Comparison of the one-year outcomes of bariatric surgery in adolescents and young adults: a matched case-control study, Tehran Obesity Treatment Study (TOTS).

PURPOSES: The increasing use of bariatric surgery in adolescents has raised some concerns regarding the postoperative outcomes and the optimal time of surgery at young ages. However, no study has yet compared the weight loss and comorbidity resolution following bariatric surgery between adolescents and young adults. METHODS: This study was conducted on a case group of adolescents (aged 11-18) and a control group of young adults (aged 19-29) undergoing bariatric surgery (sleeve gastrectomy or gastric bypass). The two groups were matched in terms of gender, body mass index (BMI), and surgery type and were assessed regarding the surgical outcomes at 1 year after surgery. RESULTS: The baseline characteristics of the adolescents (n = 118, mean age: 17.0 ± 1.6 years) and young adults (n = 236, mean age: 25.2 ± 3.2 years) were similar, as well as surgery-associated complications. The mean loss of BMI (- 15.4 ± 3.6 vs. -15.8 ± 4.6 kg/m2) and 12-month percentage of excess weight loss (80.4 ± 20.1 vs. 80.2 ± 20.1%) were similar in the two groups. Both groups showed parallel reductions in the cardiovascular risk factors. The remission of hypertension, diabetes mellitus, and dyslipidemia was similar between the groups. The increase in the hemoglobin level and copper deficiency was greater in young adults, whereas the increase in ferritin deficiency was greater in adolescents. CONCLUSION: Similar to young adults, bariatric surgery is an effective and safe method to achieve weight loss, resolve obesity-related comorbidities, and improve cardiovascular risk factors in the adolescents.

H-Ferritin Produced by Myeloid Cells Is Released to the Circulation and Plays a Major Role in Liver Iron Distribution during Infection.

During infections, the host redistributes iron in order to starve pathogens from this nutrient. Several proteins are involved in iron absorption, transport, and storage. Ferritin is the most important iron storage protein. It is composed of variable proportions of two peptides, the L- and H-ferritins (FTL and FTH). We previously showed that macrophages increase their expression of FTH1 when they are infected in vitro with Mycobacterium avium, without a significant increase in FTL. In this work, we investigated the role of macrophage FTH1 in M. avium infection in vivo. We found that mice deficient in FTH1 in myeloid cells are more resistant to M. avium infection, presenting lower bacterial loads and lower levels of proinflammatory cytokines than wild-type littermates, due to the lower levels of available iron in the tissues. Importantly, we also found that FTH1 produced by myeloid cells in response to infection may be found in circulation and that it plays a key role in iron redistribution. Specifically, in the absence of FTH1 in myeloid cells, increased expression of ferroportin is observed in liver granulomas and increased iron accumulation occurs in hepatocytes. These results highlight the importance of FTH1 expression in myeloid cells for iron redistribution during infection.

Prevalence of iron deficiency among university kendo practitioners in Japan: an observational cohort study.

BACKGROUND: Iron deficiency is widely recognized as being the cause of anemia in athletes, although iron status in athletes of Kendo, a traditional Japanese martial art based on swordsmanship and practiced as an educational sport, has not been widely investigated. METHODS: We performed a health assessment on anemia and serum ferritin levels, along with nutrient intake evaluation, for Kendo practitioners in a university in Japan. RESULTS: A total of 56 Kendo practitioners (39 male and 17 female) aged between 18 and 23 years participated in the study. No individuals exhibited WHO-defined anemia (less than 13 or 12 g/dL of hemoglobin levels in male or female), while hypoferritinemia (less than 30 ng/mL) was found in seven (41%) females but not in males. Significantly higher body mass index was found in the female athletes with hypoferritinemia compared to females with normo-ferritinemia in sub-analysis (median [interquartile range]; 25.6 [24.2, 26.9] versus 22.6 [21.7, 24.1], respectively. p < 0.05). No significant differences in the intake of iron were registered between males and females (with and without hypoferritinemia) using data from a food-frequency questionnaire survey. CONCLUSION: No apparent anemia was found in adolescent Kendo practitioners, although this study confirmed the presence of hypoferritinemia in several female athletes. Careful follow-up, involving both clinical and nutritional assessment, will be necessary for them to prevent progression into anemia. A future study with larger cohorts in multiple sites is warranted to assess the prevalence of iron deficiency for validation and, if necessary, to devise a strategy for improving the iron status in Kendo athletes.

Prevalence, risk factors, and ferritin testing to mitigate iron depletion in male plateletpheresis donors.

BACKGROUND: Most single-donor platelet (SDP) donors transition to plateletpheresis after prior red blood cell (RBC) donation. Recruitment may follow identification of a high platelet count, a marker associated with iron depletion (ID). SDP donors may have underrecognized risk for iron depletion. STUDY DESIGN AND METHODS: To assess the prevalence of ID, we performed ferritin testing on male plateletpheresis donors with hemoglobin levels less than 13.5 g/dL. Multivariable logistic regression identified risk factors for low ferritin (LF; ferritin ≤26 ng/mL) and absent iron stores (AIS; ferritin <12 ng/mL). To assess the impact of notifying donors of LF results, we compared donation behavior of "Test" subjects before and after sending an LF notification letter to that of "Control" subjects before and after increasing the minimum hemoglobin for male donors. An electronic survey to Test donors inquired about iron supplementation practices. RESULTS: Prevalence of LF was 50% and AIS was 23%, with increase in risk associated with more frequent SDP donation, both controlling for RBC donation and in donors with no recent RBC donations. Donation frequency after intervention declined less in 1272 Test donors (19%, from 13.9 to 11.2 annualized donations) than in 878 Control donors (49%, from 12.3 to 6.3 donations). Only 20% of Test donors reported taking supplemental iron when they received the LF letter; 64% of those not taking iron initiated iron supplementation following the letter. CONCLUSIONS: Donors were responsive to notification of LF and attendant messaging on iron supplementation. Ferritin testing potentially benefits donor health and a stable platelet supply.

Micronutrient Status in Diabetic Patients with Foot Ulcers.

Objective: To explore the prevalence of micronutrient deficiencies in patients with diabetic foot ulcers and correlate this with foot disease severity and other clinical factors. Approach: Prospective cohort study of diabetic patients with foot ulcers seen in multidisciplinary foot clinics across Adelaide or admitted to the Vascular Surgery Unit at the Royal Adelaide Hospital between February 2017 and September 2018. A total of 131 patients were included in the study. Plasma serum levels of vitamins A, C, D, and E, copper, zinc, and ferritin were measured. Demographic and clinical data, including BMI, smoking status, duration of diabetes, HbA1c, and WIfI score, were obtained. Results: The most prevalent nutritional deficiency found was vitamin D affecting 55.7% of patients. Suboptimal levels of vitamin C affected 73% of patients, comprising marginal levels in 22.2% and deficient levels in 50.8%. Zinc deficiency, vitamin A deficiency, and low ferritin levels were present in 26.9%, 10.9%, and 5.9% of patients, respectively. There was no correlation between BMI, grip strength, duration of diabetes, HbA1c, or smoking status with micronutrient deficiency. Increased severity of diabetic foot disease was associated with lower vitamin C levels (p = 0.02). Innovation: This study has demonstrated that the deficiency of micronutrients, especially vitamin D, vitamin C, zinc, and vitamin A, is common in diabetic patients with foot ulcers. Conclusions: The prevalence of micronutrient deficiency is high in a diabetic population with foot ulcers/wounds. Special concerns regarding the high prevalence of vitamin C and zinc deficiency, given their roles in wound healing. Although further research needs to be performed to determine the clinical implications of our findings, micronutrient deficiency should be considered in diabetic patients with foot wounds.

Avaliação da presença de anemia e de deficiência de ferritina em pacientes atendidos no Laboratório de Análises Clínicas do Centro Universitário do Estado do Pará / Evaluation of the anemia presence and ferritin deficiency in patients attended at the Clinical Analyses Laboratory of the University Center of the State of Pará

Objetivo: Este estudo buscou analisar a presença de anemia, definida como a redução nos níveis de hemoglobina, e relacioná-la com a deficiência de ferritina sérica entre pacientes com idade igual ou superior a 15 anos, identificando possíveis casos de anemia ferropriva. Métodos: Foi realizada a coleta de resultados laboratoriais de pacientes que realizaram o exame de hemograma completo acompanhado da dosagem de ferritina no Laboratório de Análises Clínicas do CESUPA durante o período de agosto de 2018 a junho de 2019. Pacientes que realizaram ambos os exames e revelaram baixos níveis de hemoglobina foram inclusos, obtendo-se assim uma amostra de 177 pacientes anêmicos. Resultados: Nos pacientes incluídos no estudo, constatou-se que a faixa etária com maior prevalência de anemia foi a de pacientes com idade entre 61 a 70 anos de idade, representando 27,1% da amostra total. Classificando-se os tipos de anemia presente com base em seus índices hematimétricos, notou-se maior frequência daquelas com perfil de normocitose e normocromia (55,4%), seguida de microcitose e hipocromia (31,6%) e de macrocitose com normocromia (2,3%). Entre os pacientes com perfil de microcitose e hipocromia, 91,1% apresentaram anisocitose. Dos 177 pacientes anêmicos, apenas 19 (10,7%) apresentaram valores baixos de ferritina, enquanto que os pacientes com níveis normais de ferritina foram os mais frequentes (59,9%). Conclusão: O perfil hematimétrico compatível com quadros de anemia ferropriva foi o segundo mais frequente neste estudo, sendo o de normocitose e normocromia o mais frequente, assim corroborando com maior parte das faixas etárias identificadas.

Objective: This study aimed to analyze the presence of anemia, being evaluated by the reduced hemoglobin levels, and associate it with serum ferritin deficiency among patients at 15 years old or greater, identifying possible cases of iron-deficiency anemia. Methods: Exam results from patients who did the complete blood count exam and the dosage of ferritin levels at the Laboratory of Clinical Analyzes from CESUPA during the interval of august 2018 to june 2019 were collected. Patients who performed both tests and revealed low hemoglobin levels were included, creating a sample of 177 anemic patients. Results: In the patients included in this study, it was found that anemia was most prevalent among patients with an age within the range of 61 to 70 years old, representing 27,1% of the total sample. Classifying the types of anemia present by use of the hematimetric paramaters, it was noted that those with the profile of normocytic and normochromic were the most frequent (55,4%), followed by the profile of microcytic and hypocromic anemia patients with microcytosis and hypochromia, 91,1% also had the presence of anisocytosis. Of the 177 patients with anemia, only 19 (10,7%) showed low ferritin levels, while those with normal ferritin levels were the most frequent (59,9%). Conclusion: The hematimetric profile compatible with iron-deficiency anemia was the second most frequent in this study, while the profile of microcytosis and hypochromia was the most frequent one, thus corroborating with most of the identified age groups.

Does Improvement of Low Serum Ferritin Improve Symptoms of Restless Legs Syndrome in a Cohort of Pediatric Patients?

STUDY OBJECTIVES: To determine whether an oral iron supplement improves restless leg/restless sleep symptoms in a pediatric population. METHODS: In a cohort study, 47 patients (age 5-18 years) exhibiting restless legs/restless sleep symptoms and low serum ferritin levels (< 50 ng/mL) were given a daily oral iron supplement (ferrous sulfate + vitamin C) and re-evaluated 8 weeks later. A diagnosis of definite Restless Legs Syndrome (RLS) was determined based on criteria established by the International RLS Study Group. Using Wilcoxon signed-rank tests and Spearman rho, the change and association between the measures of Pediatric Restless Legs Syndrome Severity Scale and serum ferritin levels were also examined. RESULTS: Overall, the median change and distribution of ferritin was statistically significantly different after 8 weeks of treatment (40.0 versus 23.0 ng/mL, P < .0001). Median RLS score was also statistically significantly lower from baseline to follow-up (4.0 versus 6.0, P = .0283). Sixteen patients met criteria for definite RLS; however, the change in RLS score was not determined to be significant in our population (9.5 versus 7.0, P = .0558), despite significant change in ferritin (25.0 versus 42.5 ng/mL, P < .0001). In addition, no correlation was observed between change in RLS score and ferritin level (rho = -.39, P = .1362). CONCLUSIONS: In preliminary findings, we found a modest, yet nonsignificant improvement in children exhibiting restless sleep and RLS symptomatology, despite significant improvement in ferritin levels. Though not statistically significant, the findings can lend to the suggested benefit of iron supplementation in patients with RLS; however, clinical judgment and further research is necessary. CITATION: Rosen GM, Morrissette S, Larson A, Stading P, Barnes TL. Does improvement of low serum ferritin improve symptoms of restless legs syndrome in a cohort of pediatric patients? J Clin Sleep Med. 2019;15(8):1149-1154.

Liposomal delivery of ferritin heavy chain 1 (FTH1) siRNA in patient xenograft derived glioblastoma initiating cells suggests different sensitivities to radiation and distinct survival mechanisms.

Elevated expression of the iron regulatory protein, ferritin heavy chain 1 (FTH1), is increasingly being associated with high tumor grade and poor survival outcomes in glioblastoma. Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and glioblastoma recurrence, have recently been shown to exhibit increased FTH1 expression. We previously demonstrated that FTH1 knockdown enhanced therapeutic sensitivity in an astrocytoma cell line. Therefore, in this study we developed a liposomal formulation to enable the in vitro delivery of FTH1 siRNA in patient xenograft derived GICs from glioblastomas with pro-neural and mesenchymal transcriptional signatures to interrogate the effect of FTH1 downregulation on their radiation sensitivity. Transfection with siRNA decreased FTH1 expression significantly in both GICs. However, there were inherent differences in transfectability between pro-neural and mesenchymal tumor derived GICs, leading us to modify siRNA: liposome ratios for comparable transfection. Moreover, loss of FTH1 expression resulted in increased extracellular lactate dehydrogenase activity, executioner caspase 3/7 induction, substantial mitochondrial damage, diminished mitochondrial mass and reduced cell viability. However, only GICs from pro-neural glioblastoma showed marked increase in radiosensitivity upon FTH1 downregulation demonstrated by decreased cell viability, impaired DNA repair and reduced colony formation subsequent to radiation. In addition, the stemness marker Nestin was downregulated upon FTH1 silencing only in GICs of pro-neural but not mesenchymal origin. Using liposomes as a siRNA delivery system, we established FTH1 as a critical factor for survival in both GIC subtypes as well as a regulator of radioresistance and stemness in pro-neural tumor derived GICs. Our study provides further evidence to support the role of FTH1 as a promising target in glioblastoma.

Evaluation of Vitamin B12, Folate and Ferritin Serum Levels in Jordanian Population.

Vitamin B12, folate, and ferritin are vital for the development of the nervous system, blood formation, and diverse metabolic functions. The aim of the current study is to evaluate the status of vitamin B12, folate and ferritin in the Jordanian population across distinct geographical locations. In this retrospective study, the cohort population included 2,880 Jordanian individuals with an average age of 47 y for males and 34 y for females (January 2014-December 2016). Vitamin B12, folate, and ferritin were measured in the blood samples by immunoassay on an automated instrument. Prevalence of low levels of vitamin B12 among males and females was similar across the four regions (24%). Equivalently high levels of folate were reported in males (24.4%) and females (23.4%). Additionally, 37.4% of males and 20.4% of females showed low levels of ferritin. Pearson's correlations did not show any association between age, vitamin B12, folate, and ferritin levels in both sexes. Univariate odd ratio (OR) and age-adjusted OR in males showed a significant decrease in low vitamin B12 risk in the region of Tafela when compared to Irbid. In conclusion, our results showed a significant difference in vitamin B12 levels between populations according to their geographical locations. Ferritin levels were low in almost a quarter of the Jordanian population with a high prevalence in males and females in Irbid and Maan, respectively. These differences might be associated with the genetic, dietary and lifestyle situation which requires further studies to elucidate the risk factors for vitamin B12 and ferritin deficiency.

Bacterioferritin of Magnetospirillum gryphiswaldense Is a Heterotetraeicosameric Complex Composed of Functionally Distinct Subunits but Is Not Involved in Magnetite Biomineralization.

The biomineralization pathway of magnetite in magnetotactic bacteria is still poorly understood and a matter of intense debates. In particular, the existence, nature, and location of possible mineral precursors of magnetite are not clear. One possible precursor has been suggested to be ferritin-bound ferrihydrite. To clarify its role for magnetite biomineralization, we analyzed and characterized ferritin-like proteins from the magnetotactic alphaproteobacterium Magnetospirillum gryphiswaldense MSR-1, employing genetic, biochemical, and spectroscopic techniques. Transmission Mössbauer spectroscopy of the wild type (WT) and a bacterioferritin (bfr) deletion strain uncovered that the presence of ferrihydrite in cells is coupled to the presence of Bfr. However, bfr and dps deletion mutants, encoding another ferritin-like protein, or even mutants with their codeletion had no impact on magnetite formation in MSR-1. Thus, ferritin-like proteins are not involved in magnetite biomineralization and Bfr-bound ferrihydrite is not a precursor of magnetite biosynthesis. Using transmission electron microscopy and bacterial two-hybrid and electrophoretic methods, we also show that MSR-1 Bfr is an atypical representative of the Bfr subfamily, as it forms tetraeicosameric complexes from two distinct subunits. Furthermore, our analyses revealed that these subunits are functionally divergent, with Bfr1 harboring a ferroxidase activity while only Bfr2 contributes to heme binding. Because of this functional differentiation and the poor formation of homooligomeric Bfr1 complexes, only heterooligomeric Bfr protects cells from oxidative stress in vivo. In summary, our results not only provide novel insights into the biomineralization of magnetite but also reveal the unique properties of so-far-uncharacterized heterooligomeric bacterioferritins.IMPORTANCE Magnetotactic bacteria like Magnetospirillum gryphiswaldense are able to orient along magnetic field lines due to the intracellular formation of magnetite nanoparticles. Biomineralization of magnetite has been suggested to require a yet-unknown ferritin-like ferrihydrite component. Here, we report the identification of a bacterioferritin as the source of ferrihydrite in M. gryphiswaldense and show that, contrary to previous reports, bacterioferritin is not involved in magnetite biomineralization but required for oxidative stress resistance. Additionally, we show that bacterioferritin of M. gryphiswaldense is an unusual member of the bacterioferritin subfamily as it is composed of two functionally distinct subunits. Thus, our findings extend our understanding of the bacterioferritin subfamily and also solve a longstanding question about the magnetite biomineralization pathway.

Association between pre-pregnancy weight status and maternal micronutrient status in early pregnancy.

OBJECTIVE: Inadequate maternal micronutrient status during pregnancy can lead to short- and long-term health risks for mother and offspring. The present study investigated the association between pre-pregnancy weight status and micronutrient status during pregnancy. DESIGN: Maternal blood samples were collected during early pregnancy (median 13, interquartile range 12-15 weeks) and were assayed for serum folate, ferritin, Fe and vitamin B12. Regression modelling was used to assess the association between pre-pregnancy underweight, normal weight, overweight and obesity, and micronutrient levels, as well as the odds for deficiencies. SETTING: The Amsterdam Born Children and their Development (ABCD) study, the Netherlands. SUBJECTS: Women with singleton pregnancies without diabetes (n 4243). RESULTS: After adjustment for covariates, overweight women and obese women had lower (ß; 95 % CI) folate (-1·2; -2·2, -0·2 and -2·3; -4·0, -0·7 nmol/l, respectively) and Fe (-1·7; -2·3, -1·1 and -3·6; -4·7, -2·6 µmol/l, respectively) levels than women with normal weight. Furthermore, overweight women had 6 % (95 % CI -9, -3 %) and obese women had 15 % (-19, -10 %), lower vitamin B12 levels, and obese women had 19 % (6, 32 %) higher ferritin levels, than normal-weight women. Obese women had higher odds (OR; 95 % CI) for folate deficiency (2·03; 1·35, 3·06), Fe deficiency (3·26; 2·09, 5·08) and vitamin B12 deficiency (2·05; 1·41, 2·99) than women with normal weight. Underweight was not associated with micronutrient status. CONCLUSIONS: During early pregnancy, women with pre-pregnancy overweight and obesity had lower serum folate, Fe and vitamin B12 status. This resulted in increased risk of serum folate, Fe and vitamin B12 deficiencies in women with obesity.

Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model.

AIM: Despite the high prevalence of chronic neck pain, there is limited consensus about the primary etiology, risk factors, diagnostic criteria and therapeutic outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable risk factors with chronic neck pain using slandered statistics and artificial intelligence neural network (ANN). METHODS: Fifty-four patients with chronic neck pain treated between February 2016 and August 2016 in King Abdullah University Hospital and 54 patients age matched controls undergoing outpatient or minor procedures were enrolled. Patients and control demographic parameters, height, weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium, phosphorus, zinc were obtained. An ANN prediction model was developed. RESULTS: The statistical analysis reveals that patients with chronic neck pain have significantly lower serum Vitamin D and Ferritin (p-value <.05). 90% of patients with chronic neck pain were females. Multilayer Feed Forward Neural Network with Back Propagation(MFFNN) prediction model were developed and designed based on vitamin D and ferritin as input variables and CNP as output. The ANN model output results show that, 92 out of 108 samples were correctly classified with 85% classification accuracy. CONCLUSIONS: Although Iron and vitamin D deficiency cannot be isolated as the sole risk factors of chronic neck pain, they should be considered as two modifiable risk. The high prevalence of chronic neck pain, hypovitaminosis D and low ferritin amongst women is of concern. Bioinformatics predictions with artificial neural network can be of future benefit in classification and prediction models for chronic neck pain. We hope this initial work will encourage a future larger cohort study addressing vitamin D and iron correction as modifiable factors and the application of artificial intelligence models in clinical practice.

Hematinic deficiencies in patients with recurrent aphthous stomatitis: variations by gender and age.

BACKGROUND: The aim of this study was to evaluate the association between hematinic deficiencies and recurrent aphthous stomatitis (RAS). MATERIAL AND METHODS: 517 RAS patients and 187 healthy controls were enrolled in the present study. Hematinic deficiencies, including serum ferritin, folic acid, and vitamin B12 deficiencies were assessed for each participant. Gender and age were taken into account and the collected data were statistically analysed. RESULTS: Compared with the healthy controls, a significantly higher overall frequency of hematinic deficiencies was found in RAS patients (p<0.001). When gender and age were taken into account, significant differences in hematinic deficiencies were observed among RAS patients. Serum ferritin deficiency was much more common in young and middle-aged female RAS patients (age<60). Serum folate deficiency and serum vitamin B12 deficiency were both much more common in the young adult group of male RAS patients (21-40 years of age). Logistic regression analysis revealed that both gender and age have significant correlation with the presence of hematinic deficiencies in the RAS patients. CONCLUSION: Significant variations in hematinic deficiencies were demonstrated in RAS patients across different genders and age groups. We suggest that further studies on the hematinic deficiencies of RAS patients should take into account the gender and age of participants.

Lack of mitochondrial ferritin aggravated neurological deficits via enhancing oxidative stress in a traumatic brain injury murine model.

Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.

Expression and characterization of the ferritin binding domain of Nuclear Receptor Coactivator-4 (NCOA4).

Ferritinophagy is the process of autophagic degradation of ferritin that participates in the regulation of cellular iron homeostasis. This process was shown to be mediated by the selective cargo-receptor Nuclear Receptor Coactivator-4 (NCOA4) that binds ferritin and targets it to emerging autophagosome. To characterize some of the biochemical properties of the interaction between the two proteins we cloned and expressed in E. coli the ferritin-binding domain of human NCOA4, fragment 383-522. It was purified and subjected to biochemical analysis. The NCOA4(383-522) fragment was expressed in soluble and dimeric form, and CD spectra indicated low level of secondary structure. The Ferritin binding activity of the fragment was investigated by developing an electrophoretic mobility shift and an ELISA assays. They showed that the NCOA4 fragment binds the H-ferritin with an affinity in the nM range, but not the R23A H-ferritin mutant and the L-ferritin chain, confirming the high specificity for the H-chain. The H-ferritin could bind up to 24 NCOA4(383-522) fragments forming highly stable and insoluble complexes. The binding was partially inhibited only by Fe(II) among the various divalent metal ions analyzed. The iron-dependent, highly-specific formation of the remarkably stable H-ferritin-NCOA4 complex shown in this work may be important for the characterization of the mechanism of ferritinophagy.

Mitochondrial Ferritin Deletion Exacerbates ß-Amyloid-Induced Neurotoxicity in Mice.

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein which protects mitochondria from iron-induced oxidative damage. Our previous studies indicate that FtMt attenuates ß-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on ß-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and Ftmt knockout mice were infused intracerebroventricularly (ICV) with Aß25-35 to establish an Alzheimer's disease model. Knockout of Ftmt significantly exacerbated Aß25-35-induced learning and memory impairment. The Bcl-2/Bax ratio in mouse hippocampi was decreased and the levels of cleaved caspase-3 and PARP were increased. The number of neuronal cells undergoing apoptosis in the hippocampus was also increased in Ftmt knockout mice. In addition, the levels of L-ferritin and FPN1 in the hippocampus were raised, and the expression of TfR1 was decreased. Increased MDA levels were also detected in Ftmt knockout mice treated with Aß25-35. In conclusion, this study demonstrated that the neurological impairment induced by Aß25-35 was exacerbated in Ftmt knockout mice and that this may relate to increased levels of oxidative stress.

Vitamin and Mineral Deficiencies in Patients With Telogen Effluvium: A Retrospective Cross-Sectional Study.

Telogen effluvium is one of the most common forms of non-scarring alopecia for which patients present to a dermatologist. It is a challenging disorder to treat and study, primarily owing to its multifactorial etiology which includes both physiologic and non-physiologic factors. Nutritional deficiency has been purported to contribute to hair shedding, and a patient's clinical history usually aids in directing laboratory evaluation. Many prior studies have either supported or failed to find a correlation between telogen effluvium and deficiencies in vitamins and minerals, in particular, vitamin D, ferritin, vitamin B12, folate, and zinc. We performed a retrospective cross-sectional study of patients with telogen effluvium in the greater Pittsburgh, Pennsylvania area, and measured the rates of these deficiencies. Our results demonstrate that the prevalence of vitamin D, ferritin, and zinc deficiencies is non-trivial and therefore justifies including these laboratory studies in initial clinical evaluation.

J Drugs Dermatol. 2016;15(10):1235-1237.

Common Bean Leaves as a Source of Dietary Iron: Functional Test in an Iron-Deficient Rat Model.

Recent findings made by our group indicate that the iron content in Phaseolus vulgaris leaves is at least four times greater than in grains therefore, we evaluated the effect of supplementation with bean leaf (iron content of 275 mg/kg on a dry basis) in iron-deficient rats. Anemia was induced by feeding rats with an iron-deficient diet (IDD) for 11 days and iron-recovery diets were subsequently tested for 14 days using a normal diet, a 10 % bean leaf-supplemented IDD (BLSD) or a ferrous sulfate-supplemented IDD. Decreased levels of leukocytes (64 %), erythrocytes (30 %), lymphocytes (62 %), granulocytes (72 %), hematocrit (34 %), hemoglobin (35 %), and ferritin (34 %) were observed in the iron-deficient rats compared to the control rats. BLSD supplementation showed the highest recovery values relative to those recorded for control rats: leukocytes (40 %), erythrocytes (24 %), lymphocytes (33 %), granulocytes (88 %), hematocrit (17 %), and hemoglobin (18 %), suggesting that common bean leaves could be a good source of bioavailable iron with possible immunomodulatory effects.

The impact of iron status and smoking on blood divalent metal concentrations in Norwegian women in the HUNT2 Study.

Low iron (Fe) stores may result in increased absorption of divalent metals, in particular cadmium (Cd). We have previously shown that in non-smoking women participating in the Norwegian HUNT2 cohort study this also included other divalent metals, e.g. manganese (Mn) and cobalt (Co). The diet is the main source of metals in non-smoking individuals, whereas in smoking individuals tobacco smoke contributes significant amounts of Cd and lead (Pb). The aim of the present study was to investigate the impact of smoking on the relationship between low iron status and divalent metals. Blood concentrations of the divalent metals Cd, Mn, Co, Pb, copper (Cu) and zinc (Zn), determined using an Element 2 sector field mass spectrometer (ICP-MS), were investigated in smoking women of fertile age (range 21-55 years) (n=267) from the HUNT2 cohort. Among these, 82 were iron-deplete (serum ferritin<12µg/L) and 28 had iron deficiency anaemia (serum ferritin<12µg/L & Hb<120g/L). 150 (56%) women smoked 10 or more cigarettes daily, 101 (38%) had smoked for more than 20 years, and 107 (40%) had smoked for 11-20 years. Results from the smoking population were compared with results from our previous study in non-smoking women (n=448) of which 132 were previous smokers, all from the same cohort. Increasing concentrations of Cd in blood were observed for previous smokers, low-to-moderate smokers and high intensity smokers in all subgroups compared to never smokers, and according to age groups, education level, BMI and serum ferritin. Smokers had higher Pb concentrations than non-smokers in all subgroups, but less pronounced than for Cd. Smoking was not associated with Mn and Co concentrations in blood. In multiple regression models, low ferritin was associated with increased blood concentrations of Cd, Pb, Mn and Co. Ferritin was strongly associated with Cd at low smoking intensity, but was not a significant factor in heavy smokers, where intensity and duration of smoking emerged as main determinants. Ferritin associations with Co and Pb varied with tertiles of blood Cd. Ferritin emerged as the main determinant of blood Co and Mn, while for blood Pb, age and smoking intensity had higher impact. Cu and Zn remained within reference values and no significant associations with ferritin were found. Strong positive associations between blood concentrations of Pb, Mn, Cd and Co were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the divalent metals studied. Mild anaemia (110