Search Results (2,354)

Crucial regulators of gamete metabolism and signaling, mitochondria synchronize energy generation with redox equilibrium and developmental proficiency. Once thought of as hazardous byproducts, reactive oxygen species (ROS) are now understood to be vital signaling molecules that provide a “redox window of competence” that is required for oocyte maturation, sperm capacitation, and early embryo development. This review presents the idea of mitochondrial metabolic checkpoints, which are phases that govern gamete quality and fertilization potential by interacting with cellular signaling, redox balance, and mitochondrial activity. Recent research shows that oocytes may sustain a nearly ROS-free metabolic state by blocking specific respiratory-chain components, highlighting the importance of mitochondrial remodeling in gamete competence. Evidence from in vitro and in vivo studies shows that ROS act as dynamic gatekeepers at critical points in oogenesis, spermatogenesis, fertilization, and early embryogenesis. However, assisted reproductive technologies (ARTs) may inadvertently disrupt this redox–metabolic equilibrium. Potential translational benefits can be obtained via targeted techniques that optimize mitochondrial function, such as modifying oxygen tension, employing mitochondria-directed antioxidants like MitoQ and SS-31, and supplementing with nutraceuticals like melatonin, CoQ10, and resveratrol. Understanding ROS-mediated checkpoints forms the basis for developing biomarkers of gamete competence and precision therapies to improve ART outcomes. By highlighting mitochondria as both metabolic sensors and redox regulators, this review links fundamental mitochondrial biology to clinical reproductive medicine. Full article

Organic and inorganic peroxides can induce intracellular redox homeostasis. In this study, a γ-cyclodextrin/genistein inclusion complex (γ-CD/GEN) was constructed to systematically elucidate the molecular mechanism by which it catalyzes GPx4-mediated peroxide reduction. The results indicate that the incorporation of γ-CD effectively disrupts the aggregated state of GEN, achieving an encapsulation efficiency (EE) exceeding 40%. Surface-enhanced Raman spectroscopy (SERS) analysis reveals significant differences in the catalytic behavior of γ-CD/GEN toward cumene hydroperoxide (CHP) and hydrogen peroxide (H₂O₂): the reduction efficiency of CHP depends on both the concentration of γ-CD/GEN and GPx4, whereas the reduction of H₂O₂ is primarily regulated by the concentration of γ-CD/GEN. Isotope effect studies demonstrate that the reduction of CHP relies more on radical-initiated reactions, while the reduction of H₂O₂ involves proton transfer, with the differences in reduction rates correlating with their respective redox mechanisms. Molecular docking and molecular dynamics simulations further confirm that γ-CD/GEN can stably bind to the Sec (Cys)-46 site in the active center of GPx4, thereby enhancing its catalytic activity. This study provides a theoretical basis for the development of antioxidant strategies based on the precise regulation of enzyme activity. Full article

Electron transfer (ET) is a foundational biogeochemical process in paddy soils, distinctively molded by alternating anaerobic-aerobic conditions from flooding-drainage cycles. Despite extensive research on heavy metal(loid) (denoted as “HM”, e.g., As, Cd, Cr, Hg) dynamics in paddies, ET has not been systematically synthesized as a unifying regulatory mechanism, and the trade-offs of ET-based mitigation strategies remain unclear. These critical gaps have drastically controlled HMs’ mobility, which further modulates bioavailability and subsequent accumulation in rice (Oryza sativa L., a staple sustaining half the global population), posing substantial food safety risks. Alongside progress in electroactive microorganism (EAM) research, extracellular electron transfer (EET) mechanism delineation, and soil electrochemical monitoring, ET’s role in orchestrating paddy soil HM dynamics has garnered unparalleled attention. This review explicitly focuses on the linkage between ET processes and HM biogeochemistry in paddy ecosystems: (1) elucidates core ET mechanisms in paddy soils (microbial EET, Fe/Mn/S redox cycling, organic matter-mediated electron shuttling, rice root-associated electron exchange) and their acclimation to flooded conditions; (2) systematically unravels how ET drives HM valence transformation (e.g., As(V) to As(III), Cr(VI) to Cr(III)), speciation shifts (e.g., exchangeable Cd to oxide-bound Cd), and mobility changes; (3) expounds on ET-regulated HM bioavailability by modulating soil retention capacity and iron plaque formation; (4) synopsizes ET-modulated HM accumulation pathways in rice (root uptake, xylem/phloem translocation, grain sequestration); (5) evaluates key factors (water management, fertilization, straw return) impacting ET efficiency and associated HM risks. Ultimately, we put forward future avenues for ET-based mitigation strategies to uphold rice safety and paddy soil sustainability. Full article

Direct hydroxylation of benzene to phenol using hydrogen peroxide is a cornerstone of sustainable green chemistry. This paper presents the results of a stability study of an iron-containing mordenite catalyst in the liquid-phase hydroxylation of benzene to phenol with a 30% aqueous hydrogen peroxide solution. The study utilizes a combination of catalytic activity measurements, dynamic light scattering (DLS), and electron paramagnetic resonance (EPR) spectra. The system is initially shown to exhibit high phenol selectivity; however, over time, DLS measurements indicate aggregation of the catalyst particles with an increase in the average particle diameter from 1.8 to 2.6 μm and the formation of byproducts–dihydroxybenzenes. Iron is present predominantly as magnetite nanoparticles (Fe₃O₄) ~10 nm in diameter, stabilized on the outer surface of mordenite, with minor leaching (<10%) due to the formation of iron ion complexes with ascorbic acid as a result of the latter’s interaction with magnetite particles. Using a thermodynamic approach based on the Ulich formalism (first and second approximations), it is shown that the reaction of benzene hydroxylation H₂O₂ in the liquid phase is thermodynamically quite favorable (ΔG° = −(289–292) kJ·mol⁻¹ in the range of 293–343 K, K = 1044–1052). It is shown that ascorbic acid acts as a redox mediator (reducing Fe³⁺ to Fe²⁺) and a regulator of the catalytic medium activity. The stability of the catalytic system is examined in terms of the Lyapunov criterion: it is shown that the total Gibbs free energy (including the surface contribution) can be considered as a Lyapunov functional describing the evolution of the system toward a steady state. Ultrasonic (US) treatment of the catalytic system is shown to redisperse aggregated particles and restore its activity. It is established that the catalytic activity is due to nanosized Fe₃O₄ particles, which react with H₂O₂ to form hydroxyl radicals responsible for the selective hydroxylation of benzene to phenol. Full article

RNA viruses are major pathogens in fish, causing high mortality and substantial economic losses in aquaculture. To uncover conserved antiviral mechanisms, we investigated the response of turbot (Scophthalmus maximus) to viral hemorrhagic septicemia virus (VHSV), infectious pancreatic necrosis virus (IPNV), and red-spotted grouper nervous necrosis virus (RGNNV) using a comparative proteomic approach complemented by in vivo and in vitro functional assays. Proteomic analyses revealed the central, conserved role of proteins involved in reactive oxygen species (ROS) production and redox homeostasis during early infection. Functional assays using head kidney-derived leukocytes identified neutrophils and macrophages as the primary ROS producers and showed that the modulation of cytoplasmic and mitochondrial ROS, as well as ROS-dependent DNA release, follows virus-specific patterns. The pharmacological inhibition of NADPH oxidase and mitochondrial ROS significantly affected viral replication, demonstrating the direct role of ROS in viral pathogenicity. Collectively, these findings highlight redox modulation as a conserved host response in teleost fish during RNA virus infection, linking oxidative stress regulation to viral progression. This knowledge provides a foundation for developing broad-spectrum therapeutic or preventive strategies to enhance disease resistance and promote sustainable aquaculture. Full article

Background/Objectives: Astrocytes are key regulators of brain energy homeostasis, integrating glucose metabolism with antioxidant support for neuronal function. Dysregulation of these processes contributes to neurodegenerative diseases, including Alzheimer’s disease. Andrographolide, a bioactive diterpenoid from Andrographis paniculata, has been reported to exert neuroprotective effects through the modulation of Wnt/β–catenin signaling and neuronal metabolism; however, its actions on astrocytic metabolic pathways remain insufficiently characterized. Methods: Here, we investigated the effects of andrographolide on metabolic and redox parameters in primary mouse cortical astrocytes. Results: Andrographolide increased glucose uptake and antioxidant capacity without affecting AMPK activation or the activity of core glycolytic enzymes. Instead, it selectively enhanced glucose-6-phosphate dehydrogenase activity, promoting glucose flux through the pentose phosphate pathway in a partially Wnt-dependent manner. This metabolic reprogramming was associated with increased NADPH availability and glutathione levels, together with a reduced ATP/ADP ratio, consistent with a shift toward redox maintenance rather than maximal energy production. Conclusions: Collectively, these findings highlight astrocytic metabolic plasticity as a relevant and underexplored target of andrographolide and support the concept that natural compounds can enhance brain resilience by modulating glial redox metabolism. Full article

Background/Objectives: Rosacea increasingly appears to involve systemic immune and metabolic disturbances rather than isolated cutaneous inflammation. To evaluate inflammatory, platelet, and oxidative–metabolic biomarkers in rosacea and explore their interrelations. Methods: 90 patients with rosacea and 90 healthy controls were evaluated for hematologic inflammatory indices—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), pan-immune–inflammation value (PIV), mean platelet volume (MPV), and C-reactive protein (CRP)—along with oxidative–metabolic regulators including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), visfatin, and irisin. Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of rosacea, while inter-marker associations were evaluated using Spearman’s rank correlation. Results: Rosacea patients showed higher NLR, PLR, SII, PIV, MPV, CRP, and LDL cholesterol (p < 0.05) and lower SIRT1, SIRT3, visfatin, and irisin (p < 0.01). MPV independently predicted rosacea (OR = 7.24; AUC = 0.827), whereas SIRT1 inversely correlated with disease risk. SIRT1, SIRT3, and visfatin showed inverse correlations with HbA1c and waist-to-height ratio, while fasting glucose and HOMA-IR remained within normal ranges. Conclusions: Rosacea exhibits dual systemic activation, an inflammatory–platelet and an oxidative–metabolic axis bridging immune dysregulation, mitochondrial stress, and vascular dysfunction. Recognition of these pathways highlights the potential of redox-targeted and metabolic interventions beyond symptomatic treatment. Full article

Hepatic ischemia–reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

Selenoprotein N (SelN or SELENON) is a selenium-containing protein of the endoplasmic/sarcoplasmic reticulum (ER/SR), encoded by the SEPN1 gene. In skeletal muscle, SelN is particularly important for regulating SR calcium homeostasis. It acts as a calcium sensor, modulating the activity of the sarcoplasmic reticulum calcium pump (SERCA) through a redox-dependent mechanism. Loss-of-function mutations in the SEPN1 gene give rise to a spectrum of skeletal muscle disorders collectively referred to as SEPN1-related myopathies (SEPN1-RM). Histopathologically, SEPN1-RM is characterized by the presence of minicores, which are localized regions within muscle fibers exhibiting mitochondrial depletion (i.e., cores) and sarcomeric disarray. As no effective therapy is currently available for SEPN1-RM, understanding SelN biology through loss-of-function models remains essential for elucidating disease mechanisms and identifying potential therapeutic targets. This review examines the current knowledge on SelN function and the pathological mechanisms underlying SEPN1 loss-of-function, with a particular focus on the connection between calcium handling, oxidative/ER stress, and muscle dysfunction. It also highlights emerging strategies aimed at restoring SelN activity or mitigating downstream defects, outlining potential therapeutic avenues for SEPN1-RM. Full article

Therapeutic peptides have emerged as promising tools in oncology due to their high specificity, favorable safety profile, and capacity to target molecular hallmarks of cancer. Their clinical translation, however, remains limited by poor stability, rapid proteolytic degradation, and inefficient biodistribution. Iron oxide nanoparticles (IONPs) offer a compelling solution to these challenges. Owing to their biocompatibility, magnetic properties, and ability to serve as both drug carriers and imaging agents, IONPs have become a versatile platform for precision nanomedicine. The integration of peptides with IONPs has generated a new class of hybrid systems that combine the biological accuracy of peptide ligands with the multifunctionality of magnetic nanomaterials. Peptide functionalization enables selective tumor targeting and deeper tissue penetration, while the IONP core supports controlled delivery, MRI-based tracking, and activation of therapeutic mechanisms such as magnetic hyperthermia. These hybrids also influence the tumor microenvironment (TME), facilitating stromal remodeling and improved drug accessibility. Importantly, the iron-driven redox chemistry inherent to IONPs can trigger regulated cell death pathways, including ferroptosis and autophagy, inhibiting opportunities to overcome resistance in aggressive or refractory tumors. As advances in peptide engineering, nanotechnology, and artificial intelligence accelerate design and optimization, peptide–IONP conjugates are poised for translational progress. Their combined targeting precision, imaging capability, and therapeutic versatility position them as promising candidates for next-generation cancer theranostics. Full article

Although oxidants are known to be deleterious for cellular homeostasis by oxidizing macromolecules like DNA or proteins, they are also involved in signaling processes essential for cellular proliferation and survival. Here, we investigated the role of superoxide anion (O₂⁻) and hydrogen peroxide (H₂O₂) homeostasis for the proliferation and survival of classical Hodgkin’s lymphoma (cHL) cell lines. Inhibition of NADPH oxidases (NOX) using apocynin (Apo) and diphenylene iodonium (DPI), or treatment with the antioxidant butylated hydroxyanisole (BHA), significantly reduced proliferation and induced apoptosis in HL cell lines. These effects correlated with transcriptomic alterations involving redox regulation, immune signaling, and cell cycle control. Interestingly, treatment with DPI or antioxidants attenuated constitutive Signal Transducer and Activator of Transcription (STAT) activity, as seen by decreased phospho-STAT6 levels and reduced STAT6 DNA binding. This suggests a sensitivity of the Janus kinase (JAK)/STAT pathway in cHL cell lines to O₂⁻ and H₂O₂ depletion. Functional assays confirmed this by demonstrating partial restoration of proliferation or apoptosis in L428 cells that expressed constitutively active STAT6 or were transfected with small interfering RNAs (siRNAs) that targeted STAT regulators. These findings highlight that oxidants, particularly H₂O₂, act as both general oxidative stressors and essential modulators of oncogenic signaling pathways. Specifically, maintenance of oxidant homeostasis is critical for sustaining JAK/STAT-mediated growth and survival programs in cHL cells. Targeting redox homeostasis might offer a promising therapeutic strategy to impair JAK/STAT-driven proliferation and survival in cHL. Full article

In this study, a strain of green microalga adapted to the extreme environmental conditions of the Tibetan Plateau was isolated from the Lalu Wetland. The isolate was identified and tentatively designated as Micractinium sp. LL-1. Following the inoculation of strain LL-1 into tannery wastewater, the ammonia nitrogen concentration was rapidly reduced, achieving a removal efficiency of 98.7%. The maximum accumulated biomass reached 1641.68 mg/L and 1461.28 mg/L. Integrated transcriptomic and label-free quantitative proteomic approaches were employed to systematically investigate the molecular response mechanisms of LL-1 under tannery wastewater stress. Transcriptomic analysis revealed that differentially expressed genes were enriched in pathways related to cell proliferation, morphogenesis, intracellular transport, protein synthesis, photosynthesis, and redox processes. Proteomic analysis indicated that LL-1 enhances cellular and enzymatic activities, strengthens regulatory capacity, modulates key metabolic pathways, and upregulates stress-responsive proteins. Under tannery wastewater stress, LL-1 exhibits dynamic adaptation involving signal perception and metabolic reconfiguration through the coordinated regulation of multiple pathways. Specifically, ribosomal translation and nucleic acid binding regulate biosynthetic capacity; the redistribution of energy metabolism boosts photosynthetic carbon fixation and ATP generation; and membrane transport coupled with antioxidant mechanisms mitigates stress-induced damage. Collectively, this study provides theoretical insights into microalgal adaptation to complex wastewater environments and offers potential targets for strain improvement and wastewater valorization. Full article

Breast cancer is a significant public health concern, with triple-negative breast cancer (TNBC) being the most aggressive subtype characterized by considerable heterogeneity and the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Currently, there are no practical alternatives to chemotherapy, which is associated with a poor prognosis. Therefore, developing new treatments for TNBC is an urgent need. Reactive oxygen species (ROS) and redox adaptation play central roles in TNBC biology. Targeting the redox state has emerged as a promising therapeutic approach, as it is vital to the survival of tumors, including TNBC. Although TNBC does not produce high levels of ROS compared to ER- or PR-positive breast cancers, it relies on mitochondria and oxidative phosphorylation (OXPHOS) to sustain ROS production and create an environment conducive to tumor progression. As a result, novel treatments that can modulate redox balance and target organelles essential for redox homeostasis, such as mitochondria, could be promising for TNBC—an area not yet reviewed in the current scientific literature, thus representing a critical gap. This review addresses that gap by synthesizing current evidence on TNBC biology and its connections to redox state and mitochondrial metabolism, with a focus on innovative strategies such as metal-based compounds (e.g., copper, gold), redox nanoparticles that facilitate anticancer drug delivery, mitochondrial-targeted therapies, and immunomodulatory peptides like GK-1. By integrating mechanistic insights into the redox state with emerging therapeutic approaches, I aim to highlight new redox-centered opportunities to improve TNBC treatments. Moreover, this review uniquely integrates mitochondrial metabolism, redox imbalance, and emerging regulated cell-death pathways, including ferroptosis, cuproptosis, and disulfidptosis, within the context of TNBC metabolic heterogeneity, highlighting translational vulnerabilities and subtype-specific therapeutic opportunities. Full article

Heme released during blood digestion represents a major oxidative challenge for hematophagous insects, promoting the generation of reactive oxygen species (ROS) and redox imbalance. Although Aedes aegypti has evolved specialized mechanisms to mitigate heme toxicity, how these responses vary across developmental stages remains poorly understood. Here, we applied quantitative proteomics to compare the effects of heme exposure in larvae and adult females. In larvae, heme treatment predominantly led to downregulation of metabolic and antioxidant proteins, consistent with a shift toward energy conservation and growth regulation. Nonetheless, selective upregulation of proteins associated with mitochondrial MnSOD activity, lipid remodeling, and cytoskeletal organization indicates the engagement of complementary protective mechanisms. In contrast, adults exhibited a coordinated bioenergetic response, characterized by enrichment of mitochondrial pathways, redox-related proteins, and molecular chaperones, reflecting enhanced resilience to oxidative stress. Enrichment of cuticle-associated proteins in both stages further suggests heme-induced structural remodeling. Together, these findings demonstrate that A. aegypti employs divergent, stage-specific proteomic strategies to cope with heme toxicity: larvae suppress metabolic activity while maintaining structural and redox homeostasis, whereas adults reinforce mitochondrial function and proteostatic defenses. These insights advance our understanding of mosquito redox biology and highlight stage-specific vulnerabilities that may be exploited for innovative vector control strategies. Full article