Iron Buildup Research Articles

Assessment of the vitamin D level and demographic characteristics of children suffering from β-thalassemia in Thi-Qar province

Beta thalassemia is a genetic disorder inherited by autosomal recessive inheritance, is present all over the world . Lifelong transfusions are necessary for people with beta-thalassemia, which can result in an iron buildup in the skin, liver, and kidneys that reduces the production of vitamin D. This study aims to evaluate vitamin D levels, blood groups, and demographic characteristics in beta-thalassemia patients. The current study was conducted at the thalassemia center and hereditary blood disease in Thi-Qar Province with eighty-eight blood samples collected from individuals. It was divided into three groups according to age range, the first group (2-6), the second group (7- 11), and the third group (12- 15). In the current study, there was a significant decrease in Vit-D3 levels among thalassemia patients compared to the control group (p ≤ 0.05) . As for age between the patients group and the control group, the highest proportion of patients in the third age group. As for gender, the results of the study found a non-significant difference at the (P ≤ 0.05 ) level between the patients group and the control group. The most common blood group in thalassemia was O followed by blood groups A, B, and AB. It also shows that the majority of the population was positive Rh.

Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer's Disease.

Elevated levels of iron occur in both cortical and subcortical regions of the CNS in patients with Alzheimer's disease. This accumulation is present early in the disease process as well as in more advanced stages. The factors potentially accounting for this increase are numerous, including: (1) Cells increase their uptake of iron and reduce their export of iron, as iron becomes sequestered (trapped within the lysosome, bound to amyloid β or tau, etc.); (2) metabolic disturbances, such as insulin resistance and mitochondrial dysfunction, disrupt cellular iron homeostasis; (3) inflammation, glutamate excitotoxicity, or other pathological disturbances (loss of neuronal interconnections, soluble amyloid β, etc.) trigger cells to acquire iron; and (4) following neurodegeneration, iron becomes trapped within microglia. Some of these mechanisms are also present in other neurological disorders and can also begin early in the disease course, indicating that iron accumulation is a relatively common event in neurological conditions. In response to pathogenic processes, the directed cellular efforts that contribute to iron buildup reflect the importance of correcting a functional iron deficiency to support essential biochemical processes. In other words, cells prioritize correcting an insufficiency of available iron while tolerating deposited iron. An analysis of the mechanisms accounting for iron accumulation in Alzheimer's disease, and in other relevant neurological conditions, is put forward.

Ferroptosis and the ubiquitin-proteasome system: exploring treatment targets in cancer.

Ferroptosis is an emerging mode of programmed cell death fueled by iron buildup and lipid peroxidation. Recent evidence points to the function of ferroptosis in the aetiology and development of cancer and other disorders. Consequently, harnessing iron death for disease treatment has diverted the interest of the researchers in the field of basic and clinical research. The ubiquitin-proteasome system (UPS) represents a primary protein degradation pathway in eukaryotes. It involves labelling proteins to be degraded by ubiquitin (Ub), followed by recognition and degradation by the proteasome. Dysfunction of the UPS can contribute to diverse pathological processes, emphasizing the importance of maintaining organismal homeostasis. The regulation of protein stability is a critical component of the intricate molecular mechanism underlying iron death. Moreover, the intricate involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for targeted treatment strategies. Besides, it highlights the potential of ferroptosis as a promising target for cancer therapy, emphasizing the combination between ferroptosis and the UPS. The molecular mechanisms underlying ferroptosis, including key regulators such as glutathione peroxidase 4 (GPX4), cysteine/glutamate transporter (system XC-), and iron metabolism, are thoroughly examined, alongside the role of the UPS in modulating the abundance and activity of crucial proteins for ferroptotic cell death, such as GPX4, and nuclear factor erythroid 2-related factor 2 (NRF2). As a pivotal regulatory system for macromolecular homeostasis, the UPS substantially impacts ferroptosis by directly or indirectly modulating iron death-related molecules or associated signaling pathways. This review explores the involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for the targeted treatment of diseases associated with ferroptosis.

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis.

Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.

Ameliorative anti-coagulant, anti-oxidative and anti-ferroptotic activities of nanocurcumin and donepezil on coagulation, oxidation and ferroptosis in Alzheimer's disease.

Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aβ) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.

Baicalein improves the symptoms of polycystic ovary syndrome by mitigating oxidative stress and ferroptosis in the ovary and gravid placenta

BackgroundPolycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PurposeThis study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. Study design and methodsPolycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. ResultsBaicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. ConclusionsOur findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.

Updates on Management of transfusion induced Iron Overload: A Systematic Review

Multiple blood transfusions lead to an excess iron buildup in the body's organs, which damages the organs. This systematic review investigated the recently published approaches to manage transfusion-induced iron overload. PubMed, SCOPUS, Web of Science, Science Direct, and Cochrane Library were systematically searched to include the relevant literature. Rayyan QRCI was used throughout this systematic approach. Our results included eleven studies with a total of 1635 patients diagnosed with transfusional iron overload. Iron excess is a major challenge in patients with chronic anemia who require frequent transfusions. Evidence from numerous clinical trials has shown that giving chelation therapy to individuals with transfusion-induced iron overload clearly reduced their iron burden and improved organ function. We found that Amlodipine, lupatercept, and chelating agents are safe and effective options for transfusion dependant thalassemia (TDT) patients. Additionally, Amlodipine or lupatercept combined with chelating agents are more efficient in lowering serum ferritin and o regularly drank green tea experienced significant reductions in iron accumulation. Deferiprone (DFP) has provided sickle cell disease (SCD) patients with a new therapeutic choice. The effects of this oral iron chelator were equivalent to those of deferoxamine (DFX) given subcutaneously in terms of reducing transfusional iron excess. In line with what had previously been seen in thalassemia syndrome patients, DFP showed a tolerable safety profile.

Fraxetin alleviates BLM-induced idiopathic pulmonary fibrosis by inhibiting NCOA4-mediated epithelial cell ferroptosis.

Idiopathic pulmonary fibrosis (IPF) is a debilitating lung condition with few available treatments. The early driver of wound repair that contributes to IPF has been extensively identified as repetitive alveolar epithelial damage. According to recent reports, IPF is linked to ferroptosis, a unique type of cell death characterized by a fatal buildup of iron and lipid peroxidation. There is little information on epithelial cells that induce pulmonary fibrosis by going through ferroptosis. In this study, we used bleomycin (BLM) to examine the impact of ferroptosis on IPF in mouse lung epithelial cells (MLE-12). We discovered that BLM increases ferroptosis in MLE-12. Additionally, we found that NCOA4 is overexpressed and plays a key role in the ferroptosis of epithelial cells throughout the IPF process. Using Molecular docking, we found that Fraxetin, a natural component extracted from Fraxinus rhynchophylla, formed a stable binding to NCOA4. In vitro investigations showed that Fraxetin administration greatly decreased ferroptosis and NCOA4 expression, which in turn lowered the release of inflammatory cytokines. Fraxetin treatment significantly alleviated BLM-induced lung inflammation and fibrosis. Our findings imply that fraxetin possesses inhibitory roles in ferroptosis and can be a potential drug against IPF.

Hypoparathyroidism and Hypothyroidism Secondary to Hemochromatosis in Beta Thalassemia Major

Hemochromatosis, an iron metabolism disorder caused by iron overload, often runs in families. It leads to various issues like cardiomyopathy, liver cirrhosis, and hormonal imbalances. This article presents a unique case of secondary hemochromatosis resulting from repeated transfusions. A 15-year-old boy with severe beta-thalassemia major received about 600 units of packed red blood cells over nine years. This led to clinical hypoparathyroidism and subclinical hypothyroidism, affecting multiple organs. Elevated ferritin and transferrin levels confirmed iron buildup, visible on MRI scans in the liver, pancreas, skeleton, heart, and thyroid gland. Such widespread organ involvement due to transfusion-related hemochromatosis is rare and makes this case noteworthy, especially considering the scarcity of similar reports in Pakistan.

The first reports of FA2H-associated neurodegeneration from two unrelated Iranian families.

NBIA (neurodegeneration with brain iron accumulation) is a diverse collection of neurodegenerative illnesses defined by iron accumulation in the basal ganglia. The fatty acid hydroxylase-associated neurodegeneration, or FAHN, is one of the uncommon subtypes of NBIAs, associated with inherited autosomal recessive mutations in gene coding the membrane-bound fatty acid 2 hydroxylase (FA2H) enzyme. Here, we report two cases with FAHN from two unrelated families from Iran confirmed by whole exome sequencing. FAHN is an uncommon variant of NBIA that may manifest as spastic paraparesis without signs of iron buildup on brain imaging. As a result, it should be taken into account while making a differential diagnosis of the hereditary spastic paraplegia (HSP) syndrome, especially in individuals who lack iron deposits.

ANALYSIS OF MALONDIALDEHYDE LEVELS IN CHILDREN WITH BETA THALASSEMIA: A CROSS-SECTIONAL STUDY

AbstractBeta thalassemia is an autosomal recessive genetic condition affecting people worldwide, including in Indonesia. Malondialdehyde levels, a peroxidation product, can be used to see if there is an iron buildup in the body due to lifelong transfusions. This research is a novelty because it analyzes malondialdehyde levels in children with beta-thalassemia: a cross-section study. The study aims to analyze malondialdehyde levels in children with beta-thalassemia. Methods in this study, a cross-sectional investigation was carried out at Dr. Hospital Wahidin Sudirohusodo, Makassar. The study was carried out between April and August of 2022. The study sample consisted of participants diagnosed with beta-thalassemia and non-thalassemia (controls) eligible to participate. Patients with and without beta-thalassemia had their malondialdehyde levels measured. The study results showed that the 60 children, aged six months until 18 years, were separated into two groups, 30 of whom had beta-thalassemia and another 30 who did not. With a significant P-value of 0.000, it was determined that beta-thalassemia children had more substantial amounts of malondialdehyde than children without the condition. Children with beta-thalassemia major had significantly higher malondialdehyde levels than those with beta-thalassemia HbE (P-value = 0.000). The conclusion was that malondialdehyde levels were more significant in beta-thalassemia kids than non-thalassemia kids. Malondialdehyde values are more effective in kids with beta-thalassemia major than those with beta-HbE thalassemia.Keywords: Malondialdehyde; Beta thalassemia; Transfusion; Children.

Ferroptosis increases obesity: Crosstalk between adipocytes and the neuroimmune system.

Ferroptosis requires not only the accumulation of iron ions, but also changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis, a deletion of FSP1 or GCH1. Surprisingly, adipose tissue (AT) in the obesity conditions is also accompanied by iron buildup, decreased GSH, and increased ROS. On the neurological side, the pro-inflammatory factor released by AT may have first caused ferroptosis in the vagus nerve by inhibiting of the NRF2-GPX4 pathway, resulting in disorders of the autonomic nervous system. On the immune side, obesity may cause M2 macrophages ferroptosis due to damage to iron-rich ATMs (MFehi) and antioxidant ATMs (Mox), and lead to Treg cells ferroptosis through reductions in NRF2, GPX4, and GCH1 levels. At the same time, the reduction in GPX4 may also trigger the ferroptosis of B1 cells. In addition, some studies have also found the role of GPX4 in neutrophil autophagy, which is also worth pondering whether there is a connection with ferroptosis. In conclusion, this review summarizes the associations between neuroimmune regulation associated with obesity and ferroptosis, and on the basis of this, highlights their potential molecular mechanisms, proposing that ferroptosis in one or more cells in a multicellular tissue changes the fate of that tissue.

Serum ferritin level in pediatric patients with acute lymphoblastic leukemia (ALL) in the early stage of diagnosis and remission phase

Background: Cancer cells increase iron absorption, interfere with iron storage, and reduce iron excretion. Acute lymphoblastic leukemia (ALL) condition may interfere with the iron synthesis, and the patients usually receive a blood transfusion which leads to iron buildup. Excess iron is linked to a poor prognosis and significantly becomes morbidity and mortality factors. Serum ferritin levels that can be assessed from complete blood count may become a low-cost and sensitive biomarker and prognostic marker for ALL. The aim of this research is to assess serum ferritin levels in pediatric patients with ALL in the diagnosis and remission phases. Methods: An analytical observational cross-sectional study was conducted on pediatric patients with ALL in the pediatric ward Haji Adam Malik hospital Medan from July – October 2021. Physical examination and blood sampling for complete blood count and serum ferritin level assessment were carried out. Bivariate analysis using the Chi-square test was used to compare serum ferritin levels during early diagnosis and remission phases in ALL pediatric patients. Results: Ferritin levels were higher in the newly diagnosed patient group with a median value of 951 µg/L (28.07-6632 µg/L) than the group in remission phase with a median value of 374.5 µg/L (29-2426 µg/L). There were no significant relationships between ferritin levels and BMI, SGOT, and SGPT in the newly diagnosed group. In contrast, the ferritin levels of the patients in the remission group were significantly correlated with SGOT and SGPT.

Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis

BackgroundIron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive. PurposeThis study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation. MethodsIron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined. ResultsMicro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload. ConclusionIron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.

Multifunctional role of natural products for the treatment of Parkinson's disease: At a glance.

Natural substances originating from plants have long been used to treat neurodegenerative disorders (NDs). Parkinson’s disease (PD) is a ND. The deterioration and subsequent cognitive impairments of the midbrain nigral dopaminergic neurons distinguish by this characteristic. Various pathogenic mechanisms and critical components have been reported, despite the fact that the origin is unknown, such as protein aggregation, iron buildup, mitochondrial dysfunction, neuroinflammation and oxidative stress. Anti-Parkinson drugs like dopamine (DA) agonists, levodopa, carbidopa, monoamine oxidase type B inhibitors and anticholinergics are used to replace DA in the current treatment model. Surgery is advised in cases where drug therapy is ineffective. Unfortunately, the current conventional treatments for PD have a number of harmful side effects and are expensive. As a result, new therapeutic strategies that control the mechanisms that contribute to neuronal death and dysfunction must be addressed. Natural resources have long been a useful source of possible treatments. PD can be treated with a variety of natural therapies made from medicinal herbs, fruits, and vegetables. In addition to their well-known anti-oxidative and anti-inflammatory capabilities, these natural products also play inhibitory roles in iron buildup, protein misfolding, the maintenance of proteasomal breakdown, mitochondrial homeostasis, and other neuroprotective processes. The goal of this research is to systematically characterize the currently available medications for Parkinson’s and their therapeutic effects, which target diverse pathways. Overall, this analysis looks at the kinds of natural things that could be used in the future to treat PD in new ways or as supplements to existing treatments. We looked at the medicinal plants that can be used to treat PD. The use of natural remedies, especially those derived from plants, to treat PD has been on the rise. This article examines the fundamental characteristics of medicinal plants and the bioactive substances found in them that may be utilized to treat PD.

Ferroptosis in Neurological Disease.

Iron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated. Iron was shown recently to induce cell death and damage via lipid peroxidation under conditions in which there is deficient glutathione-dependent antioxidant defense. This form of cell death is called ferroptosis. Iron chelation has had limited success in the treatment of neurological disease. There is therefore much interest in ferroptosis as it potentially offers new drugs that could be more effective in reducing iron-mediated lipid peroxidation within the lipid-rich environment of the CNS. In this review, we focus on the molecular mechanisms that induce ferroptosis. We also address how iron enters and leaves the CNS, as well as the evidence for ferroptosis in several neurological disorders. Finally, we highlight biomarkers of ferroptosis and potential therapeutic strategies.

Ferroptosis: A New Road towards Cancer Management

Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.

Effects of Excess Iron on the Retina: Insights From Clinical Cases and Animal Models of Iron Disorders.

Iron plays an important role in a wide range of metabolic pathways that are important for neuronal health. Excessive levels of iron, however, can promote toxicity and cell death. An example of an iron overload disorder is hemochromatosis (HH) which is a genetic disorder of iron metabolism in which the body’s ability to regulate iron absorption is altered, resulting in iron build-up and injury in several organs. The retina was traditionally assumed to be protected from high levels of systemic iron overload by the blood-retina barrier. However, recent data shows that expression of genes that are associated with HH can disrupt retinal iron metabolism. Thus, the effects of iron overload on the retina have become an area of research interest, as excessively high levels of iron are implicated in several retinal disorders, most notably age–related macular degeneration. This review is an effort to highlight risk factors for excessive levels of systemic iron build-up in the retina and its potential impact on the eye health. Information is integrated across clinical and preclinical animal studies to provide insights into the effects of systemic iron loading on the retina.

Effects of Iron Accumulation on Dental Caries, Gingivitis, and Candida albicans Infection in Children with Beta Thalassemia Major: A Narrative Review

Background. Thalassemia is a common inherited hemolytic disorder characterized by the absence or reduction of one of the globin chains. Beta thalassemia major generally has oral cavity manifestations. Patients with beta thalassemia major often require routine blood transfusion. However, this treatment has the side effect of accumulating iron in the salivary glands, which increase the risk of dental caries, gingivitis, and secondary infection from Candida albicans. Objective. The aim of this review is to explain the relationship of salivary iron levels and the effects of iron accumulation on dental caries, gingivitis, and Candida albicans infection. Methods. A comprehensive search was performed on PubMed, Scopus, and Google Scholar databases using the keywords beta thalassemia major, iron, dental caries, gingivitis, Candida albicans. Results. Iron is an essential micronutrient needed by Candida albicans for its growth and virulence. Blood transfusion in patients with beta thalassemia major can lead to a buildup of iron in the salivary glands and trigger the formation of non-transferrin bound iron (NTBI). NTBI can circulate in plasma and form a reactive oxygen species (ROS) that stimulate the formation of biofilms and increase dental caries. ROS may affect several genes associated with the inflammatory process and increase the incidence of gingivitis. It can also reduce salivary secretion in patients with thalassemia-β major that cause dysbiosis, which triggers an overgrowth of Candida albicans. Conclusion. The excess iron in patients with beta thalassemia major increase the risk of dental caries, gingivitis, and Candida albicans infection.