Iron Accumulation Research Articles

Herbal Formula Yi-Fei-Jie-Du-Tang Regulates Epithelial-Mesenchymal Transition and Vasculogenic Mimicry in Lung Cancer via HIF1A-Mediated Ferroptosis.

Traditional Chinese medicine (TCM) Yi-Fei-Jie-Du-Tang (YFJDT) has shown potential in lung cancer treatment. However, the mechanisms underlying the effects of YFJDT on lung cancer remain unclear. Bioinformatics analysis is conducted to identify potential targets of YFJDT. The impact of YFJDT on hypoxia-inducible factor 1 alpha (HIF1A), ferroptosis, and vasculogenic mimicry (VM) is investigated using xenograft tumor models and A549 cells. Additionally, A549 cells are stimulated with CoCl2 to mimic the hypoxic microenvironment of the tumor. The role of HIF1A overexpression in modulating ferroptosis is assessed. The effects of HIF1A and ferroptosis on epithelial-mesenchymal transition (EMT) and VM in vitro are evaluated. Results: YFJDT treatment led to a concentration-dependent decrease in HIF1A levels in xenograft tumors and A549 cells. Overexpression of HIF1A counteractes the inhibitory effects of YFJDT on proliferation, EMT, and VM in transplanted tumors. Moreover, HIF1A overexpression attenuates YFJDT-induced lipid peroxidation and iron accumulation, indicating inhibition of ferroptosis in A549 cells. Hypoxia-induced alterations in EMT markers and VM are reversed by YFJDT but exacerbated by HIF1A overexpression. Molecular docking identified salicylic acid and psoralen as potential components of YFJDT targeting HIF1A. YFJDT exerts anti-tumor effects in lung cancer by downregulating HIF1A and promoting ferroptosis.

Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis

Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis

Placental Ferroptosis May Be Involved in Prenatal Arsenic Exposure Induced Cognitive Impairment in Offspring.

The association between prenatal arsenic (As) exposure and offspring's cognition is still unclear, and the underlying etiology has also not been elucidated. Based on the Ma'anshan Birth Cohort (MABC) study in China, 1814 mother-child pairs were included in this study, and the association of As levels in cord serum with preschoolers' intelligence scores was explored. To validate the results from population study, in vivo models were adopted to observe the association between prenatal As exposure and spatial learning and memory abilities of mice offsprings. The As-exposure induced ferroptosis in the placenta of human beings as well as C57BL/6J mice and HTR-8/SVneo cells was explored in order to clarify the potential cause of impairment of offspring's cognitionrelated to As exposure, respectively. In the population study, we observed a significant inverse association between natural logarithm transformed (ln) As levels andpreschoolers' intelligence scores, especially forthe fluid reasoning index (FRI) [(β (95%CI): - 1.07 (- 1.98, - 0.16)] and working memory index (WMI) [β (95%CI): - 1.51 (- 2.76, - 0.25)]. Meanwhile, the data from in vivo models revealed that the learning and memory abilities of offspring mice decreased after prenatal As exposure. The occurrence of ferroptosis-like characteristics in the placenta and HTR-8/SVneo cells after As exposure was observed, accompanying with evident oxidative stress, iron accumulation, mitochondrial damage, and decreased protein levels of GPX4, xCT, and FTH1 (or FPN1). Notably, the ferroptosis-like alterations induced by NaAsO2 can be effectively alleviated by N-acetylcysteine (NAC) and ferrostatin-1 (Fer-1) treatment in HTR-8/SVneo cells, respectively. In conclusion,prenatal As exposure associates with impairment of offspring's cognition, and placental ferroptosis may be involved in the association. Further studies are needed to confirm the findings.

Plant-specific cochaperone SSR1 affects root elongation by modulating the mitochondrial iron-sulfur cluster assembly machinery.

To elucidate the molecular function of SHORT AND SWOLLEN ROOT1 (SSR1), we screened for suppressors of the ssr1-2 (sus) was performed and identified over a dozen candidates with varying degrees of root growth restoration. Among these, the two most effective suppressors, sus1 and sus2, resulted from G87D and T55M single amino acid substitutions in HSCA2 (At5g09590) and ISU1 (At4g22220), both crucial components of the mitochondrial iron-sulfur (Fe-S) cluster assembly machinery. SSR1 displayed a robust cochaperone-like activity and interacted with HSCA2 and ISU1, facilitating the binding of HSCA2 to ISU1. In comparison to the wild-type plants, ssr1-2 mutants displayed increased iron accumulation in root tips and altered expression of genes responsive to iron deficiency. Additionally, the enzymatic activities of several iron-sulfur proteins and the mitochondrial membrane potential were reduced in ssr1-2 mutants. Interestingly, SSR1 appears to be exclusive to plant lineages and is induced by environmental stresses. Although HSCA2G87D and ISU1T55M can effectively compensate for the phenotypes associated with SSR1 deficiency under favorable conditions, their compensatory effects are significantly diminished under stress. Collectively, SSR1 represents a new and significant component of the mitochondrial Fe-S cluster assembly (ISC) machinery. It may also confer adaptive advantages on plant ISC machinery in response to environmental stress.

Biotin Induces Inactive Chromosome X Reactivation and Corrects Physiopathological Alterations in Beta-Propeller-Protein-Associated Neurodegeneration

Neurodegeneration with brain iron accumulation (NBIA) involves a group of rare neurogenetic disorders often linked with iron overload in the basal nuclei of the brain presenting with spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration. Among NBIA subtypes, beta-propeller-protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45 (WD repeat domain 45). Previously, we demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism, and cell bioenergetics. In addition, antioxidant supplementation partially improved cell physiopathology; however, autophagy and cell bioenergetics remained affected. In this work, we explored the possibility of expressing the normal WDR45 allele present in the inactive chromosome X (Xi) of BPAN cells through treatment with epigenetic modulators. The aim of this study was to demonstrate whether biotin, an epigenetic nutrient, was able to restore the expression levels of WDR45 by a mechanism involving Xi reactivation and, consequently, correct BPAN defects. Our study demonstrated that biotin supplementation increases histone biotinylation and allows for the transcription of the WDR45 allele in Xi. Consequently, all physiopathological alterations in BPAN cells were notably corrected. The reactivation of Xi by epigenetic modulators can be a promising approach for the treatment of BPAN and other X-linked diseases.

Magnetic susceptibility components reveal different aspects of neurodegeneration in alpha-synucleinopathies.

Nigrostriatal dopaminergic degeneration in alpha-synucleinopathies is indirectly reflected by low dopamine transporter (DaT) uptake through [123I]FP-CIT-SPECT. Bulk magnetic susceptibility (χ) in the substantia nigra, from MRI-based quantitative susceptibility mapping (QSM), is a potential biomarker of nigrostriatal degeneration, however, QSM cannot disentangle paramagnetic (e.g. iron) and diamagnetic (e.g. myelin) sources. Using the susceptibility source-separation technique DECOMPOSE, paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) were studied in prodromal and overt alpha-synucleinopathies, and their relationships with DaT-SPECT specific binding ratio (SBR) and clinical scores. 78 participants were included (23 controls, 30 prodromal and 25 overt alpha-synucleinopathies). Prodromal patients were subdivided into groups with positive or negative DaT-SPECT (SBR Z-scores below or above -1, respectively). Correlations of putamen and caudate SBR Z-scores with PCS and DCS in the substantia nigra, putamen, and caudate were investigated. Increased PCS was observed in the substantia nigra of prodromal alpha-synucleinopathy patients with positive DaT-SPECT compared to controls and prodromal patients with negative DaT-SPECT. SBR Z-scores in the putamen correlated with increased PCS in the substantia nigra and reduced |DCS| in the putamen, which may reflect dopaminergic degeneration ascribable to iron accumulation and nigrostriatal neuron axonal loss, respectively.

Intricating connections: the role of ferroptosis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease with multiple tissue damage. However, the pathology remains elusive, and effective treatments are lacking. Multiple types of programmed cell death (PCD) implicated in SLE progression have recently been identified. Although ferroptosis, an iron-dependent form of cell death, has numerous pathophysiological features similar to those of SLE, such as intracellular iron accumulation, mitochondrial dysfunction, lipid metabolism disorders and concentration of damage associated-molecular patterns (DAMPs), only a few reports have demonstrated that ferroptosis is involved in SLE progression and that the role of ferroptosis in SLE pathogenesis continues to be neglected. Therefore, this review elucidates the potential intricate relationship between SLE and ferroptosis to provide a reliable theoretical basis for further research on ferroptosis in the pathogenesis of SLE.

Anemia and retinopathy of prematurity: A narrative review

ABSTRACTRetinopathy of prematurity (ROP) and anemia are often comorbid in preterm and low birth weight infants in the United States. However, the relationship between ROP and anemia in infants is unclear across prospective and retrospective studies due to confounding from other comorbidities of prematurity and variable study designs. Molecular mechanisms that may underlie this association include tissue hypoxia, oxidative stress, inflammation, and the timing of onset of anemia relative to the phase of ROP. Furthermore, maternal or neonatal disruptions in iron homeostasis, leading to either iron deficiency or accumulation, have been associated with ROP. Further studies, including randomized clinical trials, are needed to better elucidate the association between ROP and anemia, as well as the impact of the timing of the onset of anemia.

Glymphatic system in Pantothenase kinase associated neurodegeneration (PKAN).

To investigate if accumulation of iron in the globus pallidus as seen in patients suffering from Pantothenase Kinase Associated Neurodegeneration (PKAN), is related to damage of the cerebral glymphatic system. In a group of 24 patients and an age-matched control group, functionality of the glymphatic system was assessed by the index of Analysis aLong the Perivascular Space (ALPS) from Diffusion Tensor Imaging data and correlated to the values of the T2∗ Times of the globus pallidus and the cerebral white matter measured by a Fast Field Echo sequence. In spite of the important reduction of the T2∗ Time of the globus pallidus, ALPS values of patients and controls were very similar and did not correlate to T2∗Time values in either group. In spite of a prominent accumulation of iron in the globus pallidus of PKAN patients, which is responsible for the "eye-of-the-tiger" sign, our results are not compatible with malfunction of their glymphatic system. Obviously, increased iron content of globus pallidus alone does not necessarily indicate such sort of alteration.

A Chromosome-Level Genome Sequence Reveals Regulation of Salt Stress Response in Mesembryanthemum crystallinum.

Salt stress disturbs plant growth and photosynthesis due to its toxicity. The ice plant Mesembryanthemum crystallinum is a highly salt-tolerant facultative crassulacean acid metabolism (CAM) plant. However, the genetic basis of the salt tolerance mechanisms in ice plants remains unclear. In this study, we constructed a chromosome-level whole-genome sequence of the ice plant and performed transcriptome analysis of the effects of salt treatment on the leaves. After 24-hour 500 mM NaCl treatment to the roots, 1100 and 1394 genes, including CAM pathway, glycolysis, and inositol metabolism, were up- and down-regulated in the leaves, respectively. Salt treatment also influenced the abscisic acid (ABA) signaling components, including genes from the PYRABACTIN RESISTANCE1 (PYR1) family and the PROTEIN PHOSPHATASE 2CA (PP2CA) family. We detected the induction of the genes encoding various ion transporters after salt treatment. The expression of most v-ATPase subunits is induced, leading to vacuolar acidification, which facilitates sodium ion sequestration in the vacuoles. Additionally, some genes encoding metal ion transporters, including the genes from the ZIP family and NRAMP family, were induced by salt treatment, accompanied by the accumulation of iron, zinc, and copper ions in the leaves. Cis-motif enrichment analysis revealed that ABRE-like motifs and MYB-binding-like motifs were enriched in the upstream sequences of genes that were either up-regulated or down-regulated by salt. In conclusion, this study highlights how salt treatment induces drastic and rapid transcriptomic changes and unveils the ice plant's genomic foundation. Our resources provide further insights into the regulation of salt tolerance in the ice plants.

Crucial roles of asprosin in cisplatin-induced ferroptosis and acute kidney injury.

Ferroptosis is a type of non-apoptotic regulated cell death characterized by iron accumulation and lipid peroxidation. Cisplatin is an effective chemotherapy drug with several serious side effects including acute kidney injury (AKI). Asprosin is a peptide contributing to metabolism regulation and metabolic disorders. This study aimed to determine the role and mechanism of asprosin in AKI. Cisplatin was used to induce cell damage in mouse renal tubular epithelial (TCMK-1) cells and AKI in C57BL/6 mice. Cisplatin caused asprosin upregulation in cisplatin-treated TCMK-1cells and mice. In TCMK-1cells, asprosin overexpression led to iron overload and lipid peroxidation, while asprosin knockdown attenuated cisplatin-induced iron overload, lipid peroxidation and ferroptosis. Exogenous asprosin promoted cell damage and ferroptosis, which were attenuated by ferroptosis inhibitors. Asprosin-induced iron overload, lipid peroxidation, cell damage and SMAD1/5/8 phosphorylation were prevented by bone morphogenetic protein (BMP) type I receptor inhibitor. Integrin antagonist prevented asprosin-induced SMAD1/5/8 phosphorylation, and asprosin can specifically bind to integrin β3. Inhibition of integrin β3 reduced the asprosin-induced increases in Fe2+ and MDA levels. Asprosin knockdown relieved cisplatin-induced hepcidin upregulation, while hepcidin knockdown attenuated asprosin-induced iron overload, lipid peroxidation and ferroptosis. In cisplatin-induced AKI mice, specific knockdown of asprosin in the kidney not only attenuated renal dysfunction and damage, but also alleviated iron overload, lipid peroxidation and ferroptosis. These results indicated that excessively increased asprosin promotes TCMK-1cells ferroptosis and damage via integrin β3/BMP/hepcidin-mediated iron overload and lipid peroxidation. Silencing of asprosin attenuates renal injury and dysfunction in cisplatin-induced AKI by inhibiting ferroptosis.

Regional brain iron mapping in obstructive sleep apnea adults.

Obstructive sleep apnea (OSA) subjects show significant white matter injury, including myelin changes in several brain areas, potentially from impaired glial cells, contributing to increased iron levels that escalate neurodegeneration, but brain iron loads are unclear. Our aim was to examine regional brain iron load, using T2∗-relaxometry, in OSA adults before and after continuous positive airway pressure (CPAP) treatment over controls. We performed T2∗-weighted imaging using a 3.0-T MRI scanner on 35 OSA adults, who were followed after 3- and 9- mo CPAP treatment, and 67 controls. Using T2∗-weighted images, R2∗maps were calculated, normalized, and smoothed. The smoothed R2∗ maps, as well as average R2∗ values extracted from different brain regions were compared between OSA and controls using ANCOVA (covariates: age and sex) and paired t-tests in OSA adults. Multiple brain areas in OSA showed increased R2∗ values before CPAP, indicative of higher iron, over controls and included the amygdala, insula, hippocampus, cerebellum, medulla, and pons nearby areas. The R2∗ values continued to increase in multiple sites at 3-mo CPAP treatment in OSA, and those sites included the cerebellum, thalamus, and cingulate. However, after 9-mo CPAP usage, none of the brain regions showed increased R2∗ values in OSA over baseline. OSA patients show increased iron content in multiple sites over controls, which progressively increased in several sites, even after 3-mo CPAP use, and started to clear after 9-mo. The findings suggest a means for intervention to lessen brain injury by interfering with iron accumulation in OSA.

Iron Chelation Prevents Age-Related Skeletal Muscle Sarcopenia in Klotho Gene Mutant Mice, a Genetic Model of Aging.

A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging. Iron accumulation, especially catalytic iron (labile iron) through increased oxidative stress, could be one of the contributing factors to sarcopenia. Our study aimed to examine the effect of an iron chelator on age-related sarcopenia in mice. We investigated the effect of iron chelation (deferiprone, DFP) in sarcopenia, using mice with klotho deficiency (kl/kl), an established mouse model for aging. Four weeks old Klotho -/- male mice were treated with 25 mg/kg body weight of iron chelator deferiprone in drinking water for 8-14 weeks (n = 12/group, treated and untreated). At the end of the study, gastrocnemius, quadriceps and bicep muscles were dissected and used for western blot and immunohistochemistry analysis, histopathology and iron staining. Serum total iron, catalytic iron and cytokine ELISAs were performed with established methods. Treatment with DFP significantly reduced loss of muscle mass in gastrocnemius and quadriceps muscles (p < 0.0001). Total and catalytic iron content of serum and iron in muscles were significantly (both p < 0.0001) lower in the treated animals. The inhibitory factor of myogenesis, the myostatin protein in gastrocnemius muscles (p = 0.019) and serum (p = 0.003) were downregulated after 8 weeks of therapy accompanied by an increased in muscle contractile protein myosin heavy chain (~2.9 folds, p = 0.0004). Treatment decreased inflammation (serum IL6 and TNFα) (p < 0.0001, p = 0.005), respectively, and elevated insulin-like growth factor levels (p = 0.472). This was associated with reduced DNA damage and reduced 8-hydroxy 2 deoxyguanosine in muscle and HO-1 protein (p < 0.001, p = 079), respectively. Significant weight loss (p < 0.001) and decreased water intake (p = 0.012) were observed in untreated mice compared to treatment group. Kaplan-Meier survival curves show the median life span of treated mice was 108 days as compared to 63 days for untreated mice (p = 0.0002). In summary, our research findings indicate that deferiprone reduced age-related sarcopenia in the muscles of Klotho-/- mice. Our finding suggests chelation of excess iron could be an effective therapy to counter sarcopenia. However, additional studies are needed to evaluate and determine the efficacy in humans.

Hedyotis diffusa injection modulates the ferroptosis in bladder cancer via CAV1/JUN/VEGFA.

Hedyotis diffusa Willd. (HDW), a traditional Chinese medicinal plant, exhibits a variety of pharmacological effects and has anticancer potential for a wide range of cancer types; Ferroptosis is a non-apoptosis-regulated cell death induced by iron accumulation and subsequent lipid peroxidation; and there is currently an increasing interest in the therapeutic role of ferroptosis in cancer. However, the effects of HDW on bladder cancer and its underlying molecular mechanisms remain largely unknown. In this study, a combination of in vivo and in vitro experiments, network pharmacology and data mining methods were used to investigate the effects of HDW on BLCA. The results showed that HDW exerted its anticancer activity by inducing ferroptosis in bladder cancer cells. Subsequently, we demonstrated for the first time that HDW induced ferroptosis in vitro and in vivo. To further explore the possible targets of HDW-induced ferroptosis in bladder cancer, we performed network pharmacological analyses, transcriptomic analyses, and single-cell analyses; through integrative analyses, we identified three key pivotal genes associated with iron death, CAV1, VEGFA, and JUN.Mechanistically, we showed that CAV1, VEGFA and JUN are key determinants of HDW-induced ferroptosis in BLCA. Knockdown of target genes altered the anticancer effects of HDW in 5637 and T24 cells. In conclusion, our data show for the first time that HDW exerts its anticancer effects on BLCA through CAV1, VEGFA and JUN gene-induced ferroptosis. This is expected to provide a promising compound for bladder cancer therapy.

Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway.

Osteosarcoma is a common malignant tumor found in adolescents, characterized by a high metastatic potential and poor prognosis, but it is sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of regulated cell death induced by excessive iron accumulation, leading to lipid peroxidation that results in cellular dysfunction and death. Naringenin is a flavonoid known for its anti-cancer properties, yet its role in osteosarcoma has not been thoroughly studied. In this study, we found that naringenin significantly reduced the viability of osteosarcoma cells while increasing the accumulation of reactive oxygen species (ROS), iron overload, and the excessive expression of malondialdehyde (MDA). Bioinformatics analysis revealed that microsomal glutathione S-transferase 2 (MGST2) is highly expressed in osteosarcoma cells. Silencing MGST2 decreased the proliferation, migration, and invasion of these cells and enhanced their sensitivity to ferroptosis. Mechanistically, signal transducer and activator of transcription 3 (STAT3) binds to the MGST2 promoter, promoting its transcription. Naringenin inhibits STAT3, blocking the expression of MGST2, while the STAT3 agonist Colivelin reverses this effect. In vivo experiments further confirmed that naringenin inhibited tumor growth in subcutaneous xenograft models and exhibited good biosafety. In summary, our study demonstrates that naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway, providing a promising strategy for osteosarcoma treatment.

Whole Brain MRI Assessment of Age and Sex-Related R2* Changes in the Human Fetal Brain.

Iron in the brain is essential to neurodevelopmental processes, as it supports neural functions, including processes of oxygen delivery, electron transport, and enzymatic activity. However, the development of brain iron before birth is scarcely understood. By estimating R2* (1/T2*) relaxometry from a sizable sample of fetal multiecho echo-planar imaging (EPI) scans, which is the standard sequence for functional magnetic resonance imaging (fMRI), across gestation, this study investigates age and sex-related changes in iron, across regions and tissue segments. Our findings reveal that brain R2* levels significantly increase throughout gestation spanning many different regions, except the frontal lobe. Furthermore, females exhibit a faster rate of R2* increase compared to males, in both gray matter and white matter. This sex effect is particularly notable within the left insula. This work represents the first MRI examination of iron accumulation and sex differences in developing fetal brains. This is also the first study to establish R2* estimation methodology in fetal multiecho functional MRI.

Table Grape Ferritin1 Is Implicated in Iron Accumulation, Iron Homeostasis, and Plant Tolerance to Iron Toxicity and H2O2 Induced Oxidative Stress

Table Grape Ferritin1 Is Implicated in Iron Accumulation, Iron Homeostasis, and Plant Tolerance to Iron Toxicity and H2O2 Induced Oxidative Stress

Assessment of cardiac iron deposition and genotypic classification in pediatric beta-thalassemia major: the role of cardiac MRI

BackgroundBeta thalassemia major (β-TM) is a severe genetic anemia with considerable phenotypic heterogeneity. This study investigated whether genotype correlates with distinct myocardial iron overload patterns, assessed by cardiovascular magnetic resonance (CMR) T2* values.MethodsCMR data for cardiac iron deposition evaluation, which recruited pediatric participants between January 2021 and December 2024, were analyzed with CVI42. The patients were classified into three genetic subgroups of β0/β0, β0/β+, and β+/β+ based on their genetic outcomes. The CMR results classified patients into normal myocardial T2* value and myocardial iron overload groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics.ResultsThe study included 145 pediatric β-TM patients, with 24 (17%) exhibiting cardiac iron deposition based on CMR T2* values. There were significant differences in iron chelation treatment strategies across genotypes, with the β0/β0 genotype accounting for 54% (13/24) of patients in the cardiac iron deposition group. Regardless of genotype, the mid-inferolateral segment consistently showed the lowest CMR T2* values and the highest prevalence of iron deposition.ConclusionThe risk of cardiac iron deposition increases as age progresses, and the mid-inferolateral segment is more susceptible to iron accumulation. The β0/β0 genotype is more likely to suffer from cardiac iron overload, emphasizing the need for closer clinical monitoring and regular cardiac MRI evaluations.

Intracellular iron accumulation throughout the progression of sepsis influences the phenotype and function of activated macrophages in renal tissue damage

Intracellular iron accumulation throughout the progression of sepsis influences the phenotype and function of activated macrophages in renal tissue damage

Molecular Dynamics Simulation of Low-Cycle Fatigue Behavior of Single/Polycrystalline Iron

The fatigue plastic mechanism and dislocation characteristics of engineering materials are the key to studying fatigue damage. In this study, the molecular dynamics (MD) method was employed to investigate the microstructural characteristics and fatigue mechanical properties of both single-crystalline and polycrystalline iron under varying strain amplitudes associated with cyclic hardening, cyclic softening, and cyclic saturation. The occurrence, accumulation, and formation process of the local plastic fatigue damage of monocrystalline/polycrystalline iron under fatigue load are discussed. The local plastic initiation and accumulation of single-crystal iron occur at the intersection of slip planes, which is the dislocation source. The 1/2&lt;111&gt; dislocation plays an important role in the fatigue plastic accumulation of single-crystal iron. Polycrystalline iron undergoes grain rotation and coalescence during cyclic loading. The grain size responsible for plastic deformation gradually increases. The initiation and accumulation of local plasticity occurs at the grain boundary, which eventually leads to fatigue damage at the grain boundary.