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1.
Chemosphere ; 262: 127567, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32755692

RESUMEN

Acid mine drainage (AMD) is recognized as a challenge encountered by mining industries globally. Cyclic mineralization method, namely Fe2+ oxidation/mineralization-residual Fe3+ reduction-resultant Fe2+ oxidation/mineralization, could precipitate Fe and SO42- present in AMD into iron hydroxysulfate minerals and greatly improve the efficiency of subsequent lime neutralization, but the current Fe0-mediated reduction approach increased the mineralization cycles. This study constructed a bacteria-driven biomineralization system based on the reactions of Acidithiobacillus ferrooxidans-mediated Fe2+ oxidation and Acidiphilium multivorum-controlled Fe3+ reduction, and utilized water-dropping aeration and biofilm technology to satisfy the requirement of practical application. The resultant biofilms showed stable activity for Fe conversion: the efficiency of Fe2+-oxidation, Fe-precipitation, and Fe3+-reduction maintained at 98%, 32%, and 87%, respectively. Dissolved oxygen for Fe-oxidizing bacteria growth was continuously replenished by water-dropping aeration (4.2-7.2 mg/L), and the added organic carbon was mainly metabolized by Fe-reducing bacteria. About 89% Fe and 60% SO42- were precipitated into jarosite mineral after five biomineralization cycles. Fe was removed via forming secondary mineral precipitates, while SO42- was coprecipitated into mineral within the initial three biomineralization cycles, and then mainly precipitated with Ca2+ afterwards. Fe concentration in AMD was proven to directly correlate with subsequent lime neutralization efficiency. Biomineralization for five cycles drastically reduced the amount of required lime and neutralized sludge by 75% and 77%, respectively. The results in this study provided theoretical guidance for practical AMD treatment based on biomineralization technology.


Asunto(s)
Hierro/análisis , Contaminantes Químicos del Agua/análisis , Acidiphilium , Acidithiobacillus , Ácidos , Bacterias/metabolismo , Biodegradación Ambiental , Biomineralización , Compuestos de Calcio , Compuestos Férricos , Hierro/metabolismo , Minerales , Minería , Óxidos , Sulfatos , Contaminantes Químicos del Agua/metabolismo
3.
Biol Direct ; 15(1): 19, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-33066821

RESUMEN

The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/virología , Hepcidinas/genética , Hierro/metabolismo , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/genética , Animales , Proteínas de Transporte de Catión/metabolismo , Cisteína/química , Citocinas/metabolismo , Citoplasma/metabolismo , Hepcidinas/química , Humanos , Hipoxia , Inflamación , Interleucina-6/metabolismo , Pandemias , Dominios Proteicos , Procesamiento Proteico-Postraduccional , Alineación de Secuencia , Glicoproteína de la Espiga del Coronavirus/química , Tetraodontiformes
4.
Respir Res ; 21(1): 276, 2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33087116

RESUMEN

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. METHODS: We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. RESULTS: We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. DISCUSSION: Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04416100.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Homeostasis , Hierro/metabolismo , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/metabolismo , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo , Adulto , Anciano , Anemia/etiología , Proteína C-Reactiva/análisis , Estudios de Cohortes , Infecciones por Coronavirus/fisiopatología , Femenino , Ferritinas/sangre , Estudios de Seguimiento , Humanos , Inflamación/etiología , Inflamación/metabolismo , Interleucina-6/sangre , Enfermedades Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Pandemias , Neumonía Viral/fisiopatología , Estudios Prospectivos , Tomografía Computarizada por Rayos X
5.
PLoS One ; 15(10): e0239758, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33057367

RESUMEN

OBJECTIVE: People with HIV (PWH) continue to experience sensory neuropathy and neuropathic pain in the combination antiretroviral therapy (cART) era for unclear reasons. This study evaluated the role of iron in a previously reported association of iron-loading hemochromatosis (HFE) gene variants with reduced risk of neuropathy in PWH who received more neurotoxic cART, since an iron-related mechanism also might be relevant to neuropathic symptoms in PWH living in low-resource settings today. DESIGN: This time-to-event analysis addressed the impact of systemic iron levels on the rapidity of neuropathy onset in PWH who initiated cART. METHODS: Soluble transferrin receptor (sTFR), the sTFR-ferritin index of iron stores, and high-sensitivity C-reactive protein (hsCRP) levels were determined in stored baseline sera from participants of known HFE genotype from AIDS Clinical Trials Group (ACTG) Study 384, a multicenter randomized clinical trial that evaluated cART strategies. Associations with incident neuropathy were evaluated in proportional-hazards, time-to-event regression models, adjusting for potential confounders. RESULTS: Of 151 eligible participants with stored serum who were included in the original genetic study, 43 had cART-associated neuropathy; 108 had sufficient serum for analysis, including 30 neuropathy cases. Carriers of HFE variants had higher systemic iron (lower sTFR and sTFR-ferritin index) and lower hsCRP levels than non-carriers (all p<0.05). Higher sTFR or iron stores, the HFE 187C>G variant, and lower baseline hsCRP were associated with significantly delayed neuropathy in self-reported whites (n = 28; all p-values<0.05), independent of age, CD4+ T-cell count, plasma HIV RNA, and cART regimen. CONCLUSIONS: Higher iron stores, the HFE 187C>G variant, and lower hsCRP predicted delayed onset of neuropathy among self-reported white individuals initating cART. These findings require confirmation but may have implications for cART in HIV+ populations in areas with high endemic iron deficiency, especially those PWH in whom older, more neurotoxic antiretroviral drugs are occasionally still used.


Asunto(s)
Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Variación Genética/genética , Proteína de la Hemocromatosis/genética , Hierro/metabolismo , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Adulto , Antirretrovirales/uso terapéutico , Femenino , Ferritinas/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Hemocromatosis/genética , Heterocigoto , Humanos , Masculino , Neuralgia/inducido químicamente , Neuralgia/genética , Receptores de Transferrina/genética
6.
J Toxicol Sci ; 45(10): 619-624, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33012730

RESUMEN

Manganese (Mn) poisoning may result in a neurological disorder called manganism. Although the neurotoxic mechanism of Mn is unclear, oxidative stress may be involved based on the interactions between neurotransmitter catecholamines and metals such as iron. Here, we propose a novel mechanism in which Mn oxidizes catecholamines and inhibits cellular transcription. Mn accelerated the oxidation of adrenaline (Ad) and produced adrenochrome (AdC) more effectively than iron. Furthermore, the oxidation of DNA bases increased when Ad, Mn, and iron were present. However, despite the absence of iron, cell viability decreased in the presence of AdC or Ad with Mn, which suggests there is another mechanism independent of oxidative DNA damage. AdC or preincubated Ad with Mn reduced mRNA synthesis in T7 RNA polymerase-driven transcription. RNA synthesis decreased in AdC-treated cells dose-dependently. These results show that Mn disrupts neuronal function via catecholamine oxidation-mediated transcriptional inhibition.


Asunto(s)
Catecolaminas/genética , Catecolaminas/metabolismo , Intoxicación por Manganeso , Manganeso/toxicidad , Transcripción Genética/efectos de los fármacos , Adrenocromo/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epinefrina/metabolismo , Humanos , Hierro/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/metabolismo
7.
PLoS One ; 15(9): e0239075, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32941470

RESUMEN

Iron (Fe) deficiency is a common challenge in crop production. Screening and research of Fe-efficient cultivars could alleviate plant stress and increase crop yields in Fe-deficient soils. In the present study, we conducted two hydroponic culture experiments with a control (100 µmol/L Fe3+-EDTA) and low Fe treatment (10 µmol/L Fe3+-EDTA) to study the morphological and physiological mechanisms of response to low Fe stress in maize hybrids seedlings. In the first experiment, we investigated 32 major maize hybrids in Southwest China. We found that six of them, including Zhenghong 2 (ZH 2), were Fe-efficient. Fifteen other cultivars, such as Chuandan 418 (CD 418), were Fe-inefficient. In the second experiment, we investigated the Fe-efficient ZH 2 and Fe-inefficient CD 418 cultivars and found that low Fe stress resulted in significant decreases in root volume, root length, number of root tips, root surface area, and root dry weight, and increased root to shoot ratio, average root diameter, and Fe-dissolution ability per mass of roots in both maize cultivars. However, the increase in Fe-dissolution ability per mass of roots in ZH 2 was higher than that in CD 418, whereas for the other measurements, the low Fe stress-induced changes in ZH 2 were less pronounced than in CD 418. Therefore, under low Fe stress, the above-mentioned growth factors in ZH 2 were higher by 54.84%, 121.46%, 107.67%, 83.96%, 140.00%, and 18.16%, respectively, than those in CD 418. In addition, leaf area, chlorophyll content, net photosynthetic rate, soluble protein content, and Catalase (CAT) and Peroxidase (POD) activities in ZH 2 were higher by 274.95%, 113.95%, 223.60%, 56.04%, 17.01% and 21.13% than those in CD 418. Therefore, compared with the Fe-inefficient cultivar (CD 418), the Fe-efficient cultivar (ZH 2) had a more developed root system and greater Fe absorption capacity per mass of roots under low iron stress, promoted the efficient absorption of Fe, maintained a higher photosynthetic area and photosynthetic rate, thereby facilitating the accumulation of photosynthetic products. Moreover, higher soluble protein content and activities of CAT and POD permitted high osmotic regulation and scavenging ability, which is an important physiological mechanism for ZH 2 adaptation to low Fe stress.


Asunto(s)
Raíces de Plantas/fisiología , Plantones/fisiología , Zea mays/fisiología , Hierro/metabolismo , Fotosíntesis , Raíces de Plantas/anatomía & histología , Plantones/anatomía & histología , Estrés Fisiológico , Zea mays/anatomía & histología
8.
PLoS One ; 15(9): e0239192, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32986748

RESUMEN

BACKGROUND: Few studies have evaluated iron-rich plant-based foods, such as amaranth grain, to reduce anemia and iron deficiency anemia. Amaranth is rich in nutrients, but with high level of phytate. The objective of this trial was to evaluate the efficacy of home processed amaranth grain containing bread in the treatment of anemia, hemoglobin concentration and iron deficiency anemia among two-to-five year-old children in Southern Ethiopia. METHOD: Children with anemia (hemoglobin concentration <110.0g/L) (N = 100) were identified by random sampling and enrolled in a 1:1 cluster randomized controlled trial for six months in 2017. The amaranth group (N = 50), received 150g bread containing 70% amaranth and 30% chickpea, the amaranth grain was processed at home (soaking, germinating, and fermenting) to decrease the phytate level. The maize group (N = 50), received 150g bread, containing processed maize (roasted and fermented) to give a similar color and structure with amaranth bread. Hemoglobin, ferritin, and CRP were measured at baseline and at the end of intervention. Hemoglobin and ferritin values were adjusted for altitude and infection, respectively. Generalized estimating equation and generalized linear model were used to analyze the data. RESULT: In the last follow-up measure anemia prevalence was significantly lower in the amaranth group (32%) as compared with the maize group (56%) [adjusted risk ratios, aRR: 0.39 (95%CI: 0.16-0.77)]. Hemoglobin concentration estimate of beta coefficient was significantly higher in the amaranth group compared with the maize group [aß 8.9g/L (95%CI: 3.5-14.3)], p-value <0.01. The risk of iron deficiency anemia is significantly lower in the amaranth group [aRR: 0.44 (95%CI: 0.23-0.83)] in the intention to treat analysis but not significant in the complete case analysis. There was no significant difference between groups in iron deficiency [aRR: 0.81 (95%CI: 0.55-1.19)]. CONCLUSION: Processed amaranth bread had favorable effects on hemoglobin concentration and has the potential to minimize anemia prevalence. CLINICAL TRIAL REGISTRATION: Trial registry number: PACTR201705002283263 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2283.


Asunto(s)
Amaranthus , Anemia Ferropénica/dietoterapia , Pan , Hierro/metabolismo , Zea mays , Preescolar , Suplementos Dietéticos , Etiopía , Femenino , Ferritinas/sangre , Alimentos Fortificados , Alimentos Funcionales , Hemoglobinas/análisis , Humanos , Hierro/deficiencia , Masculino
9.
Nat Cell Biol ; 22(9): 1042-1048, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32868903

RESUMEN

Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis1,2. Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution3-6, ferroptosis is thought to result from the accumulation of unrepaired cell damage1. Previous studies have suggested that ferroptosis has the ability to spread through cell populations in a wave-like manner, resulting in a distinct spatiotemporal pattern of cell death7,8. Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell rupture is mediated by plasma membrane pores, similarly to cell lysis in pyroptosis and necroptosis3,4. We further find that intercellular propagation of death occurs following treatment with some ferroptosis-inducing agents, including erastin2,9 and C' dot nanoparticles8, but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (GPX4)10. Propagation of a ferroptosis-inducing signal occurs upstream of cell rupture and involves the spreading of a cell swelling effect through cell populations in a lipid peroxide- and iron-dependent manner.


Asunto(s)
Ferroptosis/fisiología , Ósmosis/fisiología , Muerte Celular/fisiología , Línea Celular Tumoral , Células HeLa , Humanos , Hierro/metabolismo , Células MCF-7 , Necrosis/metabolismo , Necrosis/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Células U937
10.
Ecotoxicol Environ Saf ; 205: 111337, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32979804

RESUMEN

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC50). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.


Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Ictaluridae/metabolismo , Hierro/toxicidad , Contaminantes Químicos del Agua/toxicidad , Alimentación Animal , Animales , Antioxidantes/metabolismo , Dieta , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Branquias/efectos de los fármacos , Branquias/metabolismo , Hierro/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Contaminantes Químicos del Agua/metabolismo
11.
Plant Physiol Biochem ; 154: 360-368, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32912482

RESUMEN

The nutritive tissues of galls induced by Ditylenchus gallaeformans (Nematoda) have promeristematic capacity, which may turn these galls into sinks of Al on their Melastomataceae Al-accumulating hosts. Such a sink of Al may affect gall growth and mineral nutrient intake. Based on the fact that galls are good models for plant developmental studies, we aimed to understand how Al-accumulating host plants in the Cerrado environment deal with Al toxicity in subcellular levels. Here, we used the ICP-OES method to check the variations on mineral nutrients, and the morin, hematoxylin, and Prussian blue stainings for Al and Fe histolocalization in galls induced on four Miconia species of the Brazilian Cerrado. We confirmed the new Al-accumulating feature for two Miconia species of the Cerrado environment. Furthermore, we found that Al accumulates in lesser concentrations in gall tissues than in non-galled tissues of the Miconia hosts. Staining methods indicated that the polyphenols avoid Al-binding to the apoplast and the nucleolus of the promeristematic cells, and mediated its binding to parenchyma cell walls. As well, we inferred that Fe3+ is transported by xylem and stored in gall parenchyma, where it is reduced to Fe2+, being available in gall nutritive cells. Our results demonstrated an Al compartmentalization between the apoplast and symplast of the inner cell layers in galls, as well as indicated the phenolics action against Al-toxicity and toward Fe availability for the diet of Ditylenchus gallaeformans.


Asunto(s)
Aluminio/metabolismo , Hierro/metabolismo , Melastomataceae/metabolismo , Nematodos/patogenicidad , Tumores de Planta , Animales , Brasil , Melastomataceae/parasitología , Tumores de Planta/parasitología
12.
PLoS One ; 15(9): e0233823, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32941430

RESUMEN

Lignin is the second most abundant carbon polymer on earth and despite having more fuel value than cellulose, it currently is considered a waste byproduct in many industrial lignocellulose applications. Valorization of lignin relies on effective and green methods of de-lignification, with a growing interest in the use of microbes. Here we investigate the physiology and molecular response of the novel facultative anaerobic bacterium, Tolumonas lignolytica BRL6-1, to lignin under anoxic conditions. Physiological and biochemical changes were compared between cells grown anaerobically in either lignin-amended or unamended conditions. In the presence of lignin, BRL6-1 accumulates higher biomass and has a shorter lag phase compared to unamended conditions, and 14% of the proteins determined to be significantly higher in abundance by log2 fold-change of 2 or greater were related to Fe(II) transport in late logarithmic phase. Ferrozine assays of the supernatant confirmed that Fe(III) was bound to lignin and reduced to Fe(II) only in the presence of BRL6-1, suggesting redox activity by the cells. LC-MS/MS analysis of the secretome showed an extra band at 20 kDa in lignin-amended conditions. Protein sequencing of this band identified a protein of unknown function with homology to enzymes in the radical SAM superfamily. Expression of this protein in lignin-amended conditions suggests its role in radical formation. From our findings, we suggest that BRL6-1 is using a protein in the radical SAM superfamily to interact with the Fe(III) bound to lignin and reducing it to Fe(II) for cellular use, increasing BRL6-1 yield under lignin-amended conditions. This interaction potentially generates organic free radicals and causes a radical cascade which could modify and depolymerize lignin. Further research should clarify the extent to which this mechanism is similar to previously described aerobic chelator-mediated Fenton chemistry or radical producing lignolytic enzymes, such as lignin peroxidases, but under anoxic conditions.


Asunto(s)
Aeromonadaceae/metabolismo , Hierro/metabolismo , Lignina/metabolismo , Aeromonadaceae/enzimología , Aeromonadaceae/crecimiento & desarrollo , Proteínas Bacterianas/metabolismo , Biomasa , Oxidación-Reducción , Sulfatasas/metabolismo
13.
Med Sci Monit ; 26: e926178, 2020 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-32978363

RESUMEN

BACKGROUND The aim of this study was to assess the diagnostic utility of iron homeostasis determinations for prediction of severity of COVID-19. MATERIAL AND METHODS This was a retrospective study enrolling a total of 50 patients diagnosed with the novel coronavirus disease-19 (COVID-19) from February 27, 2020 to March 30, 2020, including a severe group (12 patients) and a mild group (38 patients). For the control group, 50 healthy people were examined during the same period. We compared clinical laboratory data and iron homeostasis biomarkers among the 3 groups. ROC curve analysis was used to assess diagnoses. RESULTS Patients diagnosed with severe COVID-19 had higher hepcidin and serum ferritin levels than in other groups (p<0.001). A combination test of hepcidin and serum ferritin provided the best specificity and sensitivity in the prognosis of COVID-19 severity. Logistic regression analysis showed hepcidin and serum ferritin independently contributed to the severity of COVID-19. Hepcidin and serum ferritin tandem testing predicted COVID-19 severity with 94.6% specificity, while hepcidin and serum ferritin parallel testing had a sensitivity of 95.7%. CONCLUSIONS Iron homeostasis had a robust association with the occurrence of severe COVID-19. Iron homeostasis determinations were specific and sensitive for the early prediction of disease severity in COVID-19 patients and thus have clinical utility.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Ferritinas/sangre , Hepcidinas/sangre , Pandemias , Neumonía Viral/sangre , Adulto , Anciano , Área Bajo la Curva , Biomarcadores , Femenino , Homeostasis , Humanos , Hierro/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad
14.
Ecotoxicol Environ Saf ; 203: 111010, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32888587

RESUMEN

Manganese (Mn) toxicity is common in plants grown on very acid soils. However, some plants species that grow in this condition can take up high amounts of Mn and are referred to as hyperaccumulating species. In this study, we evaluated the capacity of Ilex paraguariensis to accumulate Mn and the effect of excessive concentrations on plant growth and nutrition. For this, a container experiment was conducted using soils from different parent materials (basalt and sandstone), with and without liming, and at six doses of applied Mn (0, 30, 90, 270, 540 and 1,080 mg kg-1). Clonal plants grown for 203 days were harvested to evaluate yield, and leaf tissue samples were evaluated for Mn and other elements. Without liming and with high Mn doses, leaf Mn concentrations reached 13,452 and 12,127 mg kg-1 in sandstone and basalt soils, respectively; concentrations in excess of 10,000 mg kg-1 are characteristic of hyperaccumulating plants. Liming reduced these values to 7203 and 8030 mg kg-1. More plant growth accompanied increased Mn leaf concentrations, with a growth reduction noted at the highest dose in unlimed soils. Elemental distribution showed Mn presence in the mesophyll, primarily in vascular bundles, without high Mn precipitates. Interveinal chlorosis of young leaves associated with high Mn concentration and lower Fe concentrations was observed, especially in sandstone soil without liming. However, the occurrence of this symptom was not associated with decreased plant growth.


Asunto(s)
Ácidos/farmacología , Ilex paraguariensis/metabolismo , Manganeso/metabolismo , Enfermedades de las Plantas/inducido químicamente , Contaminantes del Suelo/metabolismo , Ácidos/análisis , Compuestos de Calcio/análisis , Compuestos de Calcio/farmacología , Ilex paraguariensis/efectos de los fármacos , Ilex paraguariensis/crecimiento & desarrollo , Hierro/metabolismo , Manganeso/análisis , Manganeso/toxicidad , Óxidos/análisis , Óxidos/farmacología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Suelo/química , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidad
15.
Met Ions Life Sci ; 202020 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-32851828

RESUMEN

Iron-sulfur clusters are ubiquitous protein cofactors composed of iron and inorganic sulfur. These cofactors are among the most ancient ones and may have contributed to the birth of life on Earth. Therefore, they are found even today in many enzymes central to metabolic processes like nitrogen fixation, respiration, and DNA processing and repair. Due to the toxicity associated with iron and sulfur ions, living organisms evolved dedicated machineries to synthetize and then transfer iron-sulfur clusters into client proteins. The iron-sulfur cluster (ISC) machinery is responsible for iron-sulfur cluster biogenesis in prokaryotes and in the mitochondrion of eukaryotes; the sulfur mobilization (SUF) machinery is present in prokaryotes and in the chloroplasts of plants; finally, the cytosolic iron-sulfur assembly (CIA) machinery is only present in the cytoplasm of eukaryotes. Genome analysis allowed the prediction of the proteins containing iron-sulfur clusters across a broad variety of living organisms, establishing links between the size and composition of iron-sulfur proteomes and the types of organisms that encode them. For example, the iron-sulfur proteomes of aerobes are generally smaller than those of anaerobes with similar genome size; furthermore, aerobes are enriched in [2Fe-2S] proteins compared to anaerobes, which predominantly use [4Fe-4S] proteins. This relates to the lower bioavailability of iron and the higher lability of [4Fe-4S] clusters within aerobic environments. Analogous considerations apply to humans, where the occurrence and functions of iron-sulfur proteins depend on the cellular compartment where they are localized. For example, an emerging primary role for nuclear iron-sulfur proteins is in DNA maintenance. Given their key functions in metabolism, dysfunctions of mutations in iron-sulfur proteins, or in proteins participating in iron-sulfur cluster biogenesis, are associated with serious human diseases.


Asunto(s)
Hierro/metabolismo , Azufre/metabolismo , Humanos , Proteínas con Hierro-Azufre/genética , Mitocondrias/metabolismo
16.
Met Ions Life Sci ; 202020 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-32851832

RESUMEN

Enzymes relying on the interplay of nickel, iron, and sulfur in their active sites are used by prokaryotes to catalyze reactions driving the global carbon and hydrogen cycles. The three enzymes, [NiFe] hydrogenases, Ni,Fe-containing carbon monoxide dehydrogenases and acetyl-CoA synthases share an ancient origin possibly derived from abiotic processes. Although their active sites have different compositions and assemble Ni, Fe, and S in different ways and for different purposes, they share a central role of Ni in substrate binding and activation, with sulfur linking the Ni ion to one or more Fe ions, which, although indispensable for function, supports the catalytic process in less understood ways. The review gives a short overview on the properties of the three individual enzymes highlighting their parallels and differences.


Asunto(s)
Níquel/metabolismo , Sitios de Unión , Dominio Catalítico , Hidrogenasas/metabolismo , Hierro/metabolismo , Proteínas con Hierro-Azufre , Azufre
17.
Nature ; 585(7823): 113-118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32814895

RESUMEN

Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.


Asunto(s)
Ferroptosis , Linfa/metabolismo , Melanoma/patología , Metástasis de la Neoplasia/patología , Animales , Supervivencia Celular , Coenzima A Ligasas/metabolismo , Femenino , Ferroptosis/efectos de los fármacos , Glutatión/metabolismo , Humanos , Hierro/metabolismo , Masculino , Melanoma/sangre , Melanoma/metabolismo , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Ácido Oléico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Análisis de Componente Principal
18.
Nucleic Acids Res ; 48(17): 9571-9588, 2020 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-32813023

RESUMEN

Iron is essential for all bacteria. In most bacteria, intracellular iron homeostasis is tightly regulated by the ferric uptake regulator Fur. However, how Fur activates the iron-uptake system during iron deficiency is not fully elucidated. In this study, we found that YdiV, the flagella gene inhibitor, is involved in iron homeostasis in Escherichia coli. Iron deficiency triggers overexpression of YdiV. High levels of YdiV then transforms Fur into a novel form which does not bind DNA in a peptidyl-prolyl cis-trans isomerase SlyD dependent manner. Thus, the cooperation of YdiV, SlyD and Fur activates the gene expression of iron-uptake systems under conditions of iron deficiency. Bacterial invasion assays also demonstrated that both ydiV and slyD are necessary for the survival and growth of uropathogenic E. coli in bladder epithelial cells. This reveals a mechanism where YdiV not only represses flagella expression to make E. coli invisible to the host immune system, but it also promotes iron acquisition to help E. coli overcome host nutritional immunity.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Escherichia coli/metabolismo , Hierro/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Proteínas Represoras/metabolismo , Escherichia coli Uropatógena/patogenicidad , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Línea Celular , ADN Bacteriano/metabolismo , Células Epiteliales/microbiología , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Homeostasis , Humanos , Isomerasa de Peptidilprolil/genética , Conformación Proteica , Proteínas Represoras/química , Proteínas Represoras/genética , Vejiga Urinaria/microbiología , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/crecimiento & desarrollo , Escherichia coli Uropatógena/metabolismo
19.
Proc Natl Acad Sci U S A ; 117(36): 21914-21920, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32848065

RESUMEN

The structure-function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous form, it undergoes ligand release and doming upon photoexcitation, but its ferric form does not release the distal ligand, while the return to the ground state has been attributed to thermal relaxation. Here, by combining femtosecond Fe Kα and Kß X-ray emission spectroscopy (XES) with Fe K-edge X-ray absorption near-edge structure (XANES), we demonstrate that the photocycle of ferric Cyt c is entirely due to a cascade among excited spin states of the iron ion, causing the ferric heme to undergo doming, which we identify. We also argue that this pattern is common to a wide diversity of ferric heme proteins, raising the question of the biological relevance of doming in such proteins.


Asunto(s)
Citocromos c/química , Citocromos c/metabolismo , Humanos , Hierro/química , Hierro/metabolismo , Cinética , Dominios Proteicos , Espectrometría por Rayos X , Espectroscopía de Absorción de Rayos X
20.
Eur J Epidemiol ; 35(8): 763-773, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32816244

RESUMEN

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 1012 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.


Asunto(s)
Anemia/diagnóstico , Infecciones por Coronavirus , Coronavirus/metabolismo , Hierro/metabolismo , Pandemias , Neumonía Viral , Betacoronavirus , Biomarcadores/análisis , Biomarcadores/sangre , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Eritropoyetina , Ferritinas/sangre , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Hepcidinas/sangre , Hepcidinas/metabolismo , Humanos , Hierro/sangre , Neumonía Viral/epidemiología , Receptores de Transferrina/sangre , Transferrina/análisis , Transferrina/metabolismo
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