Search Results (3,667)

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson’s disease. Full article

The ²⁰³Pb and ²¹²Pb lead radioisotopes are attracting growing interest as they can aid in the development of personalized, targeted radionuclide treatment for advanced and currently untreatable cancers. In the present study, the bonding interactions of Pb²⁺ with twelve macrocyclic ligands, having an octa and nona coordination, were assessed using Density Functional Theory (DFT) calculations. The molecular structures in an aqueous solution were computed utilizing the polarized continuum model. The preference for the twisted square antiprismatic (TSAP) structure was confirmed for ten out of the eleven cyclen-based complexes. The characteristics of the bonding were assessed using a Natural Energy Decomposition Analysis (NEDA). The analysis revealed a strong electrostatic character of the bonding in the complexes, with minor variations in electrical terms. The charge transfer (CT) had a comparable energetic contribution only in the case of neutral ligands, while in general, it showed notable variations regarding the various donor groups. Our data confirmed the general superiority of the carboxylate O and aromatic N donors. The combination of the selected efficient pendant arms pointed out the superiority of the acetate pendant arms and the lack of significant cooperation between the different pendant arms in the probed ligands. Altogether, the combination led only to a marginal enhancement in the total CTs in the complexes. Full article

This research investigates the utilization of an ionic liquid combination of solidified floating organic drop micro-extraction (IL-SFODME) to augment the concentration of trace amounts of lead, working as a preliminary stage before electrothermal atomic absorption spectrometry (ETAAS) analysis without the use of chelating agents. Key parameters impacting the microextraction efficiency—including pH, the volume of the ionic liquid (1-Hexyl-3-methylimidazolium hexafluorophosphate, HMIMPF6), temperature, extraction time, and stirring speed—were methodically examined to determine optimal conditions. Under detected optimized conditions, an enhancement factor of 71.2 was obtained for a 15 mL sample solution. The calibration curve exhibited linearity within the concentration range of 0.2–2.5 µg/L, with a detection limit (3σ) of 0.054 µg/L and a quantification limit (10σ) of 0.18 µg/L. For seven replicate measurements of 0.5 µg/L lead, the relative standard deviation (RSD) was ±2.30%. This method was effectively implemented to extract and quantify lead in both reference water and different real water samples, showcasing significantly efficient extraction performance. Full article

To study the mixed fermentation technology of blueberry and corn peptide by Lacticaseibacillus rhamnosus ZYN-0417 and Lactiplantibacillus plantarum ZYN-0221 and its effect on fermentation quality, fermentation conditions were optimized using a single-factor test and a Plackett–Burman design combined with a Box–Behnken response surface methodology, with blueberry juice and corn peptide as raw materials and L. rhamnosus ZYN-0417 and Lp. plantarum ZYN-0221 as the starter. The results showed that the optimum fermentation conditions were as follows: the volume ratio of ZYN-0417 and ZYN-0221 was 1:1, the amount of blueberry juice was 20%, the amount of corn peptide was 22%, the amount of glucose was 2%, the amount of inoculation was 5%, the fermentation time was 40 h, and the fermentation temperature was 37 °C. Under optimum conditions, the viable count of lactic acid bacteria in fermented blueberry and corn peptide was 16.28 log CFU/mL, the pH value was 4.86, the total acid content was 14.00 g/L, the total sugar content was 39.98 g/100 g, the protein content was 48.34 g/100 g, the scavenging ability of the DPPH, ABTS⁺ and ·OH⁻ radicals increased by 10.14%, 10.98% and 25.02%, respectively, the chelating ability of Fe²⁺ increased by 14.92%, the content of total phenol increased by 1.43 mg/L, the content of total flavonoids increased by 150.87 g/L, the activity of superoxide dismutase increased by 122.10 U/mL, and the activation rate of alcohol dehydrogenase increased by 5.74%. The results showed that mixed lactic acid bacteria could be used as a starter of blueberry and corn peptide and effectively improve the nutritional value of the product. Full article

Antimony (Sb) is a toxic trace element for plants and animals. With the development of industrial applications and mining, Sb pollution is becoming more serious. Phytoremediation is regarded as an eco-friendly technique to reduce the threat of Sb to the environment and human health, and tall fescue that is highly adaptable to heavy metal stress can be a candidate species for Sb-contaminated soil phytoremediation. However, the mechanism of the Sb stress response in tall fescue is not clear. Therefore, transcriptomic analysis was used in this study to reveal the molecular mechanisms of Sb stress response regulation in tall fescue. The results suggested that the roots and leaves of tall fescue responded to Sb stress in different ways. In roots, the lignin and flavonoids might reduce the toxicity of Sb by anti-oxidation and Sb chelation. At the same time, the DEGs in leaves were mainly enriched in the pathways of glutathione metabolism, β-alanine metabolism, and glycine, serine, and threonine metabolism. Additionally, genes related to the pathways, such as 4CL, GST, AGXT2, and ALDH7A1, especially cytochrome P450 family genes (e.g., CYP73A, CYP75A, and CYP98A), might play key roles in the regulation of the Sb stress response in tall fescue. These findings provided a theoretical reference for the efficient use of tall fescue to control Sb-contaminated soil in the future. Full article

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder. Methods: A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases. Results: Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the PKLR gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the PKLR gene when making therapeutic decisions about starting a patient on mitapivat. Conclusions: While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat. Full article

The ability of bacteria to recycle exogenous amino acid-based peptides and amino sugars for peptidoglycan biosynthesis was extensively investigated using optical imaging. In particular, fluorescent AeK–NBD was effectively utilized to study the peptidoglycan recycling pathway in Gram-negative bacteria. Based on these promising results, we were inspired to develop the radioactive AeK conjugate [⁶⁸Ga]Ga-DOTA-AeK for the in vivo localization of bacterial infection using PET/CT. An easy-to-implement radiolabeling procedure for DOTA-AeK with [⁶⁸Ga]GaCI₃ followed by solid-phase purification was successfully established to obtain [⁶⁸Ga]Ga-DOTA-AeK with a radiochemical purity of ≥95%. [⁶⁸Ga]Ga-DOTA-AeK showed good stability over time with less protein binding under physiological conditions. The bacterial incorporation of [⁶⁸Ga]Ga-DOTA-AeK and its fluorescent Aek-NBD analog were investigated in live and heat-killed Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Unfortunately, no conclusive in vitro intracellular uptake of [⁶⁸Ga]Ga-DOTA-AeK was observed for E. coli or S. aureus live and heat-killed bacterial strains (p > 0.05). In contrast, AeK-NBD showed significantly higher intracellular incorporation in live bacteria compared to the heat-killed control (p < 0.05). Preliminary biodistribution studies of [⁶⁸Ga]Ga-DOTA-AeK in a dual-model of chronic infection and inflammation revealed limited localization at the infection site with non-specific accumulation in response to inflammatory markers. Finally, our study demonstrates proof that the intracellular incorporation of AeK is necessary for successful bacteria-specific imaging using PET/CT. Therefore, Ga-68 was not a suitable radioisotope for tracing the bacterial uptake of AeK tripeptide, as it required chelation with a bulky metal chelator such as DOTA, which may have limited its active membrane transportation. An alternative for optimization is to explore diverse chemical structures of AeK that would allow for radiolabeling with ¹⁸F or ¹¹C. Full article

This study aimed to establish the preparation process of peptide–calcium chelates (TMP-Ca) using skipjack tuna meat and investigate the function and mechanism of TMP-Ca in an osteoporosis model of rats. The results indicated that trypsin is more suitable for preparing the Ca-chelating hydrolysates of tuna meat, and the optimal hydrolysis conditions were derived as follows: digestion time 4 h, material–liquid ratio 1:10, and enzyme dose 3%. The conditions for chelating Ca with tuna meat hydrolysate were optimized to be chelation time 50 min, temperature 50 °C, pH 8.0, and a peptide–Ca ratio 1:10. The prepared hydrolysate was subjected to ultrafiltration, and the fraction (TMP) (MW <1 kDa) showed the highest Ca chelation rate (51.27 ± 1.42%) and was made into the peptide–Ca chelates (TMP-Ca). In osteoporotic rats, TMP-Ca significantly improved the decrease in ovarian indexes caused by retinoic acid. It also elevated serum Ca, phosphorus, and bone turnover indexes, increased the number of bone trabeculae, and improved bone microstructure. In addition, we confirmed that TMP-Ca could regulate the OPG/TRAF6 pathway to reduce osteoclast differentiation, inhibit bone resorption, and promote bone formation. Therefore, TMP-Ca could significantly ameliorate osteoporosis, and this study provides a functional component for the preparation of healthcare products using skipjack tuna meat to treat osteoporosis. Full article

This research studied the phenolic content compared with the antioxidant properties of various O. vulgare (Lamiaceae) cultivars grown in Poland. The research results in this paper indicate that the dominant ingredient in all oregano cultivars was rosmarinic acid, known for its strong antioxidant properties. The highest amounts of rosmarinic acid (87.16 ± 4.03 mg/g dm) were identified in the O. vulgare spp. hirtum (Link) Ietsw. Other metabolites identified in the studied extracts include luteolin O-di-glucuronide-O-di-pentoside (30.79 ± 0.38 mg/g dm in the ‘Aureum’ cultivar), 4′-O-glucopyranosyl-3′, 4′-dihydroxy benzyl-protocatechuate (19.84 ± 0.60 mg/g dm in the ‘Margerita’ cultivar), and p-coumaroyl-triacetyl-hexoside (25.44 ± 0.18 mg/g dm in the ‘Margerita’ cultivar). ‘Hot & spicy’ and ‘Margerita’ cultivars were characterized by the highest activity in eliminating OH^• and O₂^•− radicals. Extracts from Greek oregano had the highest ability to scavenge DPPH radicals and chelate iron ions. This research has also provided new evidence that oregano has anti-migratory, cytotoxic properties and influences the viability of gastric cancer cells (the highest cytotoxicity was attributed to the ‘Hot & spicy’ cultivar, which performed the worst in antioxidant properties tests). Extracts from the tested cultivars at a concentration of 0.625% effectively inhibited the growth of S. aureus and P. aeruginosa bacteria. It seems that the oregano grown in Poland is of good quality and can be successfully grown on a large scale if the appropriate use is found. Full article

AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) is a mesocyclic chelating agent forming stable complexes with several metal ions. Over the past 20 years since its inception, AAZTA and its bifunctional derivatives have gained a growing role in several applications ranging from MRI contrast agents to diagnostics and nuclear medicine. The recent market restrictions applied to nitroethane preclude the easy preparation of AAZTA, prompting the search for a suitable alternative. In this work, we report the synthesis of two structural analogs (AAZTA-Bn and AAZTA-Et) from commercially available chemicals and the thermodynamic and kinetic study of their complexing ability towards selected metal ions. A comparison of the complexing properties of AAZTA-Bn and AAZTA-Et with the former AAZTA allows us to identify the possible heir of this efficient chelating agent. Full article

Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone. Full article

Cadmium (Cd) contamination in soil has emerged as a significant challenge for agricultural production. Phytoremediation and passivation are key techniques for remediating Cd-contaminated soil. However, few studies have focused on the synergistic effects of these two techniques. In this work, the effectiveness of synergetic remediation strategies, both synchronous and asynchronous, utilizing passivation and phytoremediation techniques, was explored. The results of pot experiments and field experiments indicated that optimal remediation effects were obtained by asynchronous synergetic remediation, removing over 80% of bioavailable Cd within 14 days. Mechanistic studies conducted using XPS analysis, soil property analysis, and microbial diversity analysis confirmed that the chelation effect of SDD and soil pH value are the primary factors contributing to the effectiveness of both remediation strategies. In contrast, the variations in microbial populations are identified as the crucial factors influencing the varying outcomes of the two sequential remediation approaches. This research demonstrates that asynchronous synergistic remediation is a promising strategy for mitigating Cd contamination in soil. Full article

The essential oil and the aqueous and ethanolic extracts obtained from the aerial parts of Pelargonium graveolens cultivated in Morocco were studied for their antioxidant and insecticidal activity against rice weevils (Sitophylus oryzae). The total phenolic content of the extracts was determined by a spectrophotometric method and the phenolic compounds were extensively characterized by HPLC-PDA/ESI-MS. To evaluate antioxidant potential, three in vitro assays were used. In the DPPH test, the ethanolic extract was the most active, followed by the aqueous extract and the essential oil. In the reducing power assay, excellent activity was highlighted for both extracts, while in the Fe²⁺ chelating activity assay, weak activity was observed for both the essential oil and the ethanolic extract and no activity for the aqueous extract. Concerning insecticide activity, the toxicity of the essential oil and the extracts was tested against rice weevils; the lethal concentrations LC₅₀ and LC₉₉ were determined, as well as the lethal time required for the death of 50% (LT₅₀) and 99% (LT₉₉) of the weevils. The essential oil had the highest activity; 100% mortality of S. oryzae was observed around 5, 9, and 8 days for the essential oil and the aqueous and ethanolic extracts, respectively. Full article

Heavy metal ions such as cadmium, mercury, lead, and arsenic in the soil cannot be degraded naturally and are absorbed by crops, leading to accumulation in agricultural products, which poses a serious threat to human health. Therefore, establishing a rapid and efficient method for detecting heavy metal ions in agricultural products is of great significance to ensuring the health and safety. In this study, a novel optimized spectrometric method was developed for the rapid and specific colorimetric detection of cadmium ions based on N-(2-Acetamido)-iminodiacetic acid (ADA) and Victoria blue B (VBB) as the chromogenic unit. The safety evaluation of ADA showed extremely low biological toxicity in cultured cells and live animals. The standard curve is y = 0.0212x + 0.1723, R² = 0.9978, and LOD = 0.08 μM (0.018 mg/kg). The liner concentrations detection range of cadmium is 0.1–10 μM. An inexpensive paper strip detection method was developed with a detection limit of 0.2 μM to the naked eye and a detection time of less than 1 min. The method was successfully used to assess the cadmium content of rice, soybean, milk, grape, peach, and cabbage, and the results correlated well with those determined by inductively coupled plasma–mass spectrometry (ICP-MS). Thus, our study demonstrated a novel rapid, safe, and economical method for onsite, real-time detection of cadmium ions in agricultural products. Full article

The recovery of valuable nutritional compounds, like proteins, from waste streams and by-products is a key strategy for enhancing production sustainability and opening up new market potential. This research aimed to use high-intensity ultrasound as an innovative technique to extract the soluble proteins from the pumpkin leaves. The impact of various sonication amplitudes and duration periods on protein yield, functional properties, antioxidant qualities, and structural characteristics, were studied. Utilization of ultrasound technology significantly increased the yield of pumpkin leaf protein by up to 40%—six times higher than maceration. The ultrasound extraction provided a RuBisCO-rich protein fraction with high radical scavenging and chelating activities, especially at 40% amplitude. Cavitation modified the tertiary and secondary structures of leaf proteins: the amount of α-helix changed based on amplitude (12.3–37.7%), the amount of random coil increased to 20.4%, and the amount of β-turn reduced from 31 to 18.6%. The alteration of the protein fluorescence spectrum (blue shift in spectrum) provides further evidence that ultrasound alters the proteins’ molecular structure in comparation with maceration; the maximum tryptophan fluorescence intensity decreased from 22.000 to 17.096. The hydrophobicity values of 76.8–101.5 were substantially higher than the maceration value of 53.4, indicating that ultrasound improved the hydrophobicity of protein surfaces. Ultrasound resulted in a significant increase in solubility in an acidic environment with the increase in sonication amplitude. A 2.4-fold increase in solubility at pH 2 becomes apparent (20% amplitude; 43.1%) versus maceration (18.2%). The emulsifying ability decreases from 6.62 to 5.13 m²/g once the sonication amplitude increases by 20–70%. By combining the ultrasound periods and amplitudes, it is possible to create high-value protein leaf extracts with improved properties which can find real application as food additives and dietary supplements. Full article