Search Results (1,792)

Cellular senescence, a hallmark of aging, involves irreversible growth arrest and an enhanced senescence-associated secretory phenotype (SASP). It is often accompanied by mitochondrial dysfunction and altered inter-organelle communication. Using a chronic oxidative stress model in AML12 hepatocytes, we confirmed senescence by canonical assays (e.g., SA β-gal positivity and proliferation arrest) and observed a decline in the RNA-binding protein AUF1 (hnRNP D). AUF1 knockdown further amplified senescent phenotypes, including elongation of mitochondrial network, loss of mitochondrial membrane potential, reduced ATP level, and elevated mitochondrial reactive oxygen species (ROS). In addition, AUF1 knockdown weakened mitochondria-endoplasmic reticulum coupling and reduced mitochondrial Ca²⁺ load. At the molecular level, AUF1 binds to the 3′ untranslated regions (3′UTRs) of Opa1 and Mfn2 and limits their abundance, thereby coupling post-transcriptional control to mitochondrial dynamics. In gain-of-function experiments, ectopic expression of AUF1 attenuated Opa1/Mfn2 induction, restored mitochondrial network architecture, and preserved bioenergetic function under pro-senescent stimuli. Collectively, these findings support a model in which AUF1 preserves mitochondrial homeostasis and thereby restrains the mitochondria–senescence axis in hepatocytes. Full article

Essential oils (EOs) are complex volatile mixtures that exhibit antioxidant activity through both chemical and biological pathways. Phenolic constituents act as efficient chain-breaking radical-trapping antioxidants, whereas some non-phenolic terpenes operate through distinct mechanisms. Notably, γ-terpinene functions via a “radical export” pathway, generating hydroperoxyl radicals that intercept lipid peroxyl radicals and accelerate chain termination. Recent methodological advances, such as inhibited autoxidation kinetics, oxygen-consumption assays, and fluorescence-based lipid peroxidation probes, have enabled more quantitative evaluation of these activities. Beyond direct radical chemistry, EOs also regulate redox homeostasis by modulating signaling networks such as Nrf2/Keap1, thereby activating antioxidant response element–driven enzymatic defenses in cell and animal models. Phenolic constituents and electrophilic compounds bearing an α,β-unsaturated carbonyl structure may directly activate Nrf2 by modifying Keap1 cysteine residues, whereas non-phenolic terpenes likely depend on oxidative metabolism to form active electrophilic species. Despite broad evidence of antioxidant efficacy, molecular characterization of EO–protein interactions remains limited. This review integrates radical-chain dynamics with redox signaling biology to clarify the mechanistic basis of EO antioxidant activity and to provide a framework for future research. Full article

High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-κB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns—blood–brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1α regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

Autophagy is an evolutionarily conserved cellular process that maintains homeostasis by degrading intracellular materials. Numerous studies have investigated the role of autophagy-related genes (ATGs) in plant adaptation to abiotic stresses. In plants, hypoxia (e.g., flooding events, oxygen supply during growth) rapidly activates the autophagy pathway as a protective mechanism for cell survival. Considering the moisture-loving yet waterlogging-sensitive nature of tea plants, this study explored the role of CsATG8f in the tea plant’s response to submergence. We found that overexpression of CsATG8f formed more autophagosomes than controls under submergence. Furthermore, CsATG8f was confirmed to physically interact with CsRAP2.12. Co-overexpression of both genes partially suppressed transcription of hypoxia-response genes while activating the antioxidant system, thereby enhancing tea plants’ resistance to submergence. Consistent with this, the opposite trend was observed in silenced plants, which attempted to mitigate stress damage by increasing GABA levels in vivo. In conclusion, our study reveals the crucial roles of CsATG8f and CsRAP2.12 in tea plant tolerance to submergence and provides new insights into potential regulatory networks governing tea plant adaptation to flooding. Full article

Fine particulate matter (PM_2.5), which contains heavy metals such as Al, Fe, Mg, and Mn, among others, induces cognitive dysfunction through oxidative stress, neuroinflammation, and impaired mitochondria. This study evaluated the neuroprotective effects of a 40% ethanol extract of Polygonum multiflorum (EPM) on PM_2.5-induced cognitive dysfunction in a mouse model. Behavioral assessments demonstrated attenuated learning and memory impairment following EPM treatment. Redox homeostasis was restored through increased expression of superoxide dismutase (SOD) and glutathione (GSH) and decreased levels of malondialdehyde (MDA) and mitochondrial reactive oxygen species (mtROS) in the EPM group. Mitochondrial function was attenuated, as indicated by recovery of mitochondrial membrane potential and ATP levels. EPM inhibited neuroinflammation by downregulating the TLR4-MyD88-NF-κB pathway and maintaining blood–brain barrier integrity through the upregulation of tight junction proteins. It modulated neuronal apoptosis through the JNK pathway, reducing the accumulation of amyloid-beta and phosphorylated tau. Synaptic plasticity was preserved through upregulation of BDNF/TrkB signaling and cholinergic neurotransmission via regulation of acetylcholine (ACh), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT). To standardize EPM, high-performance liquid chromatography (HPLC) confirmed the presence of the bioactive compound, tetrahydroxystilbene glucoside (TSG). These findings suggest that EPM may be a promising functional food candidate for mitigating PM_2.5-related cognitive impairments. Full article

12-oxo-phytodienoic acid reductase (OPR) is a core component of the jasmonic acid (JA) biosynthetic pathway and participates in JA synthesis by catalyzing the reduction in the precursor 12-oxo-phytodienoic acid (OPDA), as well as broadly regulating plant development, stress response, and hormone signaling networks. This study analyzed the OPR gene family using 28 soybean genomes. A total of 15 OPR gene family members in soybean were identified, including 14 core genes and one variable gene. Analysis of gene duplication types showed that whole-genome duplication (WGD)/segmental duplication was the main mode of duplication in GmOPRs. The phylogenetic tree constructed from multiple species showed that the OPRs in subgroup VII were functionally important OPR genes and that the OPRs underwent Leguminosae and Cruciferae divergence, and large-scale duplication occurred in Leguminosae. Analysis of natural selection pressures on 28 soybean accessions indicated that the overall evolutionary pressures on GmOPRs were dominated by purifying selection, but there were also potential positive selection signals. Analysis of cis-acting elements revealed a large number of light- and hormone-responsive cis-acting elements in the GmOPRs. Some specific cis-acting elements were only present in a few genes or accessions. The protein interaction network consisted of 12 GmOPR proteins, 4 allene oxide synthase (AOS) proteins, and 6 allene oxide cyclase (AOC) proteins, where AOCs interact with GmOPRs and AOSs. Tissue transcriptome expression profiling showed that GmOPR3, GmOPR7, and GmOPR15 were specifically expressed in roots, whereas GmOPR2, GmOPR10, and GmOPR14 were specifically expressed in leaves, suggesting that these genes play an important role in the growth and development of the tissues. Moreover, GmOPRs usually responded to salt stress, and GmOPR3, GmOPR8, GmOPR9, GmOPR10, and GmOPR11 were significantly up-regulated in roots and leaves under salt stress. This suggests that these genes may be involved in biological processes such as osmoregulation, ion homeostasis, and scavenging of reactive oxygen species, thus helping soybeans to resist salt stress. This study comprehensively analyzed the OPR gene family in soybean based on the 28 soybean accessions and clarified the salt stress response pattern, which provides a new and more effective and reliable way to analyze the soybean gene family. Full article

Ferroptosis is an iron-dependent form of regulated cell death (RCD) characterized by intracellular iron homeostasis disruption and lipid peroxide accumulation. It is involved in many pathological processes, including malignant tumors, cardiovascular diseases, inflammatory diseases, and mitochondrial disorders. Cysteine desulfurase (NFS1), a key enzyme in mitochondrial iron-sulfur (Fe-S) cluster biosynthesis, participates in regulating cellular ferroptosis by maintaining Fe-S cluster homeostasis and modulating the ACO1/IRP1 axis, the Xc⁻–glutathione (GSH)–glutathione peroxidase 4 (GPX4) axis, and the p53/STAT signaling pathway. When the function of NFS1 is abnormal, the intracellular free iron level is elevated, followed by reactive oxygen species (ROS) accumulation and lipid peroxidation. NFS1 expression exhibits significant variation across different tissues. Upregulation of NFS1 in tumors can enhance tumor cell resistance to ferroptosis; thus, it can promote tumor growth, drug resistance, and metastatic ability. Conversely, downregulation of NFS1 in cardiomyocytes and neurons exacerbates ferroptosis and causes functional impairment. Here, we systematically review recent advances in the molecular mechanisms of NFS1-mediated ferroptosis and its role in various disease models, intending to clarify key components in the upstream regulatory network of ferroptosis and explore the application value of NFS1 as a potential therapeutic target. The review shows that NFS1 plays an important role in cellular fate regulation, which has significant clinical application potential in the treatment of cancer and interventions for neurological and cardiovascular diseases. Therefore, it can provide a new theoretical basis and research direction for subsequent mechanism research and targeted therapeutic strategy development. Full article

Background: Vitamin D (VD) plays a central role in calcium homeostasis during pregnancy and has been implicated in redox-related biological processes. While VD deficiency (VDD) has been consistently associated with adverse pregnancy outcomes, the relationships between VD insufficiency (VDI), maternal antioxidant-related biomarkers, and neonatal outcomes remain incompletely characterized, particularly during the third trimester. Objective: To determines the prevalence of VDI in third-trimester pregnant women and to examine its associations with antioxidant-related markers and selected neonatal outcomes. Methods: A cross-sectional study was conducted among pregnant women in the third trimester attending a tertiary referral hospital in Mexico City. Maternal serum 25-hydroxyvitamin D (25-OHD) concentrations were measured, along with a panel of redox-related markers, including 2,2-diphenyl-2-2picrylhydrazyl (DPPH) radical scavenging activity, reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and oxygen radical absorbance capacity (ORAC). Neonatal anthropometric parameters were recorded at birth. Associations between maternal VD status, redox-related markers, environmental factors, and neonatal outcomes were evaluated using appropriate statistical analyses. Results: A high prevalence of VDI was observed in the study population. Maternal VDI was associated with lower activities of GSH, GST, and GPx. Passive exposure to tobacco smoke and season of sampling were also associated with lower VD concentrations. Neonates born to women with VDI had higher birth weight compared with those born to women with sufficient VD concentrations. Maternal serum 25-OHD concentrations correlated positively with selected antioxidant enzyme activities. Conclusions: In this cohort of third-trimester pregnant women, VDI co-occurred with environmental factors, differences in maternal redox-related markers, and selected neonatal outcomes. These findings support an associative framework in which suboptimal VD status during the third trimester is accompanied by variations in redox-related markers. Longitudinal and mechanistic studies are needed to clarify the temporal sequence and biological relevance of these associations. Full article

Global warming has intensified frequency and severity of extreme heat events, critically threatening cucumber (Cucumis sativus L.) production worldwide. To elucidate the mechanisms underlying heat tolerance, a comparative study was conducted between a heat-tolerant cultivar (N24) and a heat-sensitive cultivar (G30) under 43 °C stress. Using a combination of RNA sequencing and widely targeted metabolomics, we found that genotype N24 exhibited superior phenotypic at ability, characterized by reduced leaf wilting, lower membrane lipid peroxidation, and more stable reactive oxygen species (ROS) homeostasis. Genotype N24 exhibited superior phenotypic stability, characterized by reduced leaf wilting, lower membrane lipid peroxidation, and more stable reactive oxygen species (ROS) homeostasis. Transcriptomic profiling showed genes associated with photosynthesis and thylakoid membrane function were upregulated in N24, while hormone signaling pathways was enriched in G30. 93 N24-specific and 83 G30-specific differentially expressed genes were identified, including transcription factors such as HSF, bHLH, and bZIP. Widely targeted metabolomics further demonstrated that specific protective metabolite, such as 3-methyluric acid was accumulated and showed the ABC transporter pathway was also significant enriched in N24 plants. Integrated transcriptomic and metabolomic analysis suggested that ABC transporters may enhanced thermotolerance by facilitating the transport and subcellular compartmentalization of antioxidant metabolites. Collectively, these findings indicated heat tolerance in cucumber involved a synergistic regulatory network encompassing photosynthesis maintenance, transcription factor activation, and ABC transporter-mediated metabolic reprogramming. This study provides novel insights and valuable genetic resources for breeding heat-resilient cucumber varieties in a warming climate. Full article

Arterial hypertension (AH) is a highly prevalent, multifactorial cardiovascular condition characterized by endothelial dysfunction, increased oxidative stress, and impaired nitric oxide (NO) bioavailability. While pharmacological treatment is primarily directed toward blood pressure reduction, accumulating evidence indicates that several antihypertensive drug classes also confer antioxidant and vasculoprotective benefits. Concurrently, dietary intake of inorganic nitrate and nitrite has gained attention as an adjunctive approach to restore NO signaling and redox homeostasis. This narrative review summarizes current evidence regarding the antioxidant effects of major antihypertensive drug classes and examines the contribution of nitrate- and nitrite-rich diets to the modulation of oxidative stress and vascular dysfunction in AH. A systematic search of PubMed, EMBASE, Scopus, ScienceDirect, Web of Science, Google Scholar, and Food and Drug Administration (FDA) databases was performed for studies published between August and December 2025. Experimental and clinical investigations assessing oxidative stress markers, endothelial function, or NO-related outcomes in AH were selected following title and abstract screening and full-text evaluation. Available data indicate that angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, β-blockers, and calcium channel blockers mitigate oxidative stress via mechanisms including NADPH oxidase suppression, decreased reactive oxygen species production, reinforcement of endogenous antioxidant systems, and restoration of endothelial NO bioavailability. Moreover, dietary nitrate and nitrite support vascular function through activation of the nitrate–nitrite–NO pathway. Combining nitrate- and antioxidant-rich dietary strategies with antihypertensive agents that lack inherent redox-modulating activity may enhance blood pressure control and lower cardiovascular risk. Nevertheless, well-designed long-term randomized clinical trials are needed to elucidate class-specific interactions and underlying redox mechanisms. Full article

The intestinal epithelium maintains tissue homeostasis through a dynamic balance of stem cell proliferation and differentiation. This process is spatially regulated along the crypt–villus axis, with intestinal stem cells in the crypt regions proliferating and progenitor cells differentiating as they migrate toward the villus tips. Because the lumen of the gut contains very low levels of oxygen (i.e., hypoxia), an oxygen gradient is established within the crypt–villus axis, placing the crypt regions under normoxic conditions while the villus tips reside under hypoxic conditions. Hence, intestinal epithelial cells encounter distinct oxygen microenvironments throughout their life span as they migrate along the crypt–villus structures during their proliferation and differentiation process. To investigate how oxygen availability influences intestinal stem cell proliferation and differentiation, we cultured patient-derived human ileum organoids (i.e., enteroids) under normoxic (20% oxygen) or hypoxic (1% oxygen) conditions. Under hypoxia, enteroid growth was reduced, and expression of several stem cell markers, such as OLFM4 and LGR5, was decreased. Bulk and single-cell RNA sequencing revealed that hypoxia suppressed Wnt signaling pathways and reduced stem cell activity. Importantly, pharmacological stabilization of HIF-1α under normoxic conditions recapitulated the hypoxia-induced loss of stemness, demonstrating that HIF-1α is a key mediator of oxygen-dependent stem cell regulation in enteroids. These findings establish that physiological hypoxia in the intestinal epithelium directly regulates stem cell fate through HIF-1α stabilization, providing mechanistic insight into how oxygen availability along the crypt–villus structures controls intestinal homeostasis. Full article

Salt stress represents a significant abiotic factor that constrains maize growth. Epigenetic modifications play a crucial role in enabling plants to respond effectively to such stresses. Among these alterations, m⁶A methylation, which is the most common post-transcriptional modification of eukaryotic mRNA, shows dynamic variations that are closely linked to stress responses. In this study, we conducted a transcriptome-wide m⁶A methylation analysis on maize roots from the inbred line PH4CV, following treatment with 180 mM NaCl. The results identified 1309 differentially m⁶A methylated peaks (DMPs) and 2761 differentially expressed genes (DEGs) under salt stress conditions. Association analysis revealed that 179 DEGs contain DMPs. Key pathways involved in stress responses, including Ca²⁺ signaling transduction and ABA signaling, as well as ion homeostasis regulation (involving AKT, HKT, and other families) and the reactive oxygen species scavenging system (including POD, SOD, and CAT), play crucial roles in coping with salt stress. Furthermore, we identified a total of 26 m⁶A-related genes, comprising 7 eraser genes, 10 reader genes, and 9 writer genes. Notably, several key salt-responsive genes, such as RBOHB, AKT1, HKT1, and POD12, are correlated with m⁶A modification. This study provides a comprehensive map of m⁶A methylation dynamics in maize roots under salt stress, laying a foundational resource for future investigations into the epigenetic regulation of salt tolerance in maize. Full article

Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and oxidative damage in DNA, lipids, and proteins. This redox disequilibrium initiates a cascade of cellular disturbances—including synaptic dysfunction, altered receptor activity, excitotoxicity, mitochondrial disruption, and chronic neuroinflammation—that can, in turn, impair cognitive and social functioning in metabolic and neuropsychiatric disorders via epigenetic mechanisms. In this review, we synthesize current knowledge on (1) how OS contributes to cognitive and social deficits through epigenetic dysregulation; (2) the role of disrupted one-carbon metabolism in epigenetically mediated neurological dysfunction; and (3) mechanistic links between leaky gut, OS, altered GM composition, and GM-derived epigenetic metabolites. We also highlight emerging microbiota-based therapeutic strategies capable of mitigating epigenetic abnormalities and improving cognitive and social outcomes. Understanding the OS–microbiota–epigenetic interplay may uncover new targetable pathways for therapies aimed at restoring brain and behavioral health. Full article

Background: Two natural steroids derived from cholesterol pathways are testosterone and progesterone, androgen and antiandrogen receptor binding. Steroid androgen antagonists can be prescribed to treat an array of diseases and disorders such as gender dysphoria. In men, androgen antagonists are frequently used to treat prostate cancer and hyperplasia. Sex hormones regulate the expression of the viral receptors in COVID-19 progression, and these hormones may act as a metabolic signal-mediating response to changes in glucose and Reactive Oxygen Species (ROS). The objective of the present study is to use artificial intelligence (AI) applications in healthcare to predict the targets and to assess biological assays of novel steroid derivatives prepared in house from the commercially available 16-dehydropregnenolone acetate (DPA^®) aimed at achieving the metabolic stability of glucose and steroid brain homeostasis. This suggests the introduction of aromatic or aliphatic structures in the steroid B-ring and D-ring. This is important since the roles of 5α-reductase and ROS in brain control of glucose and novel steroids homeostasis remain unclear. Methods: A tool prediction was used as a tuned algorithm, with the novel steroid derivatives data in web interface to carry out their pharmacological evaluation. The new steroidal derivatives were determined with neuroprotection effect using the select biomarkers of oxidative stress on induced hypoglycemic male rat brain and liver. The enzyme kinetics was established by the inhibition of the 5α-reductase enzyme on the brain myelin. Results: We used novel chemical structures to order the information of a Swiss data bank that allow target predictions. Biological assays suggest that steroid derivatives with an electrophilic center can interact more efficiently with the 5α-reductase enzyme, and by this way, induce neuroprotection in hypoglycemia model. All compounds were synthesized with a yield of 30–80% and evaluated with tool target prediction to understand the molecular mechanisms underlying a given phenotype or bioactivity and to rationalize possible favorable or unfavorable side effects, as well as to predict off-targets of known molecules and to clear the way for drug repurposing. Apart, they turned out to be good inhibitors for the 5α-reductase enzyme. Conclusions: The probed efficacy of these novel steroids with respect to spironolactone control appears to be a promising compound for future hormonal therapy with neuroprotection activity in glucose disorder status. However, further research with clinically meaningful endpoints is needed to optimize the use of androgen antagonists in these hormonal therapies in COVID-19 progression. Full article