Search Results (1,009)

The Keap1-Nrf2 signaling pathway is a central regulator of transcriptional responses to oxidative stress and is strongly linked to diverse pathologies, particularly cancer. In the cytoplasm, Keap1 (Kelch-like ECH-associated protein 1) promotes proteasomal degradation of Nrf2 (NF-E2–related factor 2). Oxidative stimuli disrupt the Keap1-Nrf2 interaction, facilitating Nrf2 nuclear accumulation and activation of antioxidant and detoxifying genes. Recent evidence suggests that Keap1 family proteins also enter the nucleus, bind chromatin, and regulate transcription, but the underlying mechanisms remain less understood. Here, we show that the Drosophila Keap1 ortholog, dKeap1, accumulates in the nucleus and gradually assembles stable nuclear foci in cells following oxidative treatment. FRAP analyses revealed reduced mobility of dKeap1 within these foci. Both the N-terminal (NTD) and C-terminal (CTD) domains of dKeap1 were required for foci formation. Two intrinsically disordered regions (IDRs) were identified within the CTD, and CTD-YFP fusion proteins readily formed condensates in vitro. Conversely, deletion of the Kelch domain resulted in robust cytoplasmic foci even under basal conditions, and in vitro assays also indicated that the Kelch domain suppresses dKeap1 condensate formation. Together, these findings reveal a novel molecular mechanism for the nuclear function of dKeap1, providing new insight into the broader roles of Keap1 factors in oxidative response, development, and disease. Full article

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy. Full article

Industrial synthetic dyes are among the most common and hazardous pollutants in manufacturing wastewater. In this study, effective dye-decolorizing fungi were isolated from industrial discharge and evaluated for their decolorization efficiency for various dyes, including a triphenylmethane (malachite green, MG), an anthraquinone (reactive blue 19, RB19), and an azo dye (reactive black 5, RB5). The fungus with the highest potential for MG decolorization was identified as Penicillium rubens, whereas Aspergillus fumigatus proved to be the most effective for RB19 and RB5 decolorization. Maximum decolorization for all dyes occurred at pH 9 and 30 °C after 6–7 days of shaking in the dark. Enzyme activity assays revealed that both P. rubens and A. fumigatus produced multiple oxidative and reductive enzymes, including laccase, azoreductase, anthraquinone reductase, triphenylmethane reductase, lignin peroxidase, manganese peroxidase, and tyrosinase. The decolorized filtrates of MG, RB19, and RB5 exhibited very low phytotoxicity for RB5 and no phytotoxicity for MG and RB19. Furthermore, these filtrates demonstrated significant reductions in chemical oxygen demand (46%, 63%, and 50%) and biological oxygen demand (37%, 60%, and 40%) for MG, RB19, and RB5, respectively, compared to untreated dyes. Given their efficient biological removal of dyes under alkaline conditions, these fungal isolates are promising candidates for sustainable wastewater treatment. Full article

Recent studies on novel protein sources unveiled lupins as a promising substitute for meat consumption. However, lupin cultivation and processing include significant safety concerns, such as quinolizidine alkaloids (QAs) and the possible growth of toxigenic fungi as Diaporthe toxica, which produces the mycotoxin phomopsin-A (PHO-A). Therefore, this study aims to assess the influence of gaseous and aqueous ozone on lupin beans as environmentally sustainable methods for detoxifying QAs and PHO-A mycotoxins, thereby addressing both these safety challenges. Three distinct aqueous and gaseous ozone treatments (4, 6, and 8 h, at 7.00 ppm O₃ concentration) were applied on lupin seeds inoculated with D. toxica DSM 1894. A good effectiveness of aqueous O₃ in the reduction in PHO-A (about 20%) was demonstrated, independently of the treatment duration, along with the reduction in some QAs typically encountered in lupin. Additionally, a significant reduction in D. toxica count was observed after 4 h treatment with aqueous O₃. In contrast, results for gaseous O₃ treatments did not show any significant effectiveness on either PHO-A or QAs. Conversely, none of the treatments applied significantly affected lupin color. In conclusion, aqueous ozone treatment demonstrated significant potential for the reduction in PHO-A and QAs, and the insights acquired from this work may aid in mitigating the dangers associated with lupin intake. Nevertheless, additional research is required to cover current knowledge gaps. Specifically, toxicological assays on PHO-A degradation by-products or O₃ combination with other hurdles is required to enhance treatments and preserve lupins’ nutrients. Full article

Syringic acid (SA) is a natural derivative of syringaldehyde (SD), derived from lignin depolymerization. Its application in the food industry focuses on the properties of natural functional ingredients; it is mainly used as a food antioxidant and food preservative, but can also be used as an ingredient to enhance food flavor and functional foods. This compound exhibits a remarkable spectrum of biological activities, including potent antioxidant, anti-inflammatory, neuroprotective, hypoglycemic, detoxifying, and anti-cancer effects, positioning it as a highly promising candidate for pharmaceutical and nutraceutical applications. In this study, suitable sites were first screened through homologous sequence alignment, and a variant of aryl-alcohol oxidase (CgAAO) with high efficiency in catalyzing the conversion of SD to SA was obtained via site-directed mutagenesis. A deep eutectic solvent (DES) system based on choline chloride/urea (ChCl/UR) in water was developed to enhance SA production. Additionally, key parameters of the biological reaction were optimized, including temperature, pH, metal ions, as well as the type and dosage of DES. The optimal performance was achieved using recombinant E. coli pRSFDuet-CgAAO-Y335F whole-cell biocatalysts, yielding 75% and producing 0.75 g/L SA in 100 mM KPB buffer (pH 7.0) containing 5 wt% ChCl/UR and 1 mM Fe³⁺. This study established a novel biosynthetic pathway for SA that was efficient, mild, green, and environmentally friendly. Full article

Citrus trees are mainly cultivated in acidic soils. Excessive manganese (Mn) is the second most limiting factor for crop productivity in acidic soils after aluminum toxicity. The roles of reactive oxygen species (ROS) and methylglyoxal (MG) detoxification systems in augmented pH-mediated amelioration of excessive Mn are poorly understood. ‘Sour pummelo’ (Citrus grandis (L.) Osbeck) seedlings were exposed to nutrient solution at a Mn concentration of 500 (Mn500) or 2 (Mn2) μM and a pH of 3 (P3) or 5 (P5). The increase in pH attenuated Mn500-induced increases in ROS production and MG and malondialdehyde accumulation in roots and leaves. Additionally, the increase in pH enhanced the coordinated detoxification capability of both ROS and methylglyoxal scavenging systems in these tissues under Mn500. These findings corroborated the hypothesis that augmenting pH enhances the capability of these tissues to detoxify ROS and methylglyoxal under Mn excess. Therefore, this study provided new evidence on the roles of ROS and MG detoxification systems in the augmented pH-mediated amelioration of oxidative damage in ‘Sour pummelo’ leaves and roots caused by Mn excess, as well as a basis for correcting Mn toxicity by augmenting soil pH. Full article

This comprehensive review presents the results of an in-depth analytical literature search on the biological activity of humic substances and their possible pharmacological mechanisms of action. The unique chemical structure of humic substances has determined their widespread use in many economic sectors, including medicine. Thanks to modern advances in pharmaceuticals, pharmacology, and toxicology, it has been possible to demonstrate the multifaceted biological activity of humic substances and, consequently, the possibility of using them to treat and prevent many infectious and non-infectious pathologies, including diseases considered incurable. The article presents data on their immunotropic, antibacterial, antiviral (including HIV), antitumor, antioxidant and antiradical, cardiotropic, hepatoprotective, regenerative, detoxifying, and adaptogenic effects; their influence on the intestinal microbiome; studies of the toxic properties of humic substances and the safety of their use in medicine; and the current trend of using humic substances as unique matrices for creating next-generation bionanomaterials. An analysis of data on the intracellular mechanisms that play a key role in the implementation of the effects of humic substances is conducted. Thus, the natural genesis of humic substances, their multifaceted biological activity, and the absence of toxic and allergenic properties explain the growing interest of scientists from all over the world in their study. 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

Against the backdrop of the continuous expansion of the global aquaculture industry and the growing demand for high-quality feed protein, the development of sustainable alternative protein sources to fishmeal is crucial. Cottonseed protein, particularly cottonseed protein concentrate, has emerged as a highly promising plant-based alternative raw material due to its high protein content and cost advantages. This review systematically evaluates the application effects, challenges, and mechanisms of action of cottonseed protein in fish feed. Core analysis indicates that the primary limiting factor of cottonseed protein is the antinutritional factor free gossypol. High-level replacement (typically >30%) of fishmeal can inhibit fish growth, reduce protein deposition, and impair intestinal health. These adverse effects are closely associated with the downregulation of the hepatic mTOR signaling pathway—a central regulator of protein synthesis and cell growth—shifting the organism’s energy allocation from growth to stress adaptation. Furthermore, the unique fatty acid profile of cottonseed protein may exacerbate energy metabolism imbalance. To overcome gossypol toxicity, physical, chemical, and biological detoxification technologies have been widely applied. Among these, biological methods (such as Bacillus subtilis fermentation and CotA laccase-catalyzed degradation) are particularly outstanding, not only efficiently removing gossypol (removal rate > 90%) but also degrading macromolecular proteins into more digestible and absorbable small peptides and amino acids, significantly enhancing the nutritional value of cottonseed protein. Although the application prospects for cottonseed protein are broad, gaps remain in current research, particularly concerning the deeper metabolic pathways, nutrient utilization efficiency, and long-term impacts on metabolic homeostasis of detoxified cottonseed protein in fish. Future research needs to employ molecular nutrition and multi-omics technologies to elucidate its metabolic mechanisms and optimize detoxification processes and precision feeding strategies. Glandless cottonseed varieties, which fundamentally address the gossypol issue, are considered the most transformative development direction. Through continuous technological innovation, cottonseed protein is expected to become a core feed protein ingredient promoting the sustainable development of the global aquaculture industry. Full article

Fruit losses can occur during the storage of kiwifruit due to disorders such as chilling injury. A major factor influencing storage life is antioxidant metabolism. Antioxidants detoxify reactive oxygen species (ROS) and limit oxidative stress, which otherwise damages proteins, lipids, and DNA. Oxidative stress accelerates degradation and contributes to physiological disorders such as chilling injury during storage of kiwifruit. Regulation of antioxidant metabolism is complex, involving several biochemical pathways critical for maintaining kiwifruit integrity postharvest. The objective of this review is to critically evaluate current knowledge regarding oxidative stress and antioxidant metabolism and the development of postharvest disorders of kiwifruit during cold storage, with an emphasis on chilling injury. The review will provide an overview of current knowledge regarding oxidative stress and antioxidant metabolism in kiwifruit during cold storage, identifying gaps in our knowledge. The review will also discuss how an understanding of antioxidant metabolism can be used to design treatments that have the potential to increase the storability of kiwifruit and reduce chilling injury. Full article

Superoxide dismutase (SOD) serves as a critical enzyme that is involved in plant development and abiotic stresses by effectively detoxifying reactive oxygen species (ROS). Though the SOD gene family has been reported across various plant species, its specific members and functional roles in litchi (Litchi chinensis Sonn.) remain poorly understood. In this study, a total of seven SOD (christened LcSOD) genes were identified from the litchi genome and classified into three groups across six chromosomes. Notably, genes from the same evolutionary branch had more similar structures and motif distributions. The LcSOD genes were confirmed to have a stronger collinearity with dicotyledons than with monocotyledons. Cis-acting elements analysis indicated that the LcSOD gene family was deeply involved in orchestrating growth, development, and responses to multiple phytohormones and diverse stresses. Expression patterns of the LcSOD genes across different tissues revealed universal and specific expressions. In leaves, expression levels of the LcSOD genes were induced by cold, heat, drought, and salt stresses, and transcript levels correlated positively with concomitant changes in key physiological parameters under the same conditions. In addition, the LcSOD genes were characterized for their physicochemical properties, subcellular localizations, secondary and tertiary structures, gene ontology (GO) annotations, and protein-protein interactions. Our findings offer comprehensive insights into the LcSOD gene family, enriching genetic resources. They provide a framework for functional characterization and the development of stress-resistant cultivars, driving both basic research and applied breeding programs in litchi. Full article

Streptomyces sp. MC1, a bacterium isolated from an environment contaminated with organic and inorganic pollutants, can reduce chromium and degrade lindane, making it a promising candidate for bioremediation. However, a major challenge in bioremediation trials is monitoring bacteria survival in soil. To assess the survival of Streptomyces sp. MC1 during bioremediation, we introduced fluorescence tagging and a selectable marker into this strain by intergeneric conjugation from Escherichia coli. Conjugation assays were performed using two E. coli strains (ET12567/pUZ8002 or S17-1) and Streptomyces sp. MC1 (spores or mycelium). The integrative plasmid pSC001, carrying a gene encoding the monomeric green fluorescent protein (mGFP), was used. Various donor and recipient concentrations were tested and the presence of MgCl₂ or CaCl₂ during conjugation was also evaluated. Optimal conditions included low concentrations of both Streptomyces sp. MC1 spores and E. coli S17-1, with MgCl₂ in the medium. Exconjugants were analyzed, confirming plasmid site-specific integration and mGFP expression. In bioremediation assays with soils co-contaminated with Cr(VI) and lindane, fluorescence-tagged Streptomyces sp. MC1 successfully demonstrated survival over 28 days. Our results, combined with the availability of the Streptomyces sp. MC1 genome sequence, will facilitate further characterization of this strain’s features and accelerate its development for bioremediation applications. Full article

Chlorpyrifos (CPF), a widely used organophosphate pesticide, induces hepatotoxicity primarily through oxidative stress, acetylcholinesterase (AChE) inhibition, and inflammatory responses. This study evaluated the hepatoprotective potential of detoxifying formulations prepared from four medicinal plants, Thunbergia laurifolia, Embelia sessiliflora, Morinda angustifolia, and Thunbergia coccinea, in various ratios. Among these, a formulation composed of T. laurifolia and E. sessiliflora (1:1; Formula 04) showed the highest activity, with rosmarinic acid identified by compact mass spectrometry (CMS). Formula 04 demonstrated the greatest antioxidant and pro-apoptotic potential among the seven tested formulations, as confirmed by in vitro DPPH and superoxide radical assays and apoptosis assays in hepatic stellate LX-2 cells. In vivo, Sprague–Dawley rats exposed to CPF (16 mg/kg/day, oral gavage) received Formula 04 orally 30 min prior to CPF exposure in 6 cyclic dosing regimen for 18 days. The treatment restored AChE activity, increased superoxide dismutase levels, reduced glutathione levels, and decreased malondialdehyde, indicating attenuation of oxidative stress. Serum AST levels were significantly reduced compared with the CPF group, and histopathology revealed that the hepatic architecture was preserved. These findings demonstrate that Formula 04 exerts hepatoprotective effects against CPF-induced toxicity via redox regulation and cellular protection mechanisms, demonstrating its potential as a natural detoxifying agent. Full article

This study investigated the bioaccumulation of ciguatoxins (CTXs) in dusky grouper (Epinephelus marginatus) following dietary exposure to toxic fish flesh. Two feeding groups were established: group A (amberjack (Seriola spp.) and dusky grouper flesh) and group B (moray eel (Muraena spp. and Gymnothorax spp.) flesh). CTX-like toxicity was detected in muscle and liver of group A. Flesh toxicity progressively increased from the first sampling. In contrast, CTX activity was only detected in livers in group B. Liquid chromatography–mass spectrometry analysis revealed the presence of C-CTX1 in both groups, and the 17-OH-C-CTX1 analogue was exclusively observed in group A. Toxicity in the liver peaked at 10 weeks in experimental group A, but it showed a decline by the end of the experiment while increasing the storage of the toxin in muscle tissue. These findings demonstrate the differential bioaccumulation of CTXs in grouper flesh and liver, highlighting the potential role of the liver in metabolizing and/or detoxifying ciguatoxins. The efficacy of a combination of different techniques, including the cell-based assay (CBA) and liquid chromatography—low- and high-resolution mass spectrometry (LC-MS/MS and LC-HRMS), was demonstrated to confirm the presence of CTX analogues at very low levels. The results provide insights into CTX transfer and accumulation in marine food webs, underlining the need for further studies on toxin metabolism in predatory fish species. Full article