TST has been mainly studied for its anti-tumor proliferation and antimicrobial effects, but not widely used in dermatological diseases. The mechanism of cellular damage by TST in response to H2O2-mediated oxidative stress was investigated in human skin immortalized keratinocytes (HaCaT) as an in vitro model. The findings reveal that TST treatment leads to increased oxidative stress in the cells by reducing levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). This effect is further supported by an upsurge in the expression of malondialdehyde (MDA, a pivotal marker of lipid peroxidation). Additionally, dysregulation of FoxM1 at both gene and protein levels corroborates its involvement TST associated effects. Analysis of ferroptosis-related genes confirms dysregulation following TST treatment in HaCaT cells. Furthermore, TST treatment exhibits effects on mitochondrial morphology and function, affirming its induction of apoptosis in the cells through heightened oxidative stress due to mitochondrial damage and dysregulation of mitochondrial membrane potential.

Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. To investigate the effects of PPD exposure on the risk of allergic asthma, we established a PPD exposure group in a mouse model. The dose administered for PS-MP was 0.1 mg/d and for DBP was 30 mg/kg/d, with a 5-week oral administration period. The pathological changes of airway tissue and the increase of oxidative stress and inflammatory response confirmed that PPD aggravated eosinophilic allergic asthma in mice. The mitochondrial morphological changes and metabolomics of mice confirmed that ferrotosis and oxidative stress played key roles in this process. Treatment with 100 mg/Kg deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological. Our findings suggest that the increased levels of reactive oxygen species (ROS) in the lungs lead to Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-5, and eosinophils, and reduced INF-γ levels. This inflammatory response is mediated by the NFκB pathway and exacerbates type I hypersensitivity through increased IL-4 production. In this study, the molecular mechanism by which PPD aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PPD and lays a theoretical foundation for addressing the health risks posed by PPD.

BACKGROUND: Iron deposition and ferroptosis are involved in ischemic stroke injury, but the choice of drugs for treatment is limited.
OBJECTIVE: To investigate the potential neuroprotective effects of Rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on ischemic stroke.
METHODS: Wild-type (WT) and TfR1EC cKO (specific knockout of the TfR1 gene in BMECs) mice used to establish a dMCAO model, with simultaneous administration of RosA-LIP (20 mg/kg/d, i.p.) or RosA (20 mg/kg/d, i.p.).
RESULTS: The successful synthesis of RosA-LIP resulted in enhanced stability and precise delivery in both the serum and brain. The administration of RosA-LIP effectively mitigated ischemia-induced behavioral abnormalities and pathological damage. RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation. RosA-LIP effectively improved blood‒brain barrier (BBB) permeability, increased tight junctions (TJs) protein expression and reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels. Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO.
CONCLUSIONS: RosA-LIP effectively increased the brain level of RosA and protected against ferroptosis through the regulation of TfR1 in BMECs.

UNASSIGNED: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain.
UNASSIGNED: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis.
UNASSIGNED: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development.
UNASSIGNED: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased.
UNASSIGNED: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Copper (Cu) is a common trace element additive in animal and human foods, and excessive intake of Cu has been shown to cause hepatotoxicity, but the underlying mechanism remains unclear. Our previous research found that Cu exposure dramatically upregulated mitochondrial miR-12294-5p expression and confirmed its targeted inhibition of CISD1 expression in chicken hepatocytes. Thus, we aimed to explore the potential role of mitomiR-12294-5p/CISD1 axis in Cu exposure-resulted hepatotoxicity. Here, we observed that Cu exposure resulted in Cu accumulation and pathological injury in chicken livers. Moreover, we found that Cu exposure caused mitochondrial-dependent ferroptosis in chicken hepatocytes, which were prominent on the increased mitochondrial Fe2+ and mitochondrial lipid peroxidation, inhibited levels of CISD1, GPX4, DHODH, and IDH2, and also enhanced level of PTGS2. Notably, we identified that inhibition of mitomiR-2954 level effectively mitigated Cu-exposure-resulted mitochondrial Fe2+ accumulation and mitochondrial lipid peroxidation and prevented the development of mitochondrial-dependent ferroptosis. However, increasing the mitomiR-12294-5p expression considerably aggravated the influence of Cu on these indicators. Meanwhile, the overexpression of CISD1 effectively alleviated Cu-caused mitochondrial-dependent ferroptosis, while silent CISD1 eliminated the therapeutic role of mitomiR-12294-5p inhibitor. Overall, our findings indicated that mitomiR-12294-5p/CISD1 axis played a critical function in Cu-caused hepatotoxicity in chickens by regulating mitochondrial-dependent ferroptosis.

Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with immune cells being a crucial component of the body\'s immune system. This review provides an overview and discusses the relationship between ferroptosis, programmed cell death in immune cells, and autoimmune diseases. Additionally, it summarizes the role of various key targets of ferroptosis, such as GPX4 and TFR, in immune cell immune responses. Furthermore, the release of multiple molecules, including damage-associated molecular patterns (DAMPs), following cell death by ferroptosis, is examined, as these molecules further influence the differentiation and function of immune cells, thereby affecting the occurrence and progression of autoimmune diseases. Moreover, immune cells secrete immune factors or their metabolites, which also impact the occurrence of ferroptosis in target organs and tissues involved in autoimmune diseases. Iron chelators, chloroquine and its derivatives, antioxidants, chloroquine derivatives, and calreticulin have been demonstrated to be effective in animal studies for certain autoimmune diseases, exerting anti-inflammatory and immunomodulatory effects. Finally, a brief summary and future perspectives on the research of autoimmune diseases are provided, aiming to guide disease treatment strategies.

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxidation, is involved in various cardiovascular diseases. (Pro)renin receptor (PRR) in performs as ligands in the autophagic process, and its function in diabetic cardiomyopathy (DCM) is not fully understood. We investigated whether PRR promotes ferroptosis through the nuclear receptor coactivator 4 (NCOA 4)-mediated ferritinophagy pathway and thus contributes to DCM. We first established a mouse model of DCM with downregulated and upregulated PRR expression and used a ferroptosis inhibitor. Myocardial inflammation and fibrosis levels were then measured, cardiac function and ferroptosis-related indices were assessed. In vitro, neonatal rat ventricular primary cardiomyocytes were cultured with high glucose and transfected with recombinant adenoviruses knocking down or overexpressing the PRR, along with a ferroptosis inhibitor and small interfering RNA for the ferritinophagy receptor, NCOA4. Ferroptosis levels were measured in vitro. The results showed that the knockdown of PRR not only alleviated cardiomyocyte ferroptosis in vivo but also mitigated the HG-induced ferroptosis in vitro. Moreover, administration of Fer-1 can inhibit HG-induced ferroptosis. NCOA4 knockdown blocked the effect of PRR on ferroptosis and improved cell survival. Our result indicated that inhibition of PRR and NCOA4 expression provides a new therapeutic strategy for the treatment of DCM. The effect of PRR on the pathological process of DCM in mice may be in promoting cardiomyocyte ferroptosis through the NCOA 4-mediated ferritinophagy pathway.

In recent years, the development of spatial transcriptomic technologies has enabled us to gain an in-depth understanding of the spatial heterogeneity of gene expression in biological tissues. However, a simple and efficient tool is required to analyze multiple spatial targets, such as mRNAs, miRNAs, or genetic mutations, at high resolution in formalin-fixed paraffin-embedded (FFPE) tissue sections. In this study, we developed hydrogel pathological sectioning coupled with the previously reported Sampling Junior instrument (HPSJ) to assess the spatial heterogeneity of multiple targets in FFPE sections at a scale of 180 μm. The HPSJ platform was used to demonstrate the spatial heterogeneity of 9 ferroptosis-related genes (TFRC, NCOA4, FTH1, ACSL4, LPCAT3, ALOX12, SLC7A11, GLS2, and GPX4) and 2 miRNAs (miR-185-5p and miR522) in FFPE tissue samples from patients with triple-negative breast cancer (TNBC). The results validated the significant heterogeneity of ferroptosis-related mRNAs and miRNAs. In addition, HPSJ confirmed the spatial heterogeneity of the L858R mutation in 7 operation-sourced and 4 needle-biopsy-sourced FFPE samples from patients with lung adenocarcinoma (LUAD). The successful detection of clinical FFPE samples indicates that HPSJ is a precise, high-throughput, cost-effective, and universal platform for analyzing spatial heterogeneity, which is beneficial for elucidating the mechanisms underlying drug resistance and guiding the prescription of mutant-targeted drugs in patients with tumors.

Intermittent hypoxia (IH) is an independent risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD). Copper deficiency can disrupt redox homeostasis, iron, and lipid metabolism. Here, we investigated whether hepatic copper deficiency plays a role in IH-associated MAFLD and explored the underlying mechanism(s). Male C57BL/6 mice were fed a western-type diet with adequate copper (CuA) or marginally deficient copper (CuD) and were exposed separately to room air (RA) or IH. Hepatic histology, plasma biomarkers, copper-iron status, and oxidative stress were assessed. An in vitro HepG2 cell lipotoxicity model and proteomic analysis were used to elucidate the specific targets involved. We observed that there were no differences in hepatic phenotypes between CuA-fed and CuD-fed mice under RA. However, in IH exposure, CuD-fed mice showed more pronounced hepatic steatosis, liver injury, and oxidative stress than CuA-fed mice. IH induced copper accumulation in the brain and heart and exacerbated hepatic copper deficiency and secondary iron deposition. In vitro, CuD-treated cells with IH exposure showed elevated levels of lipid accumulation, oxidative stress, and ferroptosis susceptibility. Proteomic analysis identified 360 upregulated and 359 downregulated differentially expressed proteins between CuA and CuD groups under IH; these proteins were mainly enriched in citrate cycle, oxidative phosphorylation, fatty acid metabolism, the peroxisome proliferator-activated receptor (PPAR)α pathway, and ferroptosis. In IH exposure, CuD significantly upregulated the ferroptosis-promoting factor arachidonyl-CoA synthetase long chain family member (ACSL)4. ACSL4 knockdown markedly eliminated CuD-induced ferroptosis and lipid accumulation in IH exposure. In conculsion, IH can lead to reduced hepatic copper reserves and secondary iron deposition, thereby inducing ferroptosis and subsequent MAFLD progression. Insufficient dietary copper may worsen IH-associated MAFLD.