tunable electronic properties. These excellent characteristics have been widely explored in the fields of energy storage and catalysts, yet there is no report on the development of sensors based on the outstanding optical property of GDY. In this paper, a new sensing mechanism is reported built upon the synergistic effect between inner filter effect and photoinduced electron transfer. We constructed a novel nanosensor based upon the newly-synthesized nanomaterial and demonstrated a sensitive and selective detection for both Fe3+ ion and ascorbic acid, enabling the measurements in real clinical samples. For the first time fluorescent graphdiyne oxide quantum dots (GDYO-QDs) were prepared using a facile ultrasonic protocol and they were characterized with a range of techniques, showing a strong blue-green emission with 14.6% quantum yield. The emission is quenched efficiently by Fe3+ and recovered by ascorbic acid (AA). We have fabricated an off/on fluorescent nanosensors based on this unique property. The nanosensors are able to detect Fe3+ as low as 95 nmol L-1 with a promising dynamic range from 0.25 to 200 µmol L-1. The LOD of AA was 2.5 µmol L-1, with range of 10-500 µmol L-1. It showed a promising capability to detect Fe3+ and AA in serum samples. Graphical abstract.

Developing an Analytical Method Based on Graphene Quantum Dots for Quantification of Deferiprone in Plasma.

In the world of nanotechnology, graphene quantum dots (GQDs) have been considerably employed in numerous optical sensing and bioanalytical applications. Herein, a simple and cost-efficient methodology was developed to the quantification of deferiprone in plasma samples by utilizing the selective interaction of the GQDs and drug in the presence of Fe3+ ions. GQDs were synthesized by a bottom-up technique as an advantageous fluorescent probe. Increasing levels of deferiprone ranging from 5 to 50 mg.L-1, leads to significant fluorescence quenching of GQDs. In addition, the calibration curve was revealed a linear response in this range with a sensitivity of 5 mg.L-1. The method validation was carried out according to the FDA guidelines to confirm the accuracy, precision, stability and selectivity of the developed method. The results show that this green and low-cost fluorescent probe could be used for the analysis of deferiprone.

Boron and nitrogen codoped carbon dots as fluorescence sensor for Fe3+ with improved selectivity.

Carbon dots (CDs) are popular as fluorescence sensors, and metal ions are typical analytes. However, CDs used as fluorescent sensors for Fe3+ have some interferences coming from co-existed ions. In this study, we suspect that sp3 boron atom in phenylboronic acid group will be more compatible with Fe3+ to form coordination bonds, thereby increasing the selectivity to Fe3+. Hence, we designed and synthesized boron and nitrogen codoped carbon dots (BN-CDs) for detection of Fe3+ via a hydrothermal method using o-phenylenediamine (OPA) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylchloroformate as precursors. From the results, we found that BN-CDs had superior selectivity to Fe3+ in the presence of the other common interfering metal ions like Cu2+, Fe2+ and Pb2+. Besides, the obtained BN-CDs exhibited good water solubility, favorable photostability, excellent pH stability between pH 2-11, and strong fluorescence intensity with quantum yield up to 31.5 %. These excellent properties of carbon dots validate that our idea is feasible, and can be used for design CDs for Fe3+ detection. Quenching mechanism study showed the fluorescence intensity of BN-CDs could be dramatically quenched by Fe3+ through dynamic and static synergy process. Finally, the as prepared BN-CDs were successfully applied to the determination of Fe3+ in fetal bovine serum and lake water.

A comparison between the combined effect of calcium carbonate with sucroferric oxyhydroxide and other phosphate binders: an in vitro and in vivo experimental study.

BACKGROUND: Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. METHODS: For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2-8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. RESULTS: In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. CONCLUSIONS: These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Synthesis of ficin-protected AuNCs in a droplet-based microreactor for sensing serum ferric ions.

A droplet-based microfluidic synthesis approach for preparation of ficin capped gold nano clusters (AuNCs) was developed. Well dispersed AuNCs could be procured within 8 min. Upon excitation wavelength at 340 nm, the resultant AuNCs exhibited a strong blue fluorescence with the maximum emission at 450 nm. Due to the aggregation-induced "turn-off" fluorescence mechanism, the synthesized AuNCs as a fluorescent probe displayed high sensitivity and good selectivity for sensing ferric ions. The relative fluorescence intensity versus ferric ions concentration yielded a good linear calibration in the range of 10.0-1000.0 µM (R2 = 0.998) and the limit of detection was 4.1 µM. Moreover, the possible mechanism for abated fluorescence intensity of AuNCs by adding ferric ions was discussed briefly. Further, the as-prepared fluorescent AuNCs was successfully applied for the detection of serum ferric ions. The results indicated that the droplet-based microfluidic synthesis system could provide a new way for the rapid preparation of AuNCs with good polydispersity and have potential as the sensing probes for the analysis of ferric ions in real biological samples.

A turn-on/off fluorescent sensor based on nano-structured Mg-Al layered double hydroxide intercalated with salicylic acid for monitoring of ferric ion in human serum samples.

The present work aimed to provide a novel chemosensor for ferric ion detection in human serum samples using nano-structured Mg-Al layered double hydroxide intercalated with salicylic acid (Mg-Al LDH-SA) as a sensitive fluorescence probe. The Mg-Al LDH-SA nanomaterial was synthesized and characterized via Fourier transform infrared spectroscopy, X-ray diffraction analysis, field emission scanning electron microscopy, dynamic light scattering and energy dispersive spectroscopy. The synthesized nanomaterial was applied to determine ferric ions by measuring the fluorescence intensity of Mg-Al LDH-SA sol solution at λem = 404 nm with excitation at λex = 287 nm. In the presence of ferric ions, the fluorescence intensity decreases owing to the formation of a stable complex between ferric ions and salicylic acid. Several important parameters affecting the analytical signal were studied and optimized. Under optimum conditions, the calibration graph was linear in the concentration range of 0.07-100 µmol L-1 with a corresponding detection limit of 26 nmol L-1. The intra- and inter-day relative standard deviations (n = 6 and ferric ion concentration; 50 µmol L-1) were 3.4% and 4.5%, respectively. The method was successfully employed to assess ferric ion in several human serum samples with relative recovery values between 98.7 and 104.6% for the spiked samples.

A simple assay for probing transformations of superparamagnetic iron oxide nanoparticles in human serum.

A novel approach for monitoring the biomolecular interactions of superparamagnetic nanoparticles was disclosed. Based on ultrafiltration of a human serum-nanoparticle mixture and the mass spectrometric analysis of filtrates, this assay revealed for iron oxide nanoparticles coated with poly(acrylic acid) satisfactory biopersistence and a bimodal binding to sulfur-containing biomolecules, with the formation of the protein corona completed in about 1 h.

Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Approach.

Nanomedicines are nanoparticle-based therapeutic or diagnostic agents designed for targeted delivery or enhanced stability. Nanotechnology has been successfully employed to develop various drug formulations with improved pharmacokinetic characteristics, and current research efforts are focused on the development of new innovator and generic nanomedicines. Nanomedicines, which are often denoted as complex or nonbiological complex drugs, have inherently different physicochemical and pharmacokinetic properties than conventional small molecule drugs. The tools necessary to fully evaluate nanomedicines in clinical settings are limited, which can hamper their development. One of the most successful families of nanomedicines are iron-carbohydrate nanoparticles, which are administered intravenously (IV) to treat iron-deficiency anemia. In the U.S., the FDA has approved six distinct iron-carbohydrate nanoparticles but only one generic version (sodium ferric gluconate for Ferrlecit). There is significant interest in approving additional generic iron-carbohydrate drugs; however, the lack of a direct method to monitor the fate of the iron nanoparticles in clinical samples has impeded this approval. Herein we report a novel liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) method that allows for the direct quantification of the iron-carbohydrate drugs in clinical samples, while simultaneously measuring the speciation of the iron released from the nanoparticles in biological samples. To our knowledge, this is the first time that iron nanoparticles have been observed in clinical samples, opening the door for direct pharmacokinetic studies of this family of drugs. This method has potential applications not only for iron-nanoparticle drugs but also for any nanomedicine with an inorganic component.

Effects of core size and PEG coating layer of iron oxide nanoparticles on the distribution and metabolism in mice.

INTRODUCTION: In vivo distribution of polyethylene glycol (PEG)ylated functional nanoparticles is vital for determining their imaging function and therapeutic efficacy in nanomedicine. However, contradictory results have been reported regarding the effect of core size and PEG surface of the nanoparticles on biodistribution. METHODS: To clarify this ambiguous understanding, using iron oxide nanoparticles (IONPs) as a model system, we investigated the effect of core size and PEG molecule weights on in vivo distribution in mice. Three PEGylated IONPs, including 14 nm IONP@PEG2,000, 14 nm IONP@PEG5,000, and 22 nm IONP@PEG5,000, were prepared with a hydrodynamic size of 26, 34, and 81 nm, respectively. The blood pharmacokinetics and tissue distribution were investigated in detail. RESULTS: The results indicated that the PEG layer, rather than core size, played a dominant role in determining the half-life time of IONPs. Specifically, increased molecular weight of the PEG layer led to a longer half-life time. These PEGylated IONPs were mainly excreted by liver clearance. While the PEG molecular layer constituted the key factor to determine the clearance ratio, core size affected the clearance rate. CONCLUSION: Complete blood count analysis and histopathology suggested excellent biocompatibility of PEGylated IONPs for future clinical trials.

Biomarkers of oxidative stress in blood of workers exposed to non-cholinesterase inhibiting pesticides.

In occupational settings workers are often exposed to pesticides at relatively high doses compared to environmental exposures. Long-term exposure to pesticides has been associated with numerous adverse health effects in epidemiological studies, and oxidative stress is often claimed as one of the underlying mechanisms. In fact, different pesticides have been reported to induce oxidative stress due to the generation of free radicals and/or alteration in antioxidant defense enzymes. The present study examined greenhouse workers regularly exposed to diverse pesticides under integrated production system, and a group of controls of the same geographic area without any chemical exposure. Two different periods of the same crop season were assessed, one of high exposure (with greater use of pesticides) and other of low exposure (in which a less use of these compounds was made). Non-specific biomarkers of oxidative stress, e.g. thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), gamma-glutamyl transpeptidase (GGT) and paraoxonase-1 (PON1) were measured in serum samples from all study subjects, alongside erythrocyte acetylcholinesterase (AChE). Results are suggestive of a mild increase in oxidative stress associated with pesticide exposure, which was compensated by an adaptive response to raise the antioxidant defenses and thus counter the detrimental effects of sustained oxidative stress. This response led to significantly increased levels of FRAS, SHT and PON1 in greenhouse workers relative to controls. Furthermore, AChE was decreased likely as a result of oxidative stress as workers did not use organophosphate insecticides.

A voltammetric method for Fe(iii) in blood serum using a screen-printed electrode modified with a Schiff base ionophore.

Herein, a potent electrochemical ionophore (SMS-2) based on a Schiff base has been used for the modification of a screen-printed electrode (SPE). The modified disposable electrode can selectively detect ferric ions in an aqueous medium. Redox behavior of the proposed strip was characterized using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Incorporation of the ligand in the ink of the SPE enhanced the analytical performance of the electrode, and its surface modification was confirmed by SEM and EDX analysis. Shifting/quenching of the cathodic peak potential of the ionophore after binding with Fe(iii) ions was used to detect and measure the ferric ion concentration. This sensor can identify Fe(iii) in the detection range from 0.625 µM to 7.5 µM. The modified SPE can selectively detect ferric ions in the presence of many other interfering ions and has been successfully used to determine the Fe(iii) content in blood serum samples. The metal-ionophore complex structure was optimized using DFT calculations to study the energetics of the metal-ionophore interactions.

Low-molecular-mass iron in healthy blood plasma is not predominately ferric citrate.

Blood contains a poorly characterized pool of labile iron called non-transferrin-bound iron (NTBI). In patients with iron-overload diseases such as hemochromatosis, NTBI accumulates in the liver, heart, and other organs. This material is probably nonproteinaceous and low molecular mass (LMM). However, the number, concentration, mass, and chemical composition of NTBI species remain unknown despite decades of effort. Here, solutions of plasma from humans, pigs, horses, and mice were passed through a 10 kDa cutoff membrane, affording flow-through solutions (FTSs) containing ∼1 µM iron. The FTSs were subjected to size-exclusion liquid chromatography at pH 8.5, 6.5, and 4.5. Iron was detected by an online inductively-coupled-plasma mass spectrometer. LC-ICP-MS chromatograms of the FTSs exhibited 2-6 iron-containing species with apparent masses between 400 and 2500 Da. Their approximate concentrations in plasma were 10-8-10-7 M. Not every FTS sample contained every LMM iron species, indicating individual variations. The most reproducible iron species had apparent masses of 400 and 500 Da. Chromatograms of the FTSs from established hemochromatosis patients exhibited no significant differences relative to controls. The peak positions and intensities depended on column pH. Some FTS iron adsorbed onto the column, especially at higher pH. Column-adsorbing-iron coordinated apo-transferrin whereas the more tightly coordinated iron species did not. Ferric citrate standards exhibited LMM iron peaks that were similar to but not the same as those obtained in FTSs. The results indicate that the LMM iron species in healthy blood plasma is not primarily ferric citrate; however, this may be one of many contributing complexes.

A simple LC-MS/MS method for determination of deferasirox in human plasma: Troubleshooting of interference from ferric ion in method development and its application.

As an orally active iron chelator, deferasirox forms its ion complexes in the prepared plasma samples and LC-MS mobile phase where ferric ion exists, and then comparing with the nominal concentration level, a lower detected concentration level of deferasirox would be obtained after LC-MS analysis, if no proper treatment was adopted. Meanwhile, the phenomenon would be observed that multiple repeat injections of the same deferasirox plasma sample in the same tube would show the lower and lower detected concentration levels of deferasirox, which caused by more and more ferric ions from the injection needle dissolved in the sample solution as multiple repeated injections. The addition of a proper concentration of EDTA in the mobile phase and the sample will competitively inhibit deferasirox from complexing with ferric ion, and prevent the decrease of deferasirox concentration. In this paper, an LC-MS/MS method was developed and validated for the determination of deferasirox in human plasma. To achieve the protein precipitation, the analytes were extracted from aliquots of 200 µL human plasma with acetonitrile. Chromatographic separation was performed on an ODS-C18 column with the mobile phase consisted of methanol and 0.1% formic acid containing 0.04 mM ethylenediamine tetraacetate dihydrate (EDTA) (80:20, v/v) at a flow rate of 0.5 mL/min. Deferasirox and the internal standard (IS, mifepristone) were detected using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the precursor-to-product ion transitions m/z 374.2 → 108.1 for deferasirox and m/z 430.1 → 372.2 for the IS. The method exhibited good linearity over the concentration range of 0.04-40 µg/mL for deferasirox. The method was successfully applied to a pharmacokinetic study in 10 Chinese healthy volunteers after oral administration of deferasirox.

[Transhepatic arterial embolization with superparamagnetic iron oxide and lipiodol for the treatment of VX2 tumor in rabbits].

OBJECTIVE: To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits.
 Methods: Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each): doxorubicin (DOX) group, DOX-LIP group, SPIO-DOX group, and SPIO-DOX-LIP group. Liver function (AST and ALT) was measured at 0, 1, 3, 5 and 7 d after transhepatic arterial embolization. The serum DOX level was measured at 0, 5, 15, 30, 60, and 120 minutes after transhepatic arterial embolization. MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group, while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group. All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level. The histopathologic examinations were performed including HE staining, Prussian blue staining and TUNEL assay, and then the tumor necrosis percentage and apoptosis index were calculated.
 Results: Compared to the DOX group, the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P<0.05). The levels of ALT and AST in the DOX group, DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7, there were no significant differences (P>0.05). The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P<0.05). However, the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P<0.05). The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7. Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images. Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group, and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P<0.05).
 Conclusion: This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor. It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants.

Background: Whether consumption of prebiotics increases iron absorption in infants is unclear.Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+NaFeEDTA) in Kenyan infants.Design: Infants (n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57FeFum+Na58FeEDTA or ferrous sulfate (54FeSO4). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed-effects models.Results: There was a significant group-by-compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, (P < 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3-37.5%) and 25.5% (IQR: 15.1-37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO4 (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P < 0.001) and positively correlated with Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.001).Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417.

Highly Fe3+-Selective Fluorescent Nanoprobe Based on Ultrabright N/P Codoped Carbon Dots and Its Application in Biological Samples.

Measuring the levels of Fe3+ in human body has attracted considerable attention for health monitoring as it plays an essential role in many physiological processes. In this work, we reported a selective fluorescent nanoprobe for Fe3+ detection in biological samples based on ultrabright N/P codoped carbon dots. By employing adenosine 5'-triphosphate (ATP) as the carbon, nitrogen, and phosphorus source, the N/P codoped carbon dots could be simply prepared through hydrothermal treatment. The obtained carbon dots exhibited high quantum yields up to 43.2%, as well as excellent photostability, low toxicity, and water solubility. Because of the Fe-O-P bonds formed between Fe3+ and the N/P codoped carbon dots, this nanoprobe showed high selectivity toward Fe3+ against various potential interfering substances in the presence of EDTA. The fluorescence quenching of as-fabricated carbon dots was observed with the increasing Fe3+ concentration, and the calibration curve displayed a wide linear region over the range of 1-150 µM with a detection limit of 0.33 µM. The satisfactory accuracy was further confirmed with the river samples and ferrous sulfate tablets, respectively. With the above outstanding properties, these N/P codoped carbon dots were successfully applied for direct detection of Fe3+ in biological samples including human blood serum and living cells. As compared to the most reported carbon dots-based Fe3+ sensors, this nanoprobe showed high fluorescence, good accuracy, and excellent selectivity, which presents the potential practical application for diagnosis of Fe3+ related disease.

A possible pathogenetic factor of sickle-cell disease based on fluorescent analysis via an optofluidic resonator.

Waveguide based optofluidic resonator features high precision and high sensitivity in real-time fluorescent analysis. We present a novel optofluidic resonator following the hollow-core metal-cladding waveguide structure, which is then used to record the real-time binding process of Fe2+ and Fe3+ with protoporphyrin IX (PpIX) in PBS solution, respectively. The central fluorescent wavelength of compound with Fe2+ is in good accordance with that of the normal hemoglobin, whilst the peaks of the Fe3+ compound match the hemoglobin specimen from sickle-cell disease (SCD) patients. Similar statement holds when we monitor the real-time oxidation processes of these products by injecting oxygen into the optofluidic chip. These observations lead to the speculation that the SCD is caused by replacing the Fe2+ in hemoglobin with Fe3+, which may be insightful in the discovery of new clinical routes to cure this disease.

Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.

BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.