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Background: Head and neck squamous cell carcinoma (HNSCC) remains a highly aggressive malignancy with poor clinical outcomes. Although poly(ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in tumors with homologous recombination deficiency, their efficacy in BRCA wild-type HNSCC remains limited. Reactive oxygen species (ROS)-induced DNA damage may increase cellular dependence on DNA repair pathways and thereby enhance sensitivity to PARP inhibition. This study investigated whether ROS-mediated DNA damage could sensitize BRCA wild-type HNSCC cells to the PARP inhibitor olaparib. Methods: BRCA wild-type HSC-3 and SCC-25 HNSCC cell lines were exposed to H₂O₂ to induce oxidative stress. Intracellular ROS levels were quantified using DCFDA assays, DNA double-strand breaks were evaluated by γ-H2AX ELISA, PARP activity was assessed by ELISA, and cell viability was determined using MTT assays. Expression levels of DNA repair genes (PARP1, PARP2, BRCA1, BRCA2, RAD51, and MLH1), checkpoint kinases (ATM, ATR, and CHK1), the homologous recombination regulator FANCD2, and redox defense genes (NQO1, GPX4, and SLC7A11) were analyzed by qRT-PCR. Therapeutic selectivity was assessed using HGF-1 normal human gingival fibroblasts as a normal cell control. Apoptosis was measured through caspase-3/7 activity assays, and drug interactions were evaluated using the Chou–Talalay method. Results: H₂O₂ treatment increased intracellular ROS levels in both cell lines, accompanied by significant induction of DNA damage as demonstrated by elevated γ-H2AX levels. ROS induction markedly enhanced olaparib sensitivity, significantly reducing IC₅₀ values in both HSC-3 and SCC-25 cells. Combined H₂O₂ and olaparib treatment produced strong synergistic cytotoxicity, suppressed DNA repair, checkpoint kinase, and redox defense gene expression, and increased caspase-3/7 activity compared with control cells. Importantly, the combination demonstrated selective cytotoxicity toward cancer cells, with normal HGF-1 cells retaining significantly higher viability. Conclusions: ROS-induced DNA damage significantly enhances the anti-tumor activity of olaparib in BRCA wild-type HNSCC cells through a functional synthetic lethal-like interaction involving the simultaneous collapse of DNA repair capacity, checkpoint activation, and oxidative stress buffering, culminating in apoptosis induction. These findings support the rationale for combining ROS-generating therapies with PARP inhibitors in HNSCC treatment. Full article

The sodium-coupled citrate transporter NaCT (SLC13A5) imports extracellular citrate into cells. In the CNS, SLC13A5 is described to be expressed predominantly in neurons. Cytosolic citrate levels rely on citrate generated in mitochondria and imported from other CNS cells, regulating intermediary metabolism and supplying acetyl-CoA for lipid synthesis and histone acetylation. Despite evidence for NaCT’s role in neurometabolic homeostasis, its transcriptional behavior across Alzheimer’s disease (AD) progression and across astrocyte subtypes remains uncharacterized at single-cell resolution. We analyzed single-nucleus RNA sequencing data from 1,378,211 nuclei across 84 donors in the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) Middle Temporal Gyrus dataset to profile SLC13A5 and seven citrate metabolism genes across a continuous AD pseudoprogression score. SLC13A5 expression was restricted to astrocytes (~20% prevalence) and concentrated in the Astro 2 supertype (24.0%), a homeostatic subtype characterized by low C3 (1.6%) and CD44 (5.5%), which expanded with pseudoprogression (Spearman rho = +0.345, FDR < 0.001). The A1-reactive Astro 3 supertype, where SLC13A5 prevalence was 0.87%, declined concordantly (rho = −0.393). Opposing compositional and transcriptional forces produced apparent stability in overall SLC13A5 prevalence. SLC13A3 and ACO1 showed progressive donor-level declines correlating with Braak stage and Thal phase (rho range: −0.307 to −0.349, FDR < 0.01). APOE4 carriers exhibited lower SLC13A5 prevalence specifically within Astro 2 nuclei (median 17.6% vs. 25.9%; Wilcoxon p = 0.025), though this association did not survive multivariate regression. No difference in Astro 2 SLC13A5 expression was detected between cognitively resilient and expected-AD donors with equivalent high Braak burden (p = 0.888). Contrary to the prevailing description of NaCT as a neuronal transporter, SLC13A5 transcript in the SEA-AD MTG dataset was detected almost exclusively in astrocyte nuclei, concentrated in the homeostatic Astro 2 subtype, and maintained as this subtype expanded with advancing AD pathology. Because these are nuclear transcript measurements, they delimit where SLC13A5 mRNA is detectable rather than establishing the cellular site of NaCT protein or activity, which requires in situ validation. Full article

In this study, an exploratory transcriptomic investigation was conducted to evaluate the feasibility of using feather transcriptomics to detect sex differences and gene responses to physiological changes in chickens. Feathers represent a promising non-invasive biological source of RNA, as the feather pulp of growing feathers contains living cells capable of active transcription. Growing feathers were collected from 150-day-old male and female chickens (Bionda Piemontese, a slow-growing breed) raised under a free-range system and fed two finisher diets differing in lipid content: low-lipid (LL, ether extract 3.6%) and high-lipid (HL, ether extract 9.3%) diets. RNA was extracted from feather pulp, and 12 pools were subjected to whole RNA-Seq analysis. The study was designed as 2 × 2 factorial experiments investigating the effects of diet and sex on gene expression. A total of 17,360 transcripts were detected and used for downstream analyses. Differential gene expression and functional enrichment analyses were performed. The main effects of diet and sex were estimated with an additive design using the DEseq2 package, while for the sex-specific diet analyses, subgroup comparisons were conducted on the RaNA-Seq platform. The analysis of the main effect of diet reveals that three genes associated with ether lipid metabolism (PLA2G10, PLA2G4F, and ENPP6) were upregulated in chickens fed the HL diet. In roosters, HL feeding significantly altered the expression of APOA1 and SLC27A4, suggesting an effect on lipid transport and metabolic regulation within the PPAR signaling pathway. In contrast, hens showed differential expression primarily in pathways related to apelin signaling, extracellular matrix remodeling, and cardiovascular function, rather than classical lipid metabolism pathways; additionally, gene set enrichment analysis indicated a limited enrichment of linoleic acid metabolism, suggesting secondary involvement of lipid metabolic processes. These findings are consistent with those in the literature reporting sex-related differences between males and females. The results further suggest that transcriptomic responses to dietary lipid supplementation can be investigated through the expression of selected candidate genes in feather pulp. Among the genes identified, PLA2G10, PLA2G4F, ENPP6, APOA1, and SLC27A4 emerged as potential molecular markers associated with dietary treatment, and the importance of sex-dependent transcriptional responses was highlighted. In conclusion, this study demonstrates the potential of feather pulp as a viable source of RNA for transcriptomic analyses in live chickens, providing a minimally invasive alternative to conventional tissue sampling. These preliminary results also support the hypothesis that feathers represent a practical and ethically favorable tissue for future nutrigenomic and genetic improvement studies, ultimately supporting more sustainable poultry production. Full article

Triphenyl phosphate (TPhP) is a ubiquitous environmental contaminant and endocrine disruptor potentially associated with an increased risk of thyroid cancer (TC). However, whether TPhP directly contributes to TC remains unclear. This study integrated network toxicology and machine learning to investigate potential molecular associations between TPhP exposure and thyroid oncogenesis. By integrating multi-source databases and transcriptomic data, we constructed a TPhP–TC interaction network and established a TC risk prediction model using 127 machine learning algorithm combinations, identifying ten candidate hub genes. GO and KEGG enrichment analyses indicated that these genes are predominantly enriched in phosphorus metabolism, purine metabolism, and nuclear receptor signaling pathways, implying that TPhP may be linked to tumorigenesis through the disruption of metabolic reprogramming. SHAP analysis highlighted AHR and SLC20A2 as critical contributors to model performance. Molecular docking predicted stable binding between TPhP and all hub proteins in silico, with binding energies ranging from −9.2 to −6.6 kcal/mol. This study offers two computational contributions: (1) a quantifiable framework for predicting pollutant-associated TC risk and (2) systematic computational evidence for potential TPhP thyroid toxicity. These findings address a critical gap in understanding potential links between endocrine-disrupting chemical exposure and thyroid carcinogenesis, generating hypotheses for future experimental validation. Full article

Frailty is a multidimensional geriatric syndrome that lacks a consistent definition, complicating its clinical management. Epigenetic data suggest that frailty involves altered CpG sites, potentially driven by environmental epigenetic factors (the exposome) that influence aging. Systematically reviewing studies from 2009 to 2025, we quantified frailty prevalence, pooled weighted methylation beta values for associated CpG sites, performed enrichment analysis, and conducted structural network analysis to evaluate chemical interactions, following the PRISMA 2020 guidelines and with the study prospectively registered in PROSPERO (ID 1159037). Results showed a pooled frailty prevalence of 17.4% with extreme heterogeneity (I² = 98.88%), and a combined methylated beta effect of −0.1378 (CI: −0.4156, 0.1400) with high heterogeneity (I² = 100%), highlighting sources of variability. Interestingly, we found a CpG site (cg04772644) shared between Chinese and German cohorts, and, upon mapping, four frailty-related genes (CDC42BPB, SLC1A5, RXRB, and SLC22A18AS) were shared across cohorts. Indeed, these genes are significantly enriched in pathways including thrombin signaling, G protein-coupled receptor signaling, and immune cell differentiation signaling. Finally, our system toxicology analysis demonstrated that arsenite, bisphenol A, benzamide, dorsomorphin, and trichostatin A directly interact with the four shared genes, suggesting that the chemical exposome contributes to the observed epigenetic heterogeneity of frailty and the concomitant clinical manifestations. Full article

Serotonin transporter Slc6a4a functions as a transporter in serotonin reuptake and is tightly linked with serotonergic regulation and stress responses. However, few studies have investigated its role in copper homeostasis and organogenesis in an in vivo vertebrate model. In this study, we demonstrate that slc6a4a deficiency (slc6a4a^−/−) leads to copper accumulation, retinal developmental defects, and locomotor dysfunction in zebrafish specifically. Mechanistically, slc6a4a deficiency is associated with reduced atp7b and copper accumulation, which lead to reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress, and results in Caspase-3-mediated apoptosis and retinal degeneration. Specifically, tetrathiomolybdate (TTM), a pharmacological copper chelator, partially reduces ER stress and restores retinal defects. Additionally, ectopic expression of full-length atp7b mRNA partially restores retinal defects. These findings identify serotonin transporter Slc6a4a as a novel regulator in copper homeostasis and retinal development via the regulation of Atp7b in an in vivo vertebrate model. This study supports a mechanistic link between slc6a4a deficiency, copper overload, and retinal defects and highlights copper chelation as an alternative therapeutic strategy in individuals with Slc6a4 deficiency. Full article

Rs9939609 marker in FTO Alpha-Ketoglutarate-Dependent Dioxygenase (FTO) gene, rs7895307 in Transcription Factor 7-Like 2 (TCF7L2) gene, and rs75493593 in Solute Carrier Family 16 Member 11 (SLC16A11) gene have been associated with anthropometric, metabolic, and clinical variables, but have not been concurrently studied in Mexican children and adolescents with adiposity or mental disorders. In this cross-sectional association study, we genotyped these markers by means of TaqMan real-time polymerase chain reaction in two at-risk pediatric cohorts recruited in Mexico City. Group 1 (n = 175) comprised children and adolescents with overweight/obesity. Group 2 (n = 296) consisted of non-medicated adolescents meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for Attention Deficit/Hyperactivity Disorder or a mood disorder. Anthropometric measurements (body mass index —BMI—, waist circumference, body fat percentage), metabolic indices (fasting glucose, lipid profile, Homeostatic Model Assessment for Insulin Resistance), and psychiatric diagnoses were evaluated. In Group 1, the FTO A allele (genotypes AA/AT) was significantly associated with severe obesity according to BMI Z scores (p = 0.004, O.R. 3.33, 95% CI [1.42–7.77]), and it was a predictor of waist circumference (B = 6.16, 95% CI [1.78–10.55], p = 0.006) and muscle percentage (B = 4.21%, 95% CI [0.91–7.51%], p = 0.013) using linear regression models adjusted for age and sex. In Group 2, TCF7L2 AA genotype was associated with increased odds of depression (B = 0.83, p = 0.003, OR = 2.29, 95% CI [1.32–3.96]). While SLC16A11 G allele showed a possible association with insulin resistance or glucose levels, confirmation is needed. These exploratory results highlight the need for larger, well characterized cohort studies to confirm the associations. Full article

Hepatocellular carcinoma (HCC) remains a malignancy with poor prognosis and limited therapeutic targets. Emerging evidence suggests a critical role for iron metabolism and ferroptosis in tumor progression. However, the involvement of hematopoietic lineage cell-specific protein 1 (HAX1) in HCC, particularly its regulatory role in ferroptosis, remains largely unknown. Here, we report that HAX1 is significantly upregulated in HCC tissues and correlates with advanced pathological stages and poor patient survival, suggesting its potential as an oncogene. Functionally, HAX1 overexpression promotes the proliferation and migration of HCC cells, while its knockdown inhibits these malignant phenotypes. Mechanistically, we demonstrate that HAX1 acts as a negative regulator of ferroptosis. Silencing HAX1 sensitizes HCC cells to the ferroptosis inducer IKE, leading to abnormal accumulation of intracellular ferrous iron (Fe²⁺) and increased lipid reactive oxygen species (ROS). Conversely, HAX1 overexpression suppresses iron overload and lipid peroxidation. Furthermore, we reveal that HAX1 maintains redox homeostasis by regulating the GSH/GPX4 antioxidant pathway. Knockdown of HAX1 depletes reduced glutathione (GSH), reduces glutathione peroxidase activity, and downregulates key ferroptosis defense proteins, including GPX4, FSP1, and SLC7A11. Our findings identify HAX1 as a critical promoter of HCC progression that functions by inhibiting ferroptosis through the modulation of iron homeostasis and the GSH/GPX4 pathway. Targeting the HAX1-mediated anti-ferroptotic mechanism may represent a promising therapeutic strategy for HCC treatment. Full article

The divalent metal transporter DMT1 (SLC11A2) is implicated in diverse human pathologies including cancers, inflammatory and degenerative diseases. Small molecules targeting this membrane protein are actively searched. Following the identification of the pyranocoumarin praeruptorin A as an inhibitor of ferroptosis that is able to bind to DMT1, we have investigated the interaction of related natural products with DMT1 using molecular modeling to determine structure-binding relationships. Two series of compounds were tested: praeruptorins A-H and qianhucoumarins A-J, all isolated previously from the roots of the Chinese medicinal plant Peucedanum praeruptorum Dunn (Bai-Hua Qian-Hu). The antitumor compound praeruptorin C was identified as the best DMT1 ligand in the series, with a binding capacity largely superior to that of praeruptorin A and also well superior to the reference organoselenium product ebselen, at least from an in silico perspective. Praeruptorin C, and to a lower extent praeruptorins F and H, can form stable complexes with DMT1 upon binding close to the ebselen binding site. Qianhucoumarins C and I were also identified as potential binders. Altogether, the analysis of the 18 natural products enabled identification of structural elements implicated in the target binding process. The curvature of the tricyclic pyranocoumarin scaffold and the angeloyl side chain at position 9 seem to contribute importantly to the protein interaction. An experimental validation is required but the docking study paves the way to the discovery and design of tricyclic coumarin derivatives targeting DMT1. Full article

Total RNA was isolated from sections of healthy testes and Leydig cell tumors of mixed-breed dogs using TMA Master II device. The RNA-seq libraries were sequenced on the Illumina platform. Following differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were applied with quality control obtained using FastQC and Trimmomatic. This analysis revealed 1500 transcripts, including 982 upregulated and 168 downregulated genes. The results demonstrated that a significant proportion of these differentially expressed genes are directly involved in the control of sex steroid production (CYP11A1, STAR, and 3β-HSD3B1) or tube formation, angiogenesis, and extracellular matrix remodeling in interstitial cells (ESM1, FGG, and VEGFA). Moreover, we identified the upregulation of transcripts responsible for neurotransmitter or neuroendocrine signaling (SLC6A4, GRIN2C, GABRB3) and cholesterol metabolism and its regulation (GPX3, MSMO1, DHCR24). These genes were strongly associated with the phosphatidylinositol-3-kinase (PI3K)-Protein Kinase B (Akt) cascade and extracellular matrix interactions, features shared with various malignancies. Alterations in estrogen and relaxin signaling appear to be distinctive, understudied mechanisms specific to canine Leydig cell tumors. Concurrently, downregulated genes (e.g., DMRTC2, SEMA3C, ALOX12) were linked with cell differentiation, signaling and immunoregulatory pathway suppression involved in tumorigenesis. A complex transcriptomic profile of canine Leydig cell tumors was developed, revealing a conserved oncogenic core shared in some aspects with human malignancies alongside unique species-specific alterations. Findings seem to be useful for identifying novel diagnostic biomarkers and targeted therapies in veterinary oncology, establishing canine reproductive tissues as a valuable comparative biomedical model for research in human. Full article

Background/Objectives: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurometabolic disorder with an expanding clinical spectrum, including mild and non-classical presentations. We report a boy with severe transient neonatal hyperkalemia, bilateral congenital cataracts, and later subtle neurological and neurocognitive symptoms, in whom genomic testing supported the diagnosis of mild GLUT1DS. Methods: This single-patient case report describes clinical follow-up from birth to nine years of age, including neurological, metabolic, neuropsychological, imaging, and genetic investigations. Whole-exome sequencing using next-generation sequencing technology was performed. Results: The patient required intensive care immediately after birth because of severe transient hyperkalemia of unclear etiology. Bilateral congenital cataracts were surgically corrected during infancy. Later, he developed two brief seizure episodes, reduced exercise tolerance, episodic fatigue, attentional difficulties, motor restlessness, and mild graphomotor impairment. Neuropsychological assessment showed overall average intellectual functioning, below-average verbal abilities, low-average non-verbal abilities, and attention-deficit/hyperactivity disorder. Repeated metabolic investigations, electroencephalography, and brain magnetic resonance imaging were unrevealing. Whole-exome sequencing identified an apparently de novo heterozygous SLC2A1 variant, NM_006516.4.1333_1335del, p.(Phe445del), supporting the diagnosis of mild GLUT1DS. Because of the mild phenotype and preserved everyday functioning, ketogenic diet therapy was not initiated. Conclusions: This case highlights the diagnostic challenges of mild GLUT1DS and the value of genomic testing in children with unexplained neurological or neurocognitive symptoms despite normal routine investigations. Although neonatal hyperkalemia and GLUT1DS coexisted in this patient, current evidence is insufficient to establish a causal relationship. Full article

Junken meat sheep exhibit a characteristic postnatal coat-color transition, in which the initially black fleece gradually fades and develops into a white-trunk phenotype; however, the transcriptional basis of this developmental change in follicular pigment output remains unclear. In this study, three Junken meat sheep lambs showing a natural postnatal black-to-white coat-color transition were sampled longitudinally at the newborn black-fleece stage and the 179-day white-trunk stage, generating three matched biological pairs for RNA-seq analysis. Representative candidate genes were further validated by RT-qPCR. Differential expression analysis identified 1657, 400, and 1086 differentially expressed genes in the C11 vs. C1, C22 vs. C2, and C33 vs. C3 comparisons, respectively. Functional enrichment analysis indicated that these genes were mainly associated with tyrosine metabolism, ECM–receptor interaction, focal adhesion, Phosphoinositide 3-kinase-Akt signaling pathway (PI3K-Akt), arachidonic acid metabolism, estrogen signaling, and immune-related pathways. Integrated analysis of shared downregulated genes and expression patterns highlighted candidate genes related to pigmentation, the ECM/follicular microenvironment, and regulatory or metabolic processes. Pigmentation-related genes, including SOX10, TYR, TYRP1, PMEL, OCA2 and SLC45A2, were generally downregulated in 179-day white-trunk-stage skin, while changes in ECM- and metabolism-related genes suggested altered follicular microenvironmental regulation. These findings identify candidate transcriptional features associated with developmental coat-color fading in Junken meat sheep and support a follicular microenvironment–melanogenesis expression axis as a transcriptome-based framework for further investigation. Full article

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and is mechanistically distinct from apoptosis, necrosis and pyroptosis. Increasing evidence indicates that ferroptosis plays a critical role in cancer biology, including lymphoproliferative disorders, where chronic redox imbalance, dysregulated iron metabolism, and metabolic rewiring create a permissive environment for ferroptotic vulnerability. In these malignancies, altered iron handling, elevated reactive oxygen species, and a strong reliance on antioxidant systems such as glutathione and glutathione peroxidase 4 tightly control ferroptotic sensitivity. Dysregulation of key components, including SLC7A11, lipid metabolism pathways, and intracellular iron homeostasis, further shapes the susceptibility of malignant lymphoid cells to ferroptosis. Importantly, emerging preclinical studies suggest that therapeutic targeting of ferroptosis may overcome resistance to conventional chemotherapy, targeted agents, and immunotherapy, offering novel opportunities particularly in relapsed or refractory disease. This review provides a comprehensive overview of the molecular mechanisms governing ferroptosis in lymphoproliferative disorders, highlights the interplay between ferroptosis and major cellular and metabolic pathways, and discusses current and emerging strategies to pharmacologically induce ferroptosis, with an emphasis on biomarker-driven clinical translation. Full article

The primary control mechanism for synaptic uptake of GABA is through γ-aminobutyric acid transporter 1 (GAT-1, SLC6A1), a known target for anti-epileptic drugs. Although there is a clinically used GAT-1 inhibitor, tiagabine, the development of a new ligand with an advanced pharmacological profile is desirable. For this purpose, a multi-tiered virtual approach to screening has been created, involving pharmacophore-based search; application of the Informational Spectrum Method for Small Molecules, followed by EIIP/AQVN filtering (ISM-SM); molecular docking using an ensemble of several experimentally obtained structures of GAT-1; and ADMET predictions. Pharmacophore-based screening of the ZINC database of natural products, combined with ISM-SM/EIIP filtering, yielded 237 candidate compounds. Structural separation analysis discriminated between the positives and negatives, enabling enrichment-based prioritization. The use of a composite normalized rank score based on docking affinity and structural similarity allowed for the identification of the top candidates: ZINC03643214 and ZINC67840571. Collectively, these refinements establish a more sophisticated computational model for identifying novel GAT-1 inhibitors and highlight promising candidates for future experimental evaluation. Full article

Cardiometabolic diseases are increasingly understood as disorders involving compartment-specific redox disruption rather than a uniform excess of reactive oxygen species. This narrative review synthesizes evidence for a proposed gut microbiota–mitochondria ferroptosis framework in which dysbiosis-derived lipopolysaccharide, trimethylamine N-oxide, short-chain fatty acids, bile acids, and tryptophan metabolites may modulate mitochondrial reactive species production, antioxidant defenses, iron handling, lipid peroxide detoxification, and inflammatory signaling. The reference set was assembled through searches of PubMed and Web of Science Core Collection, supplemented by targeted Google Scholar searches and citation chaining during manuscript preparation and revision through June 2026 and was organized around microbial metabolites, mitochondrial redox biology, ferroptosis pathways, disease-specific evidence, and redox-targeted interventions. Because this is a narrative synthesis rather than a systematic review, the framework should be interpreted as hypothesis-generating rather than as a systematically validated pathological model. Across atherosclerosis, diabetic cardiomyopathy, metabolic dysfunction-associated steatotic liver disease, obesity-associated insulin resistance, chronic kidney disease, and cardiorenal metabolic injury, the most consistent mechanistic links involve mtROS, impaired mitophagy, glutathione/GPX4 and SLC7A11 dysfunction, ACSL4-dependent lipid peroxidation, Nrf2 signaling, NLRP3 activation, and cGAS-STING-associated inflammation, although human causal evidence remains uneven. Importantly, much of the current literature supports local links within this sequence rather than a fully verified dysbiosis–metabolite–mitochondria ferroptosis–organ dysfunction chain in the same study. We therefore emphasize evidence tiers, terminology discipline, and biomarker requirements when interpreting ferroptosis-sensitive injury. Polyphenols, flavonoids, probiotics, postbiotics, melatonin, CoQ10-related strategies, mitochondria-targeted antioxidants, and ferroptosis-sensitive approaches may be most translatable when paired with microbiome, metabolomic, lipidomic, pharmacokinetic, and redox biomarkers. Full article