Serum Transferrin Receptor Research Articles

Iron status and anemia in a representative sample of US pregnant women is not associated with pre-pregnancy BMI: Results from the NHANES (1999-2010) study.

Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as a potential risk factor for poor iron status. Our objective was to examine the association between pre-pregnancy BMI, iron status, and anemia in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n = 1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cook's equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted linear and Poisson regression models, adjusted for confounders (age, race/ethnicity, education, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. Ferritin and total body iron trended slightly lower (p = 0.12, p = 0.14) in women with pre-pregnancy BMI in the normal and overweight categories compared to the underweight and obese categories; hemoglobin concentrations were similar across BMI groups (p = 0.76). There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR) = 1.27, 95%CI: 0.89-1.82; obesity, PR = 0.75, 95%CI: 0.39-1.45; anemia: overweight, PR = 1.08, 95%CI: 0.53-2.19; obesity, PR = 0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that total body iron, serum hemoglobin, ID, and anemia in pregnancy do not differ by pre-pregnancy BMI. Since ID and anemia during pregnancy remain significant public health concerns, NHANES should consider measuring current iron status in upcoming cycles.

Iron status correlates strongly to Insulin Resistance among U.S. adults: A nationwide population-base study.

Evidence on the link between iron status markers and insulin resistance (IR) is limited. We aimed to explore the relationship between iron status and IR among U.S. adults. This study involved 2993 participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, 2017-2020. IR is characterized by a HOMA-IR value of ≥2.5. Weighted linear and multivariable logistic regression analyses were used to examine the linear relationships between iron status and IR. Furthermore, restricted cubic splines (RCS) were used to identify the non-linear dose-response associations. Stratified analyses by age, sex, BMI and PA were also performed. Last, ROC curve was used to evaluate the predictive value of iron status in IR. In weighted linear analyses, serum iron (SI) exhibited a negative correlation with HOMA-IR (β (95% CI) = -0.03(-0.05, -0.01), P = 0.01). In weighted multivariate logistic analyses, iron intake and serum transferrin receptor (sTfR) were positively correlated with IR (OR =1.02; 95% CI=1.00-1.04, P = 0.04; OR =1.07; 95% CI=1.02-1.13, P = 0.01). Also, SI and transferrin saturation (TSAT) were negatively correlated with IR (OR =0.96; 95% CI=0.94-0.98, P <0.0001; OR =0.98; 95% CI=0.97-0.99, P <0.001) after adjusting for confounding factors. RCS depicted a nonlinear dose-response relationship between sTfR and TSAT and IR. This correlation remained consistent across various population subgroups. ROC curve showed that TSAT performed better than iron intake, SI, sTfR and TSAT in ROC analyses for IR prediction. All biomarkers demonstrated significantly lower risk of IR with increasing iron levels, which will contribute to a more comprehensive and in-depth understanding of the relationship between the two and provide a solid foundation for future exploration of the mechanisms underlying their relationship.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars

BackgroundBoars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15–21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated.Results1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters.ConclusionsDietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Improvement in Iron Burden in Patients with Transfusion-Dependent β-Thalassemia (TDT) Treated with Betibeglogene Autotemcel (Beti-cel) Gene Therapy: Up to 9 Years of Follow-up

Introduction: Beti-cel is an approved, one-time gene therapy treatment for adult and pediatric patients with TDT. Beti-cel consists of autologous hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene (β A-T87Q), which produces functional hemoglobin (Hb) and addresses the underlying genetic cause of TDT. While transfusion independence (TI) remains a critical component for assessing patient response to gene therapy, other measures, including markers of iron overload, are important for evaluating the impact of therapy and management of disease burden over time. Previously, we demonstrated that iron markers stabilized in patients who achieved TI and stopped chelation therapy. Here, we report iron management outcomes in patients who completed either a phase 1/2 or phase 3 beti-cel parent study and subsequently enrolled in the long-term follow-up study. Methods: Patients with TDT who completed a parent beti-cel study (phase 1/2 studies: HGB-204 [NCT01745120]; HGB-205 [NCT02151526]; phase 3 studies: HGB-207 [NCT02906202]; HGB-212 [NCT03207009]) could enroll in a long-term study (LTF-303 [NCT02633943]) for up to an additional 13 years of follow-up. In these studies, TI was defined as a weighted average Hb ≥9 g/dL without packed red blood cell transfusions for ≥12 months. Iron removal therapy was at the discretion of the treating physician. Liver and cardiac magnetic resonance imaging evaluated liver iron concentration (LIC) and cardiac T2*; serum ferritin and transferrin receptor (TfR) were assessed at regular intervals according to protocol. Results:As of January 30, 2023, 63 patients received beti-cel; median (range) follow-up was 60.1 (23.8-109.5) months. In phase 3 studies, 37/41 (90%) patients achieved TI and maintained TI through the last follow-up, which was 5+ years for 10 patients ( Figure 1). In phase 1/2 studies, 15/22 (68%) patients achieved TI; 14 of these patients maintained TI through the last follow-up, which was up to 9 years. One patient no longer meets protocol-defined TI as a result of Hb level &amp;lt;9g/dL at year 6 due to acute health events unrelated to β-thalassemia, which were not attributed to loss of beti-cel treatment effect. In total, 51 patients across phase 1/2 and 3 studies achieved and maintained TI through last follow-up with 35/51 (69%) patients off chelation. Thirty of 51 patients had an LIC measurement at month 48. Of these 30 patients, 21 had an LIC &amp;lt;5 mg/g at month 48 post infusion. Among these 21 patients, 5 never restarted chelation after infusion (2 received phlebotomy only), 11 restarted chelation and then were able to discontinue after iron stores normalized (1 also received phlebotomy), and 5 continue to receive chelation (none had phlebotomy). The other 9 patients who had an LIC measurement at month 48 had an iron burden ≥5 mg/g. All 9 of these patients restarted chelation; 4 were able to discontinue (2 had phlebotomy) and 5 continue to receive chelation (1 had phlebotomy). Analysis of iron marker stabilization after discontinuation of chelation will be presented. The median (range) change from baseline in LIC levels at month 48 was -3.9 (-22.3 to 10.5) mg Fe/g dry weight; the median (range) change from baseline in serum ferritin was -2119.0 (-7211 to 3889) pmoL/L. Reductions from baseline in serum TfR were observed at month 36; cardiac T2* remained stable at month 48 ( Table 1). Safety of beti-cel treatment largely reflected the known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. Conclusion: In this analysis with up to 9 years of follow up, patients treated with beti-cel who achieved TI also demonstrated sustained improvements in iron burden, and the majority of patients were able to stop chelation. Collectively, these results demonstrate the long-term durability and stability of response after beti-cel gene therapy in patients with TDT.

Serum Iron Profile in Type 2 Diabetes, A Role Beyond Anemic Marker!

Background: There are evidences of controversial study findings that iron profile has a significant role in maintenance of glycemic status. This study has therefore been done to estimate the markers of iron in subjects with type 2 diabetes mellitus as compared to impaired glycemic status and apparently healthy individuals and to look for correlation between these various iron markers and glycemic control. Methods: One hundred and fifteen (115) subjects were enrolled for the study and divided into three groups: fifty (50) each of diabetic &amp; impaired glycemic status and fifteen (15) apparently healthy individuals based on HbA1c level. Basic demographic profile like age and sex and estimation of serum random glucose, urea, ceatinine, iron, ferritin, transferrin and soluble transferring receptor (stfR) were done. Results: ANOVA test has shown a significant difference in the mean for stfR (F=11.055, p=0.000) as well as for stfR/ferritin index (F=8.68, p=0.000). ANOVA for serum iron, transferrin, and ferritin were not statistically different for the groups. A significant correlation was found between HbA1c &amp; stfR -ferritin index and between HbA1c and stfR in diabetic group. Conclusion: Iron and its markers are not only important in detecting and study of iron deficiency anemia but also might have a strong role in glucose homeostasis as well as development of intolerance and hence diabetes. stfR and stfR- ferritin index is comparatively stable and might be therefore used as additional marker along with HbA1C for monitoring blood glucose homeostasis.

The Relation of the Iron Metabolism Index to the Vulnerability Index of Carotid Plaque with Different Degrees of Stenosis.

To investigate the differences in serum iron index and iron metabolizing protein expression in plaques in patients with different degrees of carotid artery stenosis and the relationship with plaque traits. A total of 100 patients eligible for carotid endarterectomy (CEA) from August 2021 to February 2022 were included. Patients completed a computed tomography (CTA) scan for patient grouping and a magnetic resonance imaging (MRI) for precise quantification of carotid plaque traits within 1 week prior to surgery. Clinical indicators associated with the progression of carotid stenosis to occlusion were analyzed using ordered logistic regression. Twenty carotid plaques were analyzed immunohistochemically to investigate the relationship between plaque traits and the iron metabolism indexes. No significant correlation between high serum ferritin (SF), unsaturated iron binding capacity (UIBC) and progression of carotid stenosis (OR 1.100, 95% CI 0.004-0.165, p = 0.039; OR 1.050, 95% CI 0.005-0.094, p = 0.031). SF and serum transferrin receptor (sTfR) were correlated with normalized wall index (NWI) (R = 0.470, p = 0.036; R = 0.449, p = 0.046), and the results of multiple linear regression suggested that SF and sTfR remained associated with NWI (R = 0.630, R2 = 0.397, Adjusted R2 = 0.326, p = 0.014). In plaques, H-type ferritin (H-FT) was correlated with NWI and lipid-rich necrotic core (LRNC) volume (R = 0.502, p = 0.028; R = 0.468, p = 0.043). Transferrin receptor 1 (TfR1) was correlated with LRNC volume and intraplaque hemorrhage (IPH) volume (R = 0.538, p = 0.017; R = 0.707, p = 0.001). There were statistical differences in the expression of iron metabolism proteins in carotid plaques with different degrees of stenosis. Serum iron metabolism index (SF and sTfR) and expression of iron metabolizing proteins (H-FT and TfR1) in plaques were positively correlated with carotid plaque vulnerability index (NWI, LRNC volume).

ПОКАЗАТЕЛИ СОСТОЯНИЯ ЖЕЛЕЗА В КРОВИ ДОНОШЕННЫХ ДЕТЕЙ, ЗАЧАТЫХ ЕСТЕСТВЕННЫИ ПУТЕМ И ПО ТЕХНОЛОГИИ ЭКО

The paper presents the results of a study of iron metabolism in full-term infants conceived naturally and using in vitro fertilization (IVF) technology. The data obtained allowed us to conclude that there were no statistically significant differences in the studied indicators in the groups and did not reveal the effect of IVF technology on the iron metabolism of full-term newborns. The purpose of the study. To study and compare the data of iron metabolism - hemoglobin, serum iron, serum transferrin recep-tor (sTfR), ferritin, ferritin index (sTfR/logFer), transferrin saturation, zinc protoporphyrin/ heme ratio in full-term infants conceived using IVF technology and children born by natural conception. Materi-als and methods. Clinical, biochemical and statistical methods were used in the work. The indicators of hemogram and ferrokinetics were determined in 20 full-term children conceived by observation, and in 18 children born using the technology of in vitro fertilization. Research results. In full-term children born as a result of IVF procedure, the level of Hb it was 17,03 ± 0,82 g/dl. The level of serum iron was comparable in the study groups (in full–term children conceived naturally, it is 26,09 ± 0,68 μmol/l, in children conceived by IVF – 25,24 ± 0,5 μmol/l). Studies of the ferritin level in full–term children conceived in the traditional way showed values of 175,73 ± 11,63 μg/l, in children after IVF procedure – 177,04 ± 11,21 μg/l. When calculating the ferritin index (sTfR / log10 Ferritin), data were obtained - in full-term children, the ferritin index is 3,72 ± 0,28 and 4,03 ± 0,36 mg/l depending on the method of conception, the differences are not statistically significant. In full-term children conceived naturally, the TS level was determined to be 61,18 ± 4,11 %, and in full-term children born as a result of traditional conception – 61,77 ± 5,3 %. Conclusion. The study allowed us to conclude that there is no statistically significant effect of the IVF method on iron metabolism and ferrokinetic factors in full-term newborns conceived by this method.

Features of the relationship between the levels of regulation of hemodynamics and the activity of immune reactions in healthy and patients with coronary heart disease residents of the European North and the Arctic of the Russian Federation

Objective. To establish the features and interrelation of the levels of hemodynamics and the activity of immune reactions regulation in practically healthy people and patients with coronary heart disease living in the European North and the Arctic of the Russian Federation.Material and methods. The study included 430 people aged 21 to 55, 274 women and 156 men, living in Arkhangelsk region (Arkhangelsk, settlements of the Konosha district; 60° N.L., 40° E.L.), Murmansk region (settlements of Revda and Lovozero; 67° N.L., 34° E.L.) and the Spitsbergen archipelago (Barentsburg; 80° N.L., 10° E.L.). 244 of those were practically healthy at the time of the examination and 186 patients were diagnosed with coronary heart disease. The research included the study of hemogram, content of phenotypes of CD3+, CD4+, CD8+, CD16+, CD71+ lymphocytes, concentrations of sCD71, transferrin, IL-1β, epinephrine, norepinephrine, dopamine, Nt-pro-BNP, endothelin-1, total NO, endogenous NO2, nitrate NO3, cGMP, cAMP, antibodies to cardiolipin, antibodies to phospholipids, CEC IgM.Results. It was found that practically healthy residents of the Arctic, compared to people living in more favorable climatic conditions, are 2–2.5 times more likely to have elevated concentrations of transferrin, sCD71, dopamine, cortisol, endothelin-1 and Nt-pro-BNP, as well as autoantibodies to cardiolipids and IgM CIC in the plasma of venous peripheric blood. In patients with coronary heart disease, the frequency of elevated levels of trasferrin, endothelin-1, and cortisol in the blood is 1.5–2 times higher, and concentrations of natriuretic peptide, antiphospholipids, CIC and a free pool of transferrin receptors are 4–5 times higher than those in healthy people. The strongest correlations of all these factors with the concentration of the cardiomyocyte damage marker were found in sCD71, which confi rms the involvement of elevated concentrations of the serum transferrin receptor in the mechanisms of tissue damage.Conclusion. Hyperfunction of the cardiovascular system is provided by elevated reactions. A systematic increase in the levels of hemodynamic reactions, intercellular interactions, and integration of homeostasis regulation mechanisms provide correction of a certain stage of regulation and may lead to a reduction in reserve regulatory capabilities and excessive severity of adaptive processes.

Infections and nutrient deficiencies during infancy predict impaired growth at 5 years: Findings from the MAL-ED study in Pakistan.

Socio-economic, nutritional, and infectious factors have been associated with impaired infant growth, but how the presence of these factors during infancy affects growth around 5 years is not well understood. This secondary analysis of the MAL-ED cohort included 277 children from Pakistan for whom socio-demographic, breastfeeding, complementary foods, illness, nutritional biomarkers, stool pathogens and environmental enteropathy indicators between 0 and 11 months were recorded. We used linear regression models to analyze associations of these indicators with height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WLZ) at 54-66 months (~5 years), and Poisson regression with robust standard errors to estimate risk ratios for stunting and underweight ~5 years, controlling for gender, first available weight, and income. Among the 237 infants followed longitudinally and evaluated at about 5 years of age, exclusive breastfeeding was short (median = 14 days). Complementary feeding started before 6 months with rice, bread, noodles, or sugary foods. Roots, dairy products, fruits/vegetables, and animal-source foods were provided later than recommended (9-12 months). Anemia (70.9%), deficiencies in iron (22.0%), zinc (80.0%), vitamin A (53.4%) and iodine (13.3%) were common. Most infants (>90%) presented with diarrhea and respiratory infections in their first year. At ~5 years, low WAZ (mean-1.91 ± 0.06) and LAZ (-2.11 ± 0.06) resulted in high prevalence of stunting (55.5%) and underweight (44.4%) but a relatively low rate of wasting (5.5%). While 3.4% had concurrent stunting and wasting ~5 years, 37.8% of children had coexisting stunting and underweight. A higher income and receiving formula or dairy products during infancy were associated with a higher LAZ ~5 years, but infant's history of hospitalizations and more respiratory infections were associated with lower LAZ and higher risk of stunting ~5 years. Infants' intake of commercial baby foods and higher serum-transferrin receptors were associated with higher WAZ and lower risk of underweight ~5 years. Presence of Campylobacter and fecal neopterin >6.8 nmol/L in the first year were associated with increased risk of underweight ~5 years. Growth indicators ~5 years were associated with poverty, inappropriate complementary feeding, and infections during the first year of life, which supports the early start of public health interventions for preventing growth delay ~5 years.

Back Cover: Use of a solid‐state nanopore for profiling the transferrin receptor protein and distinguishing between transferrin receptor and its ligand protein

DOI: 10.1002/elps.202200147 The cover picture shows the nanopore-induced monomerization of a protein dimer. The green and purple proteins are both serum transferrin receptor proteins (TfR). TfR is a dimeric protein, as shown in the far left of the picture. As TfR transits the nanopore, the high electric field (colored arrows) disrupts the secondary interactions of the protein and induces its monomerization. In the right of the picture, each TfR molecule is completely separated and exists in its monomeric form.

A new iron supplement: The chelate of pig skin collagen peptide and Fe2+ can treat iron-deficiency anemia by modulating intestinal flora.

Iron deficiency anemia (IDA) is one of the most common nutritional diseases encountered all over the world. Nowadays, oral iron supplementation is still the mainstay of IDA treatment. In this study, a new iron nutritional supplement named pig skin collagen peptides ferrous chelates (PSCP-Fe) was prepared, and its structure was characterized by the scanning electron microscopy, sykam amino acid analyzer and Fourier transform infrared spectroscopy (FTIR). The anti-IDA activity of PSCP-Fe was evaluated in low-Fe2+ diet-induced IDA in rats. 16S amplicon sequencing technology was then used to reveal the mechanism of PSCP-Fe against IDA. The results of amino acid analysis and FTIR showed that aspartic acid (Asp), arginine (Arg), histidine (His), glutamic acid (Glu), cystine (Cys), and lysine (Lys) residued in PSCP chelated readily with Fe2+ through their functional groups. PSCP-Fe treated reversed the hematology-related indexes, such as red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentrate (MCHC), serum ferritin (SF), serum hepcidin (HEPC) and serum transferrin receptor (TFR). And its regulatory action was better than that of FeSO4. Moreover, PSCP-Fe alleviated the hepatocyte apoptosis and necrosis, Fe2+ loss, and injury in IDA rats. In addition, PSCP-Fe could significantly retrace the disturbed profile of gut microbiota in IDA rats (p < 0.05) and significantly up-regulated the relative abundances of nine bacterial genus, including Lactobacillus, Alloprevotella, unclassified_of_Oscillospiraceae, and NK4A214_group (p < 0.05). It could also downgrade the relative abundances of Subdoligranulum and Coriobacteriaceae_UCG-002 (p < 0.05). The results of Spearman's correlation analysis and distance-based redundancy analysis (db-RDA) revealed that Subdoligranulum and Christensenellaceae_R-7_group may be potential microbial markers for effective PSCP-Fe action in the treatment of IDA. Overall, our results elucidate the interactions between gut bacteria and related cytokines and reveal the mechanisms underlying the anti-IDA effect of PSCP-Fe. They will thus provide a theoretical foundation for PSCP-Fe as a new iron nutritional supplement.

Regulation of iron absorption in infants

BackgroundIron programs in low- and middle-income countries often target infants and young children. Limited data from human infants and mouse models suggest that homeostatic control of iron absorption is incomplete in early infancy. Excess iron absorption during infancy may have detrimental effects. ObjectivesOur aims were to 1) investigate determinants of iron absorption in infants aged 3–15 mo and assess whether regulation of iron absorption is fully mature during this period and 2) define the threshold ferritin and hepcidin concentrations in infancy that trigger upregulation of iron absorption. MethodsWe performed a pooled analysis of standardized, stable iron isotope absorption studies performed by our laboratory in infants and toddlers. We used generalized additive mixed modeling (GAMM) to examine relationships between ferritin, hepcidin, and fractional iron absorption (FIA). ResultsKenyan and Thai infants aged 2.9–15.1 mo (n = 269) were included; 66.8% were iron deficient and 50.4% were anemic. In regression models, hepcidin, ferritin, and serum transferrin receptor were significant predictors of FIA, whereas C-reactive protein was not. In the model including hepcidin, hepcidin was the strongest predictor of FIA (β = -0.435). In all models, interaction terms, including age, were not significant predictors of FIA or hepcidin. The fitted GAMM trend of ferritin versus FIA showed a significant negative slope until ferritin of 46.3 μg/L (95% CI: 42.1, 50.5 μg/L), which corresponded to an FIA decrease from 26.5% to 8.3%; above this ferritin value, FIA remained stable. The fitted GAMM trend of hepcidin versus FIA showed a significant negative slope until hepcidin of 3.15 nmol/L (95% CI: 2.67, 3.63 nmol/L), above which FIA remained stable. ConclusionsOur findings suggest that the regulatory pathways of iron absorption are intact in infancy. In infants, iron absorption begins to increase at threshold ferritin and hepcidin values of ∼46 μg/L and ∼3 nmol/L, respectively, similar to adult values.

Use of a solid-state nanopore for profiling the transferrin receptor protein and distinguishing between transferrin receptor and its ligand protein.

A nanopore device is capable of providing single-molecule level information of an analyte as they translocate through the sensing aperture-a nanometer-sized through-hole-under the influence of an applied electric field. In this study, a silicon nitride (Six Ny )-based nanopore was used to characterize the human serum transferrin receptor protein (TfR) under various applied voltages. The presence of dimeric forms of TfR was found to decrease exponentially as the applied electric field increased. Further analysis of monomeric TfR also revealed that its unfolding behaviors were positively dependent on the applied voltage. Furthermore, a comparison between the data of monomeric TfR and its ligand protein, human serum transferrin (hSTf), showed that these two protein populations, despite their nearly identical molecular weights, could be distinguished from each other by means of a solid-state nanopore (SSN). Lastly, the excluded volumes of TfR were experimentally determined at each voltage and were found to be within error of their theoretical values. The results herein demonstrate the successful application of an SSN for accurately classifying monomeric and dimeric molecules while the two populations coexist in a heterogeneous mixture.

Spatial distribution and identifying biochemical factors affecting haemoglobin levels among women of reproductive age for each province in Indonesia: A geospatial analysis.

Anaemia is still a public health problem in Indonesia. The iron supplement program, known as Tablet Tambah Darah (Blood Add Tablet) has not yet produced optimal results. This study aimed to identify the cause of anaemia and the factors that influence it. Biochemical indicator data are haemoglobin (Hb), C-reactive protein (CRP), ferritin and serum transferrin receptor (sTfR) from 9,463 women of reproduction age. Data from the Basic Health Research (Riskesdas) project of 2013 were used for the study. ANOVA as well as global and local regression approaches (classical regression and geo-weighted regression) were used to compare the mean Hb and CRP values between provinces and to determine the factors that influence Hb concentrations. The results showed that the distribution of anaemia in Indonesia is uneven and not always caused by iron deficiency. The lowest Hb mean coupled with the highest iron deficiency was found in Papua, where there are high rates of parasitic infections. In contrast, the highest mean Hb coupled with low iron deficiency, and also low infection rates, was found in North Sulawesi. The Hb concentrations were significantly associated by ferritin, CRP and sTfR and there were varying magnitudes between provinces. Although anaemia is mainly influenced by the iron concentration, CRP, ferritin and sTfR can also affect it through their association with inflammatory reactions. Identification of all causes of anaemia in each province needs to be done in the future, while blanket iron supplementation should be reviewed.

Iron Deficiency Anemia: A Review Into Newer Insights

Many people globally suffer from iron deficiency. It is the most common cause of iron deficiency anemia IDA that has a devastating effect on infants and their mothers. It occurs when the body's iron storage, iron intake, and iron loss are all out of balance, making it impossible for erythropoiesis to function properly. Microcytic hypochromic anemia is the medical term for this condition. Thalassemia, anemia of chronic disease, and sideroblastic anemias are among the other possible causes of microcytic anemia. Iron parameters such as MCV, MCH and RDW are cost-effective and useful in the diagnosis of iron deficiency. After routine hematological tests like CBC and hemoglobin, serum ferritin is often used as a first diagnostic check. The total iron binding capacity, transferrin saturation, and the serum iron and serum transferrin receptor levels may be beneficial. Stainable iron may be necessary to confirm the diagnosis. High rates of prevalence have negative consequences for both health and the economy. IDA has been known for a while, yet there are still unresolved problems and room for improvement in the way this condition is managed. Every day, new directions in its diagnostic and treatment choices open.

Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance.

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. In the vastus lateralis and blood of severe COPD patients with/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance.

Is Helicobacter Pylori a Reason for Unexplained Iron Deficiency Anemia: A Systematic Review.

Iron deficiency anemia (IDA) is a worldwide public health problem affecting millions, with developing nations accruing a significant disease burden. Helicobacter pylori (H. pylori) has been proposed in many studies as a causative factor for unexplained iron deficiency anemia. In this systematic review, we searched PubMed, Google Scholar, and ScienceDirect to come up with five cross-sectional studies and five Randomized Controlled Trials (RCTs), which evaluated the association between H. pylori and unexplained iron deficiency anemia and the response of IDA to anti-H. pylori therapy. H. pylori eradication therapy included triple therapy (proton pump inhibitor, clarithromycin, amoxicillin) or quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) for 10-14 days. Quadruple therapy was used if there is a penicillin allergy or a local antibiotic resistance level of more than 15% to clarithromycin. The cross-sectional studies concluded that H. pylori infection was associated with low serum ferritin levels. The RCTs confirmed that H. pylori are associated with iron deficiency anemia by demonstrating improvement in markers of iron status (ferritin, hemoglobin, Mean Corpuscular Volume (MCV), serum transferrin receptor levels) with H. pylori eradication therapy. In a nutshell, this systematic review concludes that H. pylori testing and treatment must be considered as a differential diagnosis of unexplained IDA in all age groups and serves as a benchmark for more randomized clinical trials to prove causation.

Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.

Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.

Serum Soluble Transferrin Receptor and Transferrin Levels among Regular Blood Donors

Background: The study evaluated the effects of regular blood donation on serum transferrin and soluble transferrin receptor levels at Wenchi Methodist Hospital. Methods: This was a hospital-based cross-sectional study conducted at the Medical Laboratory Department of the Wenchi Methodist Hospital in the Bono Region of Ghana. A total of eighty-nine (89) venous blood samples from apparently healthy blood donors were analyzed. Complete blood count parameters were analyzed using an automated haematology analyzer and serum transferrin and transferrin receptor using ELISA. The data were analyzed using SPSS version 22.0. Results: Haemoglobin (p&lt;0.001) and HCT (p=0.004) were significantly lower among the regular blood donors compared with the first-time donors. Regular blood donors had relatively higher serum transferrin (p&lt;0.001) and soluble transferrin receptor levels (p&lt;0.001). A negative correlation was observed between Hb and serum transferrin (r=-0.552, p&lt;0.001), as well as Hb and serum soluble transferrin receptor (r=-0.552, p&lt;0.001). Remunerated donors had lower Hb (p=0.001) and HCT% (p=0.001) but a higher transferrin receptor (p=0.041) than non-remunerated donors. Conclusion: Regular blood donors had relatively lower erythrocyte parameters but higher serum transferrin and soluble transferrin receptors, indicating a possible reduction in serum iron and iron stores. Moderate negative correlations exist between Hb and both transferrin and soluble transferrin receptors. Again, remunerated donors had lower erythrocyte parameters but higher transferrin and soluble transferrin receptors than non-remunerated donors. Periodic assessment of iron parameters among regular blood donors is recommended. A future longitudinal study to assess the entire iron profile of regular blood donors is recommended. Doi: 10.28991/SciMedJ-2022-04-03-01 Full Text: PDF