Disorder Of Iron Metabolism Research Articles

Ironing out MAFLD: Therapeutic targeting of liver ferroptosis

Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with iron metabolism disorders and ferroptosis, but the mechanisms underlying this association remain unclear. Fudi Wang's group1 used animal models, human cohorts, and multi-omics data to demonstrate the role of iron imbalance in MAFLD and the therapeutic potential of the iron chelator FerroTerminator 1 (FOT1).

Lif-deficiency promote systemic Iron metabolism disorders and increases the susceptibility of osteoblasts to ferroptosis

Leukemia inhibitory factor (LIF) is a multifunctional cytokine that plays a crucial role in various biological processes. However, LIF involvement in iron metabolism remains almost unexplored. This study aimed to explore the impact of LIF on systemic iron transportation and its potential role in ferroptosis in osteoblasts. We observed that the Lif-deficient (Lif−/−) mice is characterized by a reduction in bone mass and a decrease in bone mineral density compared with wild-type (WT) mice. Energy-dispersive X-ray spectroscopy revealed a marked increase in iron content on the surface of femurs from Lif−/− mice. Meanwhile, iron stores test lower iron levels in the spleens and higher levels in the femurs of Lif−/− mice. Besides, Lif−/− mice display increased levels of serum iron, total iron-binding capacity, unsaturated iron-binding capacity, and transferrin saturation and serum ferritin relative to WT mice. Hepcidin mRNA expression reduction in the liver of Lif−/− mice. It also holds true in the AML-12 hepatocyte cell line after Lif-knockdown. Immunohistochemistry and RT-PCR revealed elevated ferroportin (FPN) in duodenal cells of Lif−/− mice. Lif-deficiency decreases SLC7A11 levels in osteoblasts. In addition, overexpression of LIF downregulates CD71, DCYTB, and DMT1, thereby reducing iron uptake in iron-overloaded cells. Femur immunohistochemistry (IHC) revealed increased ACSL4 and decreased GPX4 and SLC7A11, indicating an increase in ferroptosis of osteoblasts in Lif−/− mice. Whole-transcriptome sequencing showed gene expression changes after Lif-knockdown, exhibiting a negative correlation with genes involved in long-chain fatty acid transport, mitochondrial organization, and the p38 MAPK signaling pathway. These results demonstrate that Lif-deficiency alter systemic iron metabolism and increases the susceptibility of osteoblasts to ferroptosis.

Preoperative serum ferritin as a biomarker for predicting delirium among elderly patients receiving non-cardiac surgery: a retrospective cohort study

Iron metabolism disorder has been identified as a contributor to the pathogenesis and progression of multiple cognitive dysfunction-related diseases, including postoperative delirium. However, the association between preoperative iron reserves and postoperative delirium risk remains elusive. This retrospective cohort study aimed to explore the impact of preoperative serum ferritin levels on the risk of postoperative delirium in elderly patients undergoing non-neurosurgical and non-cardiac procedures. Conducted at the Chinese PLA General Hospital between January 2014 and December 2021, the study finally included 12,841 patients aged 65 years and above. Preoperative serum ferritin levels were assessed within 30 days before surgery, and postoperative delirium occurrence within the first seven days after surgery was determined through medical chart review. The analyses revealed that both low and high levels of serum ferritin were associated with an increased risk of postoperative delirium. Patients in the lowest quintile of serum ferritin exhibited an 81% increased risk, while those in the highest quintile faced a 91% increased risk compared to those in the second quintile. Furthermore, mediation analyses indicated that the direct effect of preoperative serum ferritin on postoperative delirium contradicted its indirect effect mediated by hemoglobin levels. These findings suggest that maintaining serum ferritin within moderate range preoperatively could be beneficial for managing postoperative delirium risk among elderly patients.

Hereditary hemochromatosis as an independent predictor of portal vein thrombosis: national inpatient sample (2016-2020) analysis

Hereditary hemochromatosis is a common inherited metabolic disorder of iron metabolism with variable penetrance. Portal vein thrombosis has several well-known causes including cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, intra-abdominal surgery, and thrombophilia. It is unknown whether hereditary hemochromatosis is associated with portal vein thrombosis. Material and methodology. A retrospective analysis of the National Inpatient Sample database from 2016 to 2020 was conducted using International Classification of Diseases-10 codes to identify hospitalizations with portal vein thrombosis. We used multivariate regression analysis to calculate the adjusted odds ratio after controlling for age, gender, insurance type, Charlson Comorbidity Index, cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, intra-abdominal surgery, history of past thrombosis, thrombophilia, end-stage renal disease, obesity,smoking, and hyperlipidemia. Results. There were 25805 hospitalizations with primary diagnosis of portal vein thrombosis. Multivariate logistic regression showed that hereditary hemochromatosis was independently associated with portal vein thrombosis (Odds ratio= 4.7, 95% CI=1.15 to 19.35, p-value=0.03) when cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, history of thrombosis, history of abdominal surgery, history of thrombophilia, and end-stage renal disease among other factors were controlled.

Magnetically attracting hydrogel reshapes iron metabolism for tissue repair.

Ferroptosis, caused by disorders of iron metabolism, plays a critical role in various diseases, making the regulation of iron metabolism essential for tissue repair. In our analysis of degenerated intervertebral disc tissue, we observe a positive correlation between the concentration of extracellular iron ions (ex-iron) and the severity of ferroptosis in intervertebral disc degeneration (IVDD). Hence, inspired by magnets attracting metals, we combine polyether F127 diacrylate (FDA) with tannin (TA) to construct a magnetically attracting hydrogel (FDA-TA). This hydrogel demonstrates the capability to adsorb ex-iron and remodel the iron metabolism of cells. Furthermore, it exhibits good toughness and self-healing properties. Notably, it can activate the PI3K-AKT pathway to inhibit nuclear receptor coactivator 4-mediated ferritinophagy under ex-iron enrichment conditions. The curative effect and related mechanism are further confirmed in vivo. Consequently, on the basis of the pathological mechanism, a targeted hydrogel is designed to reshape iron metabolism, offering insights for tissue repair.

Causal Relationship Between Micronutrient and Sleep Disorder: A Mendelian Randomization Study.

Sleep played an important part in human health, and COVID-19 led to a continuous deterioration of sleep. However, the causal relationship between micronutrient and sleep disorder was not yet fully understood. In this research, the genetic causal relationship between micronutrient and sleep disorder was analyzed utilizing a two-sample Mendelian randomization (MR). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. The analyses were conducted using the MR-Egger, inverse variance weighted, weighted mode, weighted median, simple mode, Cochran's Q test and leave-one-out. Our results suggested that 8 genetically predicted micronutrients participated in sleep disorders, including liver iron (L-iron) and iron in sleeping too much, spleen iron (S-iron) in sleeplessness/insomnia, trouble falling or staying asleep, sleep duration (undersleepers) and nonorganic sleeping disorders, iron metabolism disorder (IMD) and vitamin B12 deficiency anaemia (VB12DA) in narcolepsy, urine sodium (uNa) in narcolepsy, sleep apnea syndrome and sleep disorder, vitamin D (VD) in sleep duration (oversleepers), 25-Hydroxyvitamin D (25(OH)D) in trouble falling or staying asleep. Our study used Mendelian randomization methods at the SNP level to explore the potential causal relationship among L-iron, iron, S-iron, IMD, uNa, 25(OH)D, VD, VB12DA with certain sleep disorder subtypes. Our results uncovered a micronutrient-based strategy for alleviating sleep disorder symptoms.

Ferroptosis and endoplasmic reticulum stress in rheumatoid arthritis.

Ferroptosis is an iron-dependent mode of cell death distinct from apoptosis and necrosis. Its mechanisms mainly involve disordered iron metabolism, lipid peroxide deposition, and an imbalance of the antioxidant system. The endoplasmic reticulum is an organelle responsible for protein folding, lipid metabolism, and Ca2+ regulation in cells. It can be induced to undergo endoplasmic reticulum stress in response to inflammation, oxidative stress, and hypoxia, thereby regulating intracellular environmental homeostasis through unfolded protein responses. It has been reported that ferroptosis and endoplasmic reticulum stress (ERS) have an interaction pathway and jointly regulate cell survival and death. Both have also been reported separately in rheumatoid arthritis (RA) mechanism studies. However, studies on the correlation between ferroptosis and ERS in RA have not been reported so far. Therefore, this paper reviews the current status of studies and the potential correlation between ferroptosis and ERS in RA, aiming to provide a research reference for developing treatments for RA.

Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion.

Anemia and iron metabolism disorders after single anastomosis sleeve ileal (SASI) bypass. Is it a real problem?

PurposeSASI (single anastomosis sleeve ileal) bypass can lead to nutritional deficiencies, including disorders of iron metabolism and anemia. This study aims to evaluate the effect of SASI bypass on weight loss, anemia, and iron deficiency in patients with obesity during the follow-up period.MethodsThis study is a retrospective analysis of prospectively collected data from patients who underwent SASI bypass at our hospital between January 2020 and February 2022.ResultsThe mean age of the patients was 42 years (range 22–58). The average duration of the follow-up period was 26 months. The mean percentage of excess weight loss (%EWL) was 90.1%, and total weight loss (%TWL) was 30.5%. During the postoperative observation period, anemia was identified in ten patients (25%), comprising 70% with normocytic anemia, 10% with microcytic anemia, and two macrocytic anemia cases (20%). Iron deficiency was observed in two patients (5%).ConclusionSASI bypass is an effective bariatric procedure in weight loss outcomes. However, there may be an increased risk of anemia and iron metabolism disruptions associated with this procedure. The common limb length (250 vs. 300 cm) did not significantly impact hemoglobin, iron, TIBC, ferritin levels, or anemia incidence among patients undergoing SASI bypass. The decrease in postoperative ferritin levels signifies a depletion in tissue iron reserves, thereby emphasizing the necessity for surveillance of iron homeostasis parameters following SASI bypass.

The Effect of Acupuncture on Brain Iron Deposition and Body Iron Metabolism in Vascular Cognitive Impairment: Protocol for a Randomized Controlled Trial.

Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients' quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration. The objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism. In total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI. Participants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial. This study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation. China Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv. PRR1-10.2196/56484.

Iron metabolism and arthritis: Exploring connections and therapeutic avenues.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Iron Metabolism and Ferroptosis in Early Brain Injury after Subarachnoid Haemorrhage.

At present, it appears that the prognosis for subarachnoid haemorrhage (SAH), which has a high death and disability rate, cannot be greatly improved by medication or other treatment. Recent research suggests that different types of cell death are implicated in early brain injury (EBI) after SAH, and this has been recognised as a major factor impacting the prognosis of SAH. Ferroptosis, which is a recently identified imbalance of iron metabolism and programmed cell death triggered by phospholipid peroxidation, has been shown to be involved in EBI after SAH and is thought to have a significant impact on EBI. The decomposition of cleaved haemoglobin during SAH involves the release of enormous amounts of free iron, resulting in iron metabolism disorders. Potential therapeutic targets for the signalling pathways of iron metabolism disorders and ferroptosis after SAH are constantly being discovered. To serve as a guide for research into other possible therapeutic targets, this paper will briefly describe the mechanisms of dysregulated iron metabolism and ferroptosis in the pathogenesis of SAH and highlight how they are involved in the development and promotion of EBI in SAH.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2–204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2–204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2–204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2–204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

Ferroptosis: First evidence in premature duck ovary induced by polyvinyl chloride microplastics

Ferroptosis is frequently observed in fibrosis and diseases related to iron metabolism disorders in various mammalian organs. However, research regarding the damage mechanism of ferroptosis in the female reproductive system of avian species remains unclear. In this study, Muscovy female ducks were divided into three groups which were given purified water, 1 mg/L polyvinyl chloride microplastics (PVC-MPs) and 10 mg/L PVC-MPs for two months respectively, to investigate the ferroptosis induced by PVC-MPs caused ovarian tissue fibrosis that lead to premature ovarian failure. The results showed that the high accumulation of PVC-MPs in ovarian tissue affected the morphology and functional activity of ovarian granulosa cells (GCs) and subsequently caused the follicular development disorders and down-regulated the immunosignaling of ovarian steroidogenesis proteins 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), CYP11A1 cytochrome (P450-11A1) and CYP17A1 cytochrome (P450-17A1) suggested impaired ovarian function. In addition, PVC-MPs significantly up-regulated positive expression of collagen fibers, significantly increased lipid peroxidation and malondialdehyde (MDA) level, along with encouraged overload of iron contents in the ovarian tissue were the characteristics of ferroptosis. Further, immunohistochemistry results confirmed that immunosignaling of ferroptosis related proteins Acyl-CoA synthetase (ACSL4), Cyclooxygenase 2 (COX2) and ferritin heavy chain 1 (FTH1) were significantly increased, but solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase (GPX4) were decreased by PVC-MPs in the ovarian tissue. In conclusion, our study demonstrates that PVC-MPs induced ferroptosis in the ovarian GCs, leading to follicle development disorders and ovarian tissue fibrosis, and ultimately contributing to various female reproductive disorders through regulating the proteins expression of ferroptosis.

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.

The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency.

The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator-iron complexes such as haem play major roles in iron metabolism and human physiology. Similarly, the mainstay treatments of the most common diseases of iron metabolism, namely iron deficiency anaemia and iron overload, involve many iron-chelator complexes and the iron-chelating drugs deferiprone (L1), deferoxamine (DF) and deferasirox. Endogenous chelators such as citric acid and glutathione and exogenous chelators such as ascorbic acid also play important roles in iron metabolism and iron homeostasis. Recent advances in the treatment of iron deficiency anaemia with effective iron complexes such as the ferric iron tri-maltol complex (feraccru or accrufer) and the effective treatment of transfusional iron overload using L1 and L1/DF combinations have decreased associated mortality and morbidity and also improved the quality of life of millions of patients. Many other chelating drugs such as ciclopirox, dexrazoxane and EDTA are used daily by millions of patients in other diseases. Similarly, many other drugs or their metabolites with iron-chelation capacity such as hydroxyurea, tetracyclines, anthracyclines and aspirin, as well as dietary molecules such as gallic acid, caffeic acid, quercetin, ellagic acid, maltol and many other phytochelators, are known to interact with iron and affect iron metabolism and related diseases. Different interactions are also observed in the presence of essential, xenobiotic, diagnostic and theranostic metal ions competing with iron. Clinical trials using L1 in Parkinson's, Alzheimer's and other neurodegenerative diseases, as well as HIV and other infections, cancer, diabetic nephropathy and anaemia of inflammation, highlight the importance of chelation therapy in many other clinical conditions. The proposed use of iron chelators for modulating ferroptosis signifies a new era in the design of new therapeutic chelation strategies in many other diseases. The introduction of artificial intelligence guidance for optimal chelation therapeutic outcomes in personalised medicine is expected to increase further the impact of chelation in medicine, as well as the survival and quality of life of millions of patients with iron metabolic disorders and also other diseases.

Iron metabolism disorder and multiple sclerosis: a comprehensive analysis.

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.

Relationship between Iron Saturation Indices and Psychiatric Disorders among Persons Seeking Care at Selected Psychiatry Health Facilities in Ghana

Aim: This study investigated the relationship between iron metabolism and psychiatric disorder and whether iron saturation indices could predict disease severity.
 Study Design: The study was a case-control study.
 Place and Duration of Study: The study was conducted between December 2020 to March 2022 in some selected psychiatric facilities in Ghana.
 Methodology: Venous blood was collected and serum iron, TIBC, ferritin, transferrin and full blood count were quantified to calculate intraindividual variation and to assess the relationships of these iron saturation indices to severity of psychiatric disorders.
 Results: Serum iron (38.98±14.55 µmol/L), ferritin (100.23±84.98 ng/mL) and transferrin saturation (44.35±14.6%) were significantly (p<0.05) higher in group with psychiatric disorders compared with the controls (29.25±8.0 µmol/L; 75.25±42.71 ng/mL and 28.66±7.1%). However, total iron binding capacity (TIBC) (102.47±15.01 µmol/L), UIBC (73.22±13.12 µmol/L) and transferrin (4.08±0.6 g/L) concentrations were considerably greater in control group than in the case subjects (88.95±19.73 µmol/L; 49.97±18.32 µmol/L and 3.54±0.79 g/L). One unit increase in BMI is associated with 1.27 (aOR=1.27, p<0.001) times risk of psychiatric disorders and males are 6 (aOR=5.87, p<0.005) times at risk of disorders. At a cut off of ≤65.79 µmol/L, UIBC can distinguish psychiatric disorders from controls.
 Conclusion: Serum iron and transferrin saturation appears to be good prognostic markers of diseases severity but serum iron at cut off of >35.23 µmol/L better classified individuals of severe form of psychiatric disorder.

An 8-Week Vitamin D3–Fortified Fruit Drink Supplementation Increases Serum Ferritin Concentration: A Randomized Controlled Trial in Malaysian Women With Low Iron Stores

BackgroundThere is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. ObjectiveThe aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). DesignAn 8-week double-blind randomized controlled trial was conducted. Subjects/settingA total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. InterventionSubjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Main outcome measuresMeasurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. Statistical analysesA mixed model, repeated measures analysis of variance was used to analyze the intervention effect. ResultsAttrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ –1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. ConclusionsOur study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

RNA-seq combined network pharmacology reveals that Fu-Gan-Wan (FGW) inhibits liver fibrosis via NF-κB/CCL2/CCR2 and lipid peroxidation via Nrf2/HMOX1 signaling pathway

Ethnopharmacological relevanceLiver fibrosis is a serious complication of liver disease characterized by excessive collagen deposition, without effective therapeutic agents in the clinic. Fu-Gan-Wan (FGW) is an empirical formula used for the clinical treatment of hepatitis and cirrhosis. It has been shown to reverse experimental liver fibrosis. However, its corresponding mechanisms remain unclear. Aim of the reviewThis study aimed to elucidate the key pathways and target genes of FGW in attenuating liver fibrosis. Materials and methodsThe therapeutic effects of different doses of FGW on liver fibrosis were investigated using a 2 mL/kg 15% CCl4-induced mouse model. Then, RNA-seq combined with network pharmacology was used to analyze the key biological processes and signaling pathways underlying the anti-liver fibrosis exertion of FGW. These findings were validated in a TGF-β1-induced model of activation and proliferation of mouse hepatic stellate cell line JS-1. Finally, the key signaling pathways and molecular targets were validated using animal tissues, and the effect of FGW on tissue lipid peroxidation was additionally observed. ResultsWe found that 19.5 g/kg FGW significantly down-regulated CCl4-induced elevation of hepatic ALT and AST, decreased collagen deposition, and inhibited the expression of pro-fibrotic factors α-SMA, COL1α1, CTGF, TIMP-1, as well as pro-inflammatory factor TGF-β1. Additionally, FGW at doses of 62.5, 125, and 250 μg/mL dose-dependently blocked JS-1 proliferation, migration, and activation. Furthermore, RNA-seq identified the NF-κB signaling pathway as a key target molecular pathway for FGW against liver fibrosis, and network pharmacology combined with RNA-seq focused on 11 key genes. Significant changes were identified in CCL2 and HMOX1 by tissue RT-PCR, Western blot, and immunohistochemistry. We further demonstrated that FGW significantly attenuated CCl4-induced increases in p-p65, CCL2, CCR2, and HMOX1, while significantly elevating Nrf2. Finally, FGW significantly suppressed the accumulation of lipid peroxidation products MDA and 4-HNE and reconfigured the oxidation-reduction balance, including promoting the increase of antioxidants GPx, GSH, and SOD, and the decrease of peroxidation products ROS and GSSG. ConclusionsThis study demonstrated that FGW exhibits potential in mitigating CCl4-induced hepatic fibrosis, lipid peroxidation, and iron metabolism disorders in mice. This effect may be mediated through the NF-κB/CCL2/CCR2 and Nrf2/HMOX1 pathways.