Transferrin Research Articles

Erythropoietin as a prophylactic measure against anemia in critically ill patients: A combined prospective and retrospective study

Background & Objective: Critically sick patients often develop moderate to severe anemia, due to various factors. We tested the hypothesis that administering prophylactic recombinant human erythropoietin (rHuEPO) together with early identification and correction of iron deficiency anemia in traumatic brain injury patients would have a positive effect on the incidence of RBCs transfusions.
 Methodology: One hundred and seventeen head-trauma patients were enrolled. They received 40,000 units of prophylactic rHuEPO, starting on day three after admission and continuing at weekly intervals for 6 weeks, with follow-up of iron biomarkers. Any patient developing iron deficiency anemia was prescribed oral or intravenous iron supplement. The incidence of RBCs transfusion was recorded.
 Results: The number of RBCs transfusion was significantly less in the prospective group (27.35%) than the retrospective group (42.86%). Hemoglobin and hematocrit levels were significantly less in the first and second weeks after admission and then began to rise. Serum iron, transferrin saturation, and ferritin were at their lowest levels in the fourth week. Meanwhile, total iron binding capacity was higher in the fourth week and lower in the sixth.
 Conclusion: The administration of prophylactic rHuEPO with early discovery and correction of iron deficiency anemia resulted in a significant reduction in the incidence of RBCs transfusion in the head-trauma patients.
 Abbreviations: rHuEPO: recombinant human erythropoietin, RBC: red blood cell, ICU: intensive care unit, TBI: traumatic brain injury, GCS: Glasgow Coma Scale, APACHE: Acute Physiology and Chronic Health Evaluation
 Citation: Amer AF, Elatrozy HI, El Mourad MB. Erythropoietin as a prophylactic measure against anemia in critically ill patients: A combined prospective and retrospective study. Anaesth. pain intensive care 2022;26(5):633−639.
 DOI: 10.35975/apic.v26i5.1481

Combined analysis of lipidomics and transcriptomics revealed the key pathways and genes of lipids in light-sensitive albino tea plant (Camellia sinensis cv. Baijiguan).

Currently, the mechanism by which light-sensitive albino tea plants respond to light to regulate pigment synthesis has been only partially elucidated. However, few studies have focused on the role of lipid metabolism in the whitening of tea leaves. Therefore, in our study, the leaves of the Baijiguan (BJG) tea tree under shade and light restoration conditions were analyzed by a combination of lipidomics and transcriptomics. The leaf color of BJG was regulated by light intensity and responded to light changes in light by altering the contents and proportions of lipids. According to the correlation analysis, we found three key lipid components that were significantly associated with the chlorophyll SPAD value, namely, MGDG (36:6), DGDG (36:6) and DGDG (34:3). Further weighted gene coexpression network analysis (WGCNA) showed that HY5 TF and GLIP genes may be hub genes involved lipid regulation in albino tea leaves. Our results lay a foundation for further exploration of the color changes in albino tea leaves.

Substitution of carbonate by non-physiological synergistic anion modulates the stability and iron release kinetics of serum transferrin

Serum transferrin (sTf) is a bi-lobal protein. Each lobe of sTf binds one Fe3+ ion in the presence of a synergistic anion. Physiologically, carbonate is the main synergistic anion but other anions such as oxalate, malonate, glycolate, maleate, glycine, etc. can substitute for carbonate in vitro. The present work provides the possible pathways by which the substitution of carbonate with oxalate affects the structural, kinetic, thermodynamic, and functional properties of blood plasma sTf. Analysis of equilibrium experiments measuring iron release and structural unfolding of carbonate and oxalate bound diferric-sTf (Fe2sTf) as a function of pH, urea concentration, and temperature reveal that the structural and iron-centers stability of Fe2sTf increase by substitution of carbonate with oxalate. Analysis of isothermal titration calorimetry (ITC) scans showed that the affinity of Fe3+ with apo-sTf is enhanced by substituting carbonate with oxalate. Analysis of kinetic and thermodynamic parameters measured for the iron release from the carbonate and oxalate bound monoferric-N-lobe of sTf (FeNsTf) and Fe2sTf at pH 7.4 and pH 5.6 reveals that the substitution of carbonate with oxalate inhibits/retards the iron release via increasing the enthalpic barriers.

Rhizobium etli CFN42 proteomes showed isoenzymes in free-living and symbiosis with a different transcriptional regulation inferred from a transcriptional regulatory network.

A comparative proteomic study at 6 h of growth in minimal medium (MM) and bacteroids at 18 days of symbiosis of Rhizobium etli CFN42 with the Phaseolus vulgaris leguminous plant was performed. A gene ontology classification of proteins in MM and bacteroid, showed 31 and 10 pathways with higher or equal than 30 and 20% of proteins with respect to genome content per pathway, respectively. These pathways were for energy and environmental compound metabolism, contributing to understand how Rhizobium is adapted to the different conditions. Metabolic maps based on orthology of the protein profiles, showed 101 and 74 functional homologous proteins in the MM and bacteroid profiles, respectively, which were grouped in 34 different isoenzymes showing a great impact in metabolism by covering 60 metabolic pathways in MM and symbiosis. Taking advantage of co-expression of transcriptional regulators (TF’s) in the profiles, by selection of genes whose matrices were clustered with matrices of TF’s, Transcriptional Regulatory networks (TRN´s) were deduced by the first time for these metabolic stages. In these clustered TF-MM and clustered TF-bacteroid networks, containing 654 and 246 proteins, including 93 and 46 TFs, respectively, showing valuable information of the TF’s and their regulated genes with high stringency. Isoenzymes were specific for adaptation to the different conditions and a different transcriptional regulation for MM and bacteroid was deduced. The parameters of the TRNs of these expected biological networks and biological networks of E. coli and B. subtilis segregate from the random theoretical networks. These are useful data to design experiments on TF gene–target relationships for bases to construct a TRN.

Évaluation du fer sérique comme facteur prédictif d’une réponse de l’hémoglobine au traitement par fer injectable chez les patients hémodialysés chroniques

BackgroundThe detection and correction of iron deficiency are essential for the treatment of anemia in chronic hemodialysis patients. The aim of our study was to assess the ability of serum iron to predict hemoglobin response to intravenous iron supplementation in hemodialysis patients. MethodsIt is a retrospective study in 91 hemodialysis patients during 2016 at Clermont-Ferrand University Hospital for whom intravenous iron supplementation had been started. A responder patient was defined as an increase in hemoglobin greater than or equal to 1 g/dL/month and/or a decrease in the dose of erythropoiesis stimulating agent after two months of iron supplementation. ResultsIn responding patients, serum iron was significantly lower (6.7 ± 2.7 μmol/L) compared to non-responding patients (8.9±2.9 μmol/L; P<0.001). The positive response to iron supplementation was significantly associated with low serum iron (odds ratio = 0.58 [0.42–0.81]; P=0.002) in a logistic regression model taking into account ferritin, transferrin saturation coefficient, dose variation monthly iron and erythropoiesis stimulating agent and the duration of dialysis. The area under the receiver operating characteristic curve of serum iron, ferritin and transferrin saturation coefficient to predict the response to iron supplementation were 0.72, 0.51 and 0.64, respectively (serum iron versus ferritin [P=0.006] and serum iron versus transferrin saturation coefficient [P=0.04]). The sensitivity for serum iron below 7.5 μmol/L was better than that for ferritin below 86 ng/mL (P<0.001) and the specificity for serum iron below 7.5 μmol/L was better than that for TSC less than 19% (P=0.02). ConclusionSerum iron below 7.5 μmol/L can predict the success of the response to iron supplementation in chronic hemodialysis patients.

Effect of Enteral and Parenteral Nutrition Support on Pulmonary Function in Elderly Patients with Chronic Obstructive Pulmonary Disease Complicated by Respiratory Failure.

Objective To investigate the effect of enteral and parenteral nutrition support (EPNS) on pulmonary function in elderly patients with chronic obstructive pulmonary disease (COPD) complicated by respiratory failure (RF). Methods A total of 127 patients who underwent treatment for elderly patients with COPD complicated by RF in our hospital from February 2020 to May 2022 were collected for a retrospective analysis. There were 41 patients with enteral nutrition support (group A), 46 with parenteral nutrition support (group B), and 40 with EPNS (group C). The levels of serum albumin (ALB), prealbumin (PA), serum hemoglobin (Hb), and serum transferrin (TRF) were measured before and after nutritional support in the three groups, and the changes in pulmonary function of patients were compared. The changes in the levels of inflammatory factors and markers of oxidative stress (OS) in serum were also detected, and the incidence of adverse reactions and length of stay (LOS) were counted. Results ALB, PA, Hb, and TRF levels were increased in all 3 groups after nutritional support, with the highest in group C (P < 0.05). Similarly, lung function was improved in all 3 groups and inflammatory factor levels and OS were suppressed, also most dramatically in group C (P < 0.05). There was no difference in the incidence of adverse reactions among the 3 groups, and the LOS in group C was shorter than those in groups A and B (P < 0.05). Conclusion EPNS can effectively improve the lung function of patients with COPD combined with RF and reduce the inflammation and OS damage. It can effectively improve the therapeutic effect of patients and has great application prospects in the treatment of COPD combined with RH in the future.

Transferrin Aptamers Increase the In Vivo Blood-Brain Barrier Targeting of Protein Spherical Nucleic Acids.

The systemic delivery of exogenous proteins to cells within the brain and central nervous system (CNS) is challenging due to the selective impermeability of the blood-brain barrier (BBB). Herein, we hypothesized that protein delivery to the brain could be improved via functionalization with DNA aptamers designed to bind transferrin (TfR) receptors present on the endothelial cells that line the BBB. Using β-galactosidase (β-Gal) as a model protein, we synthesized protein spherical nucleic acids (ProSNAs) comprised of β-Gal decorated with TfR aptamers (Transferrin-ProSNAs). The TfR aptamer motif significantly increases the accumulation of β-Gal in brain tissue in vivo following intravenous injection over both the native protein and ProSNAs containing nontargeting DNA sequences. Furthermore, the widespread distribution of β-Gal throughout the brain is only observed for Transferrin-ProSNAs. Together, this work shows that the SNA architecture can be used to selectively deliver protein cargo to the brain and CNS if the appropriate aptamer sequence is employed as the DNA shell. Moreover, this highlights the importance of DNA sequence design and provides a potential new avenue for designing highly targeted protein delivery systems by combining the power of DNA aptamers together with the SNA platform.

Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients.

PurposeThis study investigated the associations of peripheral iron status with different manifestations of restless legs syndrome (RLS), including leg movements (LMs) on polysomnography (PSG), disease severity, and impact on patients.Patients and MethodsIn this cross-sectional study, 108 patients with RLS were enrolled at Sir Run Run Shaw Hospital’s Center for Sleep Medicine. Demographic information, disease characteristics, RLS severity, and impact on patients were assessed through a semi-structured questionnaire. Peripheral iron indicators [serum ferritin, iron, and transferrin concentrations; unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC); transferrin saturation (TSAT)] were measured following PSG to assess sleep stages, respiratory events, microarousals and LM parameters. Data from patients with and without ferritin concentration < 50 µg/L were compared in crude analyses, and Spearman correlations of other iron indicators with RLS data were examined. An ordinal logistic regression model was used to adjust for age, sex, body mass index, years of education, age at the time of RLS onset, prior treatment (yes/no), C-reactive protein (CRP)/hemoglobin level, total sleep time and apnea-hypopnea index.ResultsMultivariate analysis showed that periodic LMs during sleep (PLMS) and other LM parameters were significantly associated with a ferritin concentration < 50 µg/L, UIBC, TIBC, and serum transferrin concentration, but not serum iron or TSAT. By contrast, the severity and impact of RLS were not associated with a ferritin concentration < 50 µg/L or other peripheral iron indicators in the multivariate model.ConclusionIn this study, peripheral iron status was associated mainly with motor components (LMs on PSG) rather than sensory components (severity and impact of RLS) after adequately controlling for potential confounders, such as CRP and hemoglobin levels. Commonly used peripheral iron metabolism indicators may therefore not be ideal biomarkers of RLS severity or impact on patients.

MAGNETIC RESONANCE IMAGING R2* AS A METHOD TO MONITOR IRON OVERLOAD IN PATIENTS UNDERGOING THERAPEUTIC PHLEBOTOMY FOR HEREDITARY HEMOCHROMATOSIS

: to determine if there was a reduction in liver iron overload due to therapeutic phlebotomy as a treatment for iron overload in patients with hereditary hemochromatosis. : Through a retrospective observational study, we analyzed Magnetic Resonance imaging (MRI) R2* of 5 patients, before and after phlebotomy treatment, who are in medical follow-up for hereditary hemochromatosis. Data were collected from a hospital database and included patients with the diagnosis of hereditary hemochromatosis, with two MRI R2* (one before and one after treatment with phlebotomy), and with serum ferritin and transferrin saturation (TS) data collected in a period next to each MRI. The mean number of phlebotomies between MRIs was seven for each patient. The mean interval between MRIs was 25.6 months (maximum of 66 and minimum of 12). On the first MRI, four patients presented liver iron overload (80%) and 1 did not (20%); the iron overload was severe in all four patients. On the second MRI, all patients with iron overload in the first showed a large reduction to mild overload in the deposits. The only patient who did not have it continued without an iron deposit in the liver. No patient had pancreatic iron deposits at the first or second MRI. One patient initially presented a splenic deposit (20%), which was not evidenced in the second. One liver (20%) had mild hepatic steatosis at the first MRI, which remained mild at the second. No patient developed steatosis during the study period. The mean serum ferritin on the first MRI period was 521.1 (minimum of 139 and maximum of 1000); over the second MRI, the average was 218.4 (minimum of 83 and maximum of 401). All patients showed a reduction in serum ferritin between images. The average reduction was 46.8% (minimum of 5.0% and maximum of 86.5%). The average TS in the first MRI period was 38.35% (minimum of 23% and maximum of 53%) and in the second, 37.47% (minimum of 25% and maximum of 42%). Three patients (60%) had an increase in TS, despite a decrease in serum ferritin. All patients had values within the normal range for ALT and AST in the study period. : Liver iron overload is one of the most serious complications of hereditary hemochromatosis since it is one of the main iron storage organs and the first one to show iron overload. It mayslowly lead to irreversible hepatic damage, such as cirrhosis, or even hepatocellular carcinoma, in addition to multiple organ complications. Measurement of the liver concentration of iron may guide physicians to have better decisions regarding when to initiate or stop therapeutic phlebotomy as a therapy in hereditary hemochromatosis. MRI R2* can be used for detection and quantification of liver iron content, being proposed as a non-invasive method to guide therapy. However, the exact correlation between liver iron content, number, and interval of phlebotomies prescribed, and laboratory findings are not yet well established. : Periodic phlebotomy demonstrated to be an efficient way to reduce body overload, especially liver deposits, as seen in MRI R2* images. In agreement with the literature, the liver accumulates iron before other abdominal organs, such as the pancreas and spleen. Serum ferritin appears to be a better marker for liver iron overload reduction in patients undergoing phlebotomy for hereditary hemochromatosis than transferrin saturation.

Transcriptomic Analysis to Unravel Potential Pathways and Genes Involved in Pecan (Carya illinoinensis) Resistance to Pestalotiopsis microspora.

Fruit black spot (FBS), a fungal disease of pecan (Carya illinoinensis (Wangenh) K. Koch) caused by the pathogen Pestalotiopsis microspora, is a serious disease and poses a critical threat to pecan yield and quality. However, the details of pecan responses to FBS infection at the transcriptional level remain to be elucidated. In present study, we used RNA-Seq to analyze differential gene expression in three pecan cultivars with varied resistance to FBS infection: Xinxuan-4 (X4), Mahan (M), and Wichita (W), which were categorized as having low, mild, and high susceptibility to FBS, respectively. Nine RNA-Seq libraries were constructed, comprising a total of 58.56 Gb of high-quality bases, and 2420, 4380, and 8754 differentially expressed genes (DEGs) with |log2Fold change| ≥ 1 and p-value < 0.05 were identified between M vs. X4, W vs. M, and W vs. X4, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analyses were performed to further annotate DEGs that were part of specific pathways, which revealed that out of 134 total pathways, MAPK signaling pathway, plant–pathogen interaction, and plant hormone signal transduction were highly enriched. Transcriptomic profiling analysis revealed that 1681 pathogen-related genes (PRGs), including 24 genes encoding WRKY transcription factors, potentially participate in the process of defense against Pestalotiopsis microspora infection in pecan. The correlation of WRKY TFs and PRGs was also performed to reveal the potential interaction networks among disease-resistance/pathogenesis-related genes and WRKY TFs. Expression profiling of nine genes annotated as TIFY, WRKY TF, and disease-resistance protein-related genes was performed using qRT-PCR, and the results were correlated with RNA-Seq data. This study provides valuable information on the molecular basis of pecan–Pestalotiopsis microspora interaction mechanisms and offers a repertoire of candidate genes related to pecan fruit response to FBS infection.

Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients With Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation

ObjectiveAggressive iron substitution in hemodialysis (HD) patients leads to iron overload. The association between liver siderosis and fibrosis is still debatable. We studied the association of liver siderosis with liver fibrosis in HD patients. Furthermore, we studied the performance of liver stiffness measurements (LSMs) in identifying advanced liver fibrosis. We investigated the performance of biochemical indicators of iron status in identifying advanced liver fibrosis. MethodsFifty-five HD patients (average HD duration 6 ± 2 years) with hyperferritinemia secondary to intravenous iron supplementation (weakly iron dose 252.7 ± 63 mg; median blood transfusions 3 [2-5]) were recruited. The liver fibrosis grade was determined with Fibroscan, aminotransferase-to-platelet ratio index (APRI), and Fib-4 index. Liver iron concentration (LIC) was estimated with magnetic resonance imaging (MRI). Iron parameters and liver function biochemical indicators were also assessed. ResultsThe median serum ferritin and transferrin saturation (TSAT) were 3531 μg/L and 77%, respectively. 34.5%, 20%, and 45.5% of the patients showed mild, moderate, or severe liver siderosis, respectively. All patients with severe liver siderosis showed advanced liver fibrosis. Patients with severe liver siderosis and advanced liver stiffness showed higher serum iron, TSAT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin, APRI, and Fib-4 index scores than those with mild liver siderosis. Serum iron and TSAT showed good utility in identifying advanced liver fibrosis determined with Fibroscan, APRI, and Fib-4 index. Liver stiffness exhibited good utility in identifying advanced liver fibrosis diagnosed with APRI and Fib-4 index. ConclusionsHigh weekly intravenous iron dose associated with severe hyperferritinemia, high serum iron, and TSAT might lead to severe liver siderosis and concomitant liver fibrosis in HD patients. Serum iron, TSAT, Fibroscan, Fib-4, and APRI scores might offer noninvasive tools for identifying advanced liver fibrosis in those patients.

Application strategy and effect analysis of nutritional support nursing for critically ill patients in intensive care units.

We investigate nutritional support and nursing status of critical patients in intensive care units (ICUs) to understand the latest nutritional support guidelines’ implementation by clinical medical staff; identify problems in nutritional support and nursing for these patients, analyze causes, and present suggestions; and provide a clinical/theoretical bases to improve nutritional support implementation and nursing strategies for them. Clinical case information of 304 critically ill ICU patients admitted from July 2017 to July 2021 was analyzed. They were divided into the experimental (nutritional support) and control (no nutritional support) groups to compare their laboratory indicators, 28-day case fatality rate, and infection incidence. Least significant difference was used for postanalysis of statistically significant items to obtain pairwise comparisons. Nutrition support strategies for ICU patients are consistent with guidelines but have an implementation gap. No statistically significant differences were found in hemoglobin (HB), total serum protein (TP), serum albumin (ALB), transferrin (TF), prealbumin (PA), and total lymphocyte count (TLC) in experimental group patients compared with the control group within 24 hours (before nutritional support, P > .05). No statistically significant differences were also found in HB, TP, TLC, and ALB between the enteral nutrition + parenteral nutrition (EN + PN), total EN (TEN), total PN (TPN), and control groups on admission day 7 (after nutritional support, P > .05), while statistically significant differences existed between PA and TF (P < .05). TF of patients supported by TEN was higher (statistically significant difference, P < .05). PA in patients receiving TEN and EN + PN support was higher than in control group patients (statistically significant difference, P < .05). Compared with the control group, in experimental group patients, infection incidence was significantly lower (40.2% vs 62.9%, P < .05); incidence of complications was lower, but not statistically significant (40.2% vs 57.1%, P > .05); and 28-day mortalities were significantly lower (26.7% vs 45.7%, P < .05). Nutritional support can reduce hospitalization complications and 28-day mortality in critical patients, but its implementation must be standardized. Especially for patients with gastrointestinal dysfunction, personalized/standardized nutrition strategies and nursing procedures are needed when PN support is applied, and training of clinical medical staff should be strengthened to improve nutrition support’s efficiency.

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.

Erythropoietin as a prophylactic measure against anemia in critically ill patients: A combined prospective and retrospective study.

Background: The aim of this study is to test the hypothesis that administering prophylactic recombinant human erythropoietin (rHuEPO) together with early identification and correction of iron deficiency anemia in traumatic brain injury patients would have an effect on the incidence of RBCs transfusion as a primary outcome.&#x0D; Methodology: One hundred and seventeen head-trauma patients were enrolled. They received 40,000 units of prophylactic rHuEPO, starting on day three after admission and continuing at weekly intervals for 6 weeks, with follow-up of iron biomarkers. Any patient developing iron deficiency anemia was prescribed oral or intravenous iron. The incidence of RBCs transfusion was recorded.&#x0D; Results: The incidence of RBCs transfusion was significantly less in the prospective group (27.35%) than the retrospective group (42.86%). Hemoglobin and hematocrit levels were significantly less in the first and second weeks after admission and then began to elevate. Serum iron, transferrin saturation, and ferritin were at their lowest levels in the fourth week. Meanwhile, total iron binding capacity was higher in the fourth week and lower in the sixth.&#x0D; Conclusion: The administration of prophylactic rHuEPO with early discovery and correction of iron deficiency anemia resulted in a significant reduction in the incidence of RBCs transfusion in head-trauma patients.

Identification and Characterization of Elevated Expression of Transferrin and Its Receptor TfR1 in Mouse Models of Depression.

Depression has become one of the severe mental disorders threatening global human health. In this study, we first used the proteomics approach to obtain the differentially expressed proteins in the liver between naive control and chronic social defeat stress (CSDS) induced depressed mice. We have identified the upregulation of iron binding protein transferrin (TF) in the liver, the peripheral blood, and the brain in CSDS-exposed mice. Furthermore, bioinformatics analysis of the Gene Expression Omnibus (GEO) database from various mouse models of depression revealed the significantly upregulated transcripts of TF and its receptor TfR1 in multiple brain regions in depressed mice. We also used the recombinant TF administration via the tail vein to detect its permeability through the blood-brain barrier (BBB). We demonstrated the permeability of peripheral TF into the brain through the BBB. Together, these results identified the elevated expression of TF and its receptor TfR1 in both peripheral liver and the central brain in CSDS-induced depressed mice, and peripheral administration of TF can be transported into the brain through the BBB. Therefore, our data provide a compelling information for understanding the potential role and mechanisms of the cross-talk between the liver and the brain in stress-induced depression.

Role of Fe, Transferrin and Transferrin Receptor in Anti-Tumor Effect of Vitamin C.

Simple SummaryHigh-dose vitamin C (VC) inhibits cell proliferation in a variety of tumors, which is mediated by ROS. Iron is an important factor in the Fenton reaction, in which H2O2 reacts with ferrous iron to produce hydroxyl radicals, which may enhance the killing of tumor cells. In this study, we investigated the roles of iron level and the mainly pathway of iron uptake-TF/TFR system on VC-induced cytotoxicity. We conducted a preliminary evaluation of the potential value of 68Ga-citrate imaging in the anti-tumor therapy of VC combined with iron supplementation.High-dose vitamin C (VC) exhibits anti-tumor effects, and the cytotoxicity of VC is correlated with oxidative stress. However, iron, as a redox metal, plays an important effect in redox cycling and free radical formation in cells. This study addresses the role of iron ion in the cytotoxicity of VC. We found that iron supplementation increases the anti-tumor effect of VC, which was influenced by the cellular iron uptake pathway–transferrin (TF)/transferrin receptor (TFR) system. The TFR expression of tumors can be assessed by 68Ga-citrate PET imaging, and it would be helpful to screen out the tumor type which is more sensitive to VC combined with an iron supplementation treatment.

Association of iron-related biomarkers with severity and mortality in COVID-19 patients

BackgroundNutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. Materials and methodsA total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. ResultsIn cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden’s J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. ConclusionOur study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

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.

Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis.

BackgroundThe pathogenic mechanisms of early-onset osteoporosis caused by WNT1 and PLS3 mutations are incompletely understood and diagnostic biomarkers of these disorders are limited. Recently, lipocalin-2 has been recognized as an osteokine involved in bone development and homeostasis. However, the role of lipocalin-2 in WNT1 and PLS3 osteoporosis is unknown.ObjectiveWe aimed to investigate if plasma lipocalin-2 could be utilized as a biomarker for WNT1 and PLS3 osteoporosis and to evaluate the association between lipocalin-2 and other parameters of bone metabolism.MethodsWe measured plasma lipocalin-2 in 17 WNT1 and 14 PLS3 mutation-positive patients and compared them to those of 34 mutation-negative (MN) healthy subjects. We investigated possible associations between lipocalin-2 and several bone biomarkers including collagen type I cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), type I procollagen intact N-terminal propeptide (PINP), intact and C-terminal fibroblast growth factor 23 (FGF23), dickkopf-1 (DKK1) and sclerostin as well as parameters of iron metabolism (iron, transferrin, transferrin saturation, soluble transferrin receptor and ferritin).ResultsWe found no differences in plasma lipocalin-2 levels in WNT1 or PLS3 patients compared with MN subjects. However, lipocalin-2 was associated with C-terminal FGF23 in WNT1 patients (r=0.62; p=0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (r=0.80; p<0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (r=0.72; p=0.001).ConclusionWe conclude that plasma lipocalin-2 is not altered in WNT1 or PLS3 mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.

Impaired pancreatic beta-cell function after a single dose of oral iron: A before-and-after (pre-post) study.

Although in vitro and animal studies have shown that iron loading in pancreatic beta cells impairs insulin secretion, no human studies have documented the acute effects of oral iron on beta-cell insulin secretory capacity. In the present study, we determined beta-cell insulin secretory capacity at baseline and after a single oral dose of iron (ferrous sulphate, 120 mg elemental iron) in healthy male individuals. Fifteen healthy male volunteers underwent an oral glucose tolerance test (OGTT) to document baseline glucose tolerance and insulin secretion kinetics (baseline OGTT). One week later, the same subjects underwent a second OGTT, 2 h after an oral dose of ferrous sulphate (120 mg of elemental iron) (post-iron OGTT). Changes in disposition index, insulin secretion kinetics, glucose tolerance, insulin resistance, insulin clearance and iron-related parameters in serum were determined. Compared to baseline OGTT, the areas under the curve (AUC) for serum iron and transferrin saturation increased by 125% and 118%, respectively, in the post-iron OGTT. The disposition index decreased by 20% (p = 0.009) and the AUC for glucose concentrations increased by 5.7% (p < 0.001) during the post-iron OGTT. The insulin secretion rate was marginally lower during the first hour (-3.5%, p = 0.63), but became significantly higher during the second hour (22%, p = 0.005) of the post-iron OGTT. Insulin resistance and insulin clearance rate were not affected by iron intake. The decrease in disposition index and glucose tolerance observed after the oral dose of iron points to an acute iron-induced impairment in pancreatic beta-cell insulin secretory capacity.