Iron Metabolism Indices Research Articles

Metabolomic mechanism and pharmacodynamic material basis of Buxue Yimu pills in the treatment of anaemia in women of reproductive age.

Objective: To explore the pharmacological basis and mechanism of Buxue Yimu pills (BYP) in the treatment of anaemia in women from the perspective of metabolomics and network analysis. Materials and Methods: Forty-six women of reproductive age with haemoglobin 70-110g/L were recruited. Blood samples were collected before and after 4weeks of oral BYP treatment to assess the changes in haemoglobin, coagulation function, and iron metabolism indices. An integrated analysis of metabolomics (liquid chromatography mass spectrometry) and network analysis was performed to identify the potential pharmacodynamic mechanisms of BYP. Results: After BYP treatment, the haemoglobin level of patients significantly increased from 93.67 ± 9.77g/L to 109.28 ± 12.62g/L (p < 0.01), while no significant changes were found in iron metabolism and coagulation-related indicators. A total of 22 differential metabolites were identified after metabolomics analysis, which were mainly related to the inhibition of inflammation and oxidative stress. Integrating pharmacodynamics and metabolomics, a network of drug-active components-targets-metabolic pathways-metabolomics was established. Acetylcholinesterase, phospholipase A2 group IIA, and phospholipase A2 group IVA may be the most promising therapeutic targets. Conclusion: BYP can inhibit inflammation and oxidative stress as well as promote haematopoiesis, potentially improving anaemia.

DETERMINATION OF THE IRON AND IRON-BINDING PROTEINS CONCENTRATION IN SPUTUM: VALIDATION EXPERIENCE

To date, sputum studies are mainly associated with the work of the tuberculosis service, and in the practice of clinical diagnostic laboratories remain limited to microscopic methods. At the same time, the experience of using other methods of sputum examination in various nosologies is described. However, in most cases this is in the nature of research work, but not routine practice. Nevertheless, for a certain cohort of patients, for example, patients with cystic fibrosis, the use of additional methods of examination of the separated tracheobronchial tree will help to expand the range of diagnostic capabilities and provide a personalized approach to therapy. Due to the etiopathogenetic features of the disease, infectious complications in cystic fibrosis are of paramount importance, since they develop in a short period of time and in some cases end in death. At the same time, there are data on the ratio of the level of iron and iron-binding proteins in the respiratory tract of patients with cystic fibrosis with the severity of the inflammatory process in the lungs and the infecting microflora. In this regard, the study evaluated the possibility of analyzing the indicators of iron metabolism in sputum after validating measures.

Iron metabolism abnormalities in autoimmune hemolytic anemia and Jianpishengxue keli can ameliorate hemolysis and improve iron metabolism in AIHA mouse models

Objective Autoimmune hemolytic anemia (AIHA) is rare heterogeneous disorder characterized by red blood cell (RBC) destruction via auto-antibodies, and after RBC is destroyed, proinflammatory danger-associated molecular patterns including extracellular hemoglobin, heme, and iron which causing cell injury. And oxidative stress represents one of the most significant effects of chronic hemolysis. Jianpishengxue keli can improve the symptoms of anemia patients with kidney disease and tumors and are beneficial in promoting recovery from chronic inflammation. Therefore, it is presumed that Jianpishengxue keli can improve the symptoms of AIHA. We aimed to investigate iron metabolism in AIHA and effects of Jianpishengxue keli on AIHA murine model. Methods Nineteen hemolytic episode AIHA patients, 10 remission patients and 10 healthy controls (HCs) were enrolled in this study. Serum hepcidin, ferritin and other related indicators of iron metabolism were measured. Mouse models of AIHA were established and received high, medium, or low doses of Jianpishengxue keli by gavage daily for 14 and 28 days respectively. The level of RBCs, Hb, bilirubin, LDH, hepcidin, and the expression level of hepcidin mRNA, and hepatic ferroportin 1(FPN1) protein were evaluated. Results Serum hepcidin in hemolytic episode AIHA patients and remission patients were significantly higher than that in HCs (p = 0.0083 and p = 0.0473, respectively). Serum ferritin in hemolytic AIHA patients was significantly higher than that in HCs (p = 0.008). Serum transferrin saturation levels are increased in patients with AIHA[ (57.21 ± 8.96) %]. EPO in hemolytic group was higher than that in healthy control (p＜0.05). In AIHA mouse models, IBIL decreased after 14 days of high dose drug intervention. After 28 days, TBIL and IBIL both significantly decreased in all dose groups and LDH significantly decreased in the medium-and high-dose groups. Body weight improved, and the level of RBCs, Hb and hepcidin in the high-dose group returned to normal. After 14 and 28 days of intervention, hepatic hepcidin mRNA in all dose group significantly decreased. Hepatic FPN1 protein which were significantly lower in the AIHA mouse models, increased in all dose groups after drug intervention for 28 days. Conclusion Iron metabolism abnormalities exists in AIHA patients and Jianpishengxue keli can ameliorate hemolysis and improve iron metabolism in AIHA mouse models. KEY MESSAGES Iron metabolism abnormalities exists in hemolytic episode AIHA patients. Hepcidin and ferritin levels significantly elevated and also correlated with the severity of AIHA patients. Jianpishengxue keli can ameliorate hemolysis and prompt the recovery of AIHA.

The use of carbon monoxide breath test to detect the effect of iron overload on erythrocyte lifespan in MDS.

To investigate the effect of iron overload (IO) on red blood cell (RBC) lifespan in MDS patients with the use of carbon monoxide breath test. The red blood cell lifespan of 93 patients with myelodysplastic syndrome (MDS) and 22 healthy volunteers in the control group were measured by alveolar gas carbon monoxide (CO) assay, with the detection of liver iron concentration, iron metabolism index, erythropoietin (EPO) concentration, peripheral blood inflammatory cytokines, etc. The MDS patients were divided into the severe IO group, mild IO group and non IO group according to liver iron concentration. The effect of IO on RBC lifespan was analyzed in MDS patients. The RBC lifespan of MDS patients in the severe IO group was significantly lower than that in the mild IO group (p<0.05), while the RBC life span in the mild IO group was significantly lower than that in the non IO group (p<0.05). The expression of inflammatory cytokines in the severe IO group was significantly higher than that of the mild and non IO groups. After receiving iron removal treatment(ICT), the expression of inflammatory cytokines was decreased significantly, and the RBC lifespan was significantly prolonged (p<0.05).Besides, liver iron concentration was significantly positively correlated with EPO concentration, while EPO concentration was significantly negatively correlated with RBC lifespan, especially in the MDS-RS subgroup. The RBC lifespan in the EPO>1000 group was significantly lower than that in the EPO<1000 group. IO can shorten RBC lifespan in MDS patients, which may be result from the increase of endogenous EPO and the over-expression of inflammatory cytokines. After ICT, the ineffective hematopoiesis caused by increased EPO may reduced and the decrease of inflammatory cytokine may significantly prolong the RBC lifespan in MDS patients.

Важливість молекулярно-генетичних досліджень при гіпохромній мікроцитарній анемії, рефрактерній до феротерапії, у діагностиці еритропоетичної протопорфірії

Erythropoietic protoporphyria (EPP) is a rare hereditary disease that occurs worldwide, but there are regional differences in its epidemiology. The disease is caused by a partial deficiency of ferrochelatase, which is the last enzyme in the pathway of heme biosynthesis. In typical EPP, photosensitivity appears after first exposure to the sun in early childhood. Microcytic anemia is observed in 20-60% of registered EPP patients, which is mistakenly initially diagnosed as iron-deficiency anemia and prescribed iron-containing drugs. Purpose - is to present a clinical case of iron refractory hypochromic microcytic anemia in a four-month-old boy to improve the diagnosis of EPP. Clinical case. In the publication, we report on a 4-month-old boy in whom the disease debuted with hypochromic microcytic anemia refractory to the administration of iron preparations, target-like erythrocytes, normal indicators of iron metabolism, a slight enlargement of the spleen were found in the peripheral blood smear. The emphasis in the publication is on differential diagnosis, preventive measures and modern pathogenetic treatment with the latest approaches, which are aimed at solving the main defects at the molecular or cellular level, with the prospect of significantly improving the results of this orphan disease. Verification of the disease took place with the help of genome sequencing, a heterozygous pathogenic mutation FECH c.315-48T&gt;C, characteristic of EPP which the child received from the father, was found. The experience of iron-refractory hypochromic microcytic anemia in a four-month-old boy gave grounds to expand the range of examinations, including hemoglobin electrophoresis and the use of molecular genetic studies, for differential diagnostic purposes. The report of this clinical case will be of informational value for family doctors, pediatricians, hematologists and a wide range of specialists. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Parameters of Iron Metabolism in Patients with Iron Deficiency Anemia and Erosive Lesions of the Gastroduodenal Zone

The most common disease in the world is erosive-ulcerative lesions of the gastroduodenal zone (EULGZ). These are chronic polyetiological, recurrent diseases with disruption of the neuro-endocrine and humoral mechanisms that regulate the secretory-trophic process in the gastroduodenal zone with the development of ulcers. In this disease, ulcers have different localization and clinical course, significantly reduce the quality of life, affect work capacity and personal life. Lack of timely diagnosis and treatment can have adverse consequences. The objective: to analyse the characteristics of clinical and metabolic disorders in iron deficiency anemia (IDA) and its combination with EULGZ in order to develop the methods for assessing the disease severity, optimizing diagnostics and treatment tactics. Materials and methods. The observation group included 26 patients (15 men and 11 women) with iron-deficiency anemia (IDA) on background of EULGZ with localization of ulcerative defects of the mucous membrane in the stomach or duodenal bulb. The diagnosis of IDA was verified on the basis of changes in the basic characteristics of clinical manifestations (signs of anemic hypoxia and sideropenic syndrome), specific changes in peripheral blood and indicators of iron metabolism. Patients with IDA and EULGZ, were examined by endoscopic methods, underwent ultrasound and, if necessary, radiological examination. The control group included 35 primary donors (16 women and 19 men), who underwent two laboratory tests for hepatitis B and C, as well as HIV infection/AIDS. All examined donors underwent a comprehensive examination of peripheral blood and determined biochemical indicators. The indicators of iron metabolism were determined in all participants: iron content in the blood serum (IS), total iron-binding capacity of the blood serum (TIBS). The index of unsaturated iron-binding capacity of blood serum was calculated as the difference between TIBS and IS. The coefficient of transferrin saturation with iron was determined as the ratio of the content of IS to TIBS. The content of transferrin was determined according to the TIBS indicator, ferritin – by the radiometric method. Results. Peripheral blood indicators in primary donors and morphometric changes in peripheral blood in patients with IDA were analyzed. The results of investigations of the indicators of iron exchange in blood serum are presented: iron concentration, total iron-binding capacity of serum and the degree of saturation of serum with iron. It was found that male donors have significantly higher levels of iron and ferritin in blood serum compared to female donors. The dynamic of changes in peripheral blood parameters in patients with IDA caused by long-term blood loss due to EULGZ during the treatment process is shown. Treatment of the EULGZ led to the significant changes of such indicators as the number of erythrocytes, hemoglobin concentration, erythrocyte indices towards normalization. The normalization of the reticulocyte count was observed on the 90th day of treatment. The detected changes in the number of platelets in patients with IDA due to EULGZ were observed in the absence of active bleeding from the digestive tract. Conclusions. As a result of the progression of IDA due to the erosive-ulcerative lesions of the gastroduodenal zone, the imbalance of iron metabolism deepens, serious disorders of iron metabolism develop, especially in the content of plasma ferritin. Patients with IDA caused by long-term blood loss as a result of EULGZ, should be prescribed a drug for oral use containing ferrous sulfate with a mucosa-protective effect at a dose of 2 mg/kg per day, followed by a decreased dose after normalization of the serum ferritin level.

Efficacy and Safety of Shengxuening Combined with Conventional Iron Supplementation in the Treatment of Anemia during Pregnancy: A Systematic Review and Meta-analysis.

To evaluate the efficacy and safety of Shengxuening combined with conventional iron supplementation in the treatment of anemia during pregnancy. Electronic searches of Embase, Web of Science, Cochrane Library, China Biomedical Literature Database (CBM), China Knowledge Network (CNKI), Wanfang database (Wanfang), and China Science and Technology Journal Database (VIP) were conducted. A randomized controlled trial of Shengxuening combined with conventional iron supplements for the treatment of anemia in pregnancy was included. The quality of the included trials was assessed using the Cochrane Handbook's Risk of Bias Assessment Tool (version 5.1.0), and data analysis was performed using RevMan 5.4 software and Stata 15.0 statistical software. A total of 150 studies were detected and 17 studies with a total of 1741 cases were finally included. Meta-analysis results showed that the effectiveness of Shengxuening combined with conventional iron supplementation was significantly better than that of conventional iron supplementation alone, and the adverse effects were significantly reduced compared with that of iron supplementation alone, and various anemia indicators such as Hb, RBC, MCV, and MCHC and iron metabolism indicators such as SI and TSAT were also significantly increased. The efficacy of the combination of Shengxuening and conventional iron supplementation in the treatment of anemia in pregnancy is better than that of conventional iron supplementation alone, and the adverse effects in the experimental group are much less than those in the control group, but the quality of the included studies is not high, and more high-quality randomized controlled trials are needed for further validation.

Iron Metabolism Markers and Lower Extremity Arterial Disease in People with Type 2 Diabetes.

ObjectiveTo determine the levels of serum iron, ferritin, total iron-binding capacity, and hepcidin in patients with type 2 diabetes mellitus (T2DM), and to elucidate the relationship of these biomarkers with lower extremity arterial disease (LEAD).MethodsThree hundred fifteen patients with T2DM were selected for the study and divided into non-LEAD (n = 119) and LEAD groups (n=196) based on the ankle-brachial index (ABI) results. Demographic data and clinical test results were collected from all patients. Serum iron, ferritin, total iron-binding capacity, and hepcidin levels were measured, and the transferrin saturation was calculated.ResultsHepcidin levels were substantially higher in the LEAD group (19.17 ± 8.66 ng/mL) than the non-LEAD group (15.44±7.55 ng/mL, P < 0.001), and there was a negative correlation between the ABI and serum lecithin level (r = −0.349, P < 0.001). There were no other correlations with the other iron metabolism indicators. The results of dichotomous logistic regression with LEAD as the dependent variable revealed that smoking history (OR = 4.442, P = 0.008), hypertension history (OR = 3.721, P = 0.006), cardiovascular disease history (OR = 11.126, P < 0.001), diabetes duration (OR = 1.305, P < 0.001), age (OR = 1.056, P = 0.021), hs-CRP level (OR = 1.376, P = 0.002), HbA1c concentration (OR = 1.394, P = 0.001), and hepcidin level (OR = 1.097, P = 0.003) were independent risk factors for LEAD in T2DM patients.ConclusionSerum hepcidin levels were elevated in the LEAD group compared with the non-LEAD group, and elevated hepcidin levels were associated with the development of LEAD in T2DM patients, suggesting that hepcidin may be involved in the occurrence and development of LEAD in T2DM patients.

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.

Disordered Maternal and Fetal Iron Metabolism Occurs in Preterm Births in Human

Background Increasing evidence reveals that iron deficiency during pregnancy causes adverse pregnancy outcomes. Thus far, the mechanisms underlying iron deficiency-associated preterm birth are mostly limited to animal studies. Whether the suggested mechanisms exist in human requires further investigation. The goal of this study was to characterize the iron metabolism in both the maternal side and fetal side in pregnant women with preterm birth. Methods Serum and placenta samples were collected from 42 pregnant women divided into four groups according to the gestational week. Indicators of iron metabolism, including serum iron, serum hepcidin, placental tissue iron, ferroportin (FPN), transferrin receptor 1 (TfR1), and ferritin, were surveyed using enzyme-linked immunosorbent assays (Elisa), Western blots, and real-time quantitative polymerase chain reactions (qRT-PCR). Results Significant reduction of maternal serum iron was observed in women with preterm birth relative to those with full-term birth, indicative of worsen iron deficiency in those mothers with preterm birth. Meanwhile, the maternal hepcidin levels were notably diminished in women with preterm birth, whereas the fetal hepcidin levels were comparable between the two groups. Moreover, the placental iron stores were remarkably reduced in the preterm group, associated with reduced concentration of TfR1 and increased FPN concentration relative to the normal controls. In other words, the ratio of placental FPN mass to TfR1 mass (PIDI index) was strikingly increased in the preterm group. Conclusions Dysregulated iron homeostasis in both the maternal and fetal sides was implicated in preterm births, and disordered regulations in maintaining the placental iron equilibrium were also presumed to account for the compromised fetal iron supply.

Iron Metabolism Markers in Patients with Tuberculosis Combined with HIV Infection

Background. Changes of iron metabolism in patients with tuberculosis combined with HIV infection is an important task of phthisiology, since, on the one hand, iron deficiency can have a negative effect on the course of the tuberculous process. On the other hand, compensation for iron deficiency may be creating an iron overload situation, promoting replication of M. tuberculosis. Aims to study in a comparative aspect, changes in iron metabolism markers in patients with tuberculosis combined with HIV infection and without it. Methods. The study included 284 tuberculosis patients who were divided into 2 groups. The first group included 141 patients with tuberculosis combined with HIV (TB/HIV group). The comparison group consisted of 143 tuberculosis patients without HIV (TB group). The assessment of the bodys iron supply was carried out in terms of the concentration of serum iron, transferrin (TF), and ferritin (FT). The study was conducted separately in men and women, since the indicators of iron metabolism in healthy men and women differ significantly. Results. It was found that in men with TB/HIV patients, the decrease in serum iron less than the lower limit of the norm took place in 47.6%, and in the TB group in 27.3% of cases (p 0.01). The concentration of TF in the blood serum in the group of TB/HIV patients in men decreased in 69.9%, and in the group of TB patients in 31.2% of cases (p 0.01). The level of FT in the TB/HIV group increased in 19.4%, and in the TB group in 8.3% of cases (p 0.05). In women, a decrease in iron levels in the group of TB/HIV patients was observed in 39.5%, and in the TB group only in 2.2% of cases (p 0.01), a decrease in the level of TF was observed in 55.2% and 24.3% (p 0.01). A decrease in ferritin levels below 15 ng/ml was observed in 15.7% of women with TB/HIV and in 10.6% of TB patients. A negative relationship was found between iron content and CRP levels. Conclusion. The results of studied made it possible to conclude that in all cases the decrease in iron was caused not by a true deficiency of iron, but by its redistribution in the body. At the same time, a small number of women with tuberculosis combined with HIV infection and tuberculosis without HIV infection showed a significant decrease in ferritin levels, which indicated that they had a true iron deficiency.

Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3β/Keap1-Nrf2-GPX4 Pathway.

Background Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear. Materials and Methods Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells. Results The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3β, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema. Conclusions Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.

Вплив донаторів оксиду азоту на клінічний перебіг ішемічної хвороби серця з супутньою анемією

The purpose of the study was to evaluate the effect of L-arginine on the general condition of patients with coronary artery disease and anemia, on the dynamics of laboratory parameters of iron metabolism, glucose, high-sensitivity C-reactive protein, lipid metabolism and the functional state of the kidneys in particular category of patients. Materials and methods. The study involved 53 patients with coronary heart disease and anemia, aged from 56 to 85 years. The patients were randomized into two groups. The control group included 24 patients who received standard therapy for coronary heart disease and anemia. The main group included 29 patients who, in addition to standard therapy, received L-arginine intravenously and orally according to the scheme. Results and discussion. As a result of treatment, red blood counts and iron metabolism in the main and control groups normalized. A comparative analysis of iron metabolism indicators showed that during treatment, patients who received L-arginine had a more active metabolism and accumulation of iron in the body. Restoration of hemoglobin levels in patients with coronary heart disease and anemia contributed to the improvement of the general condition and well-being in both groups. But general weakness (p&lt;0.001) and palpitations (p&lt;0.05) after treatment were less pronounced in the main group. Observations showed the dynamics of high-sensitivity C-reactive protein, indicators of lipid metabolism and the functional state of the kidneys in the main and control groups. A significant decrease in lipidogram parameters after treatment was noted both in patients of the control and the main group; but due to the addition of L-arginine, changes in total cholesterol, high density lipoprotein and atherogenic index in the main group compared with the control group were more pronounced (from p&lt;0.01 to p&lt;0.001). The inclusion of statins in the standard therapy contributed to a significant decrease in the levels of high-sensitivity C-reactive protein in patients in the main group – 17.8% (p&lt;0.001) and 11.4% (p&lt;0.05) in the control group. Conclusion. According to the results of the study, it was found that nitric oxide donors have a beneficial effect on iron metabolism, lipid profile, high-sensitivity C-reactive protein level, the functional state of the kidneys, and, probably, on the degree of heart failure. It has been established that against the background of treatment with L-arginine, the bioavailability of orally incoming iron increases; the supply of iron in the body increases significantly; there was a trend towards normalization of lipid profile and functional state of the kidneys with significant changes in creatinine and glomerular filtration rate levels; decrease in signs of heart failure (general weakness, palpitations)

Efficacy and Mechanism of Roxadustat plus Oral Iron in the Treatment of Elderly Chronic Kidney Disease with Anemia.

Objective For investigating the efficacy and mechanism of Roxadustat + oral iron in the treatment of elderly chronic kidney disease (CKD) complicated with anemia. Methods A total of 100 elderly patients with CKD and anemia admitted to our hospital between April 2020 and December 2021 were enrolled as research subjects, and the patients were assigned to control group (Con group, n = 50) or experimental group (Exp group, n = 50). The patients in the Con group were given oral iron, and those in the Exp group were given Roxadustat capsule based on the Con group. Both groups were given subcutaneous injection of recombinant human erythropoietin. The clinical efficacy, anemia indexes, iron metabolism indexes, inflammatory indexes, and adverse reactions were compared between the two groups. Results The Exp group showed a notably higher treatment effective rate than the Con group (P < 0.05). After treatment, the anemia indexes, iron metabolism indexes, and inflammatory indexes in the Exp group were notably better than those in the Con group (P < 0.05). The Exp group showed a notably lower incidence of adverse reactions during treatment than the Con group (P < 0.05). Conclusion Roxadustat plus oral iron yields a pronounced clinical efficacy in the therapy of elderly patients with CKD and anemia.

Potential clinical implications of iron metabolism in ovarian endometriosis

ObjectiveThe purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs. MethodsThree datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer. ResultsThe present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05). ConclusionThe ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs.

Causes of anemia in patients with gastric cancer during the perioperative period

The OBJECTIVE of the study was to reveal the causes of anemia in patients with gastric cancer in the perioperative period.METHODS AND MATERIALS. The object of the study were 700 patients with gastric cancer who underwent surgical treatment. All patients underwent clinical and biochemical blood test, indicators characterizing iron metabolism in the body (serum iron, ferritin, transferrin), and the level of endogenous erythropoietin during the perioperative period. The comparison group included 20 patients with gastric bleeding of non-neoplastic etiology. Both groups were comparable in age (median was 60 and 62 years old) and hemoglobin level (median Hb 95.3 g/l and 94.5 g/l).RESULTS. Anemia was diagnosed in 15 % of patients (n=105) in the perioperative period. Mild anemia was more often detected (hemoglobin level 95–110 g/l) – in 47.6 % of patients. Moderate anemia (80–94 g/l) was observed in 24.0 % of patients, severe anemia (65–79 g/l) – in 18.1 % of patients, severe (hemoglobin level below 65 g/l) – in 10.3 % of patients. A strong correlation (r=0.89; P&lt;0.05) was observed between the stage at the tumor process and the severity of anemia. At the same time, no connection was found between the macroscopic form of a stomach tumor and the severity of anemia. The analysis of the indicators of iron metabolism allowed to confirm the true iron deficiency in this category of patients, which was characterized by a decrease in the level of serum iron in patients with gastric cancer to (7.8±1.6) μmol/L (from 4.7 to 8.2 μmol/L). Comparative analysis of the level of endogenous erythropoietin in the group of patients with gastric cancer (n=20) and patients with gastrointestinal bleedings of non-neoplastic etiology (n=20) showed significantly lower values with a difference of 27.7 % in the first group of patients ((66.9±28.2) mIU/ml versus (95.6±36.7) mIU/ml; P&lt;0.05), which indicated inadequate production of erythropoietin in patients with gastric cancer.CONCLUSION. The main causes of anemia in patients with gastric cancer in the perioperative period should be considered a true iron deficiency, as well as inadequate production of endogenous erythropoietin.

МЕТАБОЛИЗМ ЖЕЛЕЗА ПРИ ДИССЕМИНИРОВАННОМ ТУБЕРКУЛЕЗЕ ЛЕГКИХ И ПНЕВМОЦИСТНОЙ ПНЕВМОНИИ У ПАЦИЕНТОВ С ВИЧ-ИНФЕКЦИЕЙ

Introduction. The main disease that complicates HIV is Pneumocystis pneumonia. It often requires differential diagnosis with tuberculosis. Aim. The aim of the study was to conduct a comparative analysis of the clinical features and main indicators of iron metabolism in HIV infection with disseminated pulmonary tuberculosis and Pneumocystis pneumonia and to identify potential differential diagnostic markers of tuberculosis. Material and methods. The study included two groups of patients with HIV infection: 42 patients with disseminated pulmonary tuberculosis and 44 patients with Pneumocystis pneumonia. The clinical and laboratory data was carried out, the main indicators of iron metabolism were determined: iron concentration, hepcidin, ferritin. Statistical data processing was performed using the MedCalc 19.2.6 statistical software. Results and discussions. In the group of patients with Pneumocystis pneumonia, the proportion of patients with a severe condition is greater, the level of CD4-lymphocytes is significantly lower - 5 times less than in tuberculosis (p &lt;0.001). Statistically significant differences between the groups were found for hepcidin and serum. The median for hepcidin is 1.4 times higher in group 1 than in group 2 (p &lt;0.001), for serum - 1.5 times less in group 1 than in group 2 (р&lt;0,001). In patients with HIV and pulmonary dissemination, a higher probability of tuberculosis was revealed with hepcidin more than 13810 pg/ml (sensitivity 80.95%, specificity 75%, ROC AUC 0.854) and with an iron concentration less than 10 μmol / L (sensitivity 85.7%, specificity 59.1%, ROC AUC 0.733). Conclusion. When examining patients with HIV infection and pulmonary dissemination syndrome who have a common anamnesis, clinical and radiological, laboratory data and a high degree of suspicion of tuberculosis, it was established by the analysis of ROC curves that the peptide hormone hepcidin has the greatest practical value for its further comprehensive study as a potential and a promising marker for the diagnosis of tuberculosis.

Features of Anemia in Extremely Preterm Children in Neonatal Period

Background. The study of anemia causes in children born prematurely remains the urgent problem due to the continuous search for effective ways to prevent and treat it.Objective. The aim of the study is to study the anemia severity in premature infants, peripheral blood test results (MCV, MCH, MCHС), serum iron, and ferritin at different gestational periods.Materials and methods. 82 medical records of preterm infants were analyzed. 12 children were extremely premature (EР), 36 were very premature (VP), 27 were moderately premature (MP), and 7 were late premature (LP). The frequency of anemia, its severity, and laboratory indicators of iron metabolism were studied.Results. In EР infants, anemia developed in 100% (severe and moderate form in 16.7%, mild in 66.6%), in VP — in 94.6% (of which severe form in 5.6%, moderate — 22%, mild — 67%). Severe forms were not detected in children over 32 weeks of gestation. In infants with ЕР, the iron level at 2 weeks Me (median) 10.6 μmol/l [8.8–12.1], which is lower than in the comparison groups: VP — 15.9 [12.3–18.9] (p = 0.007), MP — 18,7 [15.8–20.5] (p = 0.0002), LP — 14,0 [16.2–23.8] (p = 0.011). Serum ferritin in the EР group is 58.4 μg/l [52.8–71.7], lower than the level in children with OH — 165.5 μg/l [77.3–195] (p = 0.03). The indicators MCV, MCH did not reflect the etiology of anemia, MCHC is reduced in all groups. With oral subsidization of 3-valent iron, its level increase in EР: before treatment — 10.65 μmol/l [8.2–12.1], after 2 weeks — 21.95 μmol/l [17.8–23,9] (p = 0.011).Conclusion. Severe and moderate degrees of early anemia of prematurity are diagnosed in the EР and VP groups. Significant deficiency of serum iron was detected in EР at the age of 2 weeks. MCHC less than 33.1% was registered in all gestational periods, it can be the marker of early anemia of prematurity. Iron supplement is required for EР.

Serum ferritin levels are associated with advanced liver fibrosis in treatment-naive autoimmune hepatitis

Background and aimThe association between iron-metabolism-related variables and liver fibrosis in chronic hepatitis C and nonalcoholic fatty liver disease is now well known. However, the relationship has not been extensively studied in autoimmune hepatitis (AIH). We aimed to investigate the association between variables associated with iron metabolism and advanced liver fibrosis among untreated patients with AIH.MethodsNinety-seven untreated AIH patients were enrolled in this cross-sectional study. All participants underwent iron metabolism index detection and liver biopsy. Multiple logistic regression analysis was used to explore the association of iron-metabolism-related variables with advanced liver fibrosis.ResultsAmong the 97 AIH patients, 38 (39.2%) had advanced liver fibrosis, and 59 (60.8%) did not. In multivariate logistic regression analysis, immunoglobulin G (odds ratio [OR], 1.123; 95% confidence interval [CI] 1.023–1.232, P = 0.014), platelet count (OR 0.988; 95% CI 0.979–0.997, P = 0.013), prothrombin time (OR 1.758; 95% CI 1.143–2.704, P = 0.010) and ferritin (OR 1.002; 95% CI 1.001–1.004, P = 0.012) were independent risk factors for predicting advanced liver fibrosis in AIH patients.ConclusionHigher serum ferritin was independently associated with advanced liver fibrosis among patients with treatment-naive AIH.

Effects of natural iron supplement intake on EPO, Hp, and iron metabolism during rapid weight loss in university wrestlers

Background: The purpose of this study was to determine the changes in erythropoiesis and iron metabolism indicators in order to improve the maintenance of athletic performance during rapid weight loss. Methods: The subjects were 23 university wrestlers (13 male, 10 female). The first measurements in the male and female groups after natural iron supplement intake indicated weight decreases of 6.2% and 5.8%, respectively. After the 3-week washout period, the weights in the male and female groups decreased by 6.1% and 6.2%, respectively. Results: Males in the intake group experienced changes in iron metabolism after weight loss, as shown by increases in the iron indicators (Fe, p &lt; 0.041; transferrin, p &lt; 0.004; total iron binding Capacity (TIBC), p &lt; 0.031), whereas the female group showed no significant changes. Both groups experienced decreases in erythropoietin (males, p &lt; 0.021; females, p &lt; 0.027) and VO2max (p &lt;0.001) after weight loss. Blood lactate in the intake group decreased after maximal exercise immediately after the test for the male group (p &lt;0.031) and during resting time and immediately after exercise in the female group (p &lt; 0.001 and p &lt; 0.050, respectively). Conclisions: These findings suggest that a 7% loss in weight does not positively affect athletic ability. Further research on methods for iron supplement intake, weight loss, and training is necessary to confirm our conclusions.