Efectividad de la administración de hierro en forma semanal y diaria para la prevención de anemia por deficiencia de hierro en lactantes / Effectiveness of weekly and daily iron administration for the prevention of iron deficiency anemia in infants

Introducción. La deficiencia de hierro (DH) es la carencia nutricional más prevalente y la principal causa de anemia en lactantes. Existe consenso en la suplementación diaria con hierro como estrategia de prevención; también se demostró que la suplementación semanal es eficaz, pero la evidencia en lactantes es escasa. El objetivo fue comparar la efectividad de la administración diaria de hierro frente a la semanal para la prevención de la anemia por DH del lactante. Población y métodos. Ensayo clínico controlado y aleatorizado. Lactantes atendidos en un centro de salud público, sin anemia a los 3 meses de edad, aleatorizados en tres grupos: suplementación diaria (1 mg/kg/día), semanal (4 mg/kg/semana) o sin suplementación (grupo control con lactancia materna exclusiva [LME]). Se evaluó anemia y DH a los 3 y 6 meses. Se registró grado de adherencia y efectos adversos. Los datos se analizaron con el software R versión 4.0.3. Resultados. Participaron 227 lactantes. A los 6 meses el grupo de lactantes con LME sin suplementación (control) presentó prevalencias de DH y anemia por DH (ADH) mayores que los grupos intervenidos (diario y semanal). DH: 40,5 % vs. 13,5 % y 16,7 % (p = 0,002); ADH: 33,3 % vs. 7,8 % y 10 % (p < 0,001). No hubo diferencias entre los grupos diario y semanal. Tampoco hubo diferencias en el porcentaje de alta adherencia a la suplementación (50,6 % diaria vs. 57,1 % semanal), ni en los efectos adversos. Conclusiones. No se hallaron diferencias significativas en la efectividad entre la administración diaria y semanal para la prevención de ADH del lactante.

Introduction. Iron deficiency (ID) is the most prevalent nutritional deficiency and the main cause of anemia in infants. There is consensus on daily iron supplementation as a preventive strategy; and weekly iron supplementation has also been shown to be effective, but evidence in infants is scarce. The objective of this study was to compare the effectiveness of daily versus weekly iron administration for the prevention of ID anemia (IDA) in infants. Population and methods. Randomized, controlled clinical trial. Infants seen at a public health center, without anemia at 3 months of age, were randomized into 3 groups: daily supplementation (1 mg/kg/ day), weekly supplementation (4 mg/kg/week), or no supplementation (control group with exclusive breastfeeding [EB]). Anemia and ID were assessed at 3 and 6 months old. Adherence and adverse events were recorded. Data were analyzed using the R software, version 4.0.3. Results. A total of 227 infants participated. At 6 months, the group of infants with EB without supplementation(control) had a higher prevalence of ID and IDA than the intervention groups (daily and weekly). ID: 40.5% versus 13.5% and 16.7% (p = 0.002); IDA: 33.3% versus 7.8% and 10% (p < 0.001). There were no differences between the daily and weekly supplementation groups. There were also no differences in the percentage of high adherence to supplementation (50.6% daily versus 57.1% weekly) or adverse events. Conclusions. No significant differences in effectiveness were observed between daily and weekly administration for the prevention of infant IDA.

Use of iron supplement to prevent anemia in children aged six to 59 months attended at the Family Health Strategy (ESF) units in a city in Minas Gerais, Brazil / Uso de suplemento de ferro para prevenção da anemia em crianças de seis a 59 meses atendidas pela Estratégia Saúde da Família de um município de Minas Gerais, Brasil

Abstract Objectives: to evaluate the use of iron supplementation and associated factors in children aged six to 59 months attended at the Family Health Strategy units in a city in Minas Gerais (MG). Methods: a cross-sectional, analytical-exploratory study, carried out with 252 children aged six to 59 months, attended at ten units, between 2014 and 2016. A structured questionnaire was used to collect data on socioeconomic conditions, maternal health, child's health and the knowledge of those responsible regarding anemia and iron supplementation, in addition to analysis of the child's medical records /booklet to collect test results. Descriptive statistics, bivariate association analysis and logistic regression for multivariate analysis were performed. Results: only 22.6% of the children aged between six and 24 months were receiving iron supplement at the time of the interview. Considering children aged six to 59 months, 13.1% were supplemented and breastfeeding time (p=0.006) and the participation in childcare (p=0.042), were positively associated with the use of supplementation. Conclusion: most children aged six to 24 months were not receiving supplementation as recommended by the Ministry of Health, demonstrating the need to implement prevention programs, such as the National Iron Supplementation Program and training of professionals on the importance of health education in preventing childhood anemia.

Resumo Objetivos: avaliar o uso do suplemento de ferro e fatores associados em crianças de seis a 59 meses atendidas em unidades Estratégia Saúde da Família em município de Minas Gerais (MG). Métodos: estudo transversal, analítico-exploratório, realizado com 252 crianças na faixa etária seis a 59 meses, atendidas em dez unidades, entre 2014 e 2016. Utilizou-se questionário estruturado para coleta de dados sobre condições socioeconômicas, saúde materna, saúde da criança e conhecimentos dos responsáveis acerca da anemia e suplementação com ferro, além de análise do prontuário / caderneta da criança para coleta de resultados de exames. Realizou-se análise estatística descritiva, análise de associação bivariada e regressão logística para análise multivariada. Resultados: apenas 22,6% das crianças com idade entre seis e 24 meses estavam recebendo o suplemento de ferro no momento da entrevista. Considerando as crianças de seis a 59 meses, 13,1% eram suplementadas e o tempo de amamentação (p=0,006) e a participação na puericultura (p=0,042) apresentaram associação com o uso de suplemento. Conclusão: a maioria das crianças de seis a 24 meses não recebia a suplementação, demonstrando a necessidade de implementação dos programas de prevenção, como o Programa Nacional de Suplementação de Ferro e capacitação dos profissionais sobre a importância da educação em saúde para prevenção da anemia infantil.

Prevalence of inadequacy and associated indicators with mineral intake in Brazilian adolescents and young adults / Prevalência de inadequação e fatores associados à ingestão adequada de minerais em adolescentes e adultos jovens brasileiros

ABSTRACT Objective To describe the prevalence of inadequate mineral intake and associated factors with calcium, iron, zinc, magnesium, phosphorus, and sodium intakes in individuals aged 15-24.9 years. Methods We analyzed 476 individuals from the Brazilian Study of Nutrition and Health, stratified into two age groups (adolescents aged 15-18.9 years and young adults aged 19-24.9 years). Mineral intake was obtained from two 24-hour Dietary Recalls. The values of the Estimated Average Requirement and the Tolerable Upper Intake Levels were considered to calculate the prevalence of inadequacy. Multiple logistic regression was used to determine associated factors with mineral intake. Results Calcium and magnesium had the highest prevalence of inadequacy (>83%) in both sexes and age groups. Sodium intake was above Tolerable Upper Intake Levels for the majority of the population studied (>68%). The intake of all minerals was different between the sexes for the two age groups (p<0.01), and it was not different between age groups (p>0.05). The associated factors with mineral intake were sex (calcium, iron, phosphorus, and sodium), age group (calcium, magnesium, phosphorus, and sodium), and physical activity (calcium, iron, and magnesium), followed by socioeconomic level (zinc and sodium) and body weight status (iron and sodium). Conclusion The expressive portion of the studied population is at nutritional risk for calcium, magnesium, and sodium. Such data can contribute to the national public policy revision that is related to micronutrient intake and the adoption of healthier habits by adolescents and young adults.

RESUMO Objetivo Descrever as prevalências de inadequação e fatores associados à ingestão de cálcio, ferro, zinco, magnésio, fósforo e sódio em indivíduos dos 15 aos 24,9 anos. Métodos Foram analisados 476 indivíduos do Estudo Brasileiro de Nutrição e Saúde, estratificados em dois grupos etários (adolescentes de 15-18,9 anos e adultos jovens de 19-24,9 anos). A ingestão de minerais foi obtida por meio de dois recordatórios de 24hs. Os valores de Requerimento Médio Estimado e do Limite Superior Tolerável de Ingestão foram considerados para calcular as prevalências de inadequação. Regressão logística múltipla foi utilizada para determinar os fatores associados à ingestão de minerais. Resultados Cálcio e magnésio tiveram elevadas prevalências de inadequação (>83%) em pacientes de ambos os sexos e grupos etários. A ingestão de sódio foi acima Limite Superior Tolerável de Ingestão para a maioria da população estudada (>68%). O consumo de todos os minerais foi diferente entre os sexos para os dois grupos etários (p<0,01) e não foi diferente entre os grupos etários (p>0,05). Os fatores associados à ingestão dos minerais foram sexo (cálcio, ferro, fósforo e sódio), grupo etário (cálcio, magnésio, fósforo e sódio) e atividade física (cálcio, ferro e magnésio), seguidos por nível socioeconômico (zinco e sódio) e estado de peso corporal (ferro e sódio). Conclusão Expressiva parcela da população estudada encontra-se em risco nutricional para cálcio, magnésio e sódio. Esses dados podem contribuir para a revisão de políticas públicas nacionais que se relacionam à ingestão de micronutrientes e à adoção de hábitos mais saudáveis pelos adolescentes e adultos jovens.

Iron salt supplementation during gestation and gestational diabetes mellitus

ABSTRACT OBJETIVE To evaluate the association between the use of iron salts during the first two trimesters of gestation in non-anemic women and the development of gestational diabetes mellitus. METHODS The study used maternal data from the 2015 Pelotas Birth Cohort. All non-anemic women at the 24th week of gestation (n = 2,463) were eligible for this study. Gestational diabetes mellitus was self-reported by women. Crude and adjusted logistic regression were performed considering level of significance = 0.05. RESULTS Among the women studied, 69.7% were exposed to prophylactic iron supplementation in the first two trimesters of gestation. The prevalence of gestational diabetes mellitus among those exposed was 8.7% (95%CI: 7.4-10.1) and 9.3% (95%CI: 7.4-11.6) among those who were not exposed. Iron supplementation was not associated with increased risk of gestational diabetes mellitus in crude (OR = 0.9; 95%CI: 0,7-1,3) and adjusted analysis (OR = 1.1; 95%CI :0,8-1,6). CONCLUSIONS The results suggest that routine iron use in non-anemic pregnant women does not increase the risk of developing gestational diabetes. This evidence supports the existing national and international guidelines, in which prophylactic iron supplementation is recommended for all pregnant women as soon as they initiate antenatal care in order to prevent iron deficiency anemia.

The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Association between Ferrokinetic and its Prognostic Role in Coronary Artery Disease in a South American Hospital / Asociación entre la ferrocinética y su papel pronóstico en enfermedad coronaria en un hospital suramericano / Associação entre a ferrocinética e seu papel prognostico na doença cardíaca coronária em um hospital da América do Sul

Introduction: Ferrokinetic alterations are associated with the worsening of cardiovascular diseases, their role being unknown in depth. Objective: To determine the association between ferrokinetic with acute myocardial infarction with and without ST elevation in patients with coronary disease. Methods: Analytical observational study in a sample of 72 patients who were admitted to a Coronary Care Unit of a fourth level Institution during the period from July 2017 to May 2018. The statistical association analysis was performed with the Chi-square test. Results: The main gender affected was male, in ages over 56 years. The main comorbidity was arterial hyperten-sion in 53.7% for ST-elevation infarction and in 74.2% for non-ST-elevation infarction. The prevalent ferrokinetic alteration was iron deficiency, in 36.6% of the patients with ST elevation and in 41.9% without ST elevation. Low hemoglobin levels were present on admission in 24.4% of patients with ST elevation and in 32.3% of those without ST elevation, associated with low hemoglobin values on day 7 of hospitalization. Deaths occurred in 2.77%, which presented low iron levels without anemia and infarction with ST elevation and shock. The gender variable presented a statistically significant association (p = 0.034) with the serum iron level. Conclusions: Iron deficiency is a very common disorder with a higher mortality rate, so these parameters should be evaluated in cardiovascular diseases

Introducción: Las alteraciones ferrocinéticas se asocian con un empeoramiento de las enfermedades cardiovasculares, pero se desconoce en profundidad su papel.Objetivo: Determinar la asociación entre la ferrocinética con el infarto agudo al miocardio con y sin elevación del segmento ST en pacientes con enfermedad coronaria. Métodos: Estudio observacional analítico en una muestra de 72 pacientes que ingresaron a una unidad de cuidados coronarios de una institución de cuarto nivel durante el lapso de julio de 2017 a mayo de 2018. El análisis de asociación estadística se realizó con la prueba de chi cuadrado. Resultados: El principal género afectado fue el masculino, en edades superiores a 56 años. La principal comorbilidad fue hipertensión arterial, en un 53,7 % para infarto con elevación del segmento ST, y en un 74,2 % para infarto sin elevación de dicho segmento. La alteración ferrocinética prevalente fue el déficit de hierro, en un 36,6 % de los pacientes con elevación del intervalo ST y en un 41,9 % sin elevación del segmento ST. Las concentraciones bajas de hemoglobina estuvieron presentes al ingreso en el 24,4 % de los pacientes con elevación del ST y en el 32,3 % de aquellos sin elevación del ST, aso-ciado con valores bajos de hemoglobina al séptimo día de hospitalización. Ocurrieron fallecimientos en el 2,77 %, con cantidades bajas de hierro sin anemia e infarto con elevación del segmento ST y choque. La variable género presentó asociación estadísticamente significativa (p = 0,034) con el nivel de hierro sérico. Conclusiones: La ferropenia es una alteración muy frecuente con una relación de mayor mortalidad, por lo que estos parámetros deberían evaluarse en enfermedades cardiovasculares

Introdução: Os distúrbios ferrocinéticos estão associados à piora da doença cardiovascular, mas seu papel é pouco conhecido. Objetivo: Determinar a associação entre a ferrocinética e o infarto agudo do miocárdio com e sem elevação do segmento ST em pacientes com doença cardíaca coronária. Métodos: Estudo observacional analítico em uma amostra de 72 pacientes admitidos em uma unidade de tratamento coronariano de uma instituição de quarto nível durante o período de julho de 2017 a maio de 2018. A análise de associação estatística foi realizada usando o teste do qui-quadrado. Resultados: O principal gênero afetado foi o masculino, com idade superior a 56 anos. A principal comorbidade foi a hipertensão, em 53,7% para infarto do miocárdio com elevação do segmento ST e 74,2% para infarto do miocárdio sem elevação do segmento ST. O distúrbio ferrocinético preva-lente foi a deficiência de ferro em 36,6% dos pacientes com elevação do segmento ST e 41,9% sem elevação do segmento ST. Concentrações baixas de hemoglobina estavam presentes na admissão em 24,4% dos pacientes com elevação do segmento ST e em 32,3% daqueles sem elevação do segmento ST, associadas a valores baixos de hemoglobina ao sétimo dia de hospitalização. Ocorreram mortes em 2,77%, com baixo teor de ferro sem anemia e infarto com elevação do segmento ST e choque. O gênero foi associado de forma estatisticamente significativa (p = 0,034) ao nível de ferro sérico. Conclusões: A deficiência de ferro é um distúrbio muito comum com uma associação com o aumento da mortalidade, por tanto, esses parâmetros devem ser avaliados em doenças cardiovasculares

Research progress of ferroptosis in hypoxia-associated brain injury / 生理学报

Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.

Ferroptosis in acute leukemia / 中华医学杂志(英文版)

Ferroptosis is an iron-dependent cell death pathway that is different from apoptosis, pyroptosis, and necrosis. The main characteristics of ferroptosis are the Fenton reaction mediated by intracellular free divalent iron ions, lipid peroxidation of cell membrane lipids, and inhibition of the anti-lipid peroxidation activity of intracellular glutathione peroxidase 4 (GPX4). Recent studies have shown that ferroptosis can be involved in the pathological processes of many disorders, such as ischemia-reperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of acute leukemia still need to be more fully and deeply studied. This article reviews the characteristics of ferroptosis and the regulatory mechanisms promoting or inhibiting ferroptosis. More importantly, it further discusses the role of ferroptosis in acute leukemia and predicts a change in treatment strategy brought about by increased knowledge of the role of ferroptosis in acute leukemia.

Effects of iron accumulation on dental caries, gingivitis, and candida albicans infection in children with beta thalassemia major: A narrative review

Background@#Thalassemia is a common inherited hemolytic disorder characterized by the absence or reduction of one of the globin chains. Beta thalassemia major generally has oral cavity manifestations. Patients with beta thalassemia major often require routine blood transfusion. However, this treatment has the side effect of accumulating iron in the salivary glands, which increase the risk of dental caries, gingivitis, and secondary infection from Candida albicans.@*Objective@#The aim of this review is to explain the relationship of salivary iron levels and the effects of iron accumulation on dental caries, gingivitis, and Candida albicans infection.@*Methods@#A comprehensive search was performed on PubMed, Scopus, and Google Scholar databases using the keywords beta thalassemia major, iron, dental caries, gingivitis, Candida albicans.@*Results@#Iron is an essential micronutrient needed by Candida albicans for its growth and virulence. Blood transfusion in patients with beta thalassemia major can lead to a buildup of iron in the salivary glands and trigger the formation of non-transferrin bound iron (NTBI). NTBI can circulate in plasma and form a reactive oxygen species (ROS) that stimulate the formation of biofilms and increase dental caries. ROS may affect several genes associated with the inflammatory process and increase the incidence of gingivitis. It can also reduce salivary secretion in patients with thalassemia-β major that cause dysbiosis, which triggers an overgrowth of Candida albicans.@*Conclusion@#The excess iron in patients with beta thalassemia major increase the risk of dental caries, gingivitis, and Candida albicans infection.

Ferroptosis and drug-induced liver injury / 中华肝脏病杂志

Ferroptosis is a type of regulated cell death driven by iron-dependent lipid peroxidation that has received extensive attention in recent years. A growing body of evidence suggests that ferroptosis contributes to the progression of drug-induced liver injury. Therefore, the role and mechanism of ferroptosis in the process of drug-induced liver injury deserve further extensive and in-depth exploration, which will aid in the discovery of novel biomarkers as well as the identification of potential approches of targeting ferroptosis to intervene in drug-induced liver injury.

Effect of VIT1/VIT2 overexpression on Fe and Cd accumulation in rice endosperm / 生物工程学报

Iron (Fe) deficiency and excess cadmium (Cd) in rice grain are important problems to be solved in agricultural production. Previous studies have shown that OsVIT1 and OsVIT2 are vacuolar iron transporters. In this study, wild-type ZH11 was selected as the background material and OsVIT1 and OsVIT2 were overexpressed in endosperm by using endosperm specific promoter Glb-1. Field experiments were conducted to study the effect of OsVIT1 and OsVIT2 overexpression on Fe and Cd accumulation in different parts of rice. The results showed that OsVIT1 overexpression in endosperm significantly reduced Fe content in grain by about 50%, while significantly increased zinc (Zn) and copper (Cu) contents in straw and Cu content in grain. OsVIT2 overexpression in endosperm significantly decreased Fe and Cd contents in grain by about 50%, and significantly increased Fe content in straw by 45%-120%. Overexpression of OsVIT1 and OsVIT2 in endosperm did not affect the agronomic traits of rice. In conclusion, OsVIT1 and OsVIT2 overexpression in endosperm reduced Fe accumulation in rice grain, which did not achieve the expected effect. OsVIT2 overexpression in endosperm also decreased Cd accumulation in grain and increased Fe accumulation in straw, which provided reference for iron biofortification and cadmium reduction in rice.

A nested case-control study on the association of neonatal cord blood selenium, iron and copper with congenital heart disease / 中华预防医学杂志

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q1 and Q3 of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q1, Q3) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.

Establishment and evaluation of a method for phages enrichment by ferric trichloride-polyvinylidene fluoride membrane filter / 中华预防医学杂志

Objective: To establish and evaluate a method of enriching bacteriophages in natural water based on ferric trichloride-polyvinylidene fluoride (FeCl3-PVDF)membrane filter. Methods: Based on the principle of flocculation concentration, the method of recovering bacteriophage from water sample was established by using iron ion flocculation combined with membrane filter. The titer of phage was determined by Agar double layer method. The recovery efficiency of phage was detected by phage fluorescence staining and real-time fluorescence PCR reaction. Water samples from different sources were collected for simulation experiment to evaluate the enrichment effect. At the same time, the sewage discharged from hospitals was taken as the actual water sample, and the common clinical drug-resistant bacteria were used as the host indicator bacteria to further analyze the enrichment effect of FeCl3-PVDF membrane filter rapid enrichment method on the bacteriophage in natural water samples. Results: The method of enrichment of bacteriophages in natural water by iron ion concentration 50 mg/L and PVDF membrane filter was established. The recovery rate of this method for bacteriophage was 93%-100%. Under the multi-functional microscope, it was found that the bacteriophage of the enriched water sample increased significantly and the fluorescence value of the enriched water sample determined by the enzyme labeling instrument was about 13 times as high as that before enrichment. After concentration of the actual water samples from the hospital drainage, the positive rate of bacteriophage isolation in the concentrated group and the non-concentrated group was 23% and 4%, and the fluorescence value in the concentrated group was 2-24 times as high as that of the non-concentrated group. Conclusion: The method of FeCl3-PVDF membrane filter is a simple, efficient and rapid method for enriching bacteriophages in different water samples.

Alda-1 alleviates brain injury after cardiopulmonary resuscitation by regulating acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 pathway-mediated ferroptosis in swine / 中华危重病急救医学

OBJECTIVE@#To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine.@*METHODS@#Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting.@*RESULTS@#Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway.@*CONCLUSIONS@#Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.

Zooming in and out of ferroptosis in human disease / 医学前沿

Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Desenvolvimento de compostos de coordenação para aplicação foliar e elucidação do mecanismo de absorção / Development of coordination compounds for foliar application and elucidation of the absorption mechanism

O objetivo geral desse trabalho foi desenvolver compostos de coordenação com os metais cobre, manganês, zinco, cobalto, níquel e magnésio com os aminoácidos L- ácido aspártico e glutâmico para aplicação como fertilizantes foliares e elucidação de seus prováveis mecanismos de absorção pela planta. Como plano de trabalho, pretendeu-se produzir alguns complexos metálicos com agentes complexantes que confiram características específicas: alta estabilidade termodinâmica e cinética quando comparado a quelatos usados comercialmente dos mesmos metais; alta solubilidade; compatibilidade com herbicidas e fungicidas e alta estabilidade frente a variações de pH. Os compostos foram caracterizados no estado sólido e/ou em solução aquosa, através de técnicas disponíveis em nosso laboratório, na Central Analítica do IQ-USP e/ou nos laboratórios da ICL América do Sul Ind. e Com. SA. Com o desenvolvimento dos compostos de coordenação, foram avaliados alguns parâmetros considerados imprescindíveis para garantia da qualidade do produto gerado, que foram então comparados aos de quelatos de EDTA (ácido etilenodiaminotetraacético) comercializados atualmente e que demonstraram vantagens. Para avaliar a eficiência dos produtos gerados foi realizada aplicação foliar em ao menos uma cultura e verificado o teor de cada nutriente após período de absorção e resposta produtiva, evidenciando e determinando o mecanismo de absorção realizado pela planta. Como resultado, desenvolveu-se uma série de produtos com alta tecnologia agregada que trouxeram benefícios nutricionais, sustentando uma nutrição de qualidade além de serem ecologicamente favoráveis (eco-friendly portfolio)

This project aims the development of copper, manganese, zinc, cobalt, nickel and iron metal complexes with L-amino acids aspartic and glutamic acids for application as foliar fertilizers and elucidation of the probable incorporation/absorption mechanism by plants. As a work plan, it was intended to produce these metal complexes with complexing agents that provide specific characteristics: high thermodynamic and kinetic stabilities when compared to the corresponding EDTA chelates; high solubility; compatibility with herbicides and fungicides and high stability against pH variations. With the development of such coordination compounds, some parameters considered indispensable to quality assurance were then evaluated, in comparison to that of currently available commercial EDTA chelates. To evaluate the performance of the obtained compounds, two foliar applications in the same crop were carried out. Further, the content of each nutrient after the production period and the productive capacity were evaluated, aiming to elucidate the absorption mechanism of the plant. As a result, elaborated products with high added technology were obtained, capable of ameliorating the nutritional benefits, that can support an eco-friendly portfolio

Prevalencia y evolución de la anemia en embarazadas del Hospital Central de las Fuerzas Armadas / Prevalence and evolution of anemia in pregnant women at the Central Hospital of the Armed Forces / Prevalência e evolução da anemia em mulheres grávidas no Hospital Central das Forças Armadas

Introducción: de acuerdo a los datos de la Organización Mundial de la Salud la prevalencia de anemia ferropénica en el embarazo oscila entre el 20 y el 39% de los mismos en Latinoamérica, siendo asociada con resultados adversos para la salud. Materiales y métodos: se realizó un estudio observacional, descriptivo, de corte transversal, donde fue estudiada la frecuencia de la anemia en las embarazadas usuarias del Hospital Central de las Fuerzas Armadas, y su evolución posterior luego del embarazo. Resultados: se observó que el 15,7% de las pacientes presentaba anemia en el embarazo, con un buen porcentaje de pacientes que cumplían el tratamiento con hierro indicado, y que sólo un bajo porcentaje realizaba un control de la anemia luego del embarazo. Discusión: el porcentaje de pacientes con anemia en el embarazo en este centro asistencial se encuentra por debajo de los porcentajes establecidos en la literatura internacional, se analizan las causas y se verifica que existe una dificultad en el seguimiento de estas pacientes luego del embarazo.

Introduction: according to World Health Organization data, the prevalence of iron deficiency anemia in pregnancy ranges between 20 and 39% of pregnancies in Latin America, being associated with adverse health outcomes. Materials and Methods: an observational, descriptive, cross-sectional, descriptive study was carried out to study the frequency of anemia in pregnant women users of the Central Hospital of the Armed Forces of Montevideo, and its subsequent evolution after pregnancy. Results: it was observed that 15.7% of the patients had anemia during pregnancy, with a good percentage of patients who complied with the indicated iron treatment, and only a small number of patients underwent anemia control after pregnancy. Discussion: the percentage of patients with anemia in pregnancy in this health care center is below the percentages established in the international literature, the causes are analyzed and it is verified that there is a difficulty in the follow-up of these patients after pregnancy.

Introdução: de acordo com dados da Organização Mundial da Saúde, a prevalência de anemia por deficiência de ferro na gravidez varia entre 20 e 39% das gestações na América Latina, e está associada a resultados de saúde adversos. Materiais e Métodos: foi realizado um estudo observacional, descritivo, transversal e descritivo para estudar a freqüência da anemia em gestantes usuárias do Hospital Central das Forças Armadas, e sua posterior evolução após a gravidez. Resultados: observou-se que 15,7% das pacientes tiveram anemia durante a gravidez, com uma boa porcentagem de pacientes que cumpriram o tratamento com ferro indicado, e apenas uma baixa porcentagem teve controle da anemia após a gravidez. Discussão: a porcentagem de pacientes com anemia na gravidez em nosso centro de atendimento está abaixo das porcentagens estabelecidas na literatura internacional, analisamos as causas e verificamos que existe uma dificuldade em monitorar essas pacientes após a gravidez.

Hemocromatosis: revisión de la literatura a propósito de un caso clínico / Hemochromatosis: case report and literature review

Hemochromatosis (HC) is a disorder that alters the body's ability to metabolize iron, increasing its absorption, causing iron overload, and consequently an accumulation of the mineral in multiple organs such as the liver, heart, and pancreas. The amount of total iron in the body is 2-4 g in healthy individuals and remains within these limits throughout life thanks to the control of intestinal absorption. In patients with CH, this amount is increased by at least 10 times, which translates into body deposits of 20-40 grams of iron on average. Factors that increase the risk of having HC: having two copies of the mutated HFE gene, family history, ethnicity or ancestry from Northern Europe (less common in blacks, Hispanics, and Asians), and male gender.