Depressive disorder is a highly disabling condition that affects more than 300 million individuals worldwide, with women affected at a higher rate than men. With the aging of the population, the incidence of perimenopausal depression has risen markedly, seriously jeopardizing women's physical and mental health. Symptoms of perimenopausal depression include feelings of depression, stress, anxiety and endocrine dysfunctions, particularly hypogonadism and senescence. During perimenopause, estrogen and progesterone levels fluctuate erratically, adding to the risk of developing depression associated with perimenopause. As a result of these hormonal changes, proinflammatory mediators are produced and oxidative stress is induced, which finally leads to progressive neuronal damage. The present study mainly reviewed roles of neuroinflammation in perimenopausal depression and explained potential anti‑inflammatory and anti‑oxidative stress mechanisms for clinically effective therapeutic treatment.

Chronic pancreatitis (CP) is an invasive inflammatory disorder characterized by endocrine and exocrine dysfunction. There are currently no effective drugs for the treatment of CP. The present study investigated whether curcumin improves cerulein‑induced CP fibrosis in a mouse model and pancreatic stellate cells (PSCs). The CP mouse model was established by intraperitoneally injecting cerulein (50 µg/kg) for 3 weeks (six times at 1 h intervals/day; 4 days/week). To investigate the effects of curcumin, dimethyl sulfoxide or curcumin was injected intraperitoneally 1 h before the first daily injection of cerulein. To determine the severity of CP, the pancreas was harvested 24 h after the last cerulein injection for histological examination and assessment of PSC activation and collagen deposition. Additionally, levels of the nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) were evaluated to determine the mechanism underlying the anti‑fibrotic effect of curcumin in PSCs. Curcumin improved pancreatic injury associated with CP by inhibiting PSC activation and collagen deposition. Moreover, curcumin increased HO‑1 expression levels via the activation of Nrf2 in PSCs, which suppressed the activation of PSCs. In conclusion, the present results suggest that curcumin can ameliorate pancreatic fibrosis induced by repetitive cerulein challenges via the induction of HO‑1 and is a beneficial agent for the treatment of CP.

Previous studies suggest that 6:2 fluorotelomer sulfonate (6:2 FTSA) exhibits lower hepatotoxicity and reduced reproductive and developmental toxicity compared to perfluorooctane sulfonate (PFOS), indicating it may offer a safer alternative. This study aimed to investigate whether 6:2 FTSA is safer than PFOS in terms of its cytotoxic effects on pancreatic β-cells. Using rat insulinoma cells (INS-1) as a model of pancreatic β-cells, we compared the effects of 6:2 FTSA and PFOS in both their acid (6:2 FTSA-H, PFOS-H) and potassium salt forms (6:2 FTSA-K, PFOS-K) on cell viability through Cell Counting Kit-8 (CCK-8) assays, Trypan Blue staining, and apoptosis assays. Results indicated that 6:2 FTSA was less toxic to INS-1 cells than PFOS (6:2 FTSA-H < PFOS-H; 6:2 FTSA-K < PFOS-K), the LOECs of 6:2 FTSA-H, 6:2 FTSA-K, PFOS-H, and PFOS-K were 150 μM, 150 μM, 20 μM, and 10 μM under FBS free conditions, respectively. To further explore whether these compounds induce cell death via oxidative stress, we measured intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels. All four compounds induced oxidative stress in INS-1 cells, with oxidative stress levels corresponding to cytotoxicity, suggesting β-cell death may occur via an oxidative stress mechanism. In conclusion, this study supports the notion that 6:2 FTSA is a safer alternative to PFOS, particularly regarding risks related to pancreatic β-cell cytotoxic effects. While the in vitro experiments in this study provide valuable preliminary information on the compounds' effects on cells and their mechanisms, they cannot fully capture the complexity of the in vivo environment. Therefore, future research should include in vivo experiments to validate the findings from the in vitro studies and comprehensively evaluate the actual effects of the compounds in living organisms.

As a typical neonicotinoid insecticide, dinotefuran (DIN) has immunotoxicity, but its immunotoxicity effects on aquatic organisms and its molecular mechanisms are not known. In this study, zebrafish embryos were used as model to reveal its immunotoxicity and its mechanism from the perspective of inflammatory response. Zebrafish larvae were exposed to DIN at environmentally relevant concentrations (0, 2, 200, and 2000 mg/L) for 120 h, followed by comprehensive analyses of immune cell populations, immune marker activities, oxidative stress levels, and gene expression profiles. The results showed that the number of neutrophils and macrophages, two types of innate immune cells, was significantly reduced, and the activities of the immune markers, lysozyme (LYS), immunoglobulin M (IgM), and complement protein C3, were significantly inhibited. The level of oxidative stress in zebrafish larvae was significantly elevated and antioxidant enzyme activities were markedly inhibited in a dose-dependent manner after exposure to DIN. In this case, pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were also abnormally expressed, and the expression levels of the genes related to the NF-κB pathway and the JNK-STAT pathway, tlr4a, myd88, nf-κb p65, jak1, jak2, and stat3, were elevated. The expression levels of genes related to the antioxidant signaling pathway Nrf2-keap1 signaling pathway were suppressed. Taken together, our results suggest that DIN exposure causes damage to the immune system of zebrafish embryos-larvae, generating oxidative stress and inflammatory responses that lead to immunotoxicity.

NRF2 has been recognized as a central hub that neutralizes ROS and restores intracellular redox balance. In addition to KEAP1 mediated ubiquitin-proteasome degradation, post-translational modifications of NRF2 are critical for regulating its nuclear translocation and activation but precise mechanisms underly this regulation remain elusive. In this study, we found that SIRT7 was sufficient and essential for NRF2 nuclear localization and activation. Knockdown of SIRT7 significantly impaired intercellular ROS homeostasis and increased apoptosis in response to oxidative stress including chemodrug treatment. SIRT7 interacted with NRF2 and induced its deacetylation, by which inhibited binding of NRF2 to KEAP1, enhanced NRF2 protein stability and promoted its nuclear translocation. SIRT7 induced NRF2 deacetylation at K443 and K518 sites. Lysine-arginine mutations of these sites (2KR NRF2) significantly reduced KEAP1/NRF2 binding, increased NRF2 nuclear translocation and target gene expression, decreased intercellular ROS level, whereas lysine-glutamine (2KQ) mutant showed similar subcellular localization and functions with WT. Knockdown SIRT7 in hepatocyte exacerbated Oxaliplatin (Oxa) induced hepatic injury and inflammation. While AAV8-NRF2-mediated hepatic NRF2 overexpression or NRF2 agonist significantly prevented Oxa-induced elevation of ALT levels, sinusoidal dilatation and inflammation in SIRT7HKO mice. Our data thus uncovered previously unidentified role of SIRT7 in modulating NRF2 nuclear localization and activation via deacetylation. Activating SIRT7 might offer protection against chemodrug-induced liver injury.

Five phenylpropanoid dimers chrysanthephenyls A-E, with the 1-O-1'-type (1) and 1-O-2'-type (2-5) ether bond linking modes, were isolated from the aerial parts of Chrysanthemum indicum. Among them, chrysanthephenyls D and E were two pairs of enantiomers, and chrysanthephenyl E was further resolved into its enantiomers (+)-chrysanthephenyl E and (-)-chrysanthephenyl E via chiral-phase HPLC. Their structures were characterized on the basic analysis of the spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR), and their absolute configurations were determined by DP4+ NMR analysis and ECD calculation method. The antioxidant activity of chrysanthephenyls A-E was determined by measuring their free radical scavenging effects using the trolox equivalent antioxidant activity (TEAC) assay, and chrysanthephenyls D and E showed 17 and 15 times better activity respectively than that of the positive control trolox. Moreover, a mechanistic study revealed that the potential antioxidant activity of chrysanthephenyl D decreased the level of reactive oxygen species (ROS) mediated via activating nuclear factor E2-related factor 2 (Nrf2) and its downstream oxidases.

Today, diabetes is considered a growing global epidemic. In the diabetic environment, a large amount of reactive oxygen species are produced. This type of active oxygen causes severe damage to cell membranes, proteins, and DNA. Therefore, finding a solution to deal with and reduce this type of reactive oxygen is very important. One of the most effective ways to deal with oxidative damage and inflammation is the modulation of the nuclear factor erythroid 2 (Nrf2) signaling pathway. One of the useful natural substances that can be used for treatment in the signaling system is saffron. In this article, research evaluating the medicinal effects of saffron and its compounds and their mechanisms of action, especially the Nrf2 signaling pathway, have been investigated and studied. The results show that saffron and its components have the potential to treat diabetes due to their unique properties.

Deoxynivalenol (DON) is a trichothecene mycotoxin often contaminating grains used in poultry feed production and causing several adverse effects in farm animals. Therefore, it is important to investigate compounds that can be potential candidates to mitigate these effects, such as baicalin. The effects of DON and baicalin were investigated in chicken-derived 3D hepatic cell cultures, and cell viability, LDH activity, oxidative parameters (NRF-2, 8-OHdG) and inflammatory parameters (IL-6, IL-8, IFN-γ) were monitored for 24 and 48 h. Our results suggest that DON reduced cellular metabolic activity but did not prove to be cytotoxic, and baicalin was able to attenuate this adverse effect. The change in extracellular LDH activity suggests that after 48 h the cells have already started to respond to the adverse effects of the toxin and protective mechanisms were induced. Based on the measured oxidative parameters, baicalin showed antioxidant activity, but after longer exposure, our results indicate a prooxidant effect. Baicalin also had an anti-inflammatory effect based on the amount of IL-6 and IL-8, while DON exerted a dose-and time-dependent pleiotropic activity. These results suggest that DON may have an impact on cellular inflammation and oxidative homeostasis, and that baicalin could be able to alleviate these adverse effects.

Inadequate angiogenesis of endometriotic implants stimulated by the inflammatory microenvironment in the uterine region leads to the development of gynecological diseases, which significantly reduce the fertility and vitality of young women. Angiogenic processes are controlled by factors whose activities are regulated at the gene level by reactive oxygen species (ROS), hypoxia-induced factors (HIFs), and zinc-finger proteins (ZnFs) or posttranscriptionally via non-coding RNAs. The cooperation of these factors is responsible for the manifestation of pathological stimuli in the form of endometriosis of the body of the uterus, ovaries, or peritoneum, from which endometrioid carcinoma can develop. Molecules that can control gene expression by their intercalation to target DNA sequence, such as [Zn(neo)(nif)2], could prevent the hyperactivation of pro-angiogenic pathways (decrease HIF-1α, VEGF-A, TGF-β1, COX2, and ANG2/ANG1), reduce the formation of ROS, and reduce the risk of uterine neoplasticity. The NSAID-metal complex [Zn(neo)(nif)2] shows an ability to intercalate into ZNF3-7 target DNA sequence at a higher rate, which could explain its effect on genes regulated by this transcription factor. In addition, [Zn(neo)(nif)2] affects ROS production and Ca2+ level, possibly pointing to mitochondrial dysfunction as a potential cause for the described apoptosis.

Children are particularly susceptible to environmental pollutants. This study assessed the skin sensitisation risk associated with polycyclic aromatic hydrocarbons (PAHs), prevalent in toys.

To evaluate the skin sensitisation potential of PAHs using the KeratinoSens assay.

Individual PAHs (acenaphthylene, anthracene, benzo[a]anthracene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), benzo[e]pyrene, benzo[g,h,i]perylene, benzo[k]fluoranthene (B[k]F), chrysene, fluoranthene, fluorene, naphthalene, phenanthrene, pyrene and triphenylene) and ternary mixtures containing B[a]P were assessed for their ability to activate the Keap1-Nrf2-ARE pathway in human keratinocytes. The concentration addition model and additive index were used to predict and analyse mixture effects.

Among the individual PAHs, B[k]F demonstrated the most potent activation of the pathway, exhibiting a 34-fold higher potency relative to B[a]P. B[b]F, chrysene and B[a]P also exhibited significant activation, while the remaining PAHs displayed negligible or weak activation. Notably, PAH mixtures exhibited synergistic effects, except for those composed solely of potent sensitizers.

This study provides the first assessment of the skin sensitization potential of these PAHs. The findings suggest that B[k]F, B[b]F and chrysene may pose a higher risk of skin sensitisation than previously thought. Additionally, the synergistic effects observed in mixtures highlight the importance of considering combined exposures when assessing PAH exposure risk.

Insulin resistance and diabetes are associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) conditions, which are distinguished by metabolic dysfunction, oxidative stress and inflammation. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, is fundamental in regulating metabolic pathways, reducing inflammation, and improving antioxidant defenses. This is the first study to investigate the effects of SRT1720, a SIRT1 activator, in diabetic rats on a high-fat diet. SRT1720 significantly lowered fasting blood glucose and insulin levels and enhanced glucose tolerance and HOMA-IR and QUICKI scores, indicating increased insulin sensitivity. The treatment also reduced total cholesterol, triglycerides, and LDL levels, showing amelioration of dyslipidemia. Moreover, SRT1720 lowered markers of liver fibrosis, including TGF-β, TIMP-1, Col1a1, and hydroxyproline, and decreased inflammation by reducing NFκB activity and pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, SRT1720 augmented Nrf2 activity and HO-1 levels. Consequently, the SRT1720's protective role improved liver function and histology and prolonged rats' survival. These functions were suppressed by the co-administration of the SIRT1 inhibitor EX527, confirming that the beneficial effects of SRT1720 are SIRT1-dependent. Correlation analyses uncovered that increased SIRT1 activity was strongly associated with decreased oxidative stress, inflammation, insulin resistance, and fibrosis markers. To conclude, our results find that SRT1720 represents a promising therapeutic strategy for managing Type 2 diabetes in NAFLD or NASH patients possibly through the modulation of the SIRT1/Nrf2/NFκB signaling pathwa. SRT1720 could potentially halt or reverse the progression of these conditions and associated complications and merits further investigations.

This study aimed to assess the influence of Paralichthys olivaceus egg extract (POEE) treatment on the maturation and development of porcine oocytes subjected to oxidative stress during in vitro maturation (IVM). POEE, notably rich in vitamin B9 (folic acid [FA]), was assessed alongside FA for antioxidant activity across various concentrations. In the 650 ppm POEE (650 POEE) group, there was a significant rise in glutathione (GSH) levels and an improved developmental rate in porcine oocytes experiencing oxidative stress during IVM. Treatment with 0.3 FA exhibited substantial reduction in ROS activity. Both 650 POEE and 0.3 FA groups demonstrated inhibited abnormal spindle organization and chromosomal misalignment, with increased blastocyst formation and decreased apoptotic cells. Treatment with 650 POEE elevated mRNA expression of development-related genes (SOX2, NANOG, and POU5F1). In conclusion, POEE effectively mitigates oxidative stress, enhances embryonic quality, and improves developmental potential in porcine oocytes on IVM.

The increasing shift from cannabis smoking to cannabis vaping is largely driven by the perception that vaping to form an aerosol represents a safer alternative to smoking and is a form of consumption appealing to youth. Herein, we compared the chemical composition and receptor-mediated activity of cannabis smoke extract (CaSE) to cannabis vaping extract (CaVE) along with the biological response in human bronchial epithelial cells. Chemical analysis using HPLC and GC/MS revealed that cannabis vaping aerosol contained fewer toxicants than smoke; CaSE and CaVE contained teratogens, carcinogens, and respiratory toxicants. A bioluminescence resonance energy transfer (BRET)-based biosensor detected the receptor-mediated activity of the extracts, primarily driven by Δ9-tetrahydrocannabinol (Δ9-THC) concentration. RNA-sequencing showed both CaSE and CaVE induced similar transcriptional responses, significantly upregulating genes within pathways related to inflammation, cancer, and cellular stress. This was paralleled by downregulation of pathways related to lipid synthesis and metabolism from both CaSE and CaVE. Targeted metabolomics revealed significant changes in metabolites involved in lipid and membrane metabolism, energy production, nucleotide/DNA/RNA pathways, and oxidative stress response, suggesting potential impairment of lung epithelial cell repair and function. In addition, the upregulation of 5-hydroxymethylcytosine (5hmC) indicates epigenetic changes potentially contributing to inflammation, oxidative stress, and an increased risk of cancer. These findings challenge the notion that cannabis vaping is risk-free, highlighting an urgent need for comprehensive research into its respiratory health effects. This comparison of cannabis consumption methods offers insights that could inform public health policies and raise consumer awareness regarding the potential risks of inhaling cannabis aerosol.NEW & NOTEWORTHY Cannabis use is increasing worldwide amid broad acceptance and legalization. The prevalence of traditional smoking is diminishing in favor of vaping dry flower. This is the first study to provide initial evidence that cannabis aerosol contains carcinogenic, teratogenic, and respiratory toxicants that induce transcriptional responses in epithelial cells analogous to those from cannabis smoke, suggesting potential adverse pulmonary effects.

This study aimed to evaluate the effects of dietary geniposide supplementation on growth performance, lipid metabolism, health status, and ammonia stress resistance in turbot (Scophthalmus maximus). Four hundred fifty fish were randomly allocated into 5 treatments with triplicate tanks (30 fish per tank). They were hand-fed to apparent satiety for 56 d with a basal diet (GP0) or diets containing 100, 200, 400, and 800 mg/kg geniposide (termed as GP100, GP200, GP400, GP800, respectively). After the conclusion of the feeding trial, the fish were exposed to ammonia stress for 96 h. The results showed that the growth performance were not affected by geniposide (P > 0.05). Dietary supplementation with geniposide decreased crude lipid in viscera without liver, subcutaneous adipose tissue (SAT), and the liver, as well as triglyceride concentrations in plasma, the liver and SAT (P < 0.05). Dietary supplementation with 400 and 800 mg/kg geniposide significantly down-regulated lipogenesis-related gene expression, as well as fatty acid uptake-related gene expression, while significantly up-regulated triglyceride secretion-related gene expression in the liver compared with the control group (P < 0.05). The GP800 group exhibited a significant reduction in plasma malondialdehyde contents compared with the control group, while both the GP200 and GP800 groups showed a significant increase in plasma complement C3 activities (P < 0.05). Furthermore, there was a notable enhancement in plasma lysozyme and total superoxide dismutase levels in the geniposide supplemented groups compared to the control group (P < 0.05). Additionally, a significant decrease in the mRNA level of pro-inflammatory cytokine and a remarkable increase in the mRNA expression of anti-inflammatory cytokines were discovered in geniposide supplemented groups relative to the control group (P < 0.05). Cumulative survival rates after ammonia stress in the GP400 and GP800 groups were statistically higher than that in the control group (P < 0.05). In conclusion, dietary geniposide supplementation could reduce lipid deposition in turbot by regulating lipid metabolism and transportation, and remarkably enhance immunity, antioxidant ability, and resistance to ammonia stress in turbot. Based on the quadratic regression analyses, the optimal concentrations of geniposide were estimated to be 545.21 to 668.41 mg/kg feed.

Twice-daily intake of purified eicosapentaenoic acid (EPA) reduces atherosclerotic cardiovascular disease risk in patients with high triglycerides, but its exact mechanism remains unclear. We exposed non-activated CD4+ T cells to 100μM EPA, oleic acid, palmitic acid, or control, and conducted RNA and ATAC-sequencing after 48 hours. EPA exposure downregulated immune response-related genes like HLA-DRA, CD69, and IL2RA, and upregulated oxidative stress prevention genes like NQO1. Transcription factor footprinting showed decreased GATA3 and PU.1, and increased REV-ERB. These effects were specific to EPA, suggesting it induces an anti-inflammatory transcriptomic landscape in CD4+ T cells, contributing to its observed cardiovascular benefits.

Neurological disorders are defined by a deterioration or disruption of the nervous system's structure and function. These diseases, which include multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, and compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects and weak neuroprotective properties. However, when combined with other neuroprotective drugs or adjunct therapy, they may offer additional benefits and improve treatment outcomes. Phytochemicals have emerged as attractive therapeutic agents due to their ability to regulate essential neurotrophic pathways, especially the brain-derived neurotrophic factor (BDNF) signaling cascade. BDNF is an important target for neurodegenerative disease (ND) treatment since it regulates neuronal survival, synaptic plasticity, neurogenesis, and neuroprotection. This review emphasizes the molecular pathways through which various phytochemicals-such as flavonoids, terpenoids, alkaloids, and phenolic compounds-stimulate BDNF expression and modulate its downstream signaling pathways, including GSK-3β, MAPK/ERK, PI3K/Akt/mTOR, CREB, and Wnt/β-catenin. This paper also highlights how phytochemical combinations may interact to enhance BDNF activity, offering new therapeutic options for ND treatment. Despite their potential for neuroprotection, phytochemicals face challenges related to pharmacokinetics, blood-brain barrier (BBB) permeability, and absorption, highlighting the need for further research into combination therapies and improved formulations. Clinical assessment and mechanistic understanding of BDNF-targeted phytotherapy should be the main goals of future studies. The therapeutic efficacy of natural compounds in regulating neurotrophic signaling is highlighted in this review, providing a viable approach to the prevention and treatment of NDs.

Multiple sclerosis (MS) is a chronic, and potentially disabling, inflammatory disease of the central nervous system (CNS). MS is generally characterized by recurrent, and self-limited, episodes of neurological dysfunction, which occur unpredictably and often result in multifocal tissue injury within the CNS. Currently, women are affected two to three times as often as men although this may not have been the case during earlier Time-Periods. The pathogenesis of MS is known to involve both critical genetic and environmental mechanisms. Nevertheless, in addition to these two mechanisms, disease-pathogenesis also involves a "truly" random event. Indeed, it is this random mechanism, which is responsible for the currently-observed (and increasing) excess of women among patients with MS. This review summarizes the current state of knowledge regarding the pathogenesis of MS (includong its epidemiology, pathology, and genetics) and considers the therapeutic implications that these pathogenetic mechanisms have both for our currently available therapies as well as for the possible therapeutic approaches to the management of this potentially disabling condition in the future.

Metabolic-associated fatty liver disease (MAFLD) has emerged as a leading chronic liver disease. This condition is characterized by an abnormal accumulation of fat within liver and can progress from simple steatosis to more severe stages involving chronic inflammation and oxidative stress. In this study, we investigated the potential therapeutic effects and underlying mechanism of novel bioactive peptides (EWYF and EWFY) on Western diet-induced MAFLD in C57BL/6J mice. Mice fed a normal chow diet (ND group) and Western diet (WD and treatment groups) for 8 weeks. Treatment groups received EWYF and EWFY peptides in low (10 mg/kg/day) and high (50 mg/kg/day) doses were divided into four groups: EWYF10, EWYF50, EWFY10, and EWFY50. Western diet-induced body weight gain and increased liver weight along with visceral adiposity, which were markedly reversed by bioactive peptides in a dose-dependent manner. Additionally, bioactive peptides significantly reduced hepatic steatosis, liver injury and proinflammatory response. Western diet-induced glucose tolerance and insulin resistance, whereas bioactive peptides significantly improved glucose tolerance and insulin sensitivity. Persistent intake of Western diet triggered chronic inflammation and severe oxidative stress, which were significantly alleviated by bioactive peptides treatment via inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome activation and mitigated pyroptosis by modulating TLR4/NF-κB and Keap1/Nrf2/HO-1 signaling pathways. Furthermore, molecular docking studies suggest that EWYF and EWFY act as fructokinase antagonists and TLR4 inhibitors, which potentially alleviates Western diet-induced MAFLD. Collectively, these findings highlight EWYF and EWFY as promising candidates for MAFLD treatment due to their potent antioxidant and anti-inflammatory properties via specific molecular inhibition.

Recent studies have found that high temperatures cause oxidative stress and even mass mortality in Pacific oysters (Crassostrea gigas). The role of γ-aminobutyric acid (GABA) in improving antioxidative defense in aquatic animals is increasingly of interest. In the present study, the oxidative stress of Pacific oysters to high-temperature stress was examined, and the regulation of GABA on the antioxidative defense was further investigated. Following 6 h of exposure to 28 °C seawater, a significant increase in the mRNA expression levels of nuclear factor-E2-related factor 2 (Nrf2), superoxide dismutase (SOD), and catalase (CAT), as well as the activities of SOD and CAT, was observed in the gill, compared to those at 0 h. An increase of glutamate decarboxylase (GAD), GABA receptor (GABAAR-α and GABABR-B) mRNA levels, and GABA contents were also detected after 28 °C exposure compared to those at 0 h. Furthermore, the activities and mRNA expression levels of SOD and CAT were significantly upregulated after GABA treatment, while decreased after either GAD inhibitor or GABA receptor inhibitor treatment under high-temperature stress. Meanwhile, the enhanced effects of GABA on antioxidant enzyme activities were reduced when Nrf2 was inhibited by ML385, accompanied by an increase in MDA content. After high-temperature stress, compared with the GABA treatment group, the activities and mRNA expression levels of SOD and CAT were significantly upregulated by GSK-3β inhibitor treatment. Meanwhile, the elevation of antioxidant enzyme activities by GABA was attenuated by the AKT inhibitor treatment. Collectively, GABA first activated GABA receptors under high-temperature stress and then increased the activities of SOD and CAT and reduced MDA content by AKT/GSK-3β and Nrf2 pathways to protect the oysters against oxidative damage upon stress. The present results offer new insights for understanding the regulation mechanisms of antioxidative defense by the neuroendocrine system in molluscs.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

This study investigated the potential of Porphyra derivatives (PD), including Porphyra334, to activate the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in porcine oocytes to enhance oocyte competency and intracellular networks. Conventional methods for manipulating mitochondrial functions and antioxidant pathways often rely upon genetic modifications that are impractical for direct application in humans. We hypothesized that PD serves as a natural regulator of the NRF2 pathway without requiring genetic intervention. To test this hypothesis, brusatol (Bru), a direct NRF2 inhibitor, was used to evaluate the specific role of PD in NRF2-mediated processes. The results demonstrated that PD significantly improved oocyte maturation, blastocyst formation, and mitochondrial function, including subsequent lipid metabolism. PD activates NRF2 and its downstream antioxidant response elements (AREs), whereas Bru inhibits these effects. Co-treatment with PD and Bru resulted in the partial recovery of NRF2 activity. These findings suggest that PD functions as a toggle for NRF2 activation, potentially offering a non-genetic strategy for enhancing oocyte quality and embryo development by modulating antioxidant mechanisms and mitochondrial functions. This study provides new avenues for investigating natural compounds in the context of reproductive biology and assisted reproductive technologies (ARTs).

Currently, treatment options for acute lung injury (ALI) are limited. Gypenoside XLIX (Gyp-XLIX) is known for its anti-inflammatory properties, but there is a lack of extensive research on its effects against ALI. This study induced ALI in mice through cecal ligation and puncture surgery and investigated the biological activity and potential mechanisms of Gypenoside XLIX (40 mg/kg) by intraperitoneal injection. The in vitro ALI model was established using mouse lung epithelial (MLE-12) cells stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Various methods, including Hematoxylin and Eosin (H&E) staining, biochemical assay kits, Quantitative Polymerase Chain Reaction (qPCR) analysis, Western blotting, Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay, immunofluorescence, and flow cytometry, were employed for this research. The results indicated that pretreatment with Gypenoside XLIX significantly alleviated pathological damage in mouse lung tissues and reduced the expression levels of inflammatory factors. Additionally, Gypenoside XLIX inhibited ROS levels and NLRP3 inflammasome, possibly mediated by the Sirt1/Nrf2 signaling pathway. Moreover, Gypenoside XLIX significantly inhibited sepsis-induced lung cell apoptosis and excessive autophagy of mitochondria. Specifically, it suppressed mitochondrial pathway apoptosis and the Pink1/Parkin pathway of mitochondrial autophagy. These findings reveal the multifaceted effects of Gypenoside XLIX in anti-inflammatory, antioxidative, and inhibition of cell apoptosis and autophagy. This provides strong support for its therapeutic potential in sepsis-related lung injuries.

Cancers can develop resistance to treatment with ALK tyrosine kinase inhibitors (ALK-TKIs) via emergence of a subpopulation of drug-tolerant persister (DTP) cells that can survive initial drug treatment long enough to acquire genetic aberrations. DTP cells are thus a potential therapeutic target. We generated alectinib-induced DTP cells from a patient-derived ALK+ non-small-cell lung cancer (NSCLC) cell line and screened 3114 agents in the anticancer compounds library (TargetMol). We identified phospholipid hydroperoxide glutathione peroxidase GPX4 as being involved in promoting the survival of DTP cells. GPX4 was found to be upregulated in DTP cells and to promote cell survival by suppressing reactive oxygen species (ROS) accumulation; GPX4 inhibitors blocked this upregulation and facilitated ROS-mediated cell death. Activated bypass signals involving epidermal growth factor receptor (EGFR)/receptor tyrosine-protein kinase erbB-3 (HER3) were also identified in DTP cells, and co-treatment with EGFR-TKI plus ALK-TKI enhanced ROS levels. Triple combination with an ALK-TKI plus a bypass pathway inhibitor plus a GPX4 inhibitor suppressed cell growth and induced intracellular ROS accumulation more greatly than did treatment with each agent alone. The combined inhibition of ALK plus inhibition of activated bypass signals plus inhibition of GPX4 may be a potent therapeutic strategy for patients with ALK+ NSCLC to prevent the development of resistance to ALK-TKIs and lead to tumor eradication.

Screening and quantifying antioxidants from food samples, their antioxidant activity, as well as the assessment of food oxidation is critical, not only for ensuring food quality and safety, but also to understand and relate these parameters to the shelf life, sensory attributes, and health aspects of food products. For this purpose, several methods have been developed and used for decades, which regardless of their effectiveness, present a certain number of drawbacks mainly related to extensive sample preparation and technical complexity, time requirements, and the use of hazardous chemicals. Electrochemical sensors and biosensors are gaining popularity in food analysis due to their high sensitivity, specificity, rapid response times, and potential for miniaturisation and portability. Furthermore, other modern methods using whole living cells such as the cellular antioxidant activity assay, the antioxidant power 1 assay, and the catalase-like assays, may interpret more realistic antioxidant results rather than just reporting the ability to scavenge free radicals in isolated systems with extrapolation to reality. This paper provides an overview of electrochemical sensors, biosensors, and cellular antioxidant assays, and reviews the latest advancements and emerging trends in these techniques for determining oxidants and antioxidants in complex food matrices. The performances of different strategies are described for each of these approaches to provide insights into the extent to which these methods can be exploited in the field and inspire new research to fill the current gaps.

Herbicides such as paraquat (PQ) are frequently utilized particularly in developing nations. The present research concentrated on the pulmonary lesions triggered by PQ and the beneficial effect of the angiotensin receptor neprilysin inhibitor (ARNI), sacubitril/valsartan, against such pulmonary damage. Five groups of rats were established: control, ARNI, PQ (10 mg/kg), ARNI 68 + PQ, and ARNI 34 + PQ. Following euthanasia, lungs were isolated and subjected to a histopathological test, and the ELISA technique was used to evaluate oxidative stress biomarkers, toll-like receptor 4 (TLR4), nuclear factor erythroid 2-related factor 2 (Nrf2), phosphatidylinositol-3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), and inflammatory markers: nuclear factor kappa B p65 subunit (NF-κB p65), tumor necrosis factor α (TNFα), and interleukin 1beta (IL-1β). In conjunction with abnormally high levels of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS), the PQ group also displayed low levels of reduced glutathione (GSH) and total antioxidant capacity (TAC). Additionally, TLR4, PI3K, and p-AKT were significantly elevated together with unusually low level of Nrf2. Moreover, inflammatory biomarkers, NF-κB p65, TNFα, and IL-1β, were abnormally elevated. Meanwhile, ARNI-treated groups reversed all alterations precipitated by PQ in a dose-dependent manner. ARNI could mitigate pulmonary damage triggered by PQ via potential antioxidant anti-inflammatory qualities.

The worldwide obesity epidemic has led to a drastic increase in diabetes and cardiovascular disease in younger generations. Further, maintaining metabolic health during aging is frequently a challenge due to poor diets and decreased mobility. In this setting, bioactive nutrients that are naturally occurring antioxidants, such as sulforaphane (SFN), are of high nutritional interest. SFN, a bioactive compound that is present in cruciferous vegetables, is a molecule that protects cells from cytotoxic damage and mitigates oxidative stress, protecting against disease. It exerts its action through the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Many studies have been performed in animals and humans to evaluate its effects on cancer, brain health, and neurodegenerative disorders. However, fewer clinical studies have been performed to evaluate its effects on insulin resistance and the development of type 2 diabetes mellitus (T2DM) across the lifespan. Given that, in some parts of the world, particularly in Europe, the population is growing older at a significant rate, it is crucial to promote healthy habits (healthy foods, dietary pattern, precision nutrition, and physical activity) from an early stage in life and across the lifespan to avoid debilitating health conditions occurring during adulthood and aging. Thus, in this narrative review, we discuss the protective effects of SFN supplementation on inflammatory and oxidative stress pathways and relate them to metabolic disease.

Aging and age-related disease are among the most common and challenging issues worldwide. During the aging process, the accumulation of oxidative stress, DNA damage, telomere dysfunction, and other related changes lead to cellular dysfunction and the development of diseases such as neurodegenerative and cardiovascular conditions. Curcumin is a widely-used dietary supplement against various diseases such as cancer, diabetes, cardiovascular diseases and aging. This agent mediates its effects through several mechanisms, including the reduction of reactive oxygen species (ROS) and oxidative stress-induced damage, as well as the modulation of subcellular signaling pathways such as AMPK, AKT/mTOR, and NF-κB. These pathways are involved in cellular senescence and inflammation, and their modulation can improve cell function and help prevent disease. In cancer, Curcumin can induce apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing ROS production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis phosphoinositide 3-kinases (PI3K) signaling and increase the expression of mitogen-activated protein kinases (MAPKs) to induce endogenous production of ROS. Therefore, herein, we aim to summarize how curcumin affect different epigenetic processes (such as apoptosis and oxidative stress) in order to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer, Parkinson, osteoporosis, and cardiovascular diseases.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, alongside repetitive behaviors, and atypical sensory-motor patterns. The growing prevalence of ASD has driven substantial advancements in research aimed at understanding its etiology, preventing its onset, and mitigating its impact. This ongoing effort necessitates continuous updates to the body of knowledge and the identification of previously unexplored factors. The present study addresses this need by examining the roles of nutrition, oxidative stress, and trace elements in the pathophysiology of ASD. In this review, an overview is provided of the key dietary recommendations for individuals with ASD, including gluten-free and casein-free (GFCF) diets, ketogenic diets (KDs), and other nutritional interventions. Furthermore, it explores the involvement of oxidative stress in ASD and highlights the significance of trace elements in maintaining neuropsychiatric health. The impact of these factors on molecular and cellular mechanisms was discussed, alongside therapeutic strategies and their efficacy in managing ASD.

Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression of liver damage. Sirtuin-3 (SIRT3), the main NAD+-dependent deacetylase located in mitochondria, has a critical role in regulation of mitochondrial function and ROS production as well as in the mitochondrial antioxidant mechanism. This study explores the roles of astragaloside IV (AST-IV) and formononetin (FMR) in connection with SIRT3 for potential antioxidative effects. It was shown that the condition of combined pre- and post-treatment with AST-IV or FMR at all concentrations statistically increased and rescued cell proliferation. ROS levels were not affected by pre-or post-treatment individually with AST-IV or pre-treatment with FMR; however, post-treatment with FMR resulted in significant increases in ROS in all groups. Significant decreases in ROS levels were seen when pre- and post-treatment with AST-IV were combined at 5 and 10 μM, or FMR at 5 and 20 μM. In the condition of combined pre- and post-treatment with 10 μM AST-IV, there was a significant increase in SOD activity, and the transcriptional levels of Sod2, Cat, and GPX1 in all treatment groups, which is indicative of reactive oxygen species detoxification. Furthermore, AST-IV and FMR activated PGC-1α and AMPK as well as SIRT3 expression in AML12 hepatocytes exposed to t-BHP-induced oxidative stress, especially at high concentrations of FMR. This study presents a novel mechanism whereby AST-IV and FMR yield an antioxidant effect through induction of SIRT3 protein expression and activation of an antioxidant mechanism as well as mitochondrial biogenesis and mitochondrial content and potential. The findings suggest these agents can be used as SIRT3 modulators in treating oxidative-injury hepatocytes.

Astrocytes produce and export glutathione (GSH), an important thiol antioxidant essential for protecting neural cells from oxidative stress and maintaining optimal brain health. While it has been established that oxidative stress increases GSH production in astrocytes, with Nrf2 acting as a critical transcription factor regulating key components of the GSH synthetic pathway, the role of Nrf2 in controlling constitutive GSH synthetic and release mechanisms remains incompletely investigated. Our data show that naïve primary mouse astrocytes cultured from the cerebral cortices of Nrf2 knockout (Nrf2-/-) pups have significantly less intracellular and extracellular GSH levels when compared to astrocytes cultured from Nrf2 wild-type (Nrf2+/+) pups. Key components of the GSH synthetic pathway, including xCT (the substrate-specific light chain of the substrate-importing transporter, system xc-), glutamate-cysteine ligase [catalytic (GCLc) and modifying (GCLm) subunits], were affected. To wit: qRT-PCR analysis demonstrates that naïve Nrf2-/- astrocytes have significantly lower basal mRNA levels of xCT and both GCL subunits compared to naïve Nrf2+/+ astrocytes. No change in mRNA levels of glutathione synthetase (GS) or the GSH exporting transporter, Mrp1, was found. Western blot analysis reveals reduced protein levels of both subunits of GCL, while (seleno)cystine uptake into Nrf2-/- astrocytes was reduced compared to Nrf2+/+ astrocytes, confirming decreased system xc- activity. These findings suggest that Nrf2 regulates the basal production of GSH in astrocytes through constitutive transcriptional regulation of GCL and xCT.

Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood.

This study aims to explore the role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate the therapeutic potential of the Fasn inhibitor C75.

Erectile function was assessed by determining the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, followed by the collection of cavernous tissue for transcriptomic and non-targeted metabolomic analyses. In vitro, a concentration of 10-6 M angiotensin II (Ang II) was applied to rat aortic endothelial cells (RAOECs) to establish a model of hypertension. In vivo, spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections of C75 at a dose of 2 mg/kg once a week. After five weeks of treatment, the erectile function of the rats was assessed, and penile tissues were harvested for further analysis. Molecular and protein expression were assessed using Western blotting, qRT-PCR, immunofluorescence staining, and immunohistochemistry.

The SHR exhibited ED, indicated by reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum tissue of SHR showed elevated fibrosis and endothelial dysfunction. Additionally, increased expression of the NLRP3 inflammasome, Caspase-1, GSDMD, and the pro-inflammatory cytokines IL-1β and IL-18 was observed. Multi-omics analysis revealed significant enrichment in lipid metabolic pathways, with Fasn identified as a hub gene. In vitro, siFasn and C75 enhanced antioxidant markers Nrf2 and HO-1, reduced ROS accumulation, and suppressed NLRP3 and GSDMD levels. In vivo, C75 treatment restored endothelial function and reversed erectile dysfunction, accompanied by decreased oxidative stress and pyroptosis in the penile corpus cavernosum.

These findings suggest that Fasn inhibition may offer a promising therapeutic strategy for hypertension-induced ED by alleviating oxidative stress and suppressing NLRP3 inflammasome-dependent endothelial cell pyroptosis via activation of the Nrf2/HO-1 pathway.

Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia resulting from damage to the pancreatic β cells and an absolute deficiency of insulin, leading to multi-organ involvement and a poor prognosis. The progression of T1DM is significantly influenced by oxidative stress and apoptosis. The natural compound eugenol (EUG) possesses anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse model in vivo and STZ-induced pancreatic β cell MIN6 cell model in vitro to investigate the protective effects of EUG on T1DM, and tried to elucidate its potential mechanism. Our findings demonstrated that the intervention of EUG could effectively induce the activation of nuclear factor E2-related factor 2 (NRF2), leading to an up-regulation in the expressions of downstream proteins NQO1 and HMOX1, which are regulated by NRF2. Moreover, this intervention exhibited a significant amelioration in pancreatic β cell damage associated with T1DM, accompanied by an elevation in insulin secretion and a reduction in the expression levels of apoptosis and oxidative stress-related markers. Furthermore, ML385, an NRF2 inhibitor, reversed these effects of EUG. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by attenuating apoptosis and oxidative stress through the activation of the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM.

Chronic kidney disease (CKD) is a conceivable new risk factor for cognitive disorder and dementia. Uremic toxicity, oxidative stress, and peripheral-central inflammation have been considered important mediators of CKD-induced nervous disorders. Nitric oxide (NO) is a retrograde neurotransmitter in synapses, and has vital roles in intracellular signaling in neurons. This research aims to determine the effectiveness of NO in CKD-induced cognitive deficits by considering the nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway and the important roles of cystathionine beta-synthase (CBS, H2S producing enzyme). Forty rats were divided into four experimental groups: sham, five-sixth (5/6) nephrectomy (5/6Nx, CKD), CKD + NO donor (Sodium nitroprusside, SNP), CKD + SNP and a CBS inhibitor (amino-oxy acetic acid, AOAA). To assess the neurocognitive abilities, eleven weeks after 5/6Nx, behavioral tests (Novel object recognition test, Passive avoidance test, and Barnes maze test) were done. Twelfth week after 5/6Nx, blood urea nitrogen (BUN) and serum creatinine (sCr) levels, as well as the nuclear factor-erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) expression levels and neuronal injury in the hippocampus and prefrontal cortex were assessed. As predicted, the levels of BUN and sCr (both P < 0.001) and neuronal injury in the hippocampus (P < 0.001 for CA1; CA3; DG) and prefrontal cortex (P < 0.001) increased in CKD rats as well as 5/6Nx induced reduction of Nrf2 (both P < 0.001) /HO-1(P < 0.001; P < 0.01 respectively) pathway activity in the hippocampus and prefrontal cortex in CKD rats. Moreover, CKD leads to cognitive disorder and memory loss (Novel object recognition test (NOR) (P < 0.001), Passive avoidance test (PA) (P < 0.001) and Barnes maze (BA) (Escape latency (P < 0.001); Error (P < 0.001)). SNP treatment significantly improved Nrf2 (both P < 0.001) /HO-1 (P < 0.001; P < 0.05 respectively) pathways and neuronal injury (P < 0.001 for CA1; CA3; DG) in the hippocampus and prefrontal cortex in CKD rats as well as enhanced learning and memory ability in CKD rats. However, ameliorating effects of SNP on cognitive disorder (NOR (P < 0.05), PA (P < 0.001) and BA (Escape latency (P < 0.05); Error (P < 0.001)) and Nrf2 (P < 0.01; P < 0.001 in the hippocampus and prefrontal cortex respectively) /HO-1 (P < 0.05 in both) signaling pathway activity were nullified by CBS inhibitor and H2S reduction. In conclusion, this study demonstrated that NO improved CKD-induced cognitive impairment and neuronal death which is may be depended to CBS activity and endogenous H2S levels.

High-fat diet-induced metabolic syndrome (MetS) is closely associated with cardiac dysfunction. Recent research studies have indicated a potential association between MetS and ferroptosis. Furthermore, metformin can alleviate MetS-induced cardiac ferroptosis. Metformin is a classic biguanide anti-diabetic drug that has protective effects on cardiovascular diseases, which extend beyond its indirect glycemic control. This study aimed to assess whether MetS mediates cardiac ferroptosis, thereby causing oxidative stress and mitochondrial dysfunction. The results revealed that metformin can mitigate cardiac reactive oxygen species and mitochondrial damage, thereby preserving cardiac function. Mechanistic analysis revealed that metformin upregulates the expression of cardiac Nrf2. Moreover, Nrf2 downregulation compromises the cardio-protective effects of metformin. In summary, this study indicated that MetS promotes cardiac ferroptosis, and metformin plays a preventive and therapeutic role, partially through modulation of Nrf2 expression.

The process of maturing ovine oocyte in vitro has not yet been raised with acceptable results.

This study was designed to evaluate the γ-oryzanol effect as a supplement of maturation media on the development of ovine oocytes to blastocyst.

Aspirated from ovine ovaries, morphologically normal cumulus-oocyte complexes (COCs) were matured in media supplemented with or without 5 µM γ-oryzanol. Matured oocytes were divided into two parts: one evaluated for their nuclear maturation, the level of GSH and ROS, mitochondrial membrane potential (MMP) and the pattern of transcription in oocytes and respective cumulus cells (CCs), and another subjected to fertilisation and culture to assess the development of oocytes to the blastocyst.

γ-Oryzanol improved the proportion of cleaved embryos and total blastocysts in the treated group, which was linked to improved MMP, higher levels of intracellular GSH and lower levels of ROS. A lower proportion of MI and GVBD was recorded for treated oocytes in comparison with control, although the proportion of MII oocytes was not different between groups. The treated oocytes and CCs showed downregulation of genes related to apoptosis (BAX and CASP-9) and upregulation of genes related to antioxidative status (NRF2, CAT and SOD). In conclusion, our results demonstrated the improved developmental outcome of supplemented oocytes so that the antioxidant response and higher enzymatic activity were maintained, and the generation of ROS was turned off; therefore, a novel alternative for counteracting oxidative stress in ovine oocytes undergoing maturation was offered by γ-oryzanol through an antioxidative pathway.

This study investigated the effects of different dietary ratios of linseed and soybean oils on the performance, egg quality, and antioxidant capacity of late-phase laying hens. A total of 360 70-week-old Jinghong laying hens were randomly assigned to four groups of six replicates each, with 15 chickens per replicate. Diets with linseed oil to soybean oil ratios of 3:0 (T1), 2:1 (T2), 1:2 (T3), and 0:3 (T4) were fed for 4 weeks. No significant differences in egg weight, feed intake of laying hens, egg production, or feed-to-egg ratio (P > 0.05) were observed among the groups. Compared with the T4 group, the T2 group had a significantly higher number of 8-10 mm follicles. Moreover, albumen height and Haugh units were significantly higher in the T3 group than in the T4 group (P < 0.05), although significant differences were not observed among the T1, T2, and T3 groups. With an increase in linseed oil addition to the feed, the content of n-3 polyunsaturated fatty acids in chicken eggs significantly increased (P < 0.05). Compared to the T4 group, the addition of linseed oil to the diet significantly reduced the blood malondialdehyde content and increased the blood glutathione peroxidase (GSH-PX) and superoxide dismutase enzyme activity. The GSH-PX activity and total antioxidant capacity in the oviducts of the T3 group were significantly higher than those of the T4 group (P < 0.05). The protein expression levels of Nrf2, HO-1, and NQO-1 in the oviduct tissues were significantly higher in the T3 group than in the T4 group (P < 0.05). This study showed that a linseed oil to soybean oil ratio of 1:2 in the T3 group enhanced egg quality by reducing oxidative stress and improving the oviduct microenvironment.

Friedreich's ataxia (FA) is a rare genetic disorder caused by silencing of the frataxin gene (FXN), which leads to multiorgan damage. Nrf2 is a regulator of FXN, which is a modulator of oxidative stress in animals and humans. Omaveloxolone (Omav) is an Nrf2 activator and has been reported to have antioxidative potential in various disease conditions. The present review was conducted to determine the use of Omav, the only FDA-approved treatment for FA.

Three electronic databases, Cochrane, PubMed and Google Scholar, were searched with terms such as 'Omaveloxolone', 'Friedreich ataxia', 'genetic diseases', 'autosomal recessive', and 'rare disorders' using various advanced search filters. Articles were screened, extracted, and assessed for quality, and a qualitative synthesis of the data was performed. The study protocol was registered in PROSPERO (CRD42024531449).

A total of 201 records were found, with very few published research articles on the topic. Only two randomized clinical trials published in a series of three research articles were included in the current systematic review. Peak load exercise and modified Friedreich's Ataxia Rating Scale (mFARS) values were considered the major outcome measures for determining the efficacy of 150 mg Omav capsules/day in FA. Exploratory outcome measures, such as low-contrast letter visual acuity test, exercise test, T25-FW, 9-HPT, health-related quality of life, and biochemical tests, were also assessed along with adverse events in all the studies.

Although, the quality of the articles demonstrated low bias. However, the short duration, small sample size, and missing data, including the values of different measures of mFARS scores in patients, limit the generalizability of the results. Further studies with longer durations and in severe patients with foot deformities are needed to clearly define the efficacy of Omav in FA and to determine the optimal drug for FA patients in India.