Transferrin Receptor Levels Research Articles

3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells

Ferroptosis is a cell death mechanism characterized by intracellular iron accumulation and lipid peroxidation. Effects of uremic toxins on ferroptosis in the kidney are not well understood. We investigated whether protein-bound uremic toxins induce ferroptosis, resulting in cell death, using the bilateral ureteral obstruction (BUO) mouse model and kidney cells. In BUO mice, we observed elevated lipid peroxidation, increased iron concentration, and decreased glutathione peroxidase 4 (GPX4) expression. Levels of transferrin receptor 1 and system Xc-, which are involved in iron transport and storage, were also elevated, while those of ferritin heavy and light chains (FHC and FLC) were reduced. Treatment of HK-2 and NRK49F kidney cells with CMPF decreased GSH levels and the expression of GPX4, FHC, and FLC, and increased levels of ROS, lipid peroxidation, and intracellular iron concentration. CMPF-induced and erastin-induced decreases in GPX4 levels and increases in Bax and cytochrome C levels were counteracted by ferrostatin-1 pretreatment. However, GPX4 mRNA levels, protein abundance, or promoter activity were not restored by Z-VAD-FMK, a multi-caspase inhibitor. These results suggest that ferroptosis induced by CMPF treatment induces apoptosis, and inhibition of ferroptosis reduces apoptosis, suggesting that ferroptosis plays a role in triggering cell death by apoptosis.

Soluble Transferrin Receptor, Antioxidant Status and Cardiometabolic Risk in Apparently Healthy Individuals.

Body iron excess appears to be related to insulin resistance and cardiometabolic risk and increased oxidative stress might be involved in this relationship. Very few studies have described the association between soluble transferrin receptor (sTfR) levels and cardiometabolic risk in the general population or antioxidant status. There were 239 subjects (20-65 years old) included in this cross-sectional study. Linear regressions adjusting for BMI, menopausal status, insulin resistance (HOMA-IR), physical inactivity, alcohol intake and subclinical/chronic inflammation were used to describe the association between sTfR, total antioxidant capacity (TAC), and measures of cardio-metabolic risk. sTfR levels were positively associated with TAC in men (βeta [95% confidence interval ]: 0.31 [0.14 to 0.48]) and women (βeta = 0.24 [0.07 to 0.40]) in non-adjusted and adjusted models (p < 0.05). In men, sTfR levels were inversely associated with waist circumference (βeta [95% confidence interval]: -1.12 [-2.30 to -0.22]) and fasting glucose (-2.7 (-4.82 to -0.57), and positively with LDL cholesterol (12.41 (6.08 to 18.57) before and after adjustments for confounding variables. LDL cholesterol had a significant and positive association with TAC in non-adjusted and adjusted models in men (p < 0.05). sTfR levels are significantly associated with antioxidant status and a few specific cardio-metabolic risk variables, independently of covariates that included serum ferritin and hepcidin. This might imply that iron biomarkers in regard to cardiometabolic risk reflect physiological contexts other than iron metabolism.

New Insights into the Physiology of Iron Transport: An Interdisciplinary Approach

The TransCure project entitled 'Iron Transporters DMT1 and FPN1' took an interdisciplinary approach combining structural biology, chemistry and physiology to gain new insights into iron transport. Proteins studied included Divalent Metal Transporter 1 (DMT1, SLC11A2), enabling the import of Fe2+ into the cytoplasm, and the iron efflux transporter Ferroportin (FPN1, SLC40A1). The physiology and pathophysiology, and the mechanisms underlying iron transport in the gut, across the placenta and in bone were investigated. Small molecule high-throughput screening was used to identify improved modulators of DMT1. The characterization of DMT1 inhibitors have provided first detailed insights into the pharmacology of a human iron transport protein. In placental physiology, the identification of the expressional and functional alterations and underlying mechanisms in trophoblast cells clarified the association between placental iron transport by DMT1/FPN1 and gestational diabetes mellitus. In bone, iron metabolism was found to differ between cells of the monocyte/ macrophage lineages, including osteoclasts. Osteoclast development and activity depended on exogenous iron, the expression of high levels of the transferrin receptor (TFR) and low levels of FPN1 suggesting the expression of an “iron storage” phenotype by these cells. The principles and main findings of the TransCure studies on transmembrane iron transport physiology are summarized in this review.

Activated AMPK mitigates diabetes-related cognitive dysfunction by inhibiting hippocampal ferroptosis

Clinical and preclinical interest in Type 2 diabetes (T2D)-associated cognitive dysfunction (TDACD) has grown in recent years. However, the precise mechanisms underlying TDACD need to be further elucidated. Ferroptosis was reportedly involved in neurodegenerative diseases and diabetes-related organ injuries; however, its role in TDACD remains elusive. In this study, mice fed with a high-fat-diet combined with streptozotocin (HFD-STZ) were used as a T2D model to assess the role of ferroptosis in cognitive dysfunction. We found that ferroptosis was mainly activated in hippocampal neurons but not in microglia or astrocytes. Accordingly, increased levels of transferrin receptor and decreased levels of ferritin, GPX4, and SLC7A11 were observed in hippocampal neurons. In addition, pre-treatment with liproxstatin-1, a ferroptosis inhibitor, attenuated iron accumulation and oxidative stress response, which resulted in improved cognitive function in the HFD-STZ group. Furthermore, we found that p-AMP-activated protein kinase (AMPK) was decreased in the HFD-STZ group. Pre-treatment with AMPK agonist increased the expression of AMPK and GPX4, but decreased lipocalin 2 (LCN2) in the hippocampus that resulted in improved spatial learning ability in the HFD-STZ group. Taken together, we found that activation of neuronal ferroptosis in the hippocampus contributed to cognitive impairment of HFD-STZ mice. Furthermore, AMPK activation may reduce hippocampal ferroptosis, and consequently improve cognitive performance in diabetic mice.

Antiviral Response and HIV-1 Inhibition in Sickle Cell Disease

BACKGROUND: A number of host restriction factors controls HIV-1 infection. While many of these factors have been investigated in vitro, their role in controlling HIV-1 infection in vivo remains to be elucidated. Here, we investigate a naturally occurring HIV-1 restriction in Sickle cell disease (SCD), a hereditary disorder characterized by sickle cell hemoglobin polymerization and red blood cells hemolysis. We previously showed that SCD PBMCs express higher levels of ferroportin (FPN), and that reduced intracellular iron leads to the upregulation of antiviral restriction factors. Previously, HIV-1 infection was shown to inversely correlate with the expression levels of transferrin receptor (TFR), a marker of reduced intracellular iron. Iron chelation also potently inhibits HIV-1 replication as shown by us and others. Thus, iron metabolism is intrinsically connected to the HIV-1 infection and disease progression. Our study in vitro suggests that SCD environment leads to the antiviral state of T cells and macrophages, and suppression of HIV-1 infection. Here we analyzed HIV infection of SCD mice using mouse adapted EcoHIV and compared antiviral factors in SCD mouse spleenocytes and human SCD PBMCs. METHODS: The study was approved by Howard University IRB and IACUC committees. Townes SCD mice carrying human normal α (hα) and sickle hemoglobin beta (βS) genes and control Townes mice carrying human normal hα and βA genes were used in the study. EcoHIV virus obtained from David Volsky (Albert Einstein University) was constructed in pNL4-3 vector with the substitution of gp120 with the envelope-coding gp80 region from ectopic MLV. Whole blood samples were obtained from 9 SCD patients and 9 healthy individuals. RNA Seq analysis was conducted on Illumina® NextSeq 500 and the data were mapped and analyzed using Dragen software. Normalized gene counts were used for gene set enrichment analysis (GSEA) and Gene ontology (GO) analysis. RNA expression was measured by quantitative RT-PCR (Roche). Protein expression in mouse splenocytes was determined by ELISA. RESULTS: Infection of control mice with EcoHIV virus, which contained MLV envelope and was able to infect mouse cells, led to robust viral replication in spleen at 7 days post infection, as detected by the expression of HIV-1 Nef mRNA (Fig. 1) and Gag mRNA. We also detected HIV-1 p24 in splenic tissue. Comparing to the control, SCD mice showed significantly reduced EcoHIV replication both at the levels of RNA expression (Figs 1) and p24 production. GSEA analysis against the 72 genes that included all known HIV-1 restriction factors revealed strong enrichment of these genes in the human activated SCD PBMCs compared to the activated control PBMCs (Fig.2). These genes included APOBEC3A, HMOX1, CH25H, IFIT3, CDKN1A, APOBEC3B, IFITM3, SAMHD1 and TSPO. GSEA analysis also showed upregulation of several pathogen-associated molecular patterns sensing genes including NOD1, NLRC4, TRL7 and TLR9 in human PBMCS. In SCD mice splenocytes, we detected overexpression of FPN, and transferrin receptor (Tfr) genes indicating upregulation of iron metabolism similar to previously observed in human SCD PBMCs. In mouse splenocytes we detected upregulation of CDKN1A, HMOX1, IFITM3, CH25H and TSPO mRNAs. Protein expression analysis showed upregulation of FPN, TFR, HO-1, APOBEC, CH25H, IFIT3 and TSPO in SCD mouse splenocytes. CONCLUSION: Together, these data reveal, for the first time, that HIV-1 infection is suppressed in vivo in SCD mouse infected with the mouse-adapted EcoHIV. SCD mouse splenocytes expressed higher levels of FPN and TFR, and exhibited higher expression of antiviral factor, which were also observed in human SCD PBMCs. The observed upregulation of similar sets of antiviral factors in SCD PBCMs and SCD mice splenocytes suggests that these factors upregulation might be driven by the SCD-related processes such as hemolysis. Taken together, our findings point to a novel mechanism of upregulation of antiviral factors mediated by SCD that included induction of antiviral, heme- and iron- regulatory pathways. ACKNOWLEDGEMENTS: We thank Dr. David Volsky for the gift of EcoHIV and the George Washington University SPH Genomics Core for library preparation and sequencing. This work was supported by NIH grants 1R01HL125005, 5U54MD007597, 1P30AI117970-06 and 1SC1HL150685. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.

Effect of hemoglobin extracted from Tegillarca granosa on iron deficiency anemia in mice

Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. This study was aimed to evaluate the therapeutic effects of hemoglobin from Tegillarca granosa (T. granosa) on IDA in mice. Mice were randomly divided into five groups: a normal control group, an anemia model group, a positive (FeSO4) control group, a low-dose and high-dose hemoglobin groups. After 4-week iron supplements administration, it was observed that hemoglobin at 2.0 mg iron/kg body weight had better restorative effective on IDA mice than that of FeSO4 with regard to routine blood parameters and serum biochemical indicators. Meanwhile, the IDA-caused alterations of organ coefficients and liver morphology were ameliorated in mice after hemoglobin supplementation in a dose-dependent manner. Further correlation analysis of indicators showed that serum ferritin (iron storage protein) and soluble transferrin receptor (cellular iron uptake membrane glycoprotein) were susceptible to iron deficiency, indicating possibledisorder of iron metabolism caused by IDA. And levels of serum ferritin and soluble transferrin receptor were restored after administration of hemoglobin. These findings confirmed the safety and effectiveness of T. granosa derived hemoglobin in alleviating IDA in mice, suggesting its great potential as an alternative for iron supplementation.

Formulation and Effect of Iron Fortified Instant Bose Corn on Addressing Anemia among Adolescent Girls in Kupang, Indonesia.

This study aimed to develop Fe-fortified instant Bose corn (IBC), a traditional Timorese food, as a strategy to address anemia among adolescent girls in Kupang, Indonesia. Instant corn and cowpea grits were made to shorten the preparation time with various times of soaking (IBC1=10 min; IBC2=15 min; IBC3=20 min) to select the best formula. The selected IBC was then fortified with NaFeEDTA·3H2O and nutrient content was evaluated. In the intervention study, a pre-post controlled trial was applied to 40 anemic adolescent girls aged 16∼19 years. Subjects with severe anemia (Hb=8.5∼10.4 g/dL) received the fortified selected IBC, whereas those with moderate anemia (Hb=10.5∼11.5 g/dL) received the unfortified selected IBC. A total of 100 g IBC were provided three times/week for 2 months. The hemoglobin and soluble transferrin receptor (sTfR) levels were measured at baseline and endline, respectively. IBC3 produced the highest acceptance level as compared to other formulas. The fortified IBC3 met 127.4% recommended dietary allowances for iron. Moreover, both fortified and unfortified IBC3 significantly increased the hemoglobin levels of adolescent girls with the higher improvement found in the group of fortified IBC3 (1.73±1.21 g/dL; P<0.05). However, the beneficial effects of the fortified IBC3 could not be observed on sTfR levels. Since the effect on Hb levels was significant with less effect, the intervention of IBC3 for only 2 months did not adequate to improve sTfR levels. Nevertheless, this study suggests that Fe-fortified IBC may be effective in preventing anemia among adolescent girls in Kupang, Indonesia.

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.

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

Iron Deficiency and Incident Infections among Community-Dwelling Adults Age 70 Years and Older: Results from the DO-HEALTH Study.

To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults. Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial. 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up. Iron deficiency was defined as soluble transferrin receptor (sTfR) levels > 28.1 nmol/l and anemia as hemoglobin levels < 120 g/l for women and 130 g/l for men. We applied negative binomial mixed effects regression models with random effects for countries, and controlling for treatment allocation, age, sex, body mass index, polypharmacy, number of comorbidities, smoking status, living situation, alcohol intake, frailty status, and physical activity levels. A pre-defined stratified analysis was performed to explore if the associations between iron deficiency and infections were consistent by baseline anemia status. In total, 2141 participants were included in the analyses (mean age 74.9 years, 61.5% of women, 26.8% with iron deficiency). Across all participants, baseline iron deficiency was not associated with incident overall infections, but was associated with a 63% greater rate of incident severe infections requiring hospitalization (incidence rate ratio [IRR] 1.63, 95% Confidence Interval [CI] 1.11-2.41, p=0.01). This association was more pronounced among the 2000 participants who did not have anemia at baseline (IRR=1.80, 95% CI 1.20-2.69, p=0.005). Based on this prospective study among generally healthy European community-dwelling older adults, iron deficiency was not associated with the incidence rate of overall infections but may increase the incidence of severe infections. Intervention studies are needed to prove the causality of this observation.

Low Serum Soluble Transferrin Receptor Levels Are Associated with Poor Prognosis in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Iron metabolism disorder is closely related to acute-on-chronic liver failure (ACLF). This study was conducted to analyze the serum levels of soluble transferrin receptor (sTfR) in hepatitis B virus (HBV)-related ACLF and to evaluate the predictive value of sTfR for the short-term prognosis of HBV-ACLF. A total of 359 patients, including 139 with HBV-ACLF, 103 with chronic hepatitis B (CHB), and 117 healthy controls (HCs), participated in this study. We measured serum levels of ferritin, transferrin, and sTfR using nephelometry and performed data analysis using SPSS software. Ferritin levels were significantly higher in HBV-ACLF patients (both P < 0.001), while transferrin and sTfR were significantly lower (all P < 0.001) than in patients with CHB and HCs. Spearman correlation analysis demonstrated that serum sTfR significantly correlated with the alanine aminotransferase (ALT) (r = -0.366, P<0.001), aspartate aminotransferase (AST) (r = -0.322, P < 0.001), total bilirubin (TBIL) (r = -0.222, P = 0.009), alpha fetoprotein (AFP) (r = 0.329, P < 0.001), prothrombin time-international normalization ratio (PT-INR) (r = -0.428, P < 0.001), and model for end-stage liver disease (MELD) (r = -0.459, P < 0.001). Nonsurviving HBV-ACLF patients who died within 30 days had much lower serum sTfR levels than surviving patients (P < 0.001). Logistic regression analysis showed that decreased serum sTfR levels were independently associated with 30-day mortality in patients with HBV-ACLF (P = 0.003). Receiver operating characteristic (ROC) curve analysis for predicting 30-day mortality showed that the area under the curve (AUC) for serum sTfR was 0.813 (95% CI: 0.738-0.874, P < 0.001). This was similar to that of the MELD score (AUC = 0.812, 95% CI: 0.737-0.873, P < 0.001). Serum sTfR combined with MELD score significantly improved the predictive capacity for 30-day mortality in patients with HBV-ACLF (AUC = 0.871, 95% CI: 0.803-0.922, P < 0.001). Kaplan-Meier analysis revealed that the overall cumulative 30-day mortality rate was significantly higher in patients with serum sTfR levels ≤ 0.55 mg/L compared to those with serum sTfR levels > 0.55 mg/L (P < 0.001).

Hepcidin regulates neuronal ferroptosis: A mechanism for postoperative cognitive dysfunction.

Toll-like receptor 4 (TLR4) is a signaling molecule responsible for the expression of hepcidin (Hepc), while myeloid differentiation protein 2 (MD2) is one major accessory protein of TLR4. This study focuses on exploring the neurocyte ferroptosis mediated through the regulation of Hepc expression by MD2, which is also one of the mechanisms for postoperative cognitive dysfunction (POCD).An experimental study was carried out using aged wild-type (Wt) and MD2 transgenic (Tg) mice. The neurocyte ferroptosis and POCD in the mice were assessed following splenectomy. Morris water maze was utilized to assess the neurocognitive abilities, hematoxylin and eosin (H&E) assay was performed to examine histopathology, and Nissl staining was used to evaluate the neurocyte damage. The Fe2+ , superoxide dismutase(SOD), malondialdehyde(MDA), glutathione(GSH), and glutathioneperoxidase 4(GPX4) levels were determined with kits. The expressions of transferrin receptor(TFR), Hepc, and MD2 were measured by Western blotting, while the expressions of TFR and GPX4 were measured by immunohistochemical staining. In Tg mice, we observed neurocyte ferroptosis and POCD following treatment with anMD2 inhibitor. PC12 cells were used as a neurocyte model. Ferroptosis was induced after treatment with anMD2 inhibitor, and the cell viability was assayed by Cell Counting Kit-8. Immunofluorescent staining was used to measure the TFR and GPX4 expressions. Meanwhile, the intracellular levels of Fe2+ , SOD, MDA, GSH, GPX4, and Hepc were also measured.POCD occurred among aged Wt and Tg mice. The Tg-POCD mice had more apparent POCD than the Wt-POCD mice. Nissl and H&E staining revealed neurocyte damage in brain tissues. Besides this, the Fe2+ and MDA expressions were upregulated, while the SOD, GSH, and GPX4 expressions were downregulated. Elevations in tissue levels of TFR, Hepc, and MD2 were observed, which were higher than those of Wt-POCD mice. After treatment with anMD2 inhibitor, the POCD could be prominently ameliorated in Tg-POCD mice, the Fe2+ and MDA levels could be reduced, while the SOD, GSH, and GPX4 levels could be elevated. In the PC12 model, ferroptosis could be suppressed by inhibiting the expression of MD2.MD2 is capable of regulating neurocyte ferroptosis by promoting Hepc expression, which has great potential as a novel target for POCD therapy.

Role of Soluble Transferrin Receptor in Diagnostic Work Up for The Assessment of Iron Status and Iron Deficiency

Background: Iron deficiency anaemia (IDA) is the most frequent form of anaemia in human population. For diagnosing IDA usually conventional laboratory tests such as serum iron, serum ferritin and transferrin saturation are used. However, both ferritin and transferrin proteins are markedly influenced by inflammation, behaving as acute-phase reactants and making it difficult to diagnosis iron-deficiency anemia (IDA) when it is combined with any inflammatory condition. Soluble transferrin receptor (sTfR) is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Concentrations of serum sTfR are related to iron status and erythropoiesis in the body. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes.&#x0D; Aim: The aim of this study is to evaluate the significance of soluble transferrin receptors in diagnostic work up of iron deficiency.&#x0D; Materials and Methods: It was a prospective observational study carried out from June 2021 to November 2021 at the Department of Haematology and Biochemistry of Armed Forces Institute of Pathology (AFIP), Dhaka Cantonment. A total of 50 blood sample were collected and subjected to diagnose as microcytic hypochromic anaemia through complete blood count (CBC) and peripheral blood film (PBF). Then serum iron profile and serum sTfR was done by automated analyzer to evaluate differentials of microcytic hypochromic anaemia.&#x0D; Results: Among 50 cases 5 (10%) were male and 45 (90%) were female. Most of the patients were between 31-40 years age group (34%). Out of 50 patients 42 (84%) showed mild anaemia,6 (12%) showed moderately anaemia and 2(4%) showed severely anaemia according to reference range. Then serum iron profile was done. Among 50 samples 37 (74 %) had low serum iron, 18 (36 %) had high TIBC and 45 (90%) had low serum ferritin in comparison with reference range. Also this study revealed high serum sTfR than normal in 48 (96%) patients. While evaluating the frequency of sTfR level in perspective of both male and female anaemic patients, p-value was found &lt; 0.0001 which was statistically significant.&#x0D; Conclusion: This study demonstrates that sTfR level in conjunction with other biochemical markers of iron deficiency anaemia is very useful in evaluating iron status. Serum sTfR is a new diagnostic tool for evaluating of iron deficiency anemia when it is associated with other inflammatory condition.

Iron and iron-related proteins in COVID-19.

COVID-19 can cause detrimental effects on health. Vaccines have helped in reducing disease severity and transmission but their long-term effects on health and effectiveness against future viral variants remain unknown. COVID-19 pathogenesis involves alteration in iron homeostasis. Thus, a contextual understanding of iron-related parameters would be very valuable for disease prognosis and therapeutics.Accordingly, we reviewed the status of iron and iron-related proteins in COVID-19. Iron-associated alterations in COVID-19 reported hitherto include anemia of inflammation, low levels of serum iron (hypoferremia), transferrin and transferrin saturation, and high levels of serum ferritin (hyperferritinemia), hepcidin, lipocalin-2, catalytic iron, and soluble transferrin receptor (in ICU patients). Hemoglobin levels can be low or normal, and compromised hemoglobin function has been proposed. Membrane-bound transferrin receptor may facilitate viral entry, so it acts as a potential target for antiviral therapy. Lactoferrin can provide natural defense by preventing viral entry and/or inhibiting viral replication. Serum iron and ferritin levels can predict COVID-19-related hospitalization, severity, and mortality. Serum hepcidin and ferritin/transferrin ratio can predict COVID-19 severity. Here, serum levels of these iron-related parameters are provided, caveats of iron chelation for therapy are discussed and the interplay of these iron-related parameters in COVID-19 is explained.This synopsis is crucial as it clearly presents the iron picture of COVID-19. The information may assist in disease prognosis and/or in formulating iron-related adjunctive strategies that can help reduce infection/inflammation and better manage COVID-19 caused by future variants. Indeed, the current picture will augment as more is revealed about these iron-related parameters in COVID-19.

The effect of iron dextran on vitamin D3 metabolism in SD rats

BackgroundIron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood.ObjectivesTo explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism.Methods40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing.ResultsThe results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P < 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blotting, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group.ConclusionIron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation might promote the activation of VD3.

The role of mitochondria in the recovery of neurons after injury.

The role of mitochondria in the recovery of neurons after injury.

The Correlation Between Ineffective Erythropoiesis Biomarkers and Development of Extramedullary Hematopoiesis in Patients with Thalassemia.

Introduction: Extramedullary hematopoiesis (EMH) is one of the main complications in patients with thalassemia in compensation for the underlying ineffective erythropoiesis. This study aimed to evaluate the association between ineffective erythropoiesis biomarkers and EMH in patients with thalassemia.&#x0D; Methods: A cross-sectional study of thalassemia patients aged &gt;18 years old at Srinagarind Hospital was performed. Phosphatidylserine-exposed red blood cells (PS-exposed RBCs) were studied by flow cytometry. The levels of growth differentiation factor-15 (GDF15) and soluble transferrin receptor (sTfR) levels were determined using ELISA.&#x0D; Results: One hundred and thirty-one patients were enrolled. EMH was found in 34 patients (26.0%). EMH was more prevalent among patients with β-thalassemia as compared to those with α-thalassemia (36.4% vs. 4.7%). The levels of GDF15 and sTfR were different between the two groups and indicated a greater degree of ineffective erythropoiesis in β-thalassemia patients. The levels of PS-exposed RBCs showed a modest correlation with EMH. Advanced age and the PS-exposed RBC levels had a statistical significance associated with EMH.&#x0D; Conclusions: Advanced age and high PS-exposed RBC levels are associated with EMH in thalassemia. PS-exposed RBCs showed a modest correlation with EMH and may be used to predict the development of EMH in thalassemia.

A Critical Analysis of the Automated Hematology Assessment in Pregnant Women at Low and at High Altitude: Association between Red Blood Cells, Platelet Parameters, and Iron Status.

The objectives of the study were to determine differences in the parameters of red blood cells (RBC), white blood cells (WBC), and platelets at low altitude (LA) and at high altitude (HA) and with the gestation being advanced, and to determine correlations between parameters of RBC and platelets. We also studied the association of RBC and platelets with markers of iron status. In addition, markers of iron status and inflammation were measured and compared at each trimester of gestation in pregnant women at LA and HA. A cross-sectional comparative study was conducted at Lima (150 m above sea level) and Cusco at 3400 m above sea level from May to December 2019. Hematological parameters in pregnant women (233 at LA and 211 at HA) were analyzed using an automated hematology analyzer. Serum ferritin levels, soluble transferrin receptor (sTfR), hepcidin, erythropoietin, testosterone, estradiol, and interleukin-6 (IL6) levels were measured by ELISA. One-way ANOVA supplemented with post hoc test, chi-square test, and Pearson correlation test statistical analyses were performed. p < 0.05 was considered significant. Pregnant woman at HA compared to LA had significantly lower WBC (p < 0.01), associated with higher parameters of the RBC, except for the mean corpuscular volume (MCV) that was no different (p > 0.05). Platelets and mean platelet volume (MPV) were higher (p < 0.01), and platelet distribution width (PDW) was lower at HA than at LA (p < 0.01). A higher value of serum ferritin (p < 0.01), testosterone (p < 0.05), and hepcidin (p < 0.01) was observed at HA, while the concentration of sTfR was lower at HA than at LA (p < 0.01). At LA, neutrophils increased in the third trimester (p < 0.05). RBC parameters decreased with the progress of the gestation, except RDW-CV, which increased. The platelet count decreased and the MPV and PDW were significantly higher in the third trimester. Serum ferritin, hepcidin, and serum testosterone decreased, while sTfR and serum estradiol increased during gestation. At HA, the WBC and red blood cell distribution width- coefficient of variation (RDW-CV), PCT, and serum IL-6 did not change with gestational trimesters. RBC, hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), and platelet count were lower as gestation advanced. MCV, MPV, and PDW increased in the third trimester. Serum ferritin, testosterone, and hepcidin were lower in the third trimester. Serum estradiol, erythropoietin, and sTfR increased as gestation progressed. Direct or inverse correlations were observed between RBC and platelet parameters and LA and HA. A better number of significant correlations were observed at HA. Hb, Hct, and RDW-CV showed a significant correlation with serum ferritin at LA and HA. Of these parameters, RDW-CV and PDW showed an inversely significant association with ferritin (p < 0.05). In conclusion, a different pattern was observed in hematological markers as well as in iron status markers between pregnant women at LA and HA. In pregnant women a significant correlation between several RBC parameters with platelet marker parameters was also observed. Data suggest that pregnant women at HA have adequate iron status during pregnancy as reflected by higher serum ferritin levels, lower sTfR levels, and higher hepcidin values than pregnant women at LA.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy

目的再评估影响免疫抑制治疗（IST）后3个月未获血液学反应的重型/极重型再生障碍性贫血（SAA/VSAA）患者6个月疗效的因素。方法回顾性分析2017−2018 年连续收治的173例初治行IST且治疗后3个月未获血液学反应的SAA/VSAA患者的临床资料，对IST后3个月时的临床特征和血液学参数进行再评估，通过单因素和多因素分析找出影响6个月疗效获得的相关指标。结果单因素分析结果显示IST后3个月无效患者的HGB（P＝0.017）、PLT（P＝0.005）、网织红细胞绝对计数（ARC）（P<0.001）、环孢素A血药浓度谷值（CsA-C0）（P＝0.042）、血清可溶性转铁蛋白受体（sTfR）（P＝0.003）、网织红细胞绝对计数改善值（ARCΔ）（P<0.001）、血清可溶性转铁蛋白受体改善值（sTfRΔ）（P<0.001）与IST后6个月疗效有关。多因素分析结果显示PLT<10×109/L（P＝0.020）和ARCΔ<6.9×109/L（P<0.001）是IST后3个月未获血液学反应患者6个月疗效的危险因素。IST后6个月未获血液学反应组3年总生存率［（80.1±3.9）％对（97.6±2.6）％，P＝0.002］和无事件生存率［（31.4±4.5）％对（86.5±5.3）％，P<0.001］均明显低于获得血液学反应组。结论对IST后3个月未获血液学反应的SAA/VSAA患者再评估以预测其6个月疗效非常重要；IST后3个月残存造血仍是影响预后的主要参数；ARCΔ可反应骨髓造血是否正在恢复及恢复的程度；IST后3个月无效患者若ARCΔ<6.9×109/L，无论PLT为何值，IST后6个月的血液学反应率均较低。