Search Results (974)

The increased activity of δ-aminolevulinic acid synthase-1 (ALAS1) leads to the accumulation of δ-aminolevulinic acid (ALA), which may reduce the iron(III) retention ability of ferritin, resulting in iron(III) overload. The accumulation of ALA occurs in the condition of attenuation of the heme negative feedback loop over ALAS1 activity in concert with the induction of ALAS1 expression. Attenuation of the heme negative feedback loop is maintained by elevated quantities of the heme catabolizing enzyme, heme oxygenase-1 (HO-1), which, in turn, may be induced by highly increased heme concentration. The upregulation of brain HO-1 occurs in patients with Alzheimer’s and Parkinson’s diseases. A mouse with overexpressed human HMOX1 is a model of schizophrenia with concurrent iron overload. HO-1 inhibitors reduce oxidative damage to whole cells and mitochondrial compartments of rat astrocytes transfected with the HMOX1 gene. Iron reduction within the heme prosthetic moiety of P450 cytochromes in microsomes is facilitated by NADPH-cytochrome P450 oxidoreductase (CPR), while adrenodoxin reductase performs this function in the mitochondria. In partial CPR-deficient conditions, the half-life of apocytochromes is prolonged while HO-1 is induced due to the elevated heme release from unreduced cytochromes. This study posits that, before being degraded by HO-1, the released hemin triggers the oligomerization of cytochromes, as well as other oxidative damages, by producing hydroperoxyl radicals from hydrogen peroxide produced in uncoupling reaction. After reaching a specific level, iron(III) overload may trigger the saturation of CPR, resulting in the development of neuropathologies. Full article

The protective effects of herbal feed additives Withania somnifera, Silybum marianum, Centella asiatica, and silymarin (administered at feed levels of 4000 ppm, 5000 ppm, 4600 ppm, and 25,000 ppm, respectively) against the toxic effects of ochratoxin A (OTA) (administered at 2 ppm) were investigated in 48 New Zealand White rabbits (37 days old) over an 80-day experimental period. A decrease in body weight was seen in rabbits exposed to OTA alone, but that decrease was less pronounced in rabbits receiving herbal supplements. The most severe lesions in OTA-treated rabbits were found in the liver, kidneys and spleen, while milder lesions were seen in the heart, intestine and lungs. The intensity of macroscopic, histopathological and biochemical changes was highest in rabbits exposed to OTA alone, followed by rabbits additionally supplemented with herbal additives, as evidenced by histopathological findings and serum levels of blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). The most pronounced protective effects of the herbal additives were observed in the kidneys and liver. Oxidative stress was significantly increased in rabbits exposed to OTA alone, as evidenced by elevated reactive oxygen species (ROS), nitric oxide (●NO), ascorbyl radicals (●Asc), protein oxidation (PO), procollagen type I alpha 1 (COL1A1), malondialdehyde (MDA), kidney injury molecule-1 (KIM-1), hydroxyproline (Hyp), advanced glycation end products (AEGs), heme oxygenase-1 (HO-1), catalase (CAT), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well decreased superoxide dismutase (SOD) and glutathione peroxidase-1 (GPx-1) activities, while protective effects were seen for all herbal additives, and better expressed for Centella asiatica and Silybum marianum. Full article

Background and Objectives: Acute cerebral ischemia is characterized by excessive oxidative stress and impaired antioxidant defense mechanisms, in which the nuclear factor erythroid 2–related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) signaling pathway plays a pivotal regulatory role. This study aimed to investigate serum levels of Nrf2–Keap1 pathway components and associated oxidative stress biomarkers in patients with acute ischemic stroke. Materials and Methods: Eighty-eight patients diagnosed with ischemic stroke who presented within 24 h of the onset of neurological deficit and met the inclusion criteria, along with 72 healthy control subjects without a history of acute ischemic stroke, were included in the study. Serum levels of Nrf2, Keap1, glycogen synthase kinase-3β (GSK-3β), heme oxygenase-1 (HO-1), glutathione (GSH), and 4-hydroxynonenal (4-HNE) were quantified using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the biomarkers. Results: Compared with controls, patients exhibited significantly reduced Nrf2 levels and markedly elevated Keap1 and 4-HNE levels. HO-1 and GSH concentrations were also significantly increased in the patient group, whereas GSK-3β levels did not differ significantly between groups. ROC analysis demonstrated that 4-HNE and Nrf2 possessed the highest discriminative capacity for acute ischemic stroke. Conclusions: These findings suggest that acute cerebral ischemia is associated with dysregulation of the Nrf2–Keap1 axis accompanied by enhanced lipid peroxidation and oxidative burden. Although increased HO-1 and GSH levels may reflect a compensatory antioxidant response, elevated 4-HNE levels indicate persistent oxidative injury. Full article

Background/Objectives: Oxidative and electrophilic stress-response pathways contribute to cellular resilience across various chronic diseases, including neurodegenerative, hepatic, and metabolic disorders. Pharmacological activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is a validated strategy to counteract oxidative damage, as evidenced by the clinical approval of dimethyl fumarate (DMF) and monomethyl fumarate (MMF) for relapsing forms of multiple sclerosis; both electrophilic compounds activate Nrf2 via covalent Keap1 (Kelch-like ECH-associated protein 1) modification. Cynara scolymus L. contains structurally related electrophilic metabolites; however, their contribution to Nrf2-associated signaling remains undefined. This study aimed to identify and characterize the constituents responsible for Nrf2-inducing activity and benchmark their potency against DMF and MMF. Methods: Bioactivity-guided fractionation combining Soxhlet extraction, Nrf2/ARE luciferase reporter screening, semi-preparative HPLC, and spectroscopic identification was employed. Functional validation included extracellular thiol quantification, H₂O₂ cytoprotection assays, and Western blot analysis of heme oxygenase-1 (HO-1). Results: The dichloromethane extract exhibited the highest Nrf2-inducing activity (54.4-fold). Fractionation yielded five guaianolide sesquiterpene lactones (1–5), four of which were active. The α-methylene-γ-lactone moiety was essential for activity. Aguerin B (3) exhibited the highest activity (39.14 ± 11.13-fold), while TBA analysis identified cynaropicrin (2) as the dominant extract-level contributor (62.9% of total activity). Notably, aguerin B (3) and cynaropicrin (2) induced greater reporter activity than DMF and MMF. Downstream pathway induction was confirmed by concentration- and time-dependent HO-1 upregulation, elevated extracellular glutathione and cysteinylglycine levels, and significant protection against H₂O₂-induced cytotoxicity without intrinsic toxicity. Conclusions: Guaianolide sesquiterpene lactones are the primary mediators of Nrf2-associated antioxidant signaling in C. scolymus. Cynaropicrin (2) exhibited stronger in vitro ARE-reporter induction than fumarates, supporting its relevance for further pharmacological investigation. Full article

Osteoarthritis (OA) is a prevalent chronic joint disease lacking disease-modifying drugs. Animal models with distinct pathogenic mechanisms—monosodium iodoacetate (MIA) for metabolic toxicity and collagenase-induced osteoarthritis (CIOA) for matrix degradation—are essential for therapeutic evaluation. In this study, topical application of neoagarohexaose (NA6) at 5 and 10 mg/kg twice daily was assessed in MIA- and CIOA-induced mouse OA models. NA6 at both doses reduced paw swelling, improved serum oxidative stress markers (catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO)), ameliorated cartilage damage and Osteoarthritis Research Society International (OARSI) scores, and decreased inflammatory cell infiltration. Immunohistochemistry showed that NA6 downregulated interleukin-1β (IL-1β) and interleukin-6 (IL-6), upregulated NAD(P)H:quinone oxidoreductase 1 (NQO1), and restored the compensatorily elevated heme oxygenase-1 (HO-1) toward baseline levels. The high-dose NA6 (10 mg/kg) showed comparable or favorable efficacy at the tested doses relative to the positive control diclofenac. These results demonstrate that NA6 exerts anti-inflammatory, antioxidant, and chondroprotective effects in both OA models, supporting its potential as a topical therapeutic candidate for OA symptom management and structural protection. Full article

Chronic hyperglycemia and excessive reactive oxygen species (ROS) production are defining features of endothelial dysfunction, a key driver of diabetic vascular complications such as diabetic nephropathy. Microvesicles (MV-enriched fraction), a subtype of extracellular vesicles, and the stress-responsive antioxidant protein Sestrin2 (SESN2) have emerged as important contributors to these processes. This study investigated the role of the MV-enriched fraction in endothelial cell communication under diabetic conditions, with a particular focus on oxidative stress signaling. To model diabetic injury, EA.hy926 endothelial cells were treated with methylglyoxal (MGO), and the resulting MV-enriched fraction was isolated and then applied to two recipient models: naïve endothelial cells and SESN2 knockdown (KD) cells. Protein expression of key antioxidant markers, including endothelial nitric oxide synthase (eNOS), was assessed by Western blot. Nitric oxide (NO) bioavailability was quantified via nitrite measurement using 2,3-diaminonaphthalene (DAN), while mitochondrial and cytosolic ROS levels were evaluated using MitoSOX and dihydroethidium (DHE), respectively. Results demonstrated that the MV-enriched fraction derived from diabetic conditions triggers a complex antioxidant response in healthy endothelial cells, characterized by upregulation of SESN2, superoxide dismutase 1 (SOD1), and heme oxygenase-1 (HO-1). This suggests a compensatory mechanism that mitigates oxidative stress. Notably, SESN2 KD cells exhibited increased ROS production and reduced NO levels upon MV treatment, underscoring the essential role of SESN2 in maintaining redox homeostasis. Overall, this study highlights the dual role of the MV-enriched fraction as a mediator of both protective and detrimental redox signaling in diabetic endothelial dysfunction and suggests potential therapeutic targets for managing diabetic vascular complications. Full article

Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article

Nanoplastics (NPs) and heavy metal cadmium (Cd) are common co-existing pollutants in freshwater environments, but their combined toxic effects on the liver of herbivorous economic fish remain unclear. In this study, grass carp (Ctenopharyngodon idella) were exposed to polystyrene nanoplastics (PS-NPs, 100 nm) and/or Cd to investigate their individual and combined effects on hepatic toxicity. The results revealed that co-exposure interactively suppressed interleukin-10 (IL-10) expression and heme oxygenase-1 (HO-1) antioxidant response, and induced more severe hepatic necrosis, melanization, and fibrinoid necrosis, with the highest integrated biomarker response index and extensive disruption of lipid and steroid metabolism pathways. This study clarified the toxicological interaction of NPs and Cd on the liver of grass carp, and provided a theoretical basis for understanding the combined toxicity of NPs and heavy metal pollution in extreme contamination scenarios or accidental pollution events. Full article

Background: Gentamicin-induced nephrotoxicity limits clinical pharmacotherapy and involves multiple converging stress-response pathways. Ellagic acid (EA) has renoprotective potential, yet its role in coordinating endoplasmic reticulum (ER) stress-mediated apoptosis, autophagy, and inflammation remains unclear. We hypothesized that EA co-treatment would protect the kidney by modulating ER stress-dependent pathways and associated inflammatory and adaptive signaling. Methods: For an integrated mechanistic analysis in a rat model of gentamicin nephrotoxicity, 40 male Sprague-Dawley rats were assigned to control, gentamicin (100 mg/kg), EA (100 mg/kg), and gentamicin + EA groups for 14 days. Renal function, oxidative stress, inflammatory mediators, ER stress markers, apoptosis, autophagy, tubular injury markers, and histopathological changes were assessed. Results: Gentamicin induced renal dysfunction, tubular injury, and ER stress across all unfolded protein response (UPR) branches (IRE1α, PERK, ATF6), C/EBP homologous protein (CHOP)-associated apoptosis, dysregulated autophagy, and upregulated kidney injury molecule-1 (KIM-1). A selective inflammatory signature was observed, with increased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), whereas tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) remained unchanged. Co-administration of ellagic acid with gentamicin significantly improved renal function markers compared to the gentamicin group. In contrast, ellagic acid alone did not show significant differences compared to the control group. Notably, gentamicin induced compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression, while ellagic acid co-treatment attenuated this compensatory upregulation, likely secondary to reduced oxidative stress burden. Conclusions: This study provides integrated evidence that ER stress is closely associated with gentamicin nephrotoxicity. The key novel findings include selective suppression of IL-6, modulation of the apoptosis-autophagy balance, and attenuation of Nrf2/HO-1 signaling without direct reactive oxygen species (ROS) scavenging, demonstrating a multi-target framework for EA’s renoprotective effects. These findings suggest that ellagic acid mitigates renal injury in a context-dependent manner rather than confirming a direct causal mechanism. Full article

Carbon monoxide (CO) is a gasotransmitter generated by heme oxygenase (HO) isoforms during heme catabolism. The inducible HO-1 produces CO under conditions of redox imbalance, such as oxidative stress and inflammation. On the other hand, HO-2 constitutively generates CO, primarily during the physiological turnover of heme. Extensive evidence indicates that CO exerts autocrine effects by targeting hemoproteins, including soluble guanylyl cyclase, cyclooxygenase, and cytochromes. Furthermore, CO regulates many biological processes within the brain, including mitochondrial biogenesis, potassium channel activity, mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt signaling. It also controls the activity of transcription factors, such as hypoxia-inducible factor-1 and peroxisome proliferator-activated receptor-γ. Through these mechanisms, CO modulates inflammatory gene expression, promotes anti-apoptotic signaling, and contributes to local stress responses. Conversely, CO produced in the hypothalamus inhibits the stress-induced release of corticotropin-releasing hormone and arginine vasopressin under pro-inflammatory conditions, resulting in reduced adrenocorticotropin hormone release and cortisol secretion from the anterior pituitary and adrenal cortex, respectively. Moreover, hypothalamic CO acts in a paracrine manner to modulate glucocorticoid release during psychological stress, including restraint or water deprivation. Together, these findings support the view that endogenous CO is a key modulator of the stress axis, exerting pleiotropic effects that integrate neuroendocrine, immune, and metabolic responses. Full article

Associated with high morbidity and mortality, cisplatin-induced acute kidney injury (AKI) is a common clinical complication characterized by oxidative stress, inflammation, and mitochondria-associated signaling. Although multiple signaling pathways have been implicated in AKI progression, effective interventions targeting these complex mechanisms are still lacking. As a medicinal fungus with antioxidant and anti-inflammatory properties, Schizophyllum commune (SC) has shown potential biological activities; however, its renoprotective effects in cisplatin-induced AKI remain unclear. Therefore, this study aimed to investigate SC’s protective effects and underlying mechanisms in a cisplatin-induced AKI mouse model. SC treatment improved renal function and attenuated histopathological damage. It reduced oxidative stress and inflammatory responses, as evidenced by the modulation of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), and pro-inflammatory cytokines. Mechanistically, SC regulated multiple signaling pathways, including mitogen-activated protein kinase (MAPK), toll-like receptor 4/nuclear factor kappa B (TLR4/ NF-κB), PI3K/AKT, nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), and the calcium/calmodulin-dependent protein kinase kinase–AMP-activated protein kinase–sirtuin 1 (CaMKK–AMPK–Sirt1) axis. In addition, SC modulated apoptosis, autophagy, and PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy, suggesting improved mitochondrial homeostasis. These findings indicate that SC exerts renoprotective effects and may contribute to cisplatin-induced nephrotoxicity mitigation strategies. Full article

Although previous studies have indicated that heme oxygenase 1 (HO1/HY1) regulates the flowering time via the photoperiod pathway, the specific mechanism is still elusive. Here, we found that the Arabidopsis hy1-100 mutant displayed early flowering, and the characteristic expression patterns of several master genes involved in the autonomous pathway were altered. Notably, the transcript levels of FLOWERING LOCUS C (AtFLC) gene declined developmentally in both wild-type and hy1-100 mutant, with a more pronounced fold reduction observed in the mutant. Genetic evidence further underlined that hy1-100/FLCOE plants partially reversed the early flowering phenomenon of hy1-100 mutant, suggesting that AtHO1 regulated flowering at least partially through the AtFLC-involved autonomous pathway, as supported by changes in FLOWERING LOCUS T (AtFT) and SUPPRESSOR OF OVEREXPRESSION OF CO1 (AtSOC1) transcripts. Further analysis of hy1-100/ft mutants revealed that hy1-100/ft and ft mutants displayed similar late flowering phenotypes, accompanied by downregulated APETALA1 (AtAP1) and AtSOC1, indicating that AtFT played a crucial role in AtHO1-regulated flowering. Two key conclusions are drawn: first, the loss of AtHO1 function promotes early flowering in Arabidopsis, which was genetically linked to the autonomous pathway regulating AtFLC expression; second, AtFT was an essential downstream factor mediating AtHO1-regulated flowering. Full article

Ultraviolet A (UVA) radiation disrupts the redox balance of melanocytes and may lead to the development of melanoma, highlighting the need for new skin protection strategies. This study assessed the effect of phytocannabinoids [cannabigerol (CBG), cannabidiol (CBD), and CBG + CBD] on redox homeostasis in control and UVA-exposed melanocytes and in melanoma cells (SK-Mel-5). UVA radiation increased the activity of prooxidant enzymes in both melanocytes and SK-Mel-5 cells and, consequently, the level of reactive oxygen species (ROS) (approx. 2-fold). It also activated nuclear factor erythroid 2 (Nrf2), as reflected by increased expression of heme oxygenase 1 (HO-1) (melanocytes approx. 2-fold; SK-Mel-5 approx. 7-fold). Concomitantly, antioxidant mechanisms were impaired, as demonstrated by reduced superoxide dismutase (SOD1/SOD2) activity and impaired glutathione and thioredoxin function. These changes were accompanied by increased levels of oxidative damage markers (isoprostanes, 4-hydroxynonenal-4-HNE, and 4-HNE-protein adducts) (43–100%) and increased inflammatory signaling, including increased expression of nuclear factor kappa B (NF-κB) subunits (melanocytes: p52 ~2-fold, p65 ~75%; SK-Mel-5: ~4–4.5-fold) and tumor necrosis factor alpha (TNF-α; ~30%). Phytocannabinoid treatment modulated these UVA-induced changes. In SK-Mel-5 cells, phytocannabinoids normalized the activity of prooxidant enzymes and consequently reduced ROS levels (~30%). They also reduced Nrf2 activation and HO-1 expression; however, CBG increased HO-1 level in melanocytes (~25–40%). Furthermore, phytocannabinoids enhanced antioxidant defense by increasing SOD activity, particularly in melanocytes (~10–40%), and restoring the glutathione and thioredoxin systems. Markers of oxidative damage were reduced by approximately 23–37% after treatment. Furthermore, phytocannabinoids attenuated NF-κB activation (p52 ~18–28%, p65 ~25–29% in melanocytes; ~20% in SK-Mel-5), while TNF-α levels remained unchanged. The effects in non-irradiated cells were modest (<15%). These results suggest that phytocannabinoid-mediated modulation of redox balance may stabilize melanocytes exposed to UVA radiation and potentially reduce the risk of neoplastic transformation. However, the observed protective effects in SK-Mel-5 cells require further investigation and detailed molecular analysis. Full article

Premature ovarian insufficiency (POI) poses a serious risk to the reproductive health and psychological well-being of women. Here, the protective effects of hydroxytyrosol (HT), the primary phenolic component of olive oil, on POI were investigated. In vitro, human ovarian granulosa-like tumour cell lines (KGN cells) were challenged by D-galactose (D-gal) with or without HT. HT administration effectively alleviated KGN cell damage, decreased the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells, increased superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enhanced the expression level of Bcl-2, inhibited the expression level of Bax, and inhibited cell apoptosis in D-gal-treated KGN cells. In vivo, HT administration reversed the decreased ovarian index, oestrous cycle disruption, and abnormal sex hormone levels observed in D-gal-induced POI mice. HT administration increased glutathione (GSH) levels, reduced the MDA levels, and attenuated apoptosis in ovarian tissues, as evidenced by a decreased number of TUNEL-positive cells, upregulated Bcl-2 expression, and downregulated Bax expression. Mechanistically, HT downregulated the expression level of Kelch-like ECH-associated protein 1 (Keap1) and enhanced the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in vitro and in vivo. In conclusion, HT ameliorates D-gal-induced POI in vitro and in vivo by activating the Nrf2/HO-1 signalling pathway. Full article

Biomolecular condensates in the cytoplasm and nucleus contribute to carcinogenesis through aberrant signaling by assorted transcription factors and fusion oncoproteins. Oral cancer, which is highly prevalent worldwide, frequently occurs in a U-shaped “high-risk” zone (floor of mouth, side of tongue, and anterior fauces) which forms the path of liquid transit through the mouth. We previously reported that environmental stresses of saliva-like hypotonicity and beverage-like temperature changes triggered cycles of disassembly/reassembly of biomolecular condensates of GFP-tagged human myxovirus resistance protein (MxA; alias Mx1) in oral cancer cells. In the present study, we identified some of the constituents of GFP-MxA cytoplasmic condensates in oral cells. These condensates were isolated from interferon (IFN)-λ1-treated GFP-MxA expressing OECM1 human oral cancer cells using magnetic bead-based immunoisolation. Unbiased peptide identification confirmed the presence of MxA/Mx1 peptides; however, the strongest intensity was for the BACH1 transcription factor family. Immunofluorescence analyses confirmed the association of BACH1 and the family member Nrf2 with cytoplasmic human GFP-MxA condensates. Moreover, GFP-BACH1 and GFP-Nrf2 colocalized with cytoplasmic human HA-MxA condensates in transiently transfected OECM1 cells. Western blot assays confirmed the presence of BACH1 and Nrf2 proteins in complexes isolated using anti-MxA pAb. As much as BACH1 and Nrf2 regulate oxidative stress response genes, it was remarkable that immunofluorescence assays revealed the presence of heme oxygenase 1 (HO1)—a downstream redox regulator—in GFP-MxA condensates. However, these condensates were devoid of p62, KEAP1 and Cul3. In terms of aberrant function, in live cells, the Nrf2 transcription factor underwent rapid disassembly and reassembly cycles driven by saliva-like hypotonicity, and was also disassembled by sulforaphane. The data highlight the unexpected intersections in oral cells between MxA condensates and BACH1, Nrf2 and HO1—proteins well known to be involved in pathways regulating cellular responses to environmental and oxidative stresses, antiviral defense, oral epithelial dysplasia, and cancer progression and metastases. Full article