Regulation Of Redox Homeostasis Research Articles

TRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory

Post-transcriptional modification of RNA regulates gene expression at multiple levels. ALKBH8 is a tRNA-modifying enzyme that methylates wobble uridines in a subset of tRNAs to modulate translation. Through methylation of tRNA-selenocysteine, ALKBH8 promotes selenoprotein synthesis and regulates redox homeostasis. Pathogenic variants in ALKBH8 have been linked to intellectual disability disorders in the human population, but the role of ALKBH8 in the nervous system is unknown. Through in vivo studies in Drosophila, we show that ALKBH8 controls oxidative stress in the brain to restrain synaptic growth and support learning and memory. ALKBH8 null animals lack wobble uridine methylation and exhibit reduced protein synthesis in the nervous system, including a specific decrease in selenoprotein levels. Either loss of ALKBH8 or independent disruption of selenoprotein synthesis results in ectopic synapse formation. Genetic expression of antioxidant enzymes fully suppresses synaptic overgrowth in ALKBH8 null animals, confirming oxidative stress as the underlying cause of dysregulation. ALKBH8 null animals also exhibit associative memory impairments that are reversed by pharmacological antioxidant treatment. Together, these findings demonstrate the critical role of tRNA wobble uridine modification in redox homeostasis in the developing nervous system and reveal antioxidants as a potential therapy for ALKBH8-associated intellectual disability.

Carnosine Synthase (TsATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an Nfe2-like Gene in Tridacna Squamosa

As an important mollusk in reef ecosystems, Tridacna squamosa forms pro-survival symbiotic relationships that hinge on an exquisite redox equilibrium between the host and the photosynthetic symbiont, zooxanthellae. The exact regulatory mechanisms thereof remain poorly understood. In this study, a novel Nfe2-like transcription factor in T. squamosa was identified and characterized with respect to its antioxidant and cytoprotective roles. Gene structure and phylogenetic analysis reveal that T. squamosa possesses a single transcription factor TsNfe2l in contrast to mammalian Nfe2l1 (Nrf1) and Nfe2l2 (Nrf2), belonging to protein members of the bZIP-NFE2 subfamily and functionally resembling the mammalian Nfe2l1. A conserved bZIP domain permits its binding to the antioxidant response element (ARE) in vitro and in HEK293T cells. Further analyses such as promoter prediction suggest that TsNfe2l target genes engage mainly in the regulation of multiple enzymes involved in antioxidation and allied pathways. Notably, TsNfe2l transcriptionally upregulates carnosine synthase (TsATPGD), which subsequently produces L-carnosine abundantly to shield cells from oxidative damage. Moreover, the blockage of TsNfe2l nucleic acid binding reduced the expression of TsATPGD and L-carnosine content in the gill, resulting in elevated lipid peroxidation. Collectively, our findings establish novel molecular insight into TsNfe2l as a critical regulator of redox homeostasis in T. squamosa through carnosine synthesis.

Regulation Progression on Ellagic Acid Improving Poultry Production Performance by Regulating Redox Homeostasis, Inflammatory Response, and Cell Apoptosis.

It has been approximately 2000 years since the medicinal homologous theory, which primarily holds that food has the same therapeutic value as medicine in order to improve the health of both humans and animals. In recent years, this theory has also been proposed to be used in poultry breeding. Ellagic acid (EA), a natural compound primarily extracted from medicinal homologous foods such as raspberries and pomegranates, is reported to have incomparable advantages in improving the production performance and disease resistance of poultry due to its pharmacological properties, which regulate the processes of redox homeostasis, inflammatory response, and cell apoptotic death. However, the application and research of EA in poultry production are still in the initial stage, and the potential mechanisms of its biological functions affecting animal health have not been clearly identified, which requires more attention worldwide. This mini-review collects the latest 10-year achievements of research on the effects of EA on poultry health, aiming to promote the practical application of EA in maintaining animal health and formulating corresponding targeted strategies.

The Protective Role of Transcription Factor Nrf2 in Murine Macrophage Activation Syndrome.

Macrophage activation syndrome (MAS) is characterized by multi-lineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. Transcription factor Nrf2 is a master regulator of redox homeostasis. In this work we aim to investigate the role of Nrf2 in murine hyperinflammation and the mechanisms by which Nrf2 activation by red blood cell products regulates pro-inflammatory cytokine production. We induce murine MAS in wildtype and Nrf2 knockout (Nrf2 -/-) mice by repeat administration of TLR9-agonist CpG. Clinical and biochemical markers of disease were measured including complete blood counts, liver and spleen pathology, serum free heme, ferritin, and cytokine profiles. In vitro bone marrow derived macrophages and dendritic cells were used to investigate regulation of CpG-induced cytokine expression by oxidized red blood cells and hemin. Patients with hyperinflammatory disease have higher levels of Nrf2 gene expression. Mice with CpG-induced hyperinflammation have elevated systemic lipid peroxidation which is exacerbated in Nrf2 -/- mice. Compared to wildtype controls, Nrf2 -/- mice develop significantly worse organomegaly, organ pathology, and reticulocytosis. Nrf2 -/- mice have exacerbated hypercytokinemia in cytokines central MAS physiology: IL-12, IFNg, and IL-10. In vitro we found that oxidized red blood cell lysates and hemin are able to suppress IL-12 transcription and protein production from bone marrow derived dendritic cells in a Nrf2-dependent manner. Together our findings show that transcription factor Nrf2 is highly expressed in patients with hyperinflammatory disease and demonstrate a protective role for Nrf2 in a murine model of MAS in part due to Nrf2-mediated suppression of proinflammatory cytokine production.

Hydrogen-Rich Water to Enhance Exercise Performance: A Review of Effects and Mechanisms.

Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the impact of HRW on sports performance and explore the underlying molecular biological mechanisms, with the goal of elucidating how HRW might enhance athletic performance. Methods: This review synthesizes research on HRW by examining articles published between 1980 and April 2024 in databases such as PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Results: It highlights HRW's effects on various aspects of athletic performance, including endurance, strength, sprint times, lunge movements, countermovement jump height, and time to exhaustion. While the precise mechanisms by which HRW affects athletic performance remain unclear, this review investigates its general molecular biological mechanisms beyond the specific context of sports. This provides a theoretical foundation for future research aimed at understanding how HRW can enhance athletic performance. HRW targets the harmful reactive oxygen and nitrogen species produced during intense exercise, thereby reducing oxidative stress-a critical factor in muscle fatigue, inflammation, and diminished athletic performance. HRW helps to scavenge hydroxyl radicals and peroxynitrite, regulate antioxidant enzymes, mitigate lipid peroxidation, reduce inflammation, protect against mitochondrial dysfunction, and modulate cellular signaling pathways. Conclusions: In summary, while a few studies have indicated that HRW may not produce significant beneficial effects, the majority of research supports the conclusion that HRW may enhance athletic performance across various sports. The potential mechanisms underlying these benefits are thought to involve HRW's role as a selective antioxidant, its impact on oxidative stress, and its regulation of redox homeostasis. However, the specific molecular biological mechanisms through which HRW improves athletic performance remain to be fully elucidated.

Ursolic Acid Restores Redox Homeostasis and Pro-inflammatory Cytokine Production in Denervation-Induced Skeletal Muscle Atrophy.

Skeletal muscle (SkM) atrophy results from metabolic disorders causing body and muscle mass loss, affecting morbidity and mortality. Increased oxidative stress, inflammation, and poor prognosis are the leading causes of involuntary weight loss. Ursolic acid (UA), known for its antioxidant and anti-inflammatory properties, can potentially reduce oxidative stress and inflammation in muscles, but its effects on muscle mass regulation are still unknown. Therefore, the present study investigated the medicinal efficacy of UA and its mode of action against the murine model of SkM atrophy over 7days of UA supplementation. Denervation-induced SkM atrophy significantly impacts overall body weight and the weight of individual muscles (p < 0.05). However, supplementation with UA can effectively counteract these effects by promoting the synthesis of the slow-myosin heavy chain, thereby restoring body weight and myotube diameter. Moreover, UA also plays a crucial role in reducing the production levels of reactive oxygen species (ROS), lipid peroxidation (LPO), and caspase-3-like activity in atrophied muscles. UA also prevents the leakage of creatine kinase (CK) through the upregulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) expression. Furthermore, the results obtained from qRT-PCR demonstrated a significant decrease in the levels of pro-inflammatory markers, namely IL-1β, IL-6, TNF-α, and TWEAK, up to four-fold after the third day of the UA intervention. UA also upregulated PGC-1α, Bcl2, and p-Aktser473 expression towards the regulation of redox homeostasis.

Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells.

Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene TP53, wild-type (wt) for 70% of patients, regulates redox homeostasis. Glioblastoma stem cells (GSCs) increase thioredoxin (Trx) and glutathione (GSH) antioxidant systems as survival redox-adaptive mechanisms to maintain ROS below the cytotoxic threshold. Auranofin, an FDA-approved anti-rheumatoid drug, inhibits thioredoxin reductase 1 (TrxR1). L-buthionine sulfoximine (L-BSO) and the natural product piperlongumine (PPL) inhibit the GSH system. We evaluated the cytotoxic effects of Auranofin alone and in combination with L-BSO or PPL in GBM cell lines and GSCs with a known TP53 status. The Cancer Genome Atlas/GBM analysis revealed a significant positive correlation between wtp53 and TrxR1 expression in GBM. Auranofin induced ROS-dependent cytotoxicity within a micromolar range in GSCs. Auranofin decreased TrxR1 expression, AKT (Ser-473) phosphorylation, and increased p53, p21, and PARP-1 apoptotic cleavage in wtp53-GSCs, while mutant-p53 was decreased in a mutant-p53 GSC line. Additionally, p53-knockdown in a wtp53-GSC line decreased TrxR1 expression and significantly increased sensitivity to Auranofin, suggesting the role of wtp53 as a negative redox-sensitive mechanism in response to Auranofin in GSCs. The combination of Auranofin and L-BSO synergistically increased ROS, decreased IC50s, and induced long-term cytotoxicity irrespective of p53 in GBM cell lines and GSCs. Intriguingly, Auranofin increased the expression of glutathione S-transferase pi-1 (GSTP-1), a target of PPL. Combining Auranofin with PPL synergistically decreased IC50s to a nanomolar range in GSCs, supporting the potential to repurpose Auranofin and PPL in GBM.

Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis

Introduction: Doxorubicin (DOX) is an anthracycline antibiotic with considerable significance in clinics as an anticancer agent, which is limited by its cardiotoxicity, though. A large number of possible therapeutic strategies for reducing cardiotoxicity with doxorubicin have been studied. However, none of them fully meets the requirements of clinical practice. The aim of the study: to evaluate the cardioprotective effects of a new original heterocyclic compound, a pyridine-3-carboxylic acid derivative potassium 5-hydroxynicotinate. Materials and Methods: Cardiac injury was induced by intraperitoneal administration of doxorubicin (DOX) at a dose of 20 mg/kg. After 48 hours, the parameters of left ventricular contractility and StTTI coefficient were assessed on isolated heart in the Langendorff system under the conditions of 480 beats per minute for 11 seconds. Additionally, specific markers of myocardial injury were determined. The lipid peroxidation products and SOD activity were measured as well to challenge whether the compound is able to reduce oxidative stress. Results: The study showed that pretreatment by potassium 5-hydroxynicotinate (35 mg/kg, 48 h) attenuated DOX-induced damage, resulting in a significant decrease in the StТТI coefficient to 3.3 values and in the restoration of the antioxidant activity of enzymes. Conclusion: The obtained data totally demonstrate the protective effects of potassium 5-hydroxynicotinate in DOX-induced cardiomyopathy. A significant role in potassium 5-hydroxynicotinate-mediated cardioprotection is, apparently, related to the reduction of oxidative stress and down-regulation of the level of intracellular calcium.

CBR-470-1 protects against cardiomyocyte death in ischaemia/reperfusion injury by activating the Nrf2–GPX4 cascade

Cardiac ischaemia/reperfusion (I/R) impairs mitochondrial function, resulting in excessive oxidative stress and cardiomyocyte ferroptosis and death. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of redox homeostasis and has cardioprotective effects against various stresses. Here, we tested whether CBR-470-1, a noncovalent Nrf2 activator, can protect against cardiomyocyte death caused by I/R stress. Compared with vehicle treatment, the administration of CBR-470-1 (2 mg/kg) to mice significantly increased Nrf2 protein levels and ameliorated the infarct size, the I/R-induced decrease in cardiac contractile performance, and the I/R-induced increases in cell apoptosis, ROS levels, and inflammation. Consistently, the beneficial effects of CBR-470-1 on cardiomyocytes were verified in a hypoxia/reoxygenation (H/R) model in vitro, but this cardioprotection was dramatically attenuated by the GPX4 inhibitor RSL3. Mechanistically, CBR-470-1 upregulated Nrf2 expression, which increased the expression levels of antioxidant enzymes (NQO1, SOD1, Prdx1, and Gclc) and antiferroptotic proteins (SLC7A11 and GPX4) and downregulated the protein expression of p53 and Nlrp3, leading to the inhibition of ROS production and inflammation and subsequent cardiomyocyte death (apoptosis, ferroptosis and pyroptosis). In summary, CBR-470-1 prevented I/R-mediated cardiac injury possibly through inhibiting cardiomyocyte apoptosis, ferroptosis and pyroptosis via Nrf2-mediated inhibition of p53 and Nlrp3 and activation of the SLC7A11/GPX4 pathway. Our data also highlight that CBR-470-1 may serve as a valuable agent for treating ischaemic heart disease.

A responsive aggregation-induced emission fluorescent probe for the detection of cysteine in food, serum samples and oxidative stress environments

Heavy metal ions tend to accumulate through the food chain and may cause many serious diseases. As an antioxidant, cysteine (Cys) plays a crucial role in regulating redox homeostasis. In addition, Cys is also widely used in the food industry. Therefore, the development of a convenient, sensitive, and practical tool for detecting Cys is of great significance for investigating the physiological and pathological functions of Cys induced by heavy metal ions. In this paper, a fluorescent probe NYVB with aggregation-induced emission (AIE) activities has been designed and synthesized, which featured good advantages in Cys detection, including favorable selectivity, desirable sensitivity, wide linear range, and low detection limit. The prepared solid-state sensor enabled the ratiometric visual detection of Cys. Probe NYVB has been successfully implemented for testing Cys in real food samples and serum samples with satisfactory recoveries. In addition, probe NYVB has been successfully employed for detecting endogenous and exogenous Cys in SKOV3 cells. More excitingly, probe NYVB has also been used to track the detection of Cys in H2O2, Hg2+, or Cu2+-induced redox imbalance. Overall, probe NYVB will open up a new avenue for studying Cys in the amelioration of heavy metal toxicity and has practical applications.

Multiple Mechanisms of Action of Sulfodyne®, a Natural Antioxidant, against Pathogenic Effects of SARS-CoV-2 Infection.

Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of NRF2-agonist Sulfodyne®, a stabilized natural Sulforaphane, in cellular and animal models of SARS-CoV-2 infection. In pulmonary or colonic epithelial cell lines, Sulfodyne® elicited a more efficient inhibition of SARS-CoV-2 replication than NRF2-agonists DMF and CDDO. This antiviral activity was not dependent on NRF2 but was associated with the regulation of several metabolic pathways, including the inhibition of ER stress and mTOR signaling, which are activated during SARS-CoV-2 infection. Sulfodyne® also decreased SARS-CoV-2 mediated inflammatory responses by inhibiting the delayed induction of IFNB1 and type I IFN-stimulated genes in infected epithelial cell lines and by reducing the activation of human by-stander monocytes recruited after SARS-CoV-2 infection. In K18-hACE2 mice infected with SARS-CoV-2, Sulfodyne® treatment reduced both early lung viral load and disease severity by fine-tuning IFN-beta levels. Altogether, these results provide evidence for multiple mechanisms that underlie the antiviral and anti-inflammatory activities of Sulfodyne® and pinpoint Sulfodyne® as a potent therapeutic agent against pathogenic effects of SARS-CoV-2 infection.

The Dual Role of NRF2 in Colorectal Cancer: Targeting NRF2 as a Potential Therapeutic Approach.

Colorectal cancer (CRC), as the third most common bisexual cancer worldwide, requires urgent research on its underlying mechanisms and intervention methods. NRF2 is an important transcription factor involved in the regulation of redox homeostasis, protein degradation, DNA repair, and other cancer processes, playing an important role in cancer. In recent years, the complex role of NRF2 in CRC has been continuously revealed: on the one hand, it exhibits a chemopreventive effect on cancer by protecting normal cells from oxidative stress, and on the other hand, it also exhibits a protective effect on malignant cells. Therefore, this article explores the dual role of NRF2 and its related signaling pathways in CRC, including their chemical protective properties and promoting effects in the occurrence, development, metastasis, and chemotherapy resistance of CRC. In addition, this article focuses on exploring the regulation of NRF2 in CRC ferroptosis, as well as NRF2 drug modulators (activators and inhibitors) targeting CRC, including natural products, compounds, and traditional Chinese medicine formulations.

AT-hook motif nuclear localized transcription factors function redundantly in promoting root growth through modulation of redox homeostasis.

Maintaining an optimal redox status is essential for plant growth and development, particularly when the plants are under stress. AT-hook motif nuclear localized (AHL) proteins are evolutionarily conserved transcription factors in plants. Much of our understanding about this gene family has been derived from studies on clade A members. To elucidate the functions of clade B genes, we first analyzed their spatial expression patterns using transgenic plants expressing a nuclear localized GFP under the control of their promoter sequences. AHL1, 2, 6, 7, and 10 were further functionally characterized owing to their high expression in the root apical meristem. Through mutant analyses and transgenic studies, we showed that these genes have the ability to promote root growth. Using yeast one-hybrid and dual luciferase assays, we demonstrated that AHL1, 2, 6, 7, and 10 are transcription regulators and this activity is required for their roles in root growth. Although mutants for these genes did not showed obvious defects in root growth, transgenic plants expressing their fusion proteins with the SRDX repressor motif exhibited a short-root phenotype. Through transcriptome analysis, histochemical staining and molecular genetics experiments, we found that AHL10 maintains redox homeostasis via direct regulation of glutathione transferase (GST) genes. When the transcript level of GSTF2, a top-ranked target of AHL10, was reduced by RNAi, the short-root phenotype in the AHL10-SRDX expressing plant was largely rescued. These results together suggest that AHL genes function redundantly in promoting root growth through direct regulation of redox homeostasis.

A Nanozyme-Boosted MOF-CRISPR Platform for Treatment of Alzheimer's Disease.

Rectifying the aberrant microenvironment of a disease through maintenance of redox homeostasis has emerged as a promising perspective with significant therapeutic potential for Alzheimer's disease (AD). Herein, we design and construct a novel nanozyme-boosted MOF-CRISPR platform (CMOPKP), which can maintain redox homeostasis and rescue the impaired microenvironment of AD. By modifying the targeted peptides KLVFFAED, CMOPKP can traverse the blood-brain barrier and deliver the CRISPR activation system for precise activation of the Nrf2 signaling pathway and downstream redox proteins in regions characterized by oxidative stress, thereby reinstating neuronal antioxidant capacity and preserving redox homeostasis. Furthermore, cerium dioxide possessing catalase enzyme-like activity can synergistically alleviate oxidative stress. Further in vivo studies demonstrate that CMOPKP can effectively alleviate cognitive impairment in 3xTg-AD mouse models. Therefore, our design presents an effective way for regulating redox homeostasis in AD, which shows promise as a therapeutic strategy for mitigating oxidative stress in AD.

Transcription factor NF-E2-related factor 2 plays a critical role in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) by regulating ferroptosis

NRF2 is an important transcription factor that regulates redox homeostasis in vivo and exerts its anti-oxidative stress and anti-inflammatory response by binding to the ARE to activate and regulate the transcription of downstream protective protein genes, reducing the release of reactive oxygen species. Ferroptosis is a novel iron-dependent, lipid peroxidation-driven cell death mode, and recent studies have shown that ferroptosis is closely associated with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). NRF2 is able to regulate ferroptosis through the regulation of the transcription of its target genes to ameliorate ALI/ARDS. Therefore, This article focuses on how NRF2 plays a role in ALI/ARDS by regulating ferroptosis. We further reviewed the literature and deeply analyzed the signaling pathways related to ferroptosis which were regulated by NRF2. Additionally, we sorted out the chemical molecules targeting NRF2 that are effective for ALI/ARDS. This review provides a relevant theoretical basis for further research on this theory and the prevention and treatment of ALI/ARDS. The intended audience is clinicians and researchers in the field of respiratory disease.

"Two-birds-one-stone" oral nanotherapeutic designed to target intestinal integrins and regulate redox homeostasis for UC treatment.

Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM-mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.

Jasmonic Acid and Salicylic Acid improved resistance against Spodoptera frugiperda Infestation in maize by modulating growth and regulating redox homeostasis

Exploring host plant resistance and elevating plant defense mechanisms through the application of exogenous elicitors stands as a promising strategy for integrated pest management. The fall armyworm, a pernicious menace to grain crops in tropical and subtropical regions, stands as a formidable threat due to its capacity for devastation and a wide-ranging spectrum of host plants. There is no literature regarding artificially induced resistance in maize against fall armyworm (Spodoptera frugiperda) by exogenous application of phytohormones. The present investigation was performed to evaluate the role of jasmonic acid (JA) and salicylic acid (SA) on two maize hybrids namely FH-1046 and YH-1898 against fall armyworm. Results showed that plant height, biomass and lengths, fresh and dry weight of root shoot which decreased with armyworm infestation improved with phytohormonal application. JA treatment resulted in a higher increase in all attributes as compared to SA treatment. Improvement in relative water contents, photosynthetic pigments and pronounced levels of phenol and proline accumulation were observed in infested plants after JA treatment. Infested plants recovered from oxidative stress as JA application activated and increased the antioxidant enzyme activity of superoxide dismutase, peroxidase and polyphenol oxidase activity in both FH-1046 and YH-1898 . The oxidative stress reduction in infested plants after JA treatment was also evident from a fair decrease in MDA and H2O2 in both varieties. The SA and JA mediated genes expression was studied and it was found that in FH1046 maize cultivar, JA dependent genes, particularly marker genes PR1 and Lox5 were highly expressed along with TPS10 and BBT12. Whereas SPI, WRKY28, ICS and PAL were shown to be activated upon SA application. Evidently, both JA and SA elicited a robust defensive response within the maize plants against the voracious S. frugiperda, which in consequence exerted a discernible influence over the pest's developmental trajectory and physiological dynamics. A decrease in detoxification enzyme activity of the insects was observed after feeding on treated plants. Moreover, it was recorded that the survival and weight gain of FAW feeding on phytohormone treated maize plants also decelerated. In conclusion, FH-1046 was found to be more tolerant than YH-1898 against fall armyworm infestation and 1 mM JA was more effective than 1 mM SA for alleviation of fall armyworm stress. Therefore, it was inferred that phytohormones regulated redox homeostasis to circumvent oxidative damage and mediate essential metabolic events in maize under stress. To our current understanding, this study is the very first presentation of induced resistance in maize against S. frugiperda with the phytohormonal application (JA and SA).

JAK2/STAT3 signaling pathway mediates methylmercury toxicity in mouse astrocyte neuronal C8-D1A cell line.

Methylmercury (MeHg) is an environmental pollutant. Consumption of contaminated fish is the main exposure route in humans, leading to severe neurological disorders. Upon ingestion MeHg reaches the brain and selectively accumulates in astrocytes disrupting glutamate and calcium homeostasis and increasing oxidative stress. Despite extensive research, the molecular mechanisms underlying MeHg neurotoxicity remain incompletely understood. The induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role activating antioxidant responses during MeHg-induced oxidative injury have garnered significant attention as a potential therapeutic target against MeHg toxicity. However, recent studies indicate that the Nrf2 signaling pathway alone may not be sufficient to mitigate MeHg-induced damage, suggesting the existence of other protective mechanisms. The signal transducer and activator of transcription 3 (STAT3) plays a crucial role in cell growth and survival. Several studies have also highlighted its involvement in regulating redox homeostasis, thereby preventing oxidative stress through mechanisms that involve modulation of nuclear genes that encode electron transport complexes (ETC) and antioxidant enzymes. These characteristics suggest that STAT3 could serve as a viable mechanism to mitigate MeHg toxicity, either in conjunction with or as an alternative to Nrf2 signaling. Our previous findings demonstrated that MeHg activates the STAT3 signaling pathway in the GT1-7 hypothalamic neuronal cell line, suggesting its potential role in promoting neuroprotection. Here, to elucidate the role of the STAT3 signaling pathway in MeHg neurotoxicity, we pharmacologically inhibited STAT3 using AG490 in the C8D1A astrocytic cell line exposed to 10 µM MeHg. Our data demonstrated that pharmacological inhibition of STAT3 phosphorylation exacerbates MeHg-induced mortality, antioxidant responses, and ROS production, suggesting that STAT3 may contribute to neuroprotection against MeHg exposure in astrocytes.

Evaluating the Impact of an Organic Trace Mineral mix on the Redox Homeostasis, Immunity, and Performance of Sows and their Offspring.

The objective of the study was to evaluate the effects of trace mineral supplementation in sows during gestation and lactation on the performance and health status of sows and their offspring. Sows (n = 30; Landrace × Yorkshire; avg parity = 3.9) were randomly allocated into two dietary treatments. Sows received a basal diet supplemented with 12mg/kg Cu, 30mg/kg Fe, 90mg/kg Zn, 70mg/kg Mn, 0.30mg/kg Se, and 1.5 mg/kg I from an inorganic trace mineral source (ITM) or a blend of hydroxychloride and organic trace mineral source (HOTM) from day 1 of gestation until the end of the lactation period at day 21. Compared to the ITM, the HOTM supplementation increased (P < 0.05) both litter birth weight and individual piglet birth weight. Although not statistically significant, HOTM tended to increase (P = 0.069) the level of lactose in colostrum. HOTM increased (P < 0.05) the concentration of Mn and Se in the colostrum, milk, and serum of sows and/or piglets. Notably, the Zn concentration in the serum of sows was higher in sows supplemented with ITM compared to HOTM. Moreover, HOTM increased (P < 0.05) the activities of GPX and SOD in gestating sows and piglets, as well as increased (P < 0.05) cytokines (IL-1β, TNF-α, and IL-10) in the serum of sows. The immunoglobulins (IgA, IgG, and IgM) also increased in sows and/or piglets at certain experimental time points. In conclusion, HOTM supplementation positively affected piglet development and improved the health status of sows and piglets potentially by regulating redox homeostasis and immunity.

SLC7A11: the Achilles heel of tumor?

The non-natriuretic-dependent glutamate/cystine inverse transporter-system Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 serving as the primary functional component responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death, among other processes relevant to tumorigenesis. In this paper, we summarize the structure and biological functions of SLC7A11, and discuss its potential role in tumor therapy, which provides a new direction for precision and personalized treatment of tumors.