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1.
Sci. agric ; 80: e20210202, 2023. tab, graf, ilus
Artigo em Inglês | VETINDEX | ID: biblio-1366027

RESUMO

Salinity is an abiotic stressor that greatly influences crop growth and yield. Scientists are always exploring diverse methods to combat salinity depression. Here, we conducted a greenhouse experiment to study the effects of NaCl salinity (0, 50, and 100 mM) under the foliar spray with zinc-oxide, nano zinc-oxide, iron-chelate, magnetized-Fe, and graphene-oxide on tarragon. The results revealed that the treatment with foliar spray of graphene showed the highest K+/Na+. Salinity of 50 and 100 mM × all foliar applications increased superoxide dismutase activity, whereas 100 mM NaCl raised the malondialdehyde content to its highest level. All salinity levels × Zn foliar spray improved the catalase activity. The foliar spray and salinity experiment exposed to Zn-treated plants attained the highest contents of essential oils. Proline and total phenolics showed the greatest amounts with 50 and 100 mM of NaCl, respectively. The GC/MS analysis revealed 38 compounds in the oil of Artemisia dracunculus L. as estragole (81-91.8 %) was the most dominant constituent. The highest amounts of estragole were found at 50 and 100 mM NaCl foliar sprayed with ZnO. Cis-Ocimene (0.1-6.4 %) was another major constituent with a high variation between the treatments. The highest cis-ocimene content was recorded at 100 mM NaCl × foliar Fe-chelated and in the graphene treatment. Overall, salinity adversely affected the physiological responses of tarragon; however, foliar spray with both forms of Fe and Zn partially ameliorated the adverse salinity effects.


Assuntos
Zinco , Artemisia/efeitos dos fármacos , Artemisia/fisiologia , Ferro , Malondialdeído/efeitos adversos , Antioxidantes/análise
2.
J Nat Prod ; 85(3): 479-484, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35196451

RESUMO

Bacteria use small molecules to impose strict regulation over the acquisition, uptake, and sequestration of transition metal ions. Low-abundance nutrient metals, such as Fe(III), need to be scavenged from the environment by high-affinity chelating molecules called siderophores. Conversely, metal ions that become toxic at high concentrations need to be sequestered and detoxified. Often, bacteria produce a suite of compounds that bind various metal ions at different affinities in order to maintain homeostasis. Turnerbactin, a triscatecholate siderophore isolated from the intracellular shipworm symbiont Teredinibacter turnerae T7901, is responsible for iron regulation and uptake. Herein, another series of compounds are described that complex with iron, copper, and molybdenum in solution. Teredinibactins belong to a class of metal-binding molecules that utilize a phenolate-thiazoline moiety in the coordination of metal ions. In contrast to other compounds in this class, such as yersiniabactin, the phenyl ring is decorated with a 2,4-dihydroxy-3-halo substitution pattern. UV-vis absorption spectroscopy based titration experiments with CuCl2 show the formation of an intermediate complex at substoichiometric concentrations and conversion to a copper-bound complex at 1:1 molar equiv.


Assuntos
Compostos Férricos , Sideróforos , Bactérias/metabolismo , Transporte Biológico , Ferro/metabolismo , Sideróforos/química
3.
Am J Vet Res ; 83(6)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524963

RESUMO

OBJECTIVE: To evaluate IV iron sucrose safety and impact on hematologic and iron indices in healthy cats. ANIMALS: 5 healthy research cats. PROCEDURES: Cats were administered iron sucrose (0.5 mg/kg, IV) over 30 minutes. Monitoring for acute reactions (temperature, heart rate, respiratory rate, and blood pressure) was performed every 5 minutes during injection and every 15 minutes for an additional hour. Baseline, 24-hour, and 1-, 2-, and 3-week postinjection measurements of CBC with reticulocyte indices, iron panel (ferritin, total iron-binding capacity, and iron), calculated transferrin saturation (TSAT), and serum amyloid A (SAA) concentration were performed. RESULTS: No cat experienced an acute drug reaction. SAA concentration was increased at 24 hours versus baseline. TSAT and ferritin decreased over time, with 3 cats developing concurrent functional iron deficiency (FID) and anemia. Hct (Spearman correlation [rs] = 0.805), hemoglobin (rs = 0.770), and reticulocyte hemoglobin content (rs = 0.581) correlated with TSAT. CLINICAL RELEVANCE: IV iron sucrose was well tolerated in healthy cats but was associated with transient increase in the systemic inflammatory marker SAA. Efficacy evaluation of dose based on iron deficit is needed in sick cats. Despite cumulative blood draw volume below recommended limits, anemia and FID were observed, which has important implications for experimental designs and serial hematologic monitoring. Further evaluation of inflammatory response to IV iron sucrose administration is warranted.


Assuntos
Anemia Ferropriva , Anemia , Doenças do Gato , Anemia/tratamento farmacológico , Anemia/prevenção & controle , Anemia/veterinária , Anemia Ferropriva/prevenção & controle , Anemia Ferropriva/veterinária , Animais , Doenças do Gato/prevenção & controle , Gatos , Óxido de Ferro Sacarado/uso terapêutico , Ferritinas/uso terapêutico , Hemoglobinas/análise , Hemoglobinas/metabolismo , Hemoglobinas/uso terapêutico , Ferro/uso terapêutico , Flebotomia/veterinária
4.
J Immunol Res ; 2022: 1249290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528617

RESUMO

Background: Gastric cancer is one of the most common malignant tumors, and it ranks third in global cancer-related mortality. This research was aimed at identifying new targeted treatments for gastric adenocarcinoma by constructing a ferroptosis-related lncRNA prognostic feature model. Methods: The gene expression profile and clinical data of gastric adenocarcinoma patients were downloaded from TCGA database. FerrDb database was used to determine the expression of iron death-related genes. We used R software to clean the TCAG gastric adenocarcinoma gene expression cohort and screen iron death-related differential genes and lncRNAs. The potential prognostic markers and immune infiltration characteristics were determined by constructing prognostic model and multivariate validation of lncRNA related to ferroptosis prognosis. Finally, the characteristics of immune infiltration were determined by immune correlation analysis. Results: We identified 26 ferroptosis-related lncRNAs with independent prognostic value. The Kaplan-Meier analysis identified high-risk lncRNAs associated with poor prognosis of STAD. The risk scoring model constructed by AC115619.1, AC005165.1, LINC01614, and AC002451.1 was better than traditional clinicopathological features. The 1-, 3-, and 5-year survival rates of STAD patients were predicted by the nomogram. GSEA reveals the oxidative respiration and tumor-related pathways in different risk groups. Immune analysis found significant differences in the expression of immune checkpoint-related genes TNFSF9, TNFSF4, and PDCD1LG2 between the two groups of patients. Meanwhile, there were significant differences in APC co stimulation, CCR, and checkpoint between the two groups. Conclusion: Based on the prognostic characteristics of ferroptosis-related lncRNAs, we identified the potential ferroptosis-related lncRNAs and immune infiltration characteristics in gastric adenocarcinoma, which will help provide new targeted treatments for gastric adenocarcinoma.


Assuntos
Adenocarcinoma , Ferroptose , RNA Longo não Codificante , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Ferroptose/genética , Humanos , Ferro , Ligante OX40 , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
5.
Front Cell Infect Microbiol ; 12: 847846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531339

RESUMO

The transition metals iron and copper are required by virtually all organisms but are toxic in excess. Acquisition of both metals and resistance to copper excess have previously been shown to be important for virulence of the most common airborne human mold pathogen, Aspergillus fumigatus. Here we demonstrate that the ambient availability of amino acids and proteins increases the copper resistance of A. fumigatus wild type and particularly of the ΔcrpA mutant that lacks export-mediated copper detoxification. The highest-protecting activity was found for L-histidine followed by L-asparagine, L-aspartate, L-serine, L-threonine, and L-tyrosine. Other amino acids and proteins also displayed significant but lower protection. The protecting activity of non-proteinogenic D-histidine, L-histidine-mediated growth inhibition in the absence of high-affinity copper uptake, determination of cellular metal contents, and expression analysis of copper-regulated genes suggested that histidine inhibits low-affinity but not high-affinity copper acquisition by extracellular copper complexation. An increase in the cellular copper content was found to be accompanied by an increase in the iron content, and, in agreement, iron starvation increased copper susceptibility, which underlines the importance of cellular metal balancing. Due to the role of iron and copper in nutritional immunity, these findings are likely to play an important role in the host niche.


Assuntos
Aspergillus fumigatus , Ferro , Aminoácidos/metabolismo , Cobre/metabolismo , Regulação Fúngica da Expressão Gênica , Histidina/genética , Histidina/metabolismo , Humanos , Ferro/metabolismo
6.
Proc Natl Acad Sci U S A ; 119(20): e2202812119, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35533282

RESUMO

SignificanceOxygen evolution reaction plays a striking role in renewable energy storage and conversion technologies. However, efficient electrocatalysts are necessary to promote this kinetically sluggish reaction. These reported down-top preparation methods of highly efficient transition metal hydroxides usually need delicate control in complex environments, limiting their large-scale application. An iron-oxidizing bacteria corrosion approach is developed to construct iron oxides top-down from iron-oxidizing bacteria corrosion integrated with nickel-iron oxyhydroxides to boost oxygen evolution. This study demonstrates a natural bacterial corrosion strategy to prepare highly efficient electrodes top-down for efficient water oxidation, which may stimulate broad interest in multidisciplinary integration of innovative nanomaterials and emerging technologies.


Assuntos
Níquel , Oxigênio , Corrosão , Compostos Férricos , Ferro , Água
7.
Inquiry ; 59: 469580221086919, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510934

RESUMO

Anaemia during pregnancy is a major public health concern. Despite its wide scope and adverse effects including increased maternal and perinatal morbidity and mortality, and long-term adverse effects on the newborn, appropriate interventions using upstream approaches to public health have largely not been implemented. This study investigated the prevalence and associated factors of anaemia among pregnant women in four health facilities in the Kwabre East Municipality. A cross-sectional survey with a two-stage sampling technique was conducted on 220 pregnant women who attended antenatal care at the selected health facilities. Interview-based structured questionnaires were used. Bivariate and multivariate logistic regression were used to identify predictors. The prevalence of anaemia was 11.4%. Few women (25) were anaemic and morphologically, 14 (56%) had normocytic normochromic anaemia and 9 (36%) had microcytic hypochromic anaemia. Iron deficiency was reported in 19 (8.6%) pregnant women. Independent predictors of anaemia were iron sulphate intake (AOR [95% CI] = 3.16 [1.15, 7.37], ANC follow-up during pregnancy (AOR [95% CI] = 3.07 [1.59, 7.99], household size of ≥5 (AOR [95% CI] = 3.58 [1.75, 9.52], folic acid intake (AOR [95% CI] = 5.29 [2.65, 12.39] and the period in pregnancy AOR [95% CI] = ≥36 weeks 3.2 (1.3-4.5). Though anaemia prevalence has been low in urban areas as previously reported, collaborated healthcare measures that aim at eradicating the menace are encouraged. Maternal healthcare interventions including the administration of folic acid, regular iron sulphate intake and intensive education on early ANC are recommended.


Assuntos
Anemia , Gestantes , Anemia/epidemiologia , Estudos Transversais , Feminino , Ácido Fólico , Gana/epidemiologia , Humanos , Recém-Nascido , Ferro , Gravidez , Prevalência , Sulfatos
8.
Wiad Lek ; 75(3): 584-589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522862

RESUMO

OBJECTIVE: The aim: The study of the possibilities of oxidase-antioxidant system indicators regulation at patients with periodontitis under the influence of complex treatment. PATIENTS AND METHODS: Materials and methods: 36 healthy and 125 patients with chronic and exacerbated periodontitis of primary (22 and 21), I (21) and II (20) degrees were examined.Indicators of lipid peroxidation and antioxidant protection (levels of diene conjugates and malonic dialdehyde, catalase activity and transferrin iron saturation, ceruloplasmin activity) in the blood serum were studied before, 6 and 12 months after the appointed treatment. Initial periodontal therapy and a paste developed by us (spirulina microalgae powders and silica enterosorbent taken in equal amounts and 0.05% chlorhexidine bigluconate) for applications and instillations were exogenously used in the complex treatment. Spirulina tablets were prescribed per os as well. RESULTS: Results: All patients exhibit elevated levels of diene conjugates and malonic dialdehyde, decreased catalase activity and transferrin iron saturation as well as an increased ceruloplasmin activity, especially pronounced at stages I and II (p1≤0.01-0.001). Treatment contributed to long-term and reliable (p2<0.05 - 0.001) regulation of the studied parameters: reduction of diene conjugates and malonic dialdehyde, ceruloplasmin activity and increased catalase activity and transferrin iron saturation. All indicators differed slightly from the norm during the year (p1>0.05), and complete normalization of most of them lasted six months. At the same time clinical stabilization of periodontitis was reached. CONCLUSION: Conclusions: Indicators of the oxidase-antioxidant system in patients with periodontitis are significantly altered and indicate their participation in the pathogenesis of the disease. Complex treatment was able to almost completely normalize them within six months, but a year later the difference between the obtained indicators with data in healthy people was insignificant (except for ceruloplasmin). Clinical stabilization was achieved in all patients.


Assuntos
Antioxidantes , Periodontite , Antioxidantes/uso terapêutico , Catalase , Ceruloplasmina , Humanos , Ferro , Peroxidação de Lipídeos , Periodontite/tratamento farmacológico , Transferrinas
9.
Virulence ; 13(1): 833-843, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35521696

RESUMO

We exploited bacterial infection assays using the fruit fly Drosophila melanogaster to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-N-sulfonylpiperidine derivative (4a) protects Drosophila from the acute infections caused by bacterial pathogens including Pseudomonas aeruginosa. 4a did not inhibit the growth of P. aeruginosa in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, 4a displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in Drosophila infections and unique transcriptome profile. Taken together, these results delineate a Drosophila-based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.


Assuntos
Drosophila , Infecções por Pseudomonas , Animais , Drosophila melanogaster , Ferro , Quelantes de Ferro/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Sulfonamidas
10.
J Phys Chem A ; 126(18): 2818-2824, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35500128

RESUMO

An improved understanding of the P450 structure is relevant to the development of biomimetic catalysts and inhibitors for controlled CH-bond activation, an outstanding challenge of synthetic chemistry. Motivated by the experimental findings of an unusually short Fe-S bond of 2.18 Šfor the wild-type (WT) OleT P450 decarboxylase relative to a cysteine pocket mutant form (A369P), a computational model that captures the effect of the thiolate axial ligand on the iron-sulfur distance is presented. With the computational efficiency and streamlined analysis in mind, this model combines a cluster representation of the enzyme─40-110 atoms, depending on the heme and ligand truncation level─with a density functional theory (DFT) description of the electronic structure (ES) and is calibrated against the experimental data. The optimized Fe-S distances show a difference of 0.25 Šbetween the low and high spin states, in agreement with the crystallographic structures of the OleT WT and mutant forms. We speculate that this difference is attributable to the packing of the ligand; the mutant is bulkier due to an alanine-to-proline replacement, meaning that it is excluded from the energetically favored low-spin minimum because of steric constraints. The presence of pure spin-state pairs and the intersection of the low/high spin states for the enzyme model is indicative of the limitations of single-reference ES methods in such systems and emphasizes the significance of using the proper state when modeling the hydrogen atom transfer (HAT) reaction catalyzed by OleT. At the same time, the correct characterization of both the short and long Fe-S bonds within a small DFT-based model of 42 atoms paves the way for quantum dynamics modeling of the HAT step, which initiates the OleT decarboxylation reaction.


Assuntos
Heme , Ferro , Cisteína/química , Teoria da Densidade Funcional , Heme/química , Ferro/química , Ligantes
11.
Clin Transl Med ; 12(5): e854, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35538889

RESUMO

BACKGROUND: Iron is essential for all mammalian life, and either a deficiency or excess of iron can cause diseases. AMP-activated protein kinase (AMPK) is a critical regulator of metabolic homeostasis; however, it has not been established whether AMPK regulates iron metabolism. METHODS: Iron, hepcidin and ferroportin levels were examined in mice with global and hepatocyte-specific knockout of AMPKα1 and AMPKα2. Primary AMPKα1 or AMPKα2 deleted hepatocytes were isolated and cultured in hypoxia condition to explore PHD2, HIF and hydroxylated HIF1α levels. We performed immunoprecipitation, in vitro AMPK kinase assay and site-direct mutant assay to detect phosphorylation sites of PHD2. We also obtained liver tissues from patients with anaemia of chronic disease undergoing surgery, AMPKα1 and hydroxylated HIF1α levels were measured by immunohistochemical analysis. RESULTS: We found that mice with global deficiency of AMPKα1, but not AMPKα2, exhibited hypoferraemia as well as iron sequestration in the spleen and liver. Hepatocyte-specific, but not myeloid-specific, ablation of AMPKα1 also reduced serum iron levels in association with increased hepcidin and decreased ferroportin protein levels. Mechanistically, AMPKα1 directly phosphorylated prolyl hydroxylase domain-containing (PHD)2 at serines 61 and 136, which suppressed PHD2-dependent hydroxylation of hypoxia-inducible factor (HIF)1α and subsequent regulation of hepatic hepcidin-related iron signalling. Inhibition of PHD2 hydroxylation ameliorated abnormal iron metabolism in hepatic AMPKα1-deficient mice. Furthermore, we found hepatic AMPKα/PHD2/HIFα/ hepcidin axes were highly clinically relevant to anaemia of chronic disease. CONCLUSION: In conclusion, these observations suggest that hepatic AMPKα1 has an essential role in maintaining iron homeostasis by PHD2-dependent regulation of hepcidin, thus providing a potentially promising approach for the treatment of iron disturbances in chronic diseases.


Assuntos
Proteínas Quinases Ativadas por AMP , Hepcidinas , Prolina Dioxigenases do Fator Induzível por Hipóxia , Ferro , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Hepcidinas/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Ferro/metabolismo , Camundongos
12.
J Adv Res ; 37: 33-41, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35499048

RESUMO

Introduction: Phytic acid (PA) is an important antinutrient agent present in cereal grains which reduces the bioavailability of iron and zinc in human body, causing malnutrition. Inositol pentakisphosphate 2- kinase 1 (IPK1) gene has been reported to be an important gene for PA biosynthesis. Objective: A recent genome editing tool CRISPR/Cas9 has been successfully applied to develop biofortified rice by disrupting IPK1 gene, however, it remained a challenge in wheat. The aim of this study was to biofortify wheat using CRISPR/Cas9. Methods: In this study, we isolated 3 TaIPK1 homeologs in wheat designated as TaIPK1.A, TaIPK1.B and TaIPK1.D and found that the expression abundance of TaIPK1.A was stronger in early stages of grain filling. Using CRISPR/Cas9, we have disrupted TaIPK1.A gene in cv. Borlaug-2016 with two guide RNAs targeting the 1st and 2nd exons. Results: We got several genome-edited lines in the T0 generation at frequencies of 12.7% and 10.8%. Sequencing analysis revealed deletion of 1-23 nucleotides and even an addition of 1 nucleotide in various lines. Analysis of the genome-edited lines revealed a significant decrease in the PA content and an increase in iron and zinc accumulation in grains compared with control plants. Conclusion: Our study demonstrates the potential application of CRISPR/Cas9 technique for the rapid generation of biofortified wheat cultivars.


Assuntos
Ácido Fítico , Triticum , Sistemas CRISPR-Cas , Grão Comestível , Humanos , Fosfatos de Inositol , Ferro , Ácido Fítico/metabolismo , Triticum/genética , Zinco/metabolismo
13.
J Clin Invest ; 132(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499081

RESUMO

T follicular helper (Tfh) cells are a subset of CD4+ T cells that are essential in the pathogenesis of systemic lupus erythematosus (SLE). Notably, iron is required for activated CD4+ T lymphocytes to sustain high proliferation and metabolism. In this issue of the JCI, Gao et al. showed that CD4+ T cells from patients with SLE accumulated iron, augmenting their differentiation into Tfh cells and correlating with disease activity. Using human cells and murine models, the authors demonstrated that miR-21 was overexpressed in lupus T cells and inhibited 3-hydroxybutyrate dehydrogenase-2 (BDH2). The subsequent loss of BDH2 drove labile iron to accumulate in the cytoplasm and promoted TET enzyme activity, BCL6 gene demethylation, and Tfh cell differentiation. This work identifies a role for iron in CD4+ T cell biology and the development of pathogenic effectors in SLE. We await future investigations that could determine whether modulating iron levels could regulate Tfh cells in human health and disease.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T Auxiliares-Indutores , Animais , Humanos , Hidroxibutirato Desidrogenase/metabolismo , Ferro/metabolismo , Lúpus Eritematoso Sistêmico/genética , Ativação Linfocitária , Camundongos , Células T Auxiliares Foliculares
14.
J Clin Invest ; 132(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499082

RESUMO

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion of pathogenic T cells, especially T follicular helper (Tfh) cells, has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important role of iron in regulation of pathogenic T cell differentiation in SLE. We found that iron overload promoted Tfh cell expansion, proinflammatory cytokine secretion, and autoantibody production in lupus-prone mice. Mice treated with a high-iron diet exhibited an increased proportion of Tfh cell and antigen-specific GC response. Iron supplementation contributed to Tfh cell differentiation. In contrast, iron chelation inhibited Tfh cell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and further promoted Fe2+-dependent TET enzyme activity and BCL6 gene demethylation. Thus, maintaining iron homeostasis might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE.


Assuntos
Ferro , Lúpus Eritematoso Sistêmico , Animais , Diferenciação Celular , Epigênese Genética , Humanos , Hidroxibutirato Desidrogenase/genética , Camundongos , Linfócitos T Auxiliares-Indutores
15.
PLoS Med ; 19(5): e1003984, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35500028

RESUMO

BACKGROUND: It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials. METHODS AND FINDINGS: We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: -0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: -0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: -0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: -0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: -0.22, 0.44; p = 0.53) or motor scores (SMD: -0.04; 95% CI: -0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages. CONCLUSIONS: There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.


Assuntos
Desenvolvimento Infantil , Micronutrientes , Pré-Escolar , Suplementos Nutricionais , Feminino , Ácido Fólico , Humanos , Lactente , Ferro , Lipídeos/farmacologia , Micronutrientes/farmacologia , Níger , Gravidez
16.
Nat Commun ; 13(1): 2483, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513392

RESUMO

The SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes. The family is highly redundant and their transport activities coupled to metabolic state. Here, we use a pooled, dual CRISPR screening strategy that knocks out pairs of transporters in four metabolic states - glucose, galactose, OXPHOS inhibition, and absence of pyruvate - designed to unmask the inter-dependence of these genes. In total, we screen 63 genes in four metabolic states, corresponding to 2016 single and pair-wise genetic perturbations. We recover 19 gene-by-environment (GxE) interactions and 9 gene-by-gene (GxG) interactions. One GxE interaction hit illustrates that the fitness defect in the mitochondrial folate carrier (SLC25A32) KO cells is genetically buffered in galactose due to a lack of substrate in de novo purine biosynthesis. GxG analysis highlights a buffering interaction between the iron transporter SLC25A37 (A37) and the poorly characterized SLC25A39 (A39). Mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis identify A39 as critical for mitochondrial glutathione (GSH) import. Functional studies reveal that A39-mediated glutathione homeostasis and A37-mediated mitochondrial iron uptake operate jointly to support mitochondrial OXPHOS. Our work underscores the value of studying family-wide genetic interactions across different metabolic environments.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Galactose , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Glutationa , Homeostase , Ferro , Proteínas de Membrana Transportadoras/genética
17.
Clin Epigenetics ; 14(1): 59, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505416

RESUMO

BACKGROUND: Unbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother-newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation. RESULTS: Maternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs. CONCLUSION: Maternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.


Assuntos
Metilação de DNA , Epigenoma , Adolescente , Criança , Epigênese Genética , Feminino , Ferritinas/genética , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Ferro , Gravidez , Estudos Prospectivos
18.
Arkh Patol ; 84(2): 13-19, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35417944

RESUMO

OBJECTIVE: To study, using a complex morphochemical approach, the localization of alpha-synuclein, iron compounds and iron-containing proteins in the structures of the substantia nigra of the brain in Parkinson's disease (PD). MATERIAL AND METHODS: Histochemistry and immunohistochemistry methods have been used to study the localization of pathological alpha-synuclein (α-Syn-p129), iron compounds and iron-containing proteins - transferrin receptor and ferritin in neurons and neuroglia in the substantia nigra of the brain of deceased PD patients and persons with no neurological symptoms detected during life (control). RESULTS: In the substantia nigra of PD patients, in comparison with the control, a stable accumulation of pathological alpha-synuclein (α-Syn-p129) in the bodies and processes of neurons was found, and in the neuroglia and neuropil - the accumulation of iron (II) and ferritin heavy chain, the reaction of microglia to protein CD68 was moderately elevated. The transmembrane protein CD71 was detected equally in the brains of PD patients and in controls. CONCLUSION: Synaptic protein alpha-synuclein in PD turns into a pathological metabolite that accumulates in the structures of substantia nigra, and probably disrupts the conduction of nervous excitation. Excessive accumulation of the ferritin heavy chain in neuroglia can increase the concentration of reactive forms of iron and increase neurotoxicity. The uniform distribution of the transmembrane glycoprotein CD71 in the of substantia nigra structures both in the control and in PD patients indicates the preservation of non-heme iron transport during the neurodegenerative process.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Apoferritinas/metabolismo , Encéfalo/patologia , Humanos , Ferro/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/patologia , alfa-Sinucleína/metabolismo
19.
Ann Card Anaesth ; 25(2): 141-147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35417958

RESUMO

Study Objective: Preoperative anemia results in two- to sixfold increased incidence of perioperative blood transfusion requirements and reduced postoperative hemoglobin (Hb) level. This prospective study was designed to investigate the effect of preoperative intravenous infusion of iron on Hb levels, blood transfusion requirements, and incidence of postoperative adverse events in patients undergoing coronary artery bypass grafting. Design: Prospective randomized trial. Setting: Academic university hospital. Patients: Eighty patients (52-67 years old) underwent coronary artery bypass grafting and received either iron therapy or saline infusion preoperatively. Interventions: Patients were randomly allocated to iron or placebo groups. In the iron group, patients received a single intravenous dose of ferric carboxymaltose (1000 mg in 100 mL saline) infused slowly over 15 min 7 days before surgery. In placebo group, patients received a single intravenous dose of saline (100 mL saline) infused slowly over 15 min 7 days before surgery. Measurements: Patients were followed up with regards to incidence of anemia, Hb level on admission, preoperatively, postoperatively, 1 week and 4 weeks after discharge, aortic cross-clamp time, the number of packed red blood cells (pRBCs) units, the percentage of reticulocytes pre-postoperatively and 1 week later, hospital stay and intensive care unit (ICU) stay length, and the incidence of postoperative complications. Main Results: Iron therapy was associated with lower incidence of anemia 4 weeks after discharge (P < 0.001). Hb level was significantly higher in the iron group compared to the placebo group preoperatively and postoperatively, and 4 weeks after discharge (P < 0.001). Iron therapy resulted in shorter hospital and ICU stay (P < 0.001) and shorter aortic cross-clamp time, reduced pRBCs requirements postoperatively. Percentage of reticulocytes was significantly higher in placebo group than in iron group postoperatively and 1 week after discharge and the incidence of postoperative complications was similar to the placebo group. Conclusions: Preoperative IV iron infusion is a safe and feasible way to manage preoperative anemia. Preoperative administration of IV iron is associated with a higher postoperative Hb level, shorter hospital and ICU stay, and reduced perioperative red blood cell transfusion requirements with insignificant difference in incidence of postoperative complications.


Assuntos
Anemia , Idoso , Anemia/complicações , Anemia/tratamento farmacológico , Transfusão de Sangue , Ponte de Artéria Coronária/efeitos adversos , Suplementos Nutricionais , Humanos , Ferro/uso terapêutico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
20.
Front Cell Infect Microbiol ; 12: 856953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402311

RESUMO

Acinetobacter baumannii is a catalase-positive Gram-negative bacterial pathogen that causes severe infections among compromised patients. Among its noteworthy regulatory mechanisms, this microorganism regulates its lifestyle through the blue light using flavin (BLUF) protein BlsA. This protein regulates a diverse set of cellular processes that include, but are not limited to, motility, biofilm formation, phenylacetic acid metabolism, iron uptake, and catalase activity. We set out to determine how A. baumannii regulates catalase activity and other related oxidative stress phenotypes in response to light. Notably, because A. baumannii ATCC 17978 encodes four catalase homologs - which we refer to as KatA, KatE, KatE2, and KatG - we also aimed to show which of these enzymes exhibit light- and BlsA-dependent activity. Our work not only provides insight into the general function of all four catalase homologs and the impact of light on these functions, but also directly identifies KatE as a BlsA-regulated enzyme. We further demonstrate that the regulation of KatE by BlsA is dependent on a lysine residue that we previously demonstrated to be necessary for the regulation of surface motility. Furthermore, we show that BlsA's five most-C-terminal residues - previously considered dispensable for BlsA's overall function - are necessary for the light-independent and light-dependent regulation of catalase and superoxide dismutase activities, respectively. We hypothesize that these identified critical residues are necessary for BlsA's interaction with protein partners including the transcriptional regulators Fur and BfmR. Together these data expand the understanding regarding how A. baumannii uses light as a signal to control oxidative stress resistance mechanisms that are critical for its pathophysiology.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Catalase/metabolismo , Humanos , Ferro/metabolismo , Estresse Oxidativo
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