Search Results (222)

The Minxinan black rabbit (MBR) is a valuable genetic resource in China. In this study, we compared meat quality between indigenous MBR and introduced Hyla rabbit (CIR) using multi-omics and phenotypic analyses. We identified 1175 differentially expressed genes (DEGs) and 327 differentially expressed proteins (DEPs) with 32 overlapping. Antioxidant-related pathways (glutathione metabolism, peroxidase activity, and HIF-1) were enriched, with upregulated superoxide dismutase 1 (SOD1) and gamma (γ)-glutamylcyclotranserase (GGCT) (p < 0.05), enhancing the antioxidant capacity in MBR. Meanwhile, key proteins (GSTM3, ENSOCUG00000024443, and ENSOCUG00000009681) in the glutathione and cytochrome P450 pathways may regulate meat color by reducing oxidative stress. Phenotypic analysis confirmed that the MBRs had increased redness (a*), yellowness (b*), melanin, and myoglobin (p < 0.05). Additionally, proteins involved in fatty acid metabolism (ACSL6), purine metabolism (NME2 and NME4), tight junctions (MYL10), and amino acid biosynthesis (ENO1) are involved in regulating fatty acid content, which can influence meat flavor quality. Notably, MBR meat exhibited significantly increased levels of unsaturated fatty acids (UFAs) and glycine (p < 0.05), which regulate meat flavor. MBR demonstrated superior antioxidant capacity, color, and flavor, thus providing a scientific foundation for optimizing conservation strategies. Full article

This study aimed to examine the role of maternal BPS gestational and lactational exposure to BPS in neurotoxicity in offspring mice and to uncover the regulatory mechanisms driven by microglial ferroptosis. In this study, C57BL/6J mice were treated with BPS during pregnancy and lactation. The results revealed that BPS induced memory impairment and anxiety in offspring mice, accompanied by abnormal expression levels of brain neurotrophic factor and synaptic plasticity factor (PSD95, SYP). Additionally, exposure to BPS activated microglia by upregulating the expression of IBA1 and concurrently promoting the release of inflammatory factors in the hippocampus and cortex. BPS exposure also contributed to iron overload, aberrant mitochondrial morphology, oxidative stress, and abnormal expression of ferroptosis-associated genes (GPX4, SCL7A11, TFR1, ACSL4) in the brains of offspring mice. Importantly, immunofluorescence analysis demonstrated concomitant microglial activation and ferroptosis in the brain tissue of offspring mice following BPS exposure. Moreover, experiments in BV2 microglial cells showed that the ferroptosis inhibitor Fer-1 reversed BPS-induced microglial ferroptosis and the release of inflammatory cytokines. These findings collectively elucidate the regulatory role mechanism of microglial ferroptosis in BPS-induced neurotoxicity in offspring mice, and we propose potential therapeutic targets for attenuating BPS-mediated neurotoxic effects. Full article

Nickel is a pervasive heavy metal with the potential for multi-route exposure, raising significant concerns regarding systemic toxicity. Although Ni²⁺ has been implicated in nickel sulfate NiSO₄-induced neurotoxicity, its underlying mechanisms remain incompletely elucidated. The present study investigates the role of NiSO₄-induced ferroptosis as a potential contributor to neurotoxicity. C57BL/6 mice were administered NiSO₄ daily via oral gavage at doses of 50, 100, and 200 mg/kg over 28 days. Neurobehavioral assessments, histopathological examination, transmission electron microscopy, and molecular profiling were conducted to evaluate brain injury and ferroptotic activity. Gut microbiota composition and intestinal barrier integrity were systematically evaluated. In vitro, HT22 cells were subjected to NiSO₄ treatment, followed by integrative transcriptomic analysis complemented by pharmacological and genetic manipulation to delineate the contributions of ferroptosis and autophagy. The results demonstrated that NiSO₄ exposure inhibited body weight gain, elicited depression-like behaviors, and initiated ferroptosis, evidenced by ultrastructural mitochondrial damage and dysregulated expression of glutathione peroxidase 4/acyl-CoA synthetase long chain family member 4 (GPX4/ACSL4). Furthermore, NiSO₄ caused gut microbiota dysbiosis and compromised the intestinal barrier, which was correlated with the induction of ferroptosis in neuronal cells of the brain. In HT22 cells, NiSO₄ elicited dose-dependent cytotoxicity and lactate dehydrogenase (LDH) release. KEGG pathway enrichment analysis further revealed that NiSO₄ treatment significantly upregulated pathways associated with ferroptosis, autophagy, and lysosomal function. Moreover, both ferrostatin-1 and rapamycin attenuated NiSO₄-induced cytotoxicity and ferroptosis, indicating that autophagy serves a protective function against ferroptotic cell death. Additionally, overexpression of Transcription Factor EB (TFEB) attenuated NiSO₄-induced ferroptosis by downregulating ACSL4, and upregulating GPX4, implicating the autophagy–lysosome pathway in the protective regulation of this cell death process. In summary, our findings indicated that NiSO₄-induced neurotoxicity was strongly associated with gut microbiota dysbiosis and coincided with ferroptosis in the brain, while stimulation of the autophagy–lysosome pathway conferred neuroprotective effects via modulating TFEB-dependent anti-ferroptotic mechanisms. These findings offer novel insights for risk assessment and therapeutic strategies of nickel-related neurotoxicity. Full article

This study aimed to collaboratively investigate the mechanism of variations in intramuscular fat (IMF) content in Wandong cattle using transcriptomics and metabolomics techniques. Longissimus dorsi (LD) muscle samples were collected from thirteen free-range Wandong cattle in Fengyang County, Anhui Province, China. From this initial cohort, eight animals closely matched in age and body weight were selected. Based on IMF content measured by Soxhlet extraction, these eight cattle were divided into two groups: the high-IMF (HF, n = 4) and low-IMF (LF, n = 4) groups. Subsequent analyses were performed on integrated datasets comprising the transcriptome, metabolome, and fatty acid profile. The results revealed a significant increase in IMF in the HF group compared to the LF group (p < 0.05). Specifically, α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6) were significantly more abundant in the LF group compared to the HF group (p < 0.05), whereas oleic acid (C18:1n9c) and cis-9-palmitoleic acid (C16:1) predominated in the HF group. However, saturated fatty acids (SFAs), such as myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), and Margaric acid (C17:0), did not show significant differences (p > 0.05). A total of 9164 differentially expressed genes (DEGs) were identified via transcriptome analysis, with 2202 genes upregulated and 6962 genes downregulated in the HF group compared to the LF group. The expression profiles exhibited a distinct pattern, characterized by the upregulation of genes such as FABP1, SREBF1, and LIPE, while genes including SCD, PPARGC1A, and LEP were downregulated. GO enrichment analysis demonstrated that the majority of DEGs were predominantly abundant across 25 distinct functional categories distributed across the three primary ontologies. KEGG pathway analysis further identified 341 significantly enriched signaling pathways in the HF group (p < 0.05), predominantly involving metabolic pathways, FoxO, AMPK, and PPAR signaling pathways. Untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics analysis revealed 404 differential accumulated metabolites (DAMs), with 187 in positive ion mode and 217 in negative ion mode (p < 0.05). These DAMs were notably enriched in pathways such as glycerophospholipid metabolism, terpene and steroid biosynthesis, fatty acid degradation, and fatty acid metabolism. Notably, C16:1, C18:1n9c, arachidonic acid (peroxide free) (C20:4n6), oleoyl-L-carnitine, and linoleoyl-carnitine were identified as key players in lipid metabolism. Integrating transcriptomics with metabolomics data unveiled significant associations between DAMs linked to lipid metabolism and DEGs. Specifically, C18:1n9c exhibited a positive correlation with LPIN3, while C16:1 showed negative associations with PPAP2B, PPAP2A, CDS2, HADHA, LPL, HSD17B12, ELOVL5, ACSL1, and ACOX1, and positive correlations with PLA2G15, CDIPT, AGPSBG1, and GPD1. In summary, the variation in IMF content in Wandong cattle is co-regulated by key genes (SREBF1, ACSL1, SCD) via the AMPK, PPAR, and FoxO signaling pathways, coupled with alterations in specific fatty acid metabolites such as C18:1n9c, C16:1, and C20:4n6. These findings provide critical molecular insights for the genetic selection and breeding of Wandong cattle, which are renowned for their superior meat quality. Full article

Background/Objective: Colon cancer, the third most diagnosed cancer worldwide, is anatomically classified into right- and left-sided colon cancers based on embryonic origin and vascular supply. The aim of this study was to investigate molecular differences between patients with right- and left-sided colon cancer. Methods: In this pilot study, Blood samples from right-sided (n = 6) and left-sided (n = 6) colon cancer patients, as well as healthy controls (n = 6), were analyzed for 92 cancer-related genes via RT-qPCR. KEGG pathway analysis was performed with ShinyGO 0.82, and gene–metabolite interactions were assessed using EnrichR and MetaboAnalyst 6.0. Additionally, patients’ sociodemographic and clinical data were analyzed. Results: KEGG analysis revealed that p53, HIF-1, TNF, PI3K/Akt, MAPK, and Rap1 signaling pathways were enriched in right-sided colon cancer, whereas VEGF, HIF-1, MAPK, PI3K/Akt, Rap1, and Ras signaling pathways were implicated in left-sided colon cancer. In the gene–metabolite analysis, key metabolites identified in right-sided colon cancer included palmitic acid, adenosine triphosphate (ATP), glycerol, and adenosine diphosphate (ADP), associated with genes such as ACSL4, TP53, MAPK14, FLT1, AURKA, KDR, ERCC3, and PFKL. For left-sided colon cancer, glucose-6-phosphate (G6P), ATP, ADP, glycerol, and palmitoyl-CoA were key metabolites forming the basis of the gene–metabolite network, along with genes including G6PD, PFKL, MAPK14, FLT1, CDK4, AURKA, MAP2K1, ERCC3, TP53, WEE1, and GPD2. Conclusions: These findings highlight distinct molecular profiles between right- and left-sided colon cancers, particularly in pathways related to angiogenesis, apoptosis, ferroptosis, and fatty acid metabolism, which may inform therapeutic strategies. Full article

Nasopharyngeal carcinoma (NPC) is a head and neck malignancy strongly associated with Epstein–Barr virus (EBV) infection and characterized by high radiosensitivity but frequent therapy resistance. Despite advances in radiotherapy, chemotherapy, and immunotherapy, relapse and metastasis remain major challenges, underscoring the need for novel therapeutic approaches. This review aims to provide an integrated overview of the molecular mechanisms governing ferroptosis in NPC and to clarify how these pathways contribute to therapy resistance while revealing potential therapeutic vulnerabilities. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising target in NPC. Core regulators include the system xCT–GSH–GPX4 antioxidant axis, iron metabolism, and lipid remodeling enzymes such as ACSL4, with epigenetic modifiers (METTL3, IGF2BP2, HOXA9) and EBV-driven signaling further shaping ferroptosis responses. EBV-driven oncogenic programs substantially reshape ferroptosis sensitivity in NPC by activating the Nrf2/Keap1 antioxidant axis, stabilizing SLC7A11 and GPX4, and modulating iron and redox metabolism. These viral mechanisms suppress ferroptotic stress and contribute to both radioresistance and chemoresistance. Suppression of ferroptosis underlies both radioresistance and chemoresistance, whereas restoration of ferroptosis re-sensitizes tumors to treatment. Natural compounds including solasodine, berberine, cucurbitacin B, and celastrol-curcumin combinations, as well as pharmacologic modulators such as HO-1 inhibitors and GPX4 antagonists, have shown ferroptosis-inducing effects in preclinical models, although their translational potential remains to be clarified. Nanotechnology-based platforms (e.g., Bi₂Se₃ nanosheet hydrogels) further enhance efficacy and reduce toxicity by enabling controlled drug delivery. Biomarker discovery, encompassing ferroptosis-related gene signatures, epigenetic regulators, immune infiltration patterns, EBV DNA load, and on-treatment redox metabolites, provides a foundation for patient stratification. Integration of ferroptosis modulation with radiotherapy, chemotherapy, and immunotherapy represents a compelling strategy to overcome therapy resistance. In synthesizing these findings, this review highlights both the mechanistic basis and the translational promise of ferroptosis modulation as a strategy to overcome treatment resistance in NPC. Future directions include biomarker validation, optimization of drug delivery, early-phase clinical trial development, and multidisciplinary collaboration to balance ferroptosis induction in tumors while protecting normal tissues. Collectively, ferroptosis is emerging as both a vulnerability and a therapeutic opportunity for improving outcomes in NPC. Full article

This study investigates the genetic architecture of Salsk sheep—a long-established Russian Merino-type breed from the southern steppes—highlighting their broad genetic diversity, resilience to cold and drought, and dual-purpose (wool and meat) productivity as a unique gene pool shaped by natural and artificial selection. The study used data from 96 sheep. Genotyping was carried out on the Illumina Ovine Infinium^® HD BeadChip platform, and after filtering, 511,145 SNPs were retained. We assessed population structure and genetic diversity using principal component analysis (PCA), Fst, and linkage disequilibrium (LD) in comparison with four reference European breeds. To detect selection signatures, we employed a combination of complementary methods, including intra-population statistics (iHS, nSL, iHH12) and inter-population comparisons (XP-EHH). This integrated approach identified genomic regions under positive selection, reflecting the breed’s evolutionary response to both natural and artificial selection pressures. Strong selection signals were detected in genes associated with production traits like fertility and growth (CCSER1, SOX6), as well as fundamental adaptive functions, including immune response (IL6R, NLRP1) and energy metabolism (ACSL5, FANCA). These results elucidate the genetic basis of the Salsk breed’s high resilience and highlight its potential as a valuable genetic resource for improving this trait in other sheep populations. Full article

Anaplastic thyroid cancer (ATC) is among the most lethal human malignancies, characterized by rapid progression, therapeutic resistance, and a median survival of less than one year. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited effect, and targeted or immune-based treatments provide only transient benefit. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has recently emerged as a therapeutic vulnerability in ATC. This review synthesizes current evidence on ferroptosis biology, preclinical validation, and therapeutic implications in ATC. Genomic alterations such as TP53, BRAF^V600E, RAS, and PIK3CA converge on redox imbalance and metabolic rewiring, rendering ATC cells dependent on antioxidant defenses. Dysregulated iron homeostasis through ferritinophagy and HO-1 activity, together with lipid remodeling via ACSL4 and LPCAT3, further sensitizes ATC to ferroptosis. Preclinical studies show that pharmacological inducers, including vitamin C, tenacissoside H, neferine, curcumin, and shikonin, as well as targeted agents such as dabrafenib and anlotinib, can trigger or synergize with ferroptosis. Genetic regulators, including SIRT6, the GPR34–USP8 axis, and the EIF3H–β-catenin pathway, modulate ferroptosis sensitivity, while RON receptor signaling links glycolysis to ferroptosis resistance. Combination regimens provide further translational potential. Nanoplatforms also offer innovative delivery strategies. Therapeutic approaches include initiating ferroptosis through iron and PUFA enrichment, disabling defenses such as GPX4 and Nrf2, and integrating ferroptosis inducers with existing modalities. Although systemic toxicity and resistance remain obstacles, biomarker-driven selection and drug repurposing offer promise. Ferroptosis represents a mechanistically distinct and clinically exploitable pathway for ATC. Full article

Background: Previous studies have indicated an association between endoplasmic reticulum stress (ERS) and the formation of kidney stones. To further investigate this mechanism, this research sought to identify key genes linked to ERS in calcium oxalate (CaOx) kidney stones. Methods: Key cells with the highest ERS-related gene (ERSRG) scores were identified through single-cell analysis. These key cells were then categorized into high- and low-score groups based on their average ERSRG scores. To identify key genes, we analyzed the intersection of key ERSRGs and differentially expressed genes (DEGs) within key cells, focusing on genes demonstrating significant expression differences between control and CaOx kidney stone samples. A nomogram was constructed using these key genes to predict the risk of CaOx kidney stones. Gene set enrichment analysis (GSEA) was further performed to explore the functions of these key genes in the disease. Additionally, secondary clustering analysis was conducted on key cells to identify subtypes and evaluate the expression of key genes within these subtypes. Finally, the identified key genes were validated using quantitative real-time PCR (qRT-PCR) and Western blot analysis on cultured HK-2 cells, which were exposed with 2 mM CaOx for 24 h at 37 °C with 5% CO₂ or incubated with regular culture medium. Results: Endothelial cells were identified as key cells, and nine key genes were pinpointed in CaOx kidney stones: ACSL4, PTK2, DUSP4, MMP7, PHLDB2, TGM2, PPT1, SPARCL1, and LTF. The nomogram developed from these key genes demonstrated robust predictive ability for CaOx kidney stones risk. Additionally, GSEA revealed that olfactory transduction was enriched by key genes except PTK2. Secondary clustering analysis identified four key cell subtypes within endothelial cells, with LTF, MMP7, and SPARCL1 showing significantly differential expression between control and CaOx kidney stones groups across all key cell subtypes. qRT-PCR and Western blot analyses revealed that, compared to the control group, CaOx-exposed HK-2 cells exhibited significantly increased expression of ACSL4, MMP7, TGM2, PPT1, and LTF (p < 0.05), while showing significantly decreased expression of PTK2, DUSP4, SPARCL1, and PHLDB2 (p < 0.05). Conclusions: This study identified key genes associated with ERS in CaOx kidney stones through single-cell and transcriptomic analysis. The discovery of these genes provides new insights into the treatment of CaOx kidney stones and offers valuable references for subsequent research. Future research should focus on elucidating the precise roles of these candidate genes in CaOx stone pathogenesis to assess their potential for therapeutic intervention. Full article

Cerebral ischemic reperfusion injury (CIRI) induces irreversible neurological dysfunction with high morbidity and mortality, yet effective clinical interventions remain limited. This study focused on ferroptosis in CIRI and explored the neuroprotective components and mechanisms of Pomelo peel essential oil (PPEO)—a product derived from Guangxi’s characteristic Shatian pomelo. Sprague-Dawley rats were used to establish two CIRI models: focal CIRI via Middle Cerebral Artery Occlusion (MCAO) and global CIRI via Cardiac Arrest/Cardiopulmonary Resuscitation (CA/CPR). Analyses were conducted using metabolomics, transcriptomics, histopathological staining, biochemical assays, RT-qPCR, Western blotting (WB), and molecular docking. Metabolomic results showed altered lipid-related metabolites in both models, predominantly unsaturated fatty acids and components of the arachidonic acid (AA) metabolic pathway. Transcriptomic analysis revealed significant upregulation of PTGS1/2 in the MCAO model. Nootkatone and β-pinene improved neuronal morphology, increased glutathione peroxidase 4 (GPX4) levels, and enhanced neurological scores. Notably, Nootkatone exhibited strong binding affinity to ALOX15, and reduced lipid metabolic disturbances in the CA/CPR model. AA metabolism varies with CIRI severity: it is inflammation-driven in focal CIRI and ferroptosis-associated in global CIRI. As a key component of PPEO, Nootkatone antagonizes ferroptosis via the ACSL4-LPCAT3-ALOX15 axis, offering a novel therapeutic target for global CIRI after CA/CPR. Full article

Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in the pathogenesis of cardiometabolic diseases (CMDs), particularly diabetic cardiomyopathy (DCM) and atherosclerosis (AS). This review comprehensively explores the metabolic pathways underlying ferroptosis, including dysregulation of iron, lipid, amino acid, and glucose metabolism, as well as involvement of the mevalonate pathway and key regulators such as NRF2 and p53. We analyze the cell type-specific mechanisms through which ferroptosis contributes to DCM and AS, driving myocardial dysfunction, plaque instability, and inflammatory amplification. Furthermore, we discuss emerging therapeutic strategies targeting ferroptosis, such as iron chelators, antioxidants, lipoxygenase inhibitors, ACSL4 inhibitors, nitroxides, and selenium supplements, which demonstrate potential in mitigating oxidative stress, restoring iron homeostasis, and suppressing inflammation. This review underscores the clinical relevance of targeting ferroptosis and highlights its promise as a novel therapeutic avenue for treating cardiometabolic diseases. Full article

Background/Objectives: Ferroptosis, an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation, has been implicated in various acute and chronic brain disorders, including epilepsy. Although 1,4-naphthoquinone derivatives have been reported to regulate ferroptosis, their mechanistic roles in the nervous system remain underexplored. Here, we investigated the protective effects of 8-hydroxy-2-anilino-1,4-naphthoquinone (8-HANQ) on ferroptotic neuronal death in vitro and seizure behaviors in vivo. Methods: HT22 hippocampal cells were exposed to ferroptosis inducers including glutamate, glutamate plus iron, or RSL3. Lipid reactive oxygen species (ROS), ferroptosis markers, and its related molecules were assessed by flow cytometry and Western blotting. In a kainate (KA)-induced seizure model, 8-HANQ was delivered intracerebroventricularly, followed by behavioral seizure scoring and analysis of hippocampal levels of PSD95, cathepsin-B, and FGFR1 at 72 h post-seizure. Results: 8-HANQ attenuated ferroptotic death in HT22 cells, reducing lipid ROS accumulation and abnormal acyl-coA synthetase long chain family member 4 (ACSL4), suggesting 8-HANQ’s anti-ferroptotic action. Moreover, 8-HANQ also prevented aberrant STAT3-dependent cathepsin-B overexpression while modulating soluble N-cadherin-mediated FGFR1 activation. In vivo, 8-HANQ decreased KA-induced seizure behavior, restored hippocampal cathepsin-B and PSD95 expression, and partially alleviated dysregulation of FGFR1 activation. Conclusions: 8-HANQ prevents ferroptotic neuronal death and synaptic deficits involving FGFR1/STAT3/cathepsin-B-driven ferroptosis while lowering seizure severity, suggesting that 8-HANQ may serve as a potential anti-ferroptotic and anti-seizure agent. Full article

Acetamiprid (ACE), a widely used neonicotinoid insecticide, has raised concerns due to its potential reproductive toxicity. While its adverse effects on animal reproductive systems have been documented, the impact of ACE on mammalian oocytes remains poorly understood. This study aimed to investigate the potential effects of ACE exposure on porcine oocytes and evaluate whether alpha-tocopherol (α-TOC), a fat-soluble antioxidant, could alleviate ACE-induced oocyte damage. Porcine cumulus oocyte complexes (COCs) were exposed to ACE alone or co-treated with α-TOC for 44 h during in vitro maturation. ACE exposure significantly reduced the first polar body (PB1) excretion rate, arrested meiotic progression, and disrupted spindle assembly in porcine oocytes. Furthermore, ACE impaired mitochondrial function, evidenced by decreased mitochondrial membrane potential (MMP), while increasing intracellular reactive oxygen species (ROS) accumulation and lipid peroxidation (LPO). Additionally, ACE exposure induced intracellular iron overload and dysregulated ferroptosis-related genes, downregulating solute carrier family 7 member 11 (SLC7a11) and glutathione peroxidase 4 (GPX4) while upregulating transferrin receptor 1 (TfRC) and acyl-CoA synthetase long-chain family member 4 (ACSL4), contributing to the occurrence of oocyte ferroptosis. Notably, α-TOC co-treatment effectively alleviate oxidative stress and lipid peroxidation, thereby protecting oocytes from ACE-induced ferroptosis. Collectively, these findings indicate that oxidative stress-mediated ferroptosis may be a major contributing pathway through which ACE impairs oocyte maturation and suggest that α-tocopherol may serve as a protective agent against ACE-induced oocyte damage. Full article

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal vulnerability in oral squamous cell carcinoma (OSCC). This review provides an overview of ferroptosis mechanisms and their implications for OSCC pathobiology and therapy. OSCC cells exhibit heightened reliance on anti-ferroptotic defenses such as GPX4, SLC7A11, FSP1, and Nrf2, and disrupting these pathways suppresses tumor growth and restores sensitivity to chemotherapy, radiotherapy, and immunotherapy. Genetic and epigenetic regulators, including p53, PER1, circ_0000140, and STARD4-AS1, critically modulate ferroptotic sensitivity, while metabolic enzymes such as ACSL4, LPCAT3, and TPI1 link ferroptosis to cellular plasticity and resistance. Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. We further address ferroptosis within the tumor microenvironment, highlighting its immunogenic and context-dependent dual roles, and summarize genomic and transcriptomic evidence linking ferroptosis-related genes to patient prognosis. Beyond cancer, ferroptosis also contributes to non-malignant oral diseases, including pulpitis, periodontitis, and infection-associated inflammation, where inhibitors may protect tissues. Despite these advances, clinical translation is constrained by the lack of safe ferroptosis inducers and validated biomarkers. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management. Full article