Hepatitis B Virus-Associated Liver Carcinoma: The Role of Iron Metabolism and Its Modulation.

Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Iron, a central co-factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV-related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV-associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV-associated HCC and potentially identify novel therapeutic avenues for intervention.

Associations of iron metabolism and inflammation with all-cause and cardiovascular mortality in a large NHANES community sample: Moderating and mediating effects.

BACKGROUND AND AIMS: This study aimed to assess the associations between serum iron concentration, C-reactive protein (CRP) concentration and the risk of all-cause mortality and cardiovascular mortality in the general population and to explore potential mediating and moderating effects. METHODS AND RESULTS: This study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2010, encompassing 23,634 participants. Cox proportional hazards regression models were employed to investigate the independent associations of serum iron and CRP with all-cause and cardiovascular mortality. Moderation and mediation analyses explored the moderating effect of CRP on the association between the serum iron concentration and all-cause and cardiovascular mortality, and the mediating role of the serum iron concentration in the association between the CRP concentration and all-cause and cardiovascular mortality. After multivariate adjustments in the Cox model, serum iron and CRP levels were independently correlated with both all-cause and cardiovascular mortality risk. Moderation analyses revealed a more pronounced correlation between the serum iron concentration and both all-cause and cardiovascular mortality in participants with higher CRP levels. Mediation analysis indicated that the serum iron concentration partly mediated the impact of CRP on the risk of all-cause mortality (13.79%) and cardiovascular mortality (24.12%). CONCLUSION: Serum iron and CRP are independently associated with all-cause and cardiovascular mortality. Moreover, the associations between serum iron concentrations and both all-cause and cardiovascular mortality are more pronounced in individuals with elevated CRP. Serum iron partially mediates the effect of CRP on all-cause and cardiovascular mortality.

Influence of an iron dextran injection in various diseases on hematological blood parameters, including serum ferritin, neonatal dairy calves.

BACKGROUND: Feeding milk substitutes with low iron content or whole milk without iron supplementation is considered a major factor in developing iron-deficiency anemia in neonatal dairy calves. Young calves are often supplemented with iron dextran injections on the first day of life to prevent anemia. However, the effects of preventive treatment and the presence of disease on serum iron (Fe) concentrations, serum ferritin levels, and hematological blood parameters during the early neonatal stages have not been examined in detail. Therefore, we examined and evaluated the effects of iron dextran injections and health status on the development of hematocrit (Ht), red blood cells (RBC), hemoglobin concentration (Hb), erythrocyte indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration), Fe, and serum ferritin concentrations in dairy calves within the first 10 days of life. The suitability of serum ferritin as a reliable indicator of anemia in very young calves was evaluated by correlating ferritin concentrations with known laboratory diagnostic parameters of anemia. RESULTS: Iron supplementation significantly increased Fe levels (P = 0.048) but did not affect serum ferritin levels in neonatal calves. Fe concentrations were significantly lower in diseased than healthy calves (P = 0.0417). Iron supplementation significantly affected the health status, as observed in Ht (Ptreat=0.0057; Phealth=0.0097), RBC (Ptreat=0.0342; Phealth=0.0243), and Hb (Ptreat=0.0170; Phealth=0.0168). Serum ferritin levels did not significantly correlate with Fe levels. Both groups showed marked differences in ferritin levels, with the highest levels measured on day 2. Fe concentrations showed weak negative correlations with Hb and Ht levels on day 3 (ρ=-0.45; P = 0.0034 and ρ=-0.045; P = 0.0032, respectively). RBC count showed strong positive correlations with Hb and Ht levels (ρ = 0.91 and ρ = 0.93; P < 0.001). CONCLUSION: Iron dextran injections increased Fe concentrations but reduced Ht level, RBC count, and Hb level. The presence of diseases led to a reduction in Fe and higher values of Ht, RBC, and Hb in moderate disease than in severe disease. Due to physiological fluctuations during the first 3 days of life, serum ferritin level seems unuseful for evaluating iron storage before day 4 of life.

Association of urinary glyphosate levels with iron homeostasis among a representative sample of US adults: NHANES 2013-2018.

PURPOSE: Glyphosate and glyphosate-based herbicides (GBH), widely used globally, were initially considered harmless to humans. Experimental studies have suggested that these substances can disrupt iron homeostasis by interfering with iron uptake or triggering inflammatory responses. However, their potential impact on human iron homeostasis remains underexplored. APPROACH AND RESULTS: We analyzed data from 5812 participants aged three and older from the 2013 to 2018 NHANES. We investigated the relationships between urinary glyphosate levels, oral iron intake, and markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor. Higher urinary glyphosate levels were positively associated with oral iron intake (ß = 1.310, S.E. = 0.382, P = 0.001). A one-unit increase in the natural logarithm (ln)-glyphosate was associated with lower serum iron (ß = - 4.236, 95 % CI = - 6.432 to - 2.039, P < 0.001) and ferritin (ß = - 9.994, 95 % CI = - 17.342 to - 2.647, P = 0.009), and higher UIBC (ß = 5.431, 95 % CI = 1.061-9.800, P = 0.018) and transferrin receptor levels (ß = 0.139, 95 % CI = 0.015-0.263, P = 0.029). Increasing glyphosate exposure was associated with significant decreases in serum iron and ferritin across exposure quintiles (trend P-values = 0.003 and 0.018, respectively). CONCLUSIONS: Higher glyphosate exposure is associated with reduced iron availability, suggesting potential disruptions in iron absorption. These findings underscore the need for further research into the health implications of glyphosate exposure on iron homeostasis.

Impact of low serum iron on treatment outcome of PD-1 inhibitors in advanced gastric cancer.

BACKGROUND: The aim of this study was to investigate the influence of serum iron levels in advanced gastric cancer (GC) patients treated with programmed cell death protein-1 (PD-1) inhibitors. METHODS: We retrospectively reviewed 149 GC patients who were treated with PD-1 inhibitors at our center. Clinicopathological characteristics, laboratory data, and clinical outcomes were analyzed. RESULTS: Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), histological subtype, and baseline serum iron levels were independent prognostic factors for overall survival (OS), while ECOG PS, multiple metastatic sites, and baseline serum iron levels were independent prognostic factors for progression-free survival (PFS). Patients with baseline low serum iron levels (LSI) had a significantly shorter median OS and PFS compared to patients with normal serum iron levels (NSI) (Median OS: 7 vs. 14 months, p = 0.001; median PFS: 3 vs. 5 months, p = 0.005). Patients with baseline LSI had a disease control rate (DCR) of 58.3% at 2 months after PD-1 inhibitor initiation (M2), compared to 81.1% in patients with NSI (p = 0.005). Patients with baseline LSI had a DCR of 43.8% at 4 months, compared to 64.2% in patients with NSI (p = 0.017). CONCLUSIONS: LSI was associated with worse OS, PFS, and DCR in GC patients treated with PD-1 inhibitors and might be a quick and efficient biomarker to predict the efficacy of PD-1 inhibitors.

The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study.

AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.

Serum redox markers in uncomplicated type 2 diabetes mellitus accompanied with abnormal iron levels.

OBJECTIVES: This study aimed at evaluating the serum redox status in type 2 diabetes mellitus (T2DM) accompanied with an imbalance in iron concentrations. METHODS: Diabetic patients were grouped according to serum iron levels [normal (DNFe), low (DLFe), and high (DHFe)], and their clinical and redox parameters [total sulfhydryl groups (tSH), uric acid (UA), and total bilirubin (tBILI) as non-enzymatic antioxidants, and malondialdehyde (MDA) and advanced oxidation products of proteins (AOPP) as markers of oxidative stress] were determined. RESULTS: Glucose and HbA1c levels in the T2DM patients did not differ in function of serum iron. T2DM was associated with reduced tSH levels. In the diabetic patients, tSH, UA, and tBILI negatively correlated with MDA, as well as HbA1c with UA. Accordingly, AOPP and MDA were higher in the diabetic groups compared to the controls. The reduced antioxidant capacity was particularly pronounced in the DLFe group, which was further characterized by lower levels of UA and tBILI compared to the other groups. Subsequently, the level of MDA in the DLFe group was higher compared to the DNFe and DHFe groups. The positive correlation between serum iron levels and the antioxidants UA and tBILI, in conjunction with the negative correlation between serum iron levels and the markers of oxidative stress in the diabetic patients, corroborated the indication that comparatively higher level of oxidative stress is present when T2DM coexists with decreased iron levels. CONCLUSIONS: T2DM-associated redox imbalance is characterized by a decrease in serum total sulfhydryl groups and low serum iron-associated reduction in uric acid and total bilirubin levels, accompanied by increased oxidative stress markers. The relatively noninvasive and simple determination of these parameters may be of considerable interest in monitoring the pathophysiological processes in T2DM patients, and may provide useful insights into the effects of potential therapeutic or nutritional interventions.

Correlation of HbA1c with Serum Iron & Transferrin Saturation in Non-Diabetic Patients with Iron Deficiency.

Objective: To determine correlation of HbA1c with serum iron and transferrin saturation in non-diabetic patients with iron deficiency. Methods: This cross-sectional comparative study was conducted at Dr Ruth KM Pfau Civil Hospital Karachi from 15th September 2021 to 14th March 2022, on non-diabetic patients based on fasting blood sugar (FBS) of <100 mg/dl. Patients were divided into two groups. Group one included patients having iron deficiency anemia (ID), whereas group two included same number of age and sex matched healthy subjects taken as controls, without ID. Blood sample was taken for HbA1c, CBC, serum iron and total iron binding capacity. Transferrin saturation (TSAT) was calculated. Comparison of quantitative variables with ID and non-ID group was done by Student's t-test. Correlation of HbA1c with iron &TSAT was done in both groups using Kendal tau-b test, as data was not normally distributed. Results: Out of 230 patients, 83 (36.1%) were males while 147(63.9%) were females. Mean age of patients was 43.7±13.28 years. Mean HbA1c level was significantly high in ID group (5.89±0.43) as compared to non-ID group (5.52±0.50) with a p-value <.001. The HbA1c levels correlated negatively with hemoglobin, serum iron levels and transferrin saturation with a p-value <.001. Conclusion: Low serum Iron and TSAT was related to elevation in HbA1c value. Iron deficiency needs to be corrected before HbA1c interpretation.

A novel nutritional risk score and prognosis of oral cancer patients: A prospective study.

OBJECTIVES: To evaluate the prognostic performance of a novel nutritional risk score based on serum iron, hemoglobin, and body mass index (BMI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: X-tile analysis was performed to determine the optimal cutoff values of serum iron, hemoglobin, and BMI. A nutritional risk score was established by using the HR values of serum iron, hemoglobin, and BMI. Kaplan-Meier curve and multivariable Cox proportional hazards models were used to evaluate the prognostic value of the nutritional risk score in overall survival (OS) and oral cancer-specific survival (OCSS). RESULTS: Serum iron, hemoglobin, and body mass index were all inversely related to the prognosis of oral cancer. The adjusted HR of serum iron, hemoglobin, and BMI were 1.562, 1.886, and 1.465 for OS, and 1.653, 1.865, and 1.443 for OCSS. Patients with higher nutritional risk score had a poorer OS and OCSS. Additionally, chemotherapy was only associated with improved OCSS in patients with the lowest nutritional risk score, but not in patients with higher one. CONCLUSIONS: Nutritional risk score is of prognostic value in oral cancer patients. Favorable response to chemotherapy may only be observed in well-nourished oral cancer patients with lower nutritional risk score.

Toxicological effects of Tris (1,3-dichloro-2-propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period.

There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals.

Estimation of serum iron, serum lipids and serum liver enzymes in celiac disease patients of Saudi Arabia.

Objectives: To evaluate the serum biochemical levels in celiac disease (CD) patients. Methods: It was a cross-sectional study carried out on 70 subjects, including 40 patients with CD and 30 healthy controls. This study was conducted at Jouf University from November, 2020 to October, 2021. The collected blood specimens were used to perform serum iron, serum lipids, liver enzymes, and human tissue transglutaminase IgA antibodies (anti-HTTG). The hematological parameters including hematocrit and MCV were determined to establish the diagnosis of iron deficiency. Results: Serum iron was significantly lower in patients as compared to the controls. Serum iron, serum HDL, blood hematocrit and MCV were significantly lower in patients than in controls (p = 0.000). Serum levels of liver enzymes (ALT and AST) and serum human tissue transglutaminase antibodies (anti-HTTG) were significantly higher in patients than in controls (p = 0.000). The correlation studies established the negative correlation of anti-HTTG IgA with serum iron (r = -0.991, p = 0.000), hematocrit (r = -0.967, p = 0.000) and MCV (r = -0.946, p = 0.000) in patients. Conclusion: The serum iron was remarkably reduced in CD patients. A negative correlation was found between anti-HTTG IgA and serum iron, while a positive serum iron was correlated with hematocrit and MCV in CD patients.

Growth differentiation factor-15 and lactoferrin immuno-expression in breast cancer: relationship with body iron-status and survival outcome.

We aimed to evaluate the expression of growth differentiation factor-15 (GDF-15) and lactoferrin (Lf) in tumor and their relationship with the body iron-status and overall survival (OS) outcome of patients with breast cancer. A retrospective cohort study of female patients with primary breast cancer was performed. Clinical tumor samples from the Second Affiliated Hospital of Soochow University between December 2008 and June 2014 were collected. The immuno-expression of GDF-15 and Lf was stratified into positive or negative expression. Kaplan-Meier method and Cox proportional hazards regression model were used for data analysis. 74 breast cancer patients with a mean age of 52 years were included into our study. 14 (18.9%) patients were died by the end of August 1, 2019. The serum iron level of patients with GDF-15 (+)/Lf(-) expression was higher than that of patients with other expression patterns (18.2 ± 5.4 vs. 15.5 ± 5.0 µmol/L, P = 0.038), but was not associated with OS. In univariate Cox analyses, GDF-15(+) and GDF-15(+)/Lf(-) were significantly correlated with high mortality risk (HR = 3.75, 95%CI 1.05-13.48, P = 0.025; HR = 5.00, 95%CI 1.56-16.04, P = 0.004, respectively). After adjusted for age, menopause status and primary tumor grade, the association between GDF-15 and OS disappeared. However, the association between GDF-15/Lf and OS still existed in GDF-15(+)/Lf(-) (HR = 4.50, 95%CI 1.31-15.51, P = 0.017). The combined immuno-expression pattern of GDF-15 and Lf was significant associated with high serum iron level. GDF-15/Lf could be a powerful biomarker to predict survival outcome of patients with breast cancer but still needed to be confirmed by future studies.

[Correlation between serum iron level and overall survival of oral cancer].

OBJECTIVE: To explore the correlation between serum iron(Fe) and the overall survival of oral cancer. METHODS: Patients with oral cancer who met the inclusion criteria in the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Fujian Medical University from January 2010 to April 2017 were collected. The average age was(57.12±13.94) years old, including 489 males(65.46%), 258 females(34.54%) and 564 cases of squamous cell carcinoma(77.90%). Overall survival rates were calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Cox regression model was used to estimate the hazard ratio(HRs) and 95% confidence intervals(95%CIs). RESULTS: The distributions of serum iron level were non-normal distribution(P<0.001), and the serum iron level is expressed as 13.9(10.3, 17.8)µmol/L in M(P25, P75). According to X-tile, the optimal cut-off value of serum iron was 15.3 µmol/L, used as a criterion to group patients. The result showed that the mortality risk of patients with oral cancer in high serum iron level(Fe>15.3 µmol/L) was 0.72 times of patients in lower one(Fe≤15.3 µmol/L)(95%CI 0.52-0.99). Stratified analysis suggested that serum iron was a good predictor of patients with oral cancer aged 60 years(HR=0.62, 95%CI 0.39-0.99), male(HR=0.66, 95%CI 0.44-0.98), with TNM stage I-II(HR=0.42, 95%CI 0.20-0.88) and squamous cell of pathological type(HR=0.69, 95%CI 0.49-0.97). CONCLUSION: Serum iron is closely related to the overall survival of oral cancer, patients with high serum iron have a lower risk of death.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease complicated with chronic heart failure: a retrospective cohort study.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease (CHD) complicated with chronic heart failure (CHF) is still unclear. The objective of this study was to explore the effects of serum iron level without anemia on long-term prognosis of patients with CHD complicated with CHF. In this retrospective cohort study, 221 patients with CHD complicated with CHF were consecutively investigated. These patients were divided into three groups according to the tertiles of the serum iron level: low-iron group (n = 71), medium-iron group (n = 76) and high-iron group (n = 74). The overall serum iron without anemia was 13.0 ± 5.50 µmol/L and serum iron in each group was 7.58 ± 1.63 µmol/L, 11.94 ± 1.79 µmol/L, and 19.37 ± 3.81 µmol/L, respectively. Composite endpoint events were composed of major adverse cardiovascular and cerebrovascular events (MACCE), including recurrent heart failure, all-cause death, acute coronary syndrome (ACS) and ischemic stroke. The median follow-up duration was 239 days. After adjusting relevant confounding risk factors, we found that excessively low or high serum iron level is correlated to the MACCE in patients with CHD complicated with CHF and that the prognosis of patients with excessively high serum iron level is poorer than that of patients with excessively low serum iron level. We further revealed the effect of serum iron level on MACCE is U-shaped, but not linear relationship. Sensitivity analysis showed that the correlation between serum iron level and MACCE is stable. In addition, according to the test for interaction, the variables that modify the effect including CRP (P for interaction < 0.0001), diuretics (P for interaction = 0.0212) and antiplatelet drugs (P for interaction = 0.0167). This study showed that excessively low or high serum iron level without anemia is an independent risk factor of MACCE in patients with CHD complicating with CHF.

Effects of exposure to electromagnetic field from mobile phone on serum hepcidin and iron status in male albino rats.

BACKGROUND: Electromagnetic fields (EMF) created by mobile phones during communication have harmful effects on different organs. OBJECTIVES: To explore the effects of exposure to EMF of mobile phones for different durations on hematological parameters and serum hepcidin in male albino rats. METHODS: Three groups of eight rats: Sham group: rats were exposed to a mobile phone while it was switched off, Experimental group I: rats were exposed to microwave radiation from a mobile phone at 9 am for 30 min. Experimental group II: rats were exposed to microwave radiations from a mobile phone at 9 am for an hour. In all groups, the exposure was conducted daily for a total period of 5 months, followed by estimation of serum hepcidin, total leukocyte count (TLC), interleukin 6 (IL6), serum iron, serum ferritin, plasma hemoglobin (Hb), hematocrit value (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC) and 1.25 dihydroxycholecalciferol levels. RESULTS: In Experimental group II, there was a significant increase in serum hepcidin, TLC, IL6 and serum ferritin; however, serum iron, TIBC, UIBC, 1.25 dihydroxycholecalciferol, plasma Hb, Hct, MCV and MCH were significantly lower in comparison to sham-exposed group. In Experimental group I, there was a significant increase in serum hepcidin, IL6 and TLC, along with non-significant changes in the remaining studied parameters in comparison to the sham-exposed group. CONCLUSION: Chronic exposure to EMF from mobile phones increases hepcidin level with subsequent impairment of iron parameters, in addition to negatively affecting both UIBC and TIBC.

Ghrelin is Negatively Correlated with Iron in the Serum in Human and Mice.

BACKGROUND/AIMS: The studies in the patients with iron deficiency anemia (IDA) implied the existence of the association of ghrelin with iron or hepcidin levels in the plasma under the pathophysiological conditions. We hypothesized that fasting may be able to affect iron metabolism via ghrelin under the physiological conditions. METHODS: We investigated the effects of fasting on serum ghrelin and iron contents in healthy volunteers (23-31 years) and C57BL/6 male mice (8-week-olds) under the physiological conditions. RESULTS: Fasting induced a significant elevation in both total ghrelin and acylated ghrelin and a reduction in iron levels in the serum of both human and mice. Correlation analysis demonstrated that total ghrelin or acylated ghrelin is negatively correlated with iron in the serum in human and mice. CONCLUSION: Ghrelin has a role to reduce serum iron under the conditions of fasting.

Maternal protein restriction depresses the duodenal expression of iron transporters and serum iron level in male weaning piglets.

To investigate the effects of maternal dietary protein restriction on offspring Fe metabolism, twenty-four second-parity Landrace×Yorkshire sows were randomly allocated to standard-protein (SP) and low-protein (LP) groups. The SP sows were fed diets containing 15 and 18 % crude protein throughout pregnancy and lactation, respectively, whereas the LP sows were subjected to 50 % dietary protein restriction. Offspring birth weight was not affected, but the body weight at weaning (P=0·06) and average daily gain (P=0·01) of the female piglets were significantly decreased. Serum Fe level in the LP piglets was markedly decreased at weaning, especially in males (P=0·03). Serum ferritin level (P=0·08) tended to be lower, yet serum transferrin was greatly higher (P=0·01) in male weaning piglets of the LP group. Duodenal expression of the divalent metal transporter 1 (DMT1) and ferroportin (FPN) was surprisingly reduced (P<0·05) at the level of protein, but not at the mRNA level, in male weaning piglets of the LP group. Male weaning piglets born to the LP sows exhibited higher hepatic hepcidin levels (P=0·09), lower hepatic expression of transferrin (P<0·01) and transferrin receptor 1 (P<0·05) at the level of mRNA. However, no significant differences were observed for hepatic Fe storage, ferritin, transferrin and transferrin receptor 1 protein expression in male weaning piglets of the two groups. These results indicate that maternal protein restriction during pregnancy and lactation influences growth of female offspring at weaning, reduces duodenal expression of Fe transporters (DMT1 and FPN) and decreases serum Fe level in male weaning piglets.

Evaluation of serum hepcidin and iron levels in patients with PCOS: a case-control study.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation with a prevalence of 5-10% in women of reproductive age. The etiology of this disease is not well known, and hepcidin is one of the factors affecting the pathogenesis of the disease. The aim of this study was to evaluate plasma levels of hepcidin in patients with PCOS and its correlation with serum iron level. METHODS: In this case-control study, plasma levels of hepcidin, IL-6, and ferritin using ELISA method and serum iron levels using a spectrophotometric method were tested on 56 women with PCOS (case group) and 41 healthy subjects (control group). The results were analyzed using t test, General Linear Model, Binary logistic regression, and linear regression tests. RESULTS: The mean hepcidin levels were 1.97 ± 0.53 and 2.40 ± 0.25 pg/ml in the case and control groups, respectively. The t-test results showed significant difference between the two groups (p = 0.0001). The mean serum iron levels were 72.89 ± 28.97 and 70.62 ± 31.18 g/dl in the case and control groups, respectively. The t test analysis indicated no significant difference between the two groups. The serum ferritin and iron levels had no significant relation with serum hepcidin level in two groups. CONCLUSION: Despite the differences in the serum levels of hepcidin between the two groups, no significant relation was observed between serum iron levels and hepcidin level in this group of patients. This implies the need for more comprehensive studies on gene expression in hepcidin and iron pathways using real-time and Western techniques to investigate more precisely serum hepcidin level and its relationship with the factors mentioned.

Iron intake, serum iron indices and risk of colorectal adenomas: a meta-analysis of observational studies.

To provide a quantitative assessment of the association between iron intake, serum iron indices and the risk of colorectal adenoma (CRA), we summarised the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until 31 March 2015. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. A total of 10 articles, involving 3318 subjects with CRA, were used in this meta-analysis. The SRR of CRA was 0.83 (95% CI: 0.71-0.98; Pheterogeneity  = 0.694, I2  = 0) for the highest versus the lowest level of dietary iron intake. The SRR was 0.93 (95% CI: 0.62-1.42) for total (dietary and supplemental) iron intake, 1.23 (95% CI: 1.03-1.48) for haem iron intake and 0.73 (95% CI: 0.54-0.97) for supplemental iron intake. Serum iron indices were not associated with CRA risk (serum ferritin: SRR = 1.16, 95% CI: 0.81-1.66; serum iron: SRR = 1.02, 95% CI: 0.75-1.38; serum transferrin saturation: SRR = 1.01; 95% CI: 0.82-1.50). Increased intake of haem iron is associated with significantly increased risk of CRA, whereas intake of non-haem or supplemental iron is inversely associated with risk of CRA. Limited data indicate null associations between serum iron indices and CRA risk.

Mechanisms of an increased level of serum iron in gamma-irradiated mice.

The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ((60)Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions.