Quinoa snack elaborated with Lactiplantibacillus plantarum CRL 1964 sourdough increases the mineral bioavailability in mice.

BACKGROUND: Consumption of pseudocereal-based foods decreased in phytate concentration can provide better nutrition concerning mineral bioavailability. This study aimed to evaluate the mineral bioavailability of quinoa sourdough-based snacks in a murine model. The mice were divided into five groups. One group was fed with basal snacks; three control groups received quinoa-based snacks made from non-fermented dough, dough without inoculum, and chemically acidified dough; and the test group (GF) received quinoa snacks elaborated from sourdough fermented by a phytase-positive strain, Lactiplantibacillus plantarum CRL 1964. Food intake, body weight, and mineral concentration in blood and organs (liver, kidney, and femur) were determined. RESULTS: Food consumption increased during the feeding period and had the highest (16.2-24.5%) consumption in the GF group. Body weight also increased during the 6-weeks of trial. The GF group showed higher (6.0-10.2%) body weight compared with the other groups from the fifth week. The concentrations of iron, zinc, calcium, magnesium, and phosphorus in blood, iron and phosphorus in the liver, manganese and magnesium in the kidney, and calcium and phosphorus in the femur increased significantly (1.1-2.7-fold) in the GF group compared to the control groups. CONCLUSION: The diet that includes quinoa snacks elaborated with sourdough fermented by phytase-positive strain L. plantarum CRL 1964 increased the concentrations of minerals in the blood, liver, kidney, and femur of mice, counteracting the antinutritional effects of phytate. This study demonstrates that the diminution in phytate content and the consequent biofortification in minerals are a suitable tool for producing novel foods. © 2024 Society of Chemical Industry.

Amelioration of nephrotoxicity by targeting ferroptosis: role of NCOA4, IREB2, and SLC7a11 signaling.

Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.

Metabolic Reprogramming of Klebsiella pneumoniae Exposed to Serum and Its Potential Implications in Host Immune System Evasion and Resistance.

The aim of this study was to identify, using proteomics, the molecular alterations caused by human serum exposure to Klebsiella pneumoniae ACH2. The analysis was performed under two different conditions, native serum from healthy donors and heat-inactivated serum (to inactivate the complement system), and at two different times, after 1 and 4 h of serum exposure. More than 1,000 bacterial proteins were identified at each time point. Enterobactin, a siderophore involved in iron uptake, and proteins involved in translation were upregulated at 1 h, while the chaperone ProQ and the glyoxylate cycle were identified after 4 h. Enzymes involved in the stress response were downregulated, and the SOD activity was validated using an enzymatic assay. In addition, an intricate metabolic adaptation was observed, with pyruvate and thiamine possibly involved in survival and virulence in the first hour of serum exposure. The addition of exogenous thiamine contributes to bacterial growth in human serum, corroborating this result. During 4 h of serum exposure, the glyoxylate cycle (GC) probably plays a central role, and the addition of exogenous succinate suppresses the GC, inducing a decrease in serum resistance. Therefore, serum exposure causes important changes in iron acquisition, the expression of virulence factors, and metabolic reprogramming, which could contribute to bacterial serum resistance.

Transition metals and oxidation reactions trigger stargate opening during the initial stages of the replicative cycle of the giant Tupanvirus.

Tupanviruses, members of the family Mimiviridae, infect phagocytic cells. Particle uncoating begins inside the phagosome, with capsid opening via the stargate. The mechanism through which this opening takes place is unknown. Once phagocytized, metal ion flux control and ROS are induced to inactivate foreign particles, including viruses. Here, we studied the effect of iron ions, copper ions, and H2O2 on Tupanvirus particles. Such treatments induced stargate opening in vitro, as observed by different microscopy techniques. Metal-treated viruses were found to be non-infectious, leading to the hypothesis that stargate opening likely resulted in the release of the viral seed, which is required for infection initiation. To the best of our knowledge, this is the first description of a giant virus capsid morphological change induced by transition metals and H2O2, which may be important to describe new virulence factors and capsid uncoating mechanisms.

Both low and high body iron stores relate to metabolic syndrome in postmenopausal women: Findings from the VIKING Health Study-Shetland (VIKING I).

BACKGROUND: There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF-MetS association might be U/J-shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland. METHODS: We analysed cross-sectional data from the Viking Health Study-Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status-specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2-3) as the reference, were conducted to estimate the SF-MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI. RESULTS: Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17-3.38] p =.011 for Q1 and 2.10 [1.27-3.49] p =.004 for Q4) This U-shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15-200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI. CONCLUSION: Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF-MetS associations were found in men or PreMW. The ferritin-MetS association pattern differs between populations and U/J-shaped associations may exist.

Gallium: a decisive "Trojan Horse" against microorganisms.

Controlling multidrug-resistant microorganisms (MRM) has a long history with the extensive and inappropriate use of antibiotics. At the cost of these drugs being scarce, new possibilities have to be explored to inhibit the growth of microorganisms. Thus, metallic compounds have shown to be promising as a viable alternative to contain pathogens resistant to conventional antimicrobials. Gallium (Ga3+) can be highlighted, which is an antimicrobial agent capable of disrupting the essential activities of microorganisms, such as metabolism, cellular respiration and DNA synthesis. It was observed that this occurs due to the similar properties between Ga3+ and iron (Fe3+), which is a fundamental ion for the correct functioning of bacterial activities. The mimetic effect performed by Ga3+ prevents iron transporters from distinguishing both ions and results in the substitution of Fe3+ for Ga3+ and in adverse metabolic disturbances in rapidly growing cells. This review focuses on analyzing the development of research involving Ga3+, elucidating the intracellular incorporation of the "Trojan Horse", summarizing the mechanism of interaction between gallium and iron and comparing the most recent and broad-spectrum studies using gallium-based compounds with antimicrobial scope.

Signal-sensing triggers the shutdown of HemKR, regulating heme and iron metabolism in the spirochete Leptospira biflexa.

Heme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant. Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses. HemKR is a TCS present in both saprophytic and pathogenic Leptospira species, involved in the control of heme metabolism. However, the molecular means by which HemKR is switched on/off in a signal-dependent way, are still unknown. Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. Using the saprophytic species Leptospira biflexa as a model, we now show that 5-aminolevulinic acid (ALA) triggers the shutdown of the HemKR pathway in live cells, and does so by stimulating the phosphatase activity of HemK towards phosphorylated HemR. Phospho~HemR dephosphorylation leads to differential expression of multiple genes, including of heme metabolism and transport systems. Besides the heme-biosynthetic genes hemA and the catabolic hmuO, which we had previously reported as phospho~HemR targets, we now extend the regulon identifying additional genes. Finally, we discover that HemR inactivation brings about an iron-deficit tolerant phenotype, synergistically with iron-responsive signaling systems. Future studies with pathogenic Leptospira will be able to confirm whether such tolerance to iron deprivation is conserved among Leptospira spp., in which case HemKR could play a vital role during infection where available iron is scarce. In sum, HemKR responds to abundance of porphyrin metabolites by shutting down and controlling heme homeostasis, while also contributing to integrate the regulation of heme and iron metabolism in the L. biflexa spirochete model.

Heme metabolism in Strigomonas culicis: Implications of H2O2 resistance induction and symbiont elimination.

Monoxenous trypanosomatid Strigomonas culicis harbors an endosymbiotic bacterium, which enables the protozoa to survive without heme supplementation. The impact of H2O2 resistance and symbiont elimination on intracellular heme and Fe2+ availability was analyzed through a comparison of WT strain with both WT H2O2-resistant (WTR) and aposymbiotic (Apo) protozoa. The relative quantification of the heme biosynthetic pathway through label-free parallel reaction monitoring targeted mass spectrometry revealed that H2O2 resistance does not influence the abundance of tryptic peptides. However, the Apo strain showed increased coproporphyrinogen III oxidase and ferrochelatase levels. A putative ferrous iron transporter, homologous to LIT1 and TcIT from Leishmania major and Trypanosoma cruzi, was identified for the first time. Label-free parallel reaction monitoring targeted mass spectrometry also showed that S. culicis Iron Transporter (ScIT) increased 1.6- and 16.4-fold in WTR and Apo strains compared to WT. Accordingly, antibody-mediated blockage of ScIT decreased by 28.0% and 40.0% intracellular Fe2+concentration in both WTR and Apo strains, whereas no effect was detected in WT. In a heme-depleted medium, adding 10 µM hemin decreased ScIT transcript levels in Apo, whereas 10 µM PPIX, the substrate of ferrochelatase, increased intracellular Fe2+ concentration and ferric iron reduction. Overall, the data suggest mechanisms dependent on de novo heme synthesis (and its substrates) in the Apo strain to overcome reduced heme availability. Given the importance of heme and Fe2+ as cofactors in metabolic pathways, including oxidative phosphorylation and antioxidant systems, this study provides novel mechanistic insights associated with H2O2 resistance in S. culicis.

Advancing glioblastoma treatment through iron metabolism: A focus on TfR1 and Ferroptosis innovations.

Glioblastoma (GBM) represents a formidable challenge in oncology, characterized by aggressive proliferation and poor prognosis. Iron metabolism plays a critical player in GBM progression, with dysregulated iron uptake and utilization contributing to tumor growth and therapeutic resistance. Iron's pivotal role in DNA synthesis, oxidative stress, and angiogenesis underscores its significance in GBM pathogenesis. Elevated expression of iron transporters, such as transferrin receptor 1 (TfR1), highlights the tumor's reliance on iron for survival. Innovative treatment strategies targeting iron dysregulation hold promise for overcoming therapeutic challenges in GBM management. Approaches such as iron chelation therapies, induction of ferroptosis to nanoparticle-based drug delivery systems exploit iron-dependent vulnerabilities, offering avenues for enhance treatment efficacy and improve patient outcomes. As research advances, understanding the complexities of iron-mediated carcinogenesis provides a foundation for developing precision medicine approaches tailored to combat GBM effectively. This review explores the intricate relationship between iron metabolism and GBM, elucidating its multifaceted implications and therapeutic opportunities. By consolidating the latest insights into iron metabolism in GBM, this review underscores its potential as a therapeutic target for improving patient care in combination with the standard of care approach.

High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload.

BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

Iron and vitamin D intake on a diet are able to modify the in vitro immune response to Mycobacterium leprae.

BACKGROUND: The impact of nutrient availability on the survival of Mycobacterium leprae and the development of leprosy remains largely unknown. Iron is essential for the survival and replication of pathogens, while vitamin D has been involved with pathogen elimination and immunoregulation. OBJECTIVES: We evaluated the influence of dietary iron and vitamin D supplementation and restriction on the inflammatory response of mouse immune cells in vitro. METHODS: After 30 days of standard or modified diets, peritoneal cells and splenocytes were stimulated with the alive microorganisms and sonicated antigens of M. leprae, respectively. The production of inflammatory cytokines, reactive oxygen species, and cell proliferation were evaluated. FINDINGS: In peritoneal cells, vitamin D supplementation and iron restriction reduced the production of IL-6 and TNF in response to M. leprae, while splenocytes presented a reduction in TNF production under the same conditions. Lower levels of IFN-γ and TNF were observed in both iron-supplemented and iron-deficient splenocytes. Besides, iron supplementation also reduced the production of IL-6 and IL-10. No changes in the production of reactive oxygen species or in cell proliferation were observed related to different diets. MAIN CONCLUSIONS: Taken together, these data point to an interference of the status of these nutrients on the interaction between the host and M. leprae, with the potential to interfere with the progression of leprosy. Our results highlight the impact of nutritional aspects on this neglected disease, which is significantly associated with unfavourable social conditions.

Dynamics of Fe, Mn, and potentially harmful elements under reducing conditions in iron ore tailings after dam collapse in the Doce River basin-Brazil: flooded and non-flooded rice cultivations.

Potentially harmful element (PHE) bioavailability is important to environmental contamination and must be checked under several soil conditions. This study aimed to assess Fe, Mn, and PHE uptake by rice (Oryza sativa) grown on flooded and non-flooded Fe tailings collected from the Doce River basin after its collapse in Brazil. After 65 days of sowing, shoots and roots were harvested to determine PHE concentrations. The mean concentrations of Mn in shoots and Fe in the roots of rice grown on the flooded tailings were 2140 mg kg-1 and 15,219 mg kg-1, respectively. Mn was extensively translocated from roots to shoots (translocation factor (TF) = 2). Conversely, Fe accumulated in roots (TF = 0.015) and caused morphological damage to this rice organ. The application of macro and micronutrients lessened Fe toxicity in the roots of rice cultivated on the flooded tailings. The flooding of tailings influenced more Fe accumulation than Mn accumulation by rice plants. The PHE Ag, As, Cd, Ni, Hg, Pb, and Sb exhibited low total concentrations (maximum of 9 mg kg-1 for Ni and a minimum of 0.2 mg kg-1 for Cd, Hg, and Sb), and it was not observed an increase in their availability under tailings flooding conditions.

Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

The Ubiquity of the Reaction of the Labile Iron Pool That Attenuates Peroxynitrite-Dependent Oxidation Intracellularly.

Although the labile iron pool (LIP) biochemical identity remains a topic of debate, it serves as a universal homeostatically regulated and essential cellular iron source. The LIP plays crucial cellular roles, being the source of iron that is loaded into nascent apo-iron proteins, a process akin to protein post-translational modification, and implicated in the programmed cell death mechanism known as ferroptosis. The LIP is also recognized for its reactivity with chelators, nitric oxide, and peroxides. Our recent investigations in a macrophage cell line revealed a reaction of the LIP with the oxidant peroxynitrite. In contrast to the LIP's pro-oxidant interaction with hydrogen peroxide, this reaction is rapid and attenuates the peroxynitrite oxidative impact. In this study, we demonstrate the existence and antioxidant characteristic of the LIP and peroxynitrite reaction in various cell types. Beyond its potential role as a ubiquitous complementary or substitute protection system against peroxynitrite for cells, the LIP and peroxynitrite reaction may influence cellular iron homeostasis and ferroptosis by changing the LIP redox state and LIP binding properties and reactivity.

The transcriptional regulator Fur modulates the expression of uge, a gene essential for the core lipopolysaccharide biosynthesis in Klebsiella pneumoniae.

BACKGROUND: Klebsiella pneumoniae is a Gram-negative pathogen that has become a threat to public health worldwide due to the emergence of hypervirulent and multidrug-resistant strains. Cell-surface components, such as polysaccharide capsules, fimbriae, and lipopolysaccharides (LPS), are among the major virulence factors for K. pneumoniae. One of the genes involved in LPS biosynthesis is the uge gene, which encodes the uridine diphosphate galacturonate 4-epimerase enzyme. Although essential for the LPS formation in K. pneumoniae, little is known about the mechanisms that regulate the expression of uge. Ferric uptake regulator (Fur) is an iron-responsive transcription factor that modulates the expression of capsular and fimbrial genes, but its role in LPS expression has not yet been identified. This work aimed to investigate the role of the Fur regulator in the expression of the K. pneumoniae uge gene and to determine whether the production of LPS by K. pneumoniae is modulated by the iron levels available to the bacterium. RESULTS: Using bioinformatic analyses, a Fur-binding site was identified on the promoter region of the uge gene; this binding site was validated experimentally through Fur Titration Assay (FURTA) and DNA Electrophoretic Mobility Shift Assay (EMSA) techniques. RT-qPCR analyses were used to evaluate the expression of uge according to the iron levels available to the bacterium. The iron-rich condition led to a down-regulation of uge, while the iron-restricted condition resulted in up-regulation. In addition, LPS was extracted and quantified on K. pneumoniae cells subjected to iron-replete and iron-limited conditions. The iron-limited condition increased the amount of LPS produced by K. pneumoniae. Finally, the expression levels of uge and the amount of the LPS were evaluated on a K. pneumoniae strain mutant for the fur gene. Compared to the wild-type, the strain with the fur gene knocked out presented a lower LPS amount and an unchanged expression of uge, regardless of the iron levels. CONCLUSIONS: Here, we show that iron deprivation led the K. pneumoniae cells to produce higher amount of LPS and that the Fur regulator modulates the expression of uge, a gene essential for LPS biosynthesis. Thus, our results indicate that iron availability modulates the LPS biosynthesis in K. pneumoniae through a Fur-dependent mechanism.

Computational 3D Models of Fe2+/3+-Aß1-42 Complexes Associated with Alzheimer's Disease.

The interaction between iron and amyloid-beta (Aß) peptides has received significant attention in Alzheimer's disease (AD) research due to its potential implications in developing this pathology. However, the coordination preferences of iron and Aß1-42 have not been thoroughly investigated or remain unknown. This study employs a computational protocol that combines homology modeling techniques with quantum mechanics (DTF-xTB) calculations to build and evaluate several 3D models of Fe2+/3+-Aß1-42. Our results reveal well-defined complexes for both the metal and peptide moieties, and we discuss the molecular interactions stabilizing these complexes by elucidating the coordinating environments and binding preferences. These proposed models offer valuable insights into the role of iron in Alzheimer's disease (AD) pathology.

Proteomic characterization of Tenacibaculum dicentrarchi under iron limitation reveals an upregulation of proteins related to iron oxidation and reduction metabolism, iron uptake systems and gliding motility.

A strategy for vaccine design involves identifying proteins that could be involved in pathogen-host interactions. The aim of this proteomic study was to determine how iron limitation affects the protein expression of Tenacibaculum dicentrarchi, with a primary focus on virulence factors and proteins associated with iron uptake. The proteomic analysis was carried out using two strains of T. dicentrarchi grown under normal (control) and iron-limited conditions, mimicking the host environment. Our findings revealed differences in the proteins expressed by the type strain CECT 7612T and the Chilean strain TdCh05 of T. dicentrarchi. Nonetheless, both share a common response to iron deprivation, with an increased expression of proteins associated with iron oxidation and reduction metabolism (e.g., SufA, YpmQ, SufD), siderophore transport (e.g., ExbD, TonB-dependent receptor, HbpA), heme compound biosynthesis, and iron transporters under iron limitation. Proteins involved in gliding motility, such as GldL and SprE, were also upregulated in both strains. A negative differential regulation of metabolic proteins, particularly those associated with amino acid biosynthesis, was observed under iron limitation, reflecting the impact of iron availability on bacterial metabolism. Additionally, the TdCh05 strain exhibited unique proteins associated with gliding motility machinery and phage infection control compared to the type strain. These groups of proteins have been identified as virulence factors within the Flavobacteriaceae family, including the genus Tenacibaculum. These results build upon our previous report on iron acquisition mechanisms and could lay the groundwork for future studies aimed at elucidating the role of some of the described proteins in the infectious process of tenacibaculosis, as well as in the development of potential vaccines.

Chemical composition and in vitro iron bioavailability of extruded and open-pan cooked germinated and ungerminated pearl whole millet "Pennisetum glaucum (L.) R. Br."

This study aimed to evaluate the effect of extrusion and of open-pan cooking on whole germinated and non-germinated grains of pearl millet (Pennisetum glaucum L. R. Br.), on its chemical-nutritional composition and in vitro iron bioavailability. The experimental design consisted of three flours: non-germination open-pan cooked millet flour (NGOPCMF), germination open-pan cooked millet flour (GOPCMF), and extrusion cooked millet flour (ECMF). The ECMF increased the carbohydrates, iron, manganese, diosmin, and cyanidin and decreased the total dietary fiber, resistant starch, lipids, and total vitamin E, in relation to NGOPCMF. The GOPCMF increased the lysine and vitamin C and decreased the phytate, lipids, total phenolic, total vitamin E, and riboflavin concentration, in relation to NGOPCMF. Furthermore, germinated cooked millet flour and extruded millet flour improved iron availability in vitro compared to non-germinated cooked millet flour. GOPCMF and ECMF generally preserved the chemical-nutritional composition of pearl millet and improved in vitro iron bioavailability; therefore, they are nutritionally equivalent and can be used to develop pearl millet-based products.

Molecular modeling of multi-target analogs of huperzine A and applications in Alzheimer's disease.

CONTEXT: Given the diverse pathophysiological mechanisms underlying Alzheimer's disease, it is improbable that a single targeted drug will prove successful as a therapeutic strategy. Therefore, exploring various hypotheses in drug design is imperative. The sequestration of Fe(II) and Zn(II) cations stands out as a crucial mechanism based on the mitigation of reactive oxygen species. Moreover, inhibiting acetylcholinesterase represents a pivotal strategy to enhance acetylcholine levels in the synaptic cleft. This research aims to investigate the analogs of Huperzine A, documented in scientific literature, considering of these two hypotheses. Consequently, the speciation chemistry of these structures with Fe(II) and Zn(II) was scrutinized using quantum chemistry calculations, molecular docking simulations, and theoretical predictions of pharmacokinetics properties. From the pharmacokinetic properties, only two analogs, HupA-A1 and HupA-A2, exhibited a theoretical permeability across the blood-brain barrier; on the other hand, from a thermodynamic standpoint, the enantiomers of HupA-A2 showed negligible chelation values. The enantiomers with the most favorable interaction parameters were S'R'HupA-A1 (ΔGBIND = -40.0 kcal mol-1, fitness score = 35.5) and R'R'HupA-A1 (ΔGBIND = -35.5 kcal mol-1, fitness score = 22.61), being compared with HupA (ΔGBIND = -41.75 kcal mol-1, fitness score = 39.95). From this study, some prime candidates for promising drug were S'R'HupA-A1 and R'R'HupA-A1, primarily owing to their favorable thermodynamic chelating capability and potential anticholinesterase mechanism. METHODS: Quantum chemistry calculations were carried out at B3LYP/6-31G(d) level, considering the IEF-PCM(UFF) implicit solvent model for water. The coordination compounds were assessed using the Gibbs free energy variation and hard and soft acid theory. Molecular docking calculations were conducted using the GOLD program, based on the crystal structure of the acetylcholinesterase protein (PDB code = 4EY5), where the ChemScore function was employed with the active site defined as the region within a 15-Å radius around the centroid coordinates (X = -9.557583, Y = -43.910473, Z = 31.466687). Pharmacokinetic properties were predicted using SwissADME, focusing on Lipinski's rule of five.

Facilitating Seed Iron Uptake through Amine-Epoxide Microgels: A Novel Approach to Enhance Cucumber (Cucumis sativus) Germination.

Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.