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Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the worlds poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

Objective(s): This investigation explored the mechanism by which the total flavonoids of Selaginella tamariscina (P.Beauv.) Spring (TFST) mitigate oxidative stress through the activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), thereby ameliorating acute lung injury (ALI) induced by diabetes. Materials and Methods: Male mice weighing 20-25 grams were divided into four groups: a control group, a diabetic group, a diabetic group treated with TFST, and a diabetic group treated with TFST and ML385. Various biological specimens were collected for analysis, including bronchoalveolar lavage fluid (BALF), blood, and tissue samples. These were subjected to a range of assessments covering hematological and BALF parameters tumor necrosis factor-alpha (TNF-α), interleukin-6 [IL-6]), biochemical markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione peroxidase [GSH], Nrf2, and HO-1 levels), along with histopathological evaluations. Results: Pre-treatment with TFST demonstrated a significant decrease in pulmonary tissue damage, evidenced by decreased wet-to-dry (W/D) lung ratios (P<0.001), reduced lung injury scores (P<0.0001 ), and lower levels of TNF-α, IL-6 (P<0.0001), as well as oxidative stress markers like MDA (P<0.05). Moreover, there was an elevation in the activity of anti-oxidative enzymes, specifically SOD and GSH (P<0.05), coupled with an enhanced expression of Nrf2 and HO-1 in the diabetic group (P<0.01). Conclusion: The study findings demonstrate that TFST can suppress oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby ameliorating diabetes-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Background: CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. Methods: Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2'-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. Results: Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. Conclusions: Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic cataract (DC) is a major cause of blindness worldwide. Prion protein (PRNP) was proved to be up-regulated and hypomethylated in DC samples. Here, we investigated whether PRNP was involved in DC progression in N6-methyladenosine (m6A)-dependent manner, and its potential mechanisms. Methods: Levels of genes and proteins were assayed using qRT-PCR and western blotting. Cell proliferation and apoptosis were determined using Cell Counting Kit-8 assay, 5-thynyl-2'-deoxyuridine (EdU) assay, and flow cytometry, respectively. Oxidative stress was analyzed by measuring the production of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and malondialdehyde (MDA). The m6A modification was determined by RNA immunoprecipitation (Me-RIP) assay. The interaction between RBM15 (RNA binding motif protein 15) and PRNP was probed using RIP assay. Results: PRNP was highly expressed in DC patients and HG-induced HLECs. Functionally, PRNP deficiency reversed HG-induced apoptosis and oxidative stress in HLECs. Mechanistically, RBM15 induced PRNP m6A modification and directly bound to PRNP. Knockdown of RBM15 abolished HG-induced apoptotic and oxidative injury in HLECs, while these effects were rescued after PRNP overexpression. Conclusion: RBM15 silencing suppressed HG-induced lens epithelial cell injury by regulating PRNP in an m6A-mediated manner, hinting a novel therapeutic strategy for DC patients. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is a surfactant that is detected in small quantities across various environments away from its manufacturing zones. Despite the widespread detection of PFOA in aquatic ecosystems, the impact of this compound on phytoplankton populations remains poorly understood. This study aimed to determine the physiological effects of PFOA on Microcystis aeruginosa. The cyanobacterium was exposed to 1‒10 000 μg l‒1 PFOA for 7 days under controlled laboratory conditions. The EC50 of PFOA for the test species after 7 days of exposure was 30.03 μg l‒1. Cell density significantly decreased at all PFOA concentrations (1‒10 000 μg l‒1). Chlorophyll a and carotenoid concentrations increased on day 1 (except for 1 μg l‒1, the lowest PFOA treatment) but then decreased across all treatment concentrations on day 7 of the experiment. When M. aeruginosa was exposed to PFOA, the total lipid, protein and carbohydrate content generally increased across all treatment concentrations. The concentration of intracellular hydrogen peroxide increased with increasing surfactant concentrations. In different treatments, lipid peroxidation increased, with 100 μg l‒1 PFOA producing the highest malondialdehyde content. Peroxidase and glutathione S-transferase activities increased across all treatment concentrations, demonstrating progressive changes consistent with the increase in reactive oxygen species observed. Total microcystin concentration increased in cultures exposed to 1000 and 10 000 µg l‒1 PFOA. These findings suggest that PFOA can adversely affect the survival of M. aeruginosa populations in contaminated aquatic ecosystems, with potential cascading effects on the general health of the environment. [ABSTRACT FROM AUTHOR]

Introduction: Testicular cancer is a significant malignancy affecting males, and understanding the underlying biochemical changes associated with the disease is essential for improved management and treatment strategies. Prolidase enzyme, has been implicated in various disease processes. The assessment of serum prolidase activity and its relationship with testicular cancer can provide valuable insights into the pathophysiology of the disease. The objective of this study was to investigate serum prolidase activity, oxidative stress markers, and antioxidant enzyme levels in patients with testicular cancer and evaluate their potential associations, aiming to enhance our understanding of the biochemical alterations and potential implications for testicular cancer management. Methods: A total of 33 male patients diagnosed with testicular cancer were included, along with 35 age-matched male volunteers as the control group. Serum samples were collected and stored at −20°C until analysis. The measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels was performed. Results: The findings demonstrated significantly elevated serum prolidase activity and malondialdehyde (MDA) levels in testicular cancer patients compared to the control group (all, p < 0.05). Conversely, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and glutathione-S-transferase (GST) levels were significantly lower in testicular cancer patients (p < 0.05). Conclusion: In this study, serum prolidase activity and biochemical markers associated with oxidative stress were investigated in testicular cancer patients. Oxidative stress markers and serum prolidase activity were found to be elevated in testicular cancer. Long-term prospective studies are needed to determine the effectiveness of antioxidant use in cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Liver injury caused by sepsis seriously impairs the normal physiology of the liver. Wedelactone (WED) has an obvious anti-inflammatory effect against liver damage caused by various factors. Nevertheless, further research is needed to determine if WED might mitigate acute liver damage linked to sepsis by influencing macrophage polarization. Methods: We first assessed the effect of WED on lipopolysaccharides-triggered liver injury by biochemistry assay and tissue staining. Inflammatory factors were assessed using the ELISA kits. The expression of Cluster of Differentiation 86 (CD86) and Cluster of Differentiation 206 (CD206) was measured by immunofluorescence assay. The protein levels of inducible nitric oxide sythase (iNOS), Arginase 1 (Arg-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), PI3K phosphorylation (p-PI3K), AKT phosphorylation (p-AKT), inhibitor of kappa B kinase (IKK), inhibitor of kappa B (IκB), and nuclear factor kappa-B (NF-kB) p65 were quantified by western blot analysis. Results: WED decreased the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and malondialdehyde, and increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Moreover, WED exerted effective anti-inflammatory effects by decreasing the level of Tumor necrosis factor-a (TNF-a) and Interleukin 6 (IL-6) and increasing the level of Interleukin 10 (IL-10) in serum and cells. WED not only decreased CD86 and iNOS expression but also increased CD206 and Arg-1 expression. WED also downregulated the increased expression of PI3K, AKT, p-PI3K, p-AKT, IKK, and NF-kB p65 induced by lipopolysaccharides, while up-regulated the decreased expression of IkB. Besides, LY294002 with WED decreased the expression of protein PI3K, AKT, p-PI3K, p-AKT, IKK and NF-kB p65, and raised the expression of IkBa. Conclusion: Wedelolactone could attenuate sepsis-associated acute liver injury, and its mechanism may be associated with balancing pro-inflammatory and anti-inflammatory by the regulation of M1/M2 macrophage polarization via the PI3K/AKT/NF-kB signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK‐6) is a peptide with both antioxidant and anti‐inflammatory properties. The antioxidant and anti‐inflammatory mechanisms of KK‐6 are still unclear. When we studied the functional mechanism of KK‐6, we found that the antioxidant property of KK‐6 has a synergistic and promoting effect on anti‐inflammatory properties. RESULTS: KK‐6 enhances cellular resistance to LPS via the MAPK/NF‐κB signaling pathway, leading to increased levels of inflammatory factors: interleukin‐1β (764.81 ng mL−1), interleukin‐6 (1.06 ng mL−1) and tumor necrosis factor‐α (4440.45 ng mL−1). KK‐6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL−1; superoxide dismutase: 0.589 μg mL−1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL−1). CONCLUSION: Our findings highlight the great potential of KK‐6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti‐inflammatory agent, KK‐6 offers a promising avenue for alleviating inflammation‐related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Selenium in its organic form (such as selenoproteins) is involved in human metabolism, acting as an antioxidant and reducing inflammatory biomarkers associated with overweight and obesity. Nevertheless, their functionality depends on the selenium intake and individuals' physiological status. The adequate intake of this nutrient has been revised for health experts, and slight adjustments to the Daily Intake Reference Values occurred to avoid toxicity or deficiency and to exert beneficial effects in specific biomarkers such as glutathione peroxidase activity and SELENOP concentration. However, there is a gap in understanding the metabolic effects of selenocompounds in subjects or experimental models with obesity, but promising results have been documented to be included as a coadjutant in this disease treatment. In this sense, many strategies have been developed worldwide to produce Se-enriched foods and supplements containing selenocompounds to increase the accessibility for consumers. In this review, the effects of Se and selenocompounds on the central overweight and obesity biomarkers in different experimental models are addressed. Likewise, the most recent strategies for selenium enrichment in agricultural products and the main trends in selenium-enriched foods and supplements on the global market are discussed. [ABSTRACT FROM AUTHOR]

In this presented study, the aim was to investigate the toxic effects of bisphenol S (BPS), one of the bisphenol A analogues, on the thyroid glands of male Wistar albino rats. Toward this aim, the rats (n = 28) were given a vehicle (control) or BPS at 3 different doses, comprising 20, 100, and 500 mg/kg of body weight (bw) via oral gavage for 28 days. According to the results, BPS led to numerous histopathological changes in the thyroid tissue. The average proliferation index values among the thyroid follicular cells (TFCs) displayed increases in all of the BPS groups, and significant differences were observed in the BPS-20 and BPS-100 groups. The average apoptotic index values in the TFCs were increased significantly in the BPS-500 group. The serum thyroid-stimulating hormone and serum free thyroxine levels did not show significant changes after exposure to BPS; however, the serum free triiodothyronine levels displayed significant decreases in all 3 of the BPS groups. BPS was determined to cause significant increases in the antioxidant enzyme activities of catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, as well as a significantly decreased content of reduced glutathione. The malondialdehyde level in the thyroid tissue was elevated significantly in the BPS-500 group. The data obtained herein revealed that BPS has thyroid-disrupting potential based on structural changes, follicle cell responses, and biochemical alterations including a decreased serum free triiodothyronine level and increased oxidative stress. [ABSTRACT FROM AUTHOR]

N-Methyl-N-Nitrosourea (MNU) is a compound that induces oxidative stress resulting in high levels of oxidants and damage to body cells. Red okra contains polyphenol and flavonoid active ingredients as antioxidants. This study aims to analyze the effect of ethanol extract of red okra pods (ROPE) on oxidant levels, antioxidant enzymes, and damage to rat kidney proximal tubule cells due to NMU. This study used 30 rats divided into six treatment groups, namely CN (normal), N (negative control; MNU 50 mg/kg BW), P (positive control; MNU and MTX 50 mg/kg BW), T1 (MNU and ROPE 50 mg/kg BW), T2 (MNU and ROPE 100 mg/kg BW), and T3 (MNU and ROPE 200 mg/kg BW). The treatment was carried out on all groups after eight weeks. The results indicate that malondialdehyde (MDA) and nitrogen oxide (NO) decrease with the ROPE treatment. The glutathione reductase (GSH) activity as an antioxidant enzyme increased T1 and T2, while glutathione peroxidase (GPx) showed an increase in T2 and T3. Furthermore, the biochemical marker of the rat kidney showed lower blood urea nitrogen (BUN) and creatinine (Cre) levels in all treatment groups. Then, the repair of damaged proximal tubule cells showed an increase in normal cells and lower swollen cells; however, there was a degradation in necrotic cells in T2 and T3. It can be indicated that the ROPE can act as an antioxidant that can reduce MDA and NO levels, increase GSH and GPx levels, and reduce damage to proximal renal tubule cells due to MNU. [ABSTRACT FROM AUTHOR]

Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly by an imbalance in the activity of inhibitory and excitatory neural networks. Recurrent or prolonged seizures lead to neuronal death, which in turn promotes epileptogenesis and epileptic seizures. Ferrous ion-mediated cell death is known as ferroptosis, which is due to the accumulation of lipid peroxidation products resulting from compromise of the glutathione (GSH)-dependent antioxidant system. The pathophysiology of epilepsy has been linked to anomalies in the glutathione peroxidase 4 (GPX4)/GSH redox pathway, lipid peroxidation, and iron metabolism. Studies have shown that inhibiting ferroptosis may alleviate cognitive impairment and decrease seizures, indicating that it is neuroprotective. With the hope of aiding the development of more novel approaches for the management of epilepsy, this research aimed to examine the role of ferroptosis in this disease. [ABSTRACT FROM AUTHOR]

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Background Objectives Materials and methods Results Discussion and conclusion Testicular torsion is a common urological emergency in children and teenagers that, in most cases, requires surgical exploration and detorsion. However, even after a successful intervention, a high number of patients still develop irreversible damage.To investigate whether the administration of phosphodiesterase inhibitors (PDE) in animal models of testicular torsion can reduce damages caused by the ischemia–reperfusion syndrome.A systematic search of the Medline, Web of Science, Embase, and Ovid databases for studies up to December 2023 was performed using PRISMA guidelines. A detailed search was conducted using the following key terms: “testicles,” “ischemia,” “reperfusion,” and “phosphodiesterase inhibitors.” There was no restriction regarding language or year of publication. We investigated spermatogenesis by the Johnsen's biopsy score (JTBS) and histological damage by the Cosentino's biopsy score (CBS). Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) testicular levels were also analyzed.Initially, 296 articles were identified. However, only 20 studies met the inclusion criteria. PDE inhibitors improved JTBS (MD = 2.53, CI = 1.94 to 3.13), CBS (MD = −1.11, CI = −1.25 to −0.97) and SOD (SMD = 3.27, CI = 1.59 to 4.95) outcomes. PDE did not improve MDA (SMD = −0.93, CI = −2.19 to 0.34), NO (SMD = −0.54, CI = −1.56 to 0.48), and GPx (SMD = 0.77, CI = −0.38 to 1.92) outcomes. A higher dose of PDE inhibitors only improved CBS outcome.This review indicates that the administration of PDE inhibitors in rats ameliorated the outcomes, representing a promising complementary strategy for spermatogenesis recovery following testicular torsion. Our review suggests that JTBS and CBS could be translated into future human studies, validating and extending these findings within the context of human physiopathology, while providing applicability of interventions in real clinical practice. [ABSTRACT FROM AUTHOR]

Despite its effectiveness in exterminating tumor cells, ferroptosis is seriously hampered by the high expression of antioxidant glutathione (GSH) and the inadequacy of endogenous H2O2 in tumors. Herein, metal‐phenolic nanoformulations (FNCP NFs) composed of sonosensitizer Chlorin e6 (Ce6), the phenolic GSH consumer naphthazarin, and Fe3+, followed by the modification of PEG2000, are strategically designed and fabricated for ultrasound‐boosted ferroptosis in tumor cells through triple regulatory pathways. The carrier‐free FNCP NFs can rapidly dissociate under tumor microenvironment response with the assistance of ultrasound, releasing Fe2+, Ce6, and naphthazarin. Ce6 and Fe2+ are capable of producing singlet oxygen (1O2) and hydroxyl radicals (·OH) by ultrasound‐activated sonodynamic therapy and Fenton reaction‐mediated chemodynamic therapy (CDT), respectively, which not only induce apoptotic cell death but also lead to the effective accumulation of lipid peroxidation (LPO), resulting in ferroptosis. Meanwhile, the released naphthazarin and the self‐cycling valence alternations of Fe3+/Fe2+ promote the significant decrease of intracellular GSH contents, further inducing the inactivation of glutathione peroxidase 4 (GPX4) and the up‐regulation of LPO levels, eventually realizing the synergistically enhanced ferroptosis. This facile and feasible design for versatile metal‐phenolic nanoformulations offers a new strategy for effectively improving ferroptosis efficiency and multimodal cancer therapies. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is a nutritional element required for fish growth and physiology functions. In this study, we examined the effect of Mn on the intestinal digestive function, antioxidant response, and muscle quality in coho salmon (Oncorhynchus kisutch). Nine hundred salmons with initial weight approximately 0.35 g were fed with six isoproteic and isoenergetic diets formulated to contain 2.4, 8.5, 14.8, 19.8, 24.6, and 33.7 mg/kg Mn for 84 days. The result showed that the activity of trypsin and lipase was elevated, whereas α‐amylase activity was not affected by various Mn diets in intestine. Dietary Mn elevated the activity of Mn‐superoxide dismutase (Mn‐SOD), total superoxide dismutase (T‐SOD), glutathione peroxidase (GSH‐PX), and catalase (CAT), but had no influence on copper/zinc‐superoxide dismutase (Cu/Zn‐SOD) in intestine. Dietary Mn at 8.5, 14.8, 19.8, 24.6, and 33.7 mg/kg enhanced the gene expression level of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). In addition, the accumulation of Mn in muscle was enhanced with increasing levels of dietary Mn. Dietary Mn elevated the content of sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), but the content of iron (Fe) and Zn was decreased by dietary Mn in the salmon muscle. The content of fatty acids and amino acids was enhanced by various levels of dietary Mn in muscle. Moreover, a significant quadratic effect was observed on the texture of salmon muscle. The dietary Mn requirement was 16.9–25.7 mg/kg Mn to acquire the highest value of muscle texture using the quadratic regression model. The diets at 14.8 and 19.8 mg/kg Mn had a higher score of sensory evaluation for raw muscle. Our result showed that dietary Mn affected the intestinal digestion function and antioxidant response, which may further result in the change of muscle quality in coho salmon. The result will provide reference for detecting the effect of dietary micronutrients on the muscle quality of salmons. [ABSTRACT FROM AUTHOR]

Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

1. This study investigated the role of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis, a form of programmed cell death, in muscle biochemistry and meat quality, utilising broiler chickens whose ante-mortem GPX4 activity was inhibited pharmacologically.2. Male broilers were divided into two groups, each receiving ante-mortem administration of the GPX4 inhibitor, Ras-selective lethal 3 (RSL3), or a vehicle only. After slaughter, breast muscles were collected and stored for 48 h. The expressions of ferroptosis-related genes, glutathione levels, pH, colour and water-holding capacity were evaluated at multiple time points during the storage period.3. The RSL3 treatment decreased the expression of GPX4 and ferritin heavy chain 1, which are negative regulators of ferroptosis, while it increased the expression of a ferroptosis accelerator, acyl-CoA synthetase long chain family member 4. The ratio of reduced to oxidised glutathione was significantly decreased in the RSL3 group. The RSL3 treatment decelerated post-mortem pH decline and colour changes, such as a decrease in L* and an increase in a* were observed in the RSL3 group. In addition, the RSL3 group showed increased levels of water-holding capacity.4. These findings suggested that ante-mortem GPX4 activity plays a role in determining meat quality, implying the possible involvement of ferroptosis in the mechanism by which skeletal muscle is converted after slaughter into meat that is eaten. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the levels of oxidant and antioxidant markers in patients with obsessive-compulsive disorder (OCD) and to investigate whether these levels change in the presence of major depressive disorder (MDD) comorbidity. Methods: This study was completed with 23 OCD patients with MDD comorbidity (OCD+MDD), 21 OCD patients without MDD comorbidity (OCD- MDD) and 21 healthy controls. Oxidative stress levels of the cases’ were determined by ischemia modified albumin (IMA) and malondialdehyde (MDA) measurements and antioxidant levels were determined by superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measurements. One- way analysis of variance (ANOVA) and unpaired Student’s t-test were used to compare the study groups. Post hoc Bonferroni test was used for the degree of significance between groups, and repeated measures analysis of covariance (ANCOVA) was used to investigate the effect of age and gender. Results: IMA and MDA levels were significantly higher in the OCD group compared to the control group, and SOD, CAT and GSH-Px levels were lower in the OCD group compared to the control group (p<0.01). IMA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group, while SOD, CAT and GSH-Px levels were significantly lower in the OCD+MDD group compared to the OCD-MDD group (p<0101). MDA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group (p=0.009). When the entire OCD patient group was examined, significant, powerful, positive correlations were observed between Y-BOCS and HDRS scores and IMA and MDA, and significant powerful negative correlations between Y-BOCS and HDRS scores and SOD, CAT, and GSH-Px (p<0.001 for all). In OCD+MDD group, oxidative stress markers increased significantly in parallel with the severity of depression, while antioxidant levels decreased (p=0.003 for IMA, p<0.001 for others). Conclusions: We believe that parameters indicating impaired oxidant/antioxidant balance in patients with obsessive-compulsive disorder may help to elucidate the cause of the disease and may be potentially useful biomarkers in the diagnosis and determination of the severity of comorbid MDD. [ABSTRACT FROM AUTHOR]

Introduction: Resveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation). Methods: Twenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet. Results: Res increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation. Discussion: There findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites. [ABSTRACT FROM AUTHOR]

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. [ABSTRACT FROM AUTHOR]

Purpose: Excessive fluoride induces kidney injury by reducing the antioxidant capacity and causing oxidative stress. Our previous studies have shown that moderately forced treadmill running alleviates oxidative injury. However, the impact of voluntary wheel-running exercise on fluoride-intoxicated mice remains unclear. In this study, we investigated the effects of voluntary wheel-running exercise on oxidative stress-induced renal injury in fluoride-intoxicated mice. Methods: 80 Institute of Cancer Research (ICR) mice (half male and half female), were randomly divided into one of eight experimental groups: four receiving distilled water and the other four ingesting 100 mg/L sodium fluoride. Each group was subdivided to incorporate different exercise regimens--no wheelrunning, daytime, nighttime, and all-day wheel-running exercises. After 6 months, mice were euthanized for subsequent analyses. Results: HE staining revealed that 6 months of fluoride exposure caused structural damage in the kidneys of mice, elevated blood urea nitrogen (BUN), and uric acid (UA) levels in the serum. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), hydrogen peroxide (H2O2), and catalase (CAT) enzyme activity significantly increased. In contrast, glutathione (GSH) content and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities obviously decreased. Interestingly, these above changes were reversed by free-wheel movement. Correlation analysis demonstrated that negative relationships exist between ROS, MDA, H2O2 levels, CAT enzyme activity, and movement distance. Additionally, T-SOD and GSH-PX enzyme activities were positively associated with exercise distance. Conclusions: Voluntary wheel-running exercise mitigated renal injury induced by sodium fluoride in mice, and the extent of renal recovery was positively correlated with the distance covered during voluntary wheel-running exercise. [ABSTRACT FROM AUTHOR]

Background: Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Methods: Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. Results: NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. Conclusions: NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage. [ABSTRACT FROM AUTHOR]

Simple Summary: The wild population of Brachymystax tsinlingensis is a Grade II protected species in China. This population faces slow growth, harsh habitats, serious individual miniaturization, and a low survival rate of fry during its early developmental stage. To improve the aquaculture efficiency of this species, and thus increase the survival rate, protect species resources, and enrich species numbers, the present study was conducted to investigate the changes in intestinal tissue structure, digestive enzymes, malondialdehyde content, and antioxidant enzyme activities and their patterns during the early developmental stage of Brachymystax tsinlingensis. This information can be applied to increase the survival rate of fry, protect the species resources, and enrich the species' quantity. This work explores the digestive system characteristics of Brachymystax tsinlingensis during early developmental stages and aims to solve the problem of high lethality of fry during the transgression period, which is crucial for the artificial propagation and population conservation of endangered fishes. This study was carried out on intestinal tissue, digestive enzymes, and antioxidant enzyme activities in the early development stage of Brachymystax tsinlingensis. Ten random samples during endogenous nutrition (7, 10, and 11 days after hatching), mixed nutrition (13 and 19 DAH), and exogenous nutrition (31, 33, 39, 45, and 73 DAH) were collected by histological and biochemical analysis methods. The results showed that the intestine of Brachymystax tsinlingensis already has four layers initially at 7 DAH, and the intestinal gland tissue is evident at 73 DAH. The contents of total protein (TP) and the activities of lipase (LPS) and trypsin (TPS) were maximal at 39 DAH, and the activities were 3.20 ± 0.26 mg/mL, 2.52 ± 0.69 U/g, and 2717.45 ± 295.26 U/mg, respectively. Catalase (CAT) and glutathione peroxidase (GSH-PX) activities both showed the lowest values at 39 DAH, which were 0.57 ± 0.11 U/mg and 3.35 ± 0.94 U/mg, respectively. The activity of amylase (AMS) and the content of malonaldehyde (MDA) increased, and the highest values were reached at 45 DAH (1.32 ± 0.41 U/mg) and 73 DAH (1.29 ± 0.43 nmoL/mg), respectively. Superoxide dismutase (SOD) and GSH-PX activities both showed a peak value at 7 DAH (126.58 ± 20.13 U/mg and 6.47 ± 1.86 U/mg). Overall, the changes in intestinal tissue, digestive enzymes, and antioxidant enzyme activities at 39 DAH of Brachymystax tsinlingensis are inseparable from different vegetative stages during the developmental period, and these results can provide a reference for the proliferation and cultivation of Brachymystax tsinlingensis resources. [ABSTRACT FROM AUTHOR]

Simple Summary: Shrimp lack an adaptive immune system, which makes the oral delivery of antibodies a potential therapeutic strategy for treating diseases in these animals. Single-domain antibodies (sdAbs) derived from camelids against the white spot syndrome virus exhibit promising therapeutic potential for disease prevention and treatment, and they have emerged as effective feed additives in shrimp diets. The results of the present study demonstrated that the inclusion of sdAbs did not negatively affect juvenile whiteleg shrimp at the organism and tissue levels; however, it did impact molecular pathways associated with growth, cold stress, and antioxidant responses. A six-week feeding trial was conducted to assess the safety of single-domain antibodies (sdAbs) derived from camelids against the white spot syndrome virus (WSSV) (WSSVvp28 was used as the antigen), focusing on the whole-organism responses and molecular-level changes in juvenile whiteleg shrimp (Litopenaeus vannamei). Five experimental diets with varying levels of sdAbs were formulated: CON (no sdAb supplementation); SDA8.2 (8.20% of sdAbs); SDA16.4 (16.40% of sdAbs); SDA24.6 (24.60% of sdAbs); and SDA32.8 (32.80% of sdAbs). In the CON diet, 450 mL of water per kg of diet (45%) was used to form a feed dough, while sdAbs were used to replace the water in the treatment diets. A total of 450 shrimp, with an initial body weight of 3.27 ± 0.02 g (mean ± SEM), were randomly distributed in 15 tanks (30 shrimp per tank; three tanks per treatment). Each tank was filled with 30 L of seawater (77 L capacity) in an indoor semi-recirculating system with a constant water flow rate of 1.2 L min−1. The photoperiod was maintained at 12 h of light and 12 h of dark. The water temperature, pH, salinity, and dissolved oxygen were 27.3 ± 0.1 °C, 7.61 ± 0.01, 34 ± 1 ppt, and 5.94 ± 0.04 mg L−1, respectively. During the feeding trial, the shrimp were fed the experimental diet (40% protein and 11% lipid) three times a day for six weeks. Following the feeding trial, an acute cold-water-temperature stress test was conducted by abruptly exposing the shrimp from each treatment to 15 °C for 4 h, down from 27 °C. The results showed no significant differences in the growth performance (weight gain, feed utilization efficiency, survival, etc.), plasma metabolites (aspartate aminotransferase activity, alanine aminotransferase activity, total protein, and glucose), or antioxidant enzymes (superoxide dismutase and glutathione peroxidase) among all the experimental diets (p > 0.05). In the acute cold-temperature stress test, there was no significant interaction between sdAb supplementation and temperature stress, nor any main effect from either factor, except for the main effect of temperature stress on the glucose levels, which was significantly higher in shrimp exposed to cold-temperature stress (p < 0.05). The next-generation sequencing of differentially expressed genes (DEGs) in the hepatopancreases of shrimp fed the CON, SDA16.4, and SDA32.8 diets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, indicated that DEGs were significantly enriched in signaling pathways associated with growth, cold stress, and antioxidant systems. Overall, the results from conventional measurements suggest that the use of sdAbs against the WSSV may be safe for juvenile whiteleg shrimp. However, findings from the sophisticated analysis indicate that further research is needed to understand the molecular mechanisms underlying the observed changes, and to evaluate the long-term effects of sdAb supplementation in shrimp diets. [ABSTRACT FROM AUTHOR]

Ferroptosis, a lipid peroxidation- and iron-mediated type of regulated cell death, relates to both neuroinflammation, which is common in relapsing-remitting multiple sclerosis (RRMS), and neurodegeneration, which is prevalent in progressive (P)MS. Currently, findings related to the molecular markers proposed in this paper in patients are scarce. We analyzed circulatory molecular indicators of the main ferroptosis-related processes, comprising lipid peroxidation (malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and hexanoyl–lysine adduct (HEL)), glutathione-related antioxidant defense (total glutathione (reduced (GSH) and oxidized (GSSG)) and glutathione peroxidase 4 (GPX4)), and iron metabolism (iron, transferrin and ferritin) to estimate their contributions to the clinical manifestation of MS and differences between RRMS and PMS disease course. In 153 patients with RRMS and 69 with PMS, plasma/serum lipid peroxidation indicators and glutathione were quantified using ELISA and colorimetric reactions, respectively. Iron serum concentrations were determined using spectrophotometry, and transferrin and ferritin were determined using immunoturbidimetry. Compared to those with RRMS, patients with PMS had decreased 4-HNE (median, 1368.42 vs. 1580.17 pg/mL; p = 0.03). Interactive effects of MS course (RRMS/PMS) and disease-modifying therapy status on MDA (p = 0.009) and HEL (p = 0.02) levels were detected. In addition, the interaction of disease course and self-reported fatigue revealed significant impacts on 4-HNE levels (p = 0.01) and the GSH/GSSG ratio (p = 0.04). The results also show an association of MS course (p = 0.03) and EDSS (p = 0.04) with GSH levels. No significant changes were observed in the serum concentrations of iron metabolism indicators between the two patient groups (p > 0.05). We suggest circulatory 4-HNE as an important parameter related to differences between RRMS and PMS. Significant interactions of MS course and other clinically relevant parameters with changes in redox processes associated with ferroptosis support the further investigation of MS with a larger sample while taking into account both circulatory and central nervous system estimation. [ABSTRACT FROM AUTHOR]

Nocardia cyriacigeorgica causes bovine mastitis, reduces milk quantity and quality, and is often resistant to antimicrobials. Selenomethionine (SeMet) is a form of selenium, which reduces reactive oxygen species (ROS)-mediated apoptosis and intramammary infections. However, the protective effects of SeMet on N. cyriacigeorgica-infected bovine mammary epithelial cells (bMECs) are unclear. The objective of this study was to evaluate whether SeMet mitigated N. cyriacigeorgica-induced inflammatory injury, oxidative damage and apoptosis in bMECs. Cells were cultured with or without being pretreated with 40 µM of SeMet for 12 h, then challenged with N. cyriacigeorgica (multiplicity of infection = 5:1) for 6 h. Although N. cyriacigeorgica was resistant to lincomycin, erythromycin, enrofloxacin, penicillin, amoxicillin, cephalonium, cephalexin, and ceftriaxone, 40 μM SeMet increased cell viability and inhibited lactate dehydrogenase release in infected bMECs. Furthermore, N. cyriacigeorgica significantly induced mRNA production and protein expression of TNF-α, IL-1β, IL-6, and IL-8 at 6 h. Cell membrane rupture, cristae degeneration and mitochondria swelling were evident with transmission electron microscopy. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities were down-regulated after 3, 6, or 12 h, whereas malondialdehyde (MDA) and ROS contents were significantly upregulated, with cell damage and apoptosis rapidly evident (the latter increased significantly in a time-dependent manner). In contrast, bMECs pretreated with 40 μM SeMet before infection, SOD, and GSH-px activities were upregulated (p < 0.05); MDA and ROS concentrations were downregulated (p < 0.05), and apoptosis was reduced (p < 0.05). In conclusion, 40 μM SeMet alleviated inflammation, oxidative stress and apoptosis induced by N. cyriacigeorgica in bMECs cultured in vitro. [ABSTRACT FROM AUTHOR]

The goal of the current study was to develop a pig model to investigate oxidative stress with a low negative impact on piglet welfare. Four independent trials (A, B, C, and D) were performed using a single intraperitoneal shot of lipopolysaccharide (LPS) as an immune challenge, aiming to assess the minimal LPS dose for piglets of different age to trigger a measurable acute oxidative stress response in healthy animals. In trial A, piglets received an LPS dose of 25 µg/KgBW at 41 days post-weaning (p.w.). In trial B, piglets received 25 µg/KgBW of LPS at 28 days p.w., in trials C And D, piglets were injected with 50 µg/KgBW of LPS at 21 days p.w., respectively. Piglets were randomly allocated either to the T1) Control group with saline solution (Ctrl), or T2) LPS challenge (LPS). The oxidative stress response was measured through the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT), in both plasma and intestinal tissues. Intestinal gene expression of oxidative stress and inflammatory markers was assessed. Discomfort behaviors (panting, prostration, trembling, and vomits) were also recorded. Plasmatic and intestinal oxidative stress response was inconsistent across the four trials even when the dose and pig age were similar, possibly due to individual variability. Relative gene expression differences of anti-inflammatory cytokines (IL10), oxidation precursor (iNOS), and antioxidant markers (GPx4, MnSOD, and CAT) were detected between Ctrl and LPS treatment (P < 0.05) when assessed. Behavioral observations were sensitive to the LPS dose relative to Ctrl (P < 0.05) in all four trials. These results suggest that behavioral observations can be used as a non-invasive methodology to detect the presence of oxidative stress in pigs in challenging conditions. Behavioral observations were more sensitive than other indicators (i.e., biomarkers and gene expression) in the current study. However, a sensitivity scale system needs to be developed to qualify and rank the impact of oxidative stress in pigs. [ABSTRACT FROM AUTHOR]

AbstractThis study is aimed to evaluate the impact of methanolic extract of Artemisia vulgaris and isolated plant compound, β-Caryophyllene oxide against carrageenan-induced paw edema in rat model and its therapeutic potential compared with reference drug, Indometacin. Methanolic extract of A. vulgaris was characterized using FTIR, LC-MS, NMR spectral studies. Paw edema was induced by sub-plantar injection of 100 µl of 1% carrageenan. Oxidative enzymes, such as super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), lipid peroxidation and C-reactive protein levels were measured in paw tissue. In silico evaluation of anti-inflammatory activity of plant compounds was evaluated against the molecular targets of inflammation. C-reactive protein and lipid-peroxidation levels were significantly increased whereas the activity levels of oxidative enzymes were significantly decreased in inflammation-induced rats. The recovery of oxidative enzyme levels was seen in treated groups in a dose dependent manner. C-reactive protein and lipid-peroxidation levels were significantly decreased in treated groups, indicating the anti-inflammatory activity of the plant extract and the plant compound. Computational analysis rationalizes the inhibitory ability of plant derived compound possibly by altering the inflammatory signaling pathway. [ABSTRACT FROM AUTHOR]

Background: While gamma irradiation's damaging biological effects are well-established, the natural radioprotective agents from agricultural waste remain an underexplored area of significant potential. Aim of study: This study was to investigate the novel use of pomegranate peel ethanol extract (PE) as a radioprotective agent against gamma radiation damage. Methods: We pretreated Wistar rats with PE (100 mg/kg) for 14 days prior to 6 Gy gamma irradiation. We analyzed blood biochemicals, oxidative stress, and inflammatory markers. These included tests of red cell membrane integrity, lipid and protein oxidation, antioxidant enzyme levels, and cytokine profiles. Results: The study showed that PE demonstrated remarkable radioprotective effects across multiple parameters. Antioxidants were significantly enhanced, as evidenced by increased glutathione peroxidase activity (87.00 ± 6.11 mg/ml in PE-treated irradiated rats compared to 26.40 ± 1.21 mg/ml in irradiated controls). Oxidative damage was markedly reduced, with MDA levels dropping from 9.59 ± 0.24 nmol/ml in irradiated controls to near-control levels in PE-treated rats. Notably, PE treatment resulted in unprecedented maintenance of red blood cell membrane integrity post-irradiation. Furthermore, PE exhibited novel modulation of inflammatory cytokines, effectively reducing pro-inflammatory markers IL-6 and TNF-α while simultaneously boosting anti-inflammatory IL-4 and IL-10 levels. These multifaceted protective effects highlight PE's potential as a comprehensive radioprotective agent. Conclusion: This study presents PE as an effective new natural radioprotective agent. Its protective effect is due to its high polyphenol content, which enhances antioxidant defenses, reduces oxidative damage, and prevents inflammation. The findings open new avenues for sustainable, cost-effective radioprotection strategies and demonstrate the potential for repurposing agricultural byproducts for critical health applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Increasing evidence suggests that the accumulations of reactive oxygen species (ROS), β-amyloid (Aβ), and neuroinflammation are crucial pathological hallmarks for the onset of Alzheimer's disease (AD), yet there are few effective treatment strategies. Therefore, design of nanomaterials capable of simultaneously elimination of ROS and inhibition of Aβ aggregation and neuroinflammation is urgently needed for AD treatment. Herein, we designed human serum albumin (HSA)-embedded ultrasmall copper nanoclusters (CuNCs@HSA) via an HSA-mediated fabrication strategy. The as-prepared CuNCs@HSA exhibited outstanding multiple enzyme-like properties, including superoxide dismutase (>5000 U/mg), catalase, and glutathione peroxidase activities as well as hydroxyl radicals scavenging ability. Besides, CuNCs@HSA prominently inhibited Aβ fibrillization, and its inhibitory potency was 2.5-fold higher than native HSA. Moreover, CuNCs@HSA could significantly increase the viability of Aβ-treated cells from 60 % to over 96 % at 40 μg/mL and mitigate Aβ-induced oxidative stresses. The secretion of neuroinflammatory cytokines by lipopolysaccharide-induced BV-2 cells, including tumor necrosis factor-α and interleukin-6, was alleviated by CuNCs@HSA. In vivo studies manifested that CuNCs@HSA effectively suppressed the formation of plaques in transgenic C. elegans , reduced ROS levels, and extended C. elegans lifespan by 5 d. This work, using HSA as a template to mediate the fabrication of copper nanoclusters with robust ROS scavenging capability, exhibited promising potentials in inhibiting Aβ aggregation and neuroinflammation for AD treatment. [ABSTRACT FROM AUTHOR]

Abstract\nNOVELTY STATEMENT\nHIGHLIGHTSThe effects of Paenibacillus favisporus CHP14 inoculation on selenium (Se) accumulation and Se tolerance of Pakchoi were studied by a pot experiment conducted in greenhouse. The results revealed that the growth traits such as plant height, root length, and biomass were significantly elevated during CHP14 treatment at 0 ∼ 8.0 mg·kg−1 Se(IV) levels. CHP14-inoculated plants accumulated more Se in root and shoot, which were 24.1%∼57.3% and 7.5%∼50.9% higher than those of non-inoculated plants. The contents of leaf nitrogen (N), phosphorus (P), magnesium (Mg), and iron (Fe), as well as the ratio of indoleacetic acid and abscisic acid contents (IAA/ABA) were increased by CHP14 inoculation, and positively associated with photosynthetic pigment contents (p < 0.05). At ≥ 4.0 mg·kg−1 Se(IV) levels, superoxide dismutase, peroxidase, and glutathione peroxidase activities of Pakchoi roots were increased with CHP14 inoculation, by 9.9%∼17.1%, 28.4%∼40.7%, and 7.4%∼15.3%, respectively. Moreover, CHP14 inoculation enhanced ascorbate-glutathione (AsA-GSH) metabolism in roots by upregulating the related enzymes activities and antioxidant contents under excess Se(IV) stress. These findings suggest that CHP14 is beneficial to improve plant growth and enhance Se(IV) resistance of Pakchoi, and can be exploited as potential inoculants for phytoremediation process in Se contaminated soil.This work assesses the effects of plant growth-promoting bacterium (PGPB) on physiology and biochemistry of Pakchoi plant under different exogenous selenite levels. P. favisporus CHP14 inoculation was found to be a positive way for promoting plant growth, improving Se accumulation and reducing Se toxicity in plant. It also provides the first evidence that PGPB improves plant Se tolerance by influencing ascorbate-glutathione (AsA-GSH) cycle.Both Se deficiency and Se pollution cause a serious threat to the ecological environment and human health. The absorption of Se from soil by plant is not only a desirable way to supplement this micro-nutrient in human body, but also an effective method for Se remediation. However, the range between the beneficial and toxic doses of Se to plants is extremely narrow. The Se application slightly exceeding the required dose would significantly inhibit growth and Se accumulation in plants, since most of them have a very limited tolerance to Se. Plant growth-promoting bacteria (PGPBs) are drawing much attention due to their important benefits for improving resistance of plant to various biotic or abiotic stresses. Recent evidences have suggested that PGPBs may become the potential enhancers for Se biofortification. Therefore, the study on plant-bacteria interaction in Se-rich conditions should be strengthened. The significance of our research is in revealing the effect of endophyte inoculation on Se accumulation and Se tolerance of Pakchoi and in providing a microorganism material with potential application values for Se biofortification and improving Se tolerance of Pakchoi. [ABSTRACT FROM AUTHOR]

Lung inflammation caused by fine particulate matter (PM), particularly PM2.5, poses a significant public health challenge, with oxidative stress and inflammation playing central roles in its pathophysiology. This study evaluates the protective effects of phytosome-encapsulated extract of purple waxy corn tassel (PPT) against PM2.5-induced lung inflammation. Male Wistar rats received PPT at doses of 100, 200, and 400 mg/kg BW for 21 days prior to exposure and continued to receive the same doses for 27 days during PM2.5 exposure. Significant reductions in inflammatory markers, including cyclooxygenase-2 (COX-II), various interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB), were observed, indicating that PPT effectively regulates the inflammatory response. Additionally, PPT improved oxidative stress markers by reducing malondialdehyde (MDA) levels and enhancing antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby restoring lung antioxidant defenses. Notably, the study revealed that PPT modulates epigenetic mechanisms, as evidenced by decreased histone deacetylase (HDAC) activity and upregulation of sirtuins in lung tissue. These epigenetic modifications likely contribute to the reduction in inflammation and oxidative stress, suggesting a multifaceted protective role of PPT that involves both direct biochemical pathways and epigenetic regulation. The interplay between reduced inflammatory signaling, enhanced antioxidant capacity, and epigenetic modulation underscores PPT's potential as a therapeutic agent for managing respiratory inflammation-related diseases and its promise for the development of future functional food products. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI), a neonicotinoid pesticide, has been widely used due to its high efficiency against insect pests. However, its prolonged exposure may pose significant risks to non-target organisms, including mammals. Recent studies have raised concerns about its potential neurotoxicity, yet the underlying mechanisms remain poorly understood. This study aimed to assess the neurotoxic effects of chronic Imidacloprid exposure in Wistar rats, focusing on oxidative stress, mitochondrial dysfunction, and lysosomal disruption. Wistar rats were orally administered two doses of Imidacloprid (5 mg/kg and 50 mg/kg body weight) for three months. Neurotoxic effects were assessed by measuring key biochemical markers such as the enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione S-transferase (GST). Non-enzymatic markers, including glutathione (GSH) levels and malondialdehyde (MDA) index, were also evaluated. Mitochondrial function was assessed by analyzing oxygen consumption, swelling, and membrane permeability and histopathological changes. Lysosomal stability was examined using the Neutral Red Retention Time (NRRT) assay. Neutral red is a dye that accumulates in the acidic environment of lysosomes. Healthy lysosomes retain the dye, while compromised lysosomes lose it, indicating destabilization. By measuring the amount of neutral red retained in lysosomes, the NRRT assay assesses lysosomal integrity. Lysosomal pH variations were also monitored to evaluate functional changes. Microscopic analysis provided insight into structural changes in lysosomes and other cell components. Lysosomal destabilization was further confirmed by morphological alterations observed through light microscopy, revealing a progressive, time-dependent degeneration of lysosomal structures, including lysosomal expansion, neutral red dye leakage, and cell rounding. These changes reflected a temporal evolution of lysosomal damage, progressing from minor structural disruptions to more severe alterations as exposure continued, observable at the microscopic level. During the study, clinical observations of intoxicated rats included symptoms such as lethargy, reduced activity levels, and impaired motor coordination. High-dose Imidacloprid exposure led to noticeable behavioral changes, including decreased exploratory behavior and altered grooming patterns. Additionally, signs of neurotoxic effects, such as tremors or ataxia, were observed in the rats exposed to the higher dose, reflecting the systemic impact of chronic pesticide exposure. The results revealed a significant decrease in the enzymatic activities of CAT, GPx, and SOD, accompanied by an increase in GST activity. A notable reduction in glutathione levels and a rise in MDA index were observed, indicating enhanced oxidative stress in the brain. Mitochondrial impairment was evidenced by disturbances in oxygen consumption, increased swelling, and altered membrane permeability. Lysosomal destabilization was confirmed by reduced retention of neutral red dye, structural changes in lysosomes, and a significant rise in lysosomal pH in the IMI-exposed groups. In addition, the histopathological features indicate that imidacloprid at the given dose and exposure duration may have caused notable neurotoxic effects in Wistar rat brain tissue. Chronic exposure to Imidacloprid induces oxidative stress, mitochondrial dysfunction, lysosomal disruption and histopathological alterations in the central nervous system of Wistar rats. These findings provide valuable insights into the neurotoxic mechanisms of neonicotinoid pesticides, highlighting the need for further research to understand the long-term effects of Imidacloprid exposure on mammalian health. [ABSTRACT FROM AUTHOR]

Objectives: 8-hydroxydeoxyguanosine (8-OHdG) and Malondialdehyde (MDA) are commonly used as markers to evaluate oxidative DNA and Lipid damage in disorders including chronic inflammatory diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) protect tissues against oxidative injury from free oxygen radicals generated by various metabolic processes. The aim of this study was to evaluate 8-OHdG and MDA levels, and SOD and GPx activities in whole saliva of patients with peri-implant diseases. Materials and methods: A cross-sectional study was conducted on a sum of 60 age gender balanced; peri-implantitis (n = 20), peri-mucositis (n = 20) and healthy (n = 20) individuals. Unstimulated whole saliva samples were collected and to determine the clinical condition of each subject; the plaque index (PI), gingival index (GI), peri-implant probing pocket depth (PIPD), peri-implant presence of bleeding on probing (BOP) (with/without suppuration) and radiographic signs of crestal bone loss (BL) were measured. The salivary 8-OHdG level was measured using the ELISA method. SOD, GPx activities and MDA levels were determined spectrophotometrically. Results: A total of 60 individuals had evaluations of 318 implants. In comparison to the peri-mucositis and peri-implantitis groups, the healthy group had significantly lower PI and GI scores (p < 0.001). The PIPD value differed amongst the groups, with the peri-implantitis group having the highest value (p < 0.001). Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher BL score (p < 0.001 and p < 0.001, respectively). The peri-implantitis group showed a significantly higher 8-OHdG level (p < 0.001; p < 0.001 respectively) than the peri-mucositis and control groups. Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher MDA level (p < 0.001 and p < 0.001, respectively). The peri-implantitis group had a significantly higher SOD level (p < 0.001 and p < 0.001, respectively) in comparison to the peri-mucositis and control groups. There was no significant difference in GPx levels between the peri-mucositis and control groups (p > 0.05), while the peri-implantitis group had significantly lower GPx levels than the peri-mucositis and control groups (p < 0.001 and p < 0.001, respectively). Conclusions: Elevated levels of oxidative stress in saliva may indicate the onset of pathological bone loss surrounding the implant and may be an indication of peri-implantitis. Clinical relevance: In peri-implant diseases, changes may occur in the levels of 8-OHdG, MDA, SOD and GPx in saliva, which may lead to a deterioration in the oxidant/antioxidant balance. [ABSTRACT FROM AUTHOR]

Vascular endothelial damage due to ionizing radiation is the main pathological process of radiation injury and the main cause of damage to various organs in nuclear accidents. Ferroptosis plays an important role in ionizing radiation-induced cell death. We have previously reported that luteolin is highly resistant to ferroptosis. In the present study, body weight, microvessel count, H&E, and Masson staining results showed that luteolin rescued radial vascular injury in vivo. Cell Counting Kit 8 (CCK8), Giemsa staining clarified the anti-ferroptosis ability of luteolin with low toxicity. Malondialdehyde (MDA), superoxide dismutase (SOD), NADP+/NADPH, Fe2+ staining, dihydroethidium (DHE) and MitoTracker assays for ferroptosis-related metrics, we found that luteolin enhances human umbilical vein endothelial cells (HUVECs) antioxidant damage capacity. Drug affinity responsive target stability (DARTS), surface plasmon resonance (SPR), computer simulated docking and western blot showed that heat shock protein beta-1 (HSPB1) is one of the targets of luteolin action. Luteolin inhibits ferroptosis by promoting the protein expression of HSPB1/solute carrier family 7 member 11 (SLC7A11)/ glutathione peroxidase 4 (GPX4). In conclusion, we have preliminarily elucidated the antioxidant damage ferroptosis ability and the target of action of luteolin to provide a theoretical basis for the application of luteolin in radiation injury diseases. [ABSTRACT FROM AUTHOR]

Lowering nanoparticles (NPs) toxicity before discharge into aquatic environments and employing agricultural waste materials for environmental sustainability are necessary nowadays. Since this has never been done, this work examines how green CuO NPs treated with rice husk (RH) as a bio-adsorbent may be safer for Nile tilapia (Oreochromis niloticus) than chemically manufactured ones. So, five groups of fish were randomly placed in glass aquaria. One group was a control, and four groups received 50 mg/L green and chemically produced CuO NPs (GS and CS) with and without RH for 24, 48, and 96 h. RH was collected from all groups, and the results showed GS-CuO NPs had a greater adsorptive capacity than CS-CuO NPs after all time intervals. After analyzing fish indicators in all groups compared to the control, higher Cu bioaccumulation was exhibited in the liver and gills. The liver and gills showed elevated levels of glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS), while the levels of glutathione reduced (GSH) were significantly lower. In addition, Cu exposure impaired liver and gill histology. Finally, our results indicated that using RH as an adsorbent for CuO NPs after their green synthesis instead of chemical synthesis before they enter the aquatic environment can enhance the overall health of fish and environmental sustainability. [ABSTRACT FROM AUTHOR]

Background: Intracellular hydroperoxides are harmful reactive oxygen species that can cause damage. Cells depend on antioxidant enzymes such as glutathione peroxidase (GPx) to prevent their accumulation. GPx is present in all cell compartments, including the cytosol, mitochondria, and peroxisomes. This article will present a rapid and reliable method for measuring GPx activity, which has been rigorously tested and proven dependable. Results: The enzyme samples are incubated in a phosphate buffer containing specific concentrations of glutathione (GSH) and peroxide and then incubated for a suitable time to react before Ellman's reagent (5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) is added. This method, designed for ease of use, is effective and straightforward. When GSH reacts with DTNB, mixed disulfides (GS-S-DTNB) are formed, where the thiol group replaces one of the nitrobenzoic acid moieties in DTNB. The release of the nitrobenzoic acid group as nitro-2-thiobenzoate anion (TNB−) creates a yellow anion that can be measured spectrophotometrically at a wavelength of 412 nm. The intensity of the yellow color is directly proportional to the unreacted glutathione concentration. GPx activity was linked to decreased absorbance of the TNB− anion, providing a sensitive and relatively specific method for detecting thiol groups in various biological samples. Conclusion: This study utilized a Box–Behnken design (BBD) to apply to response surface modeling (RSM) to determine the best conditions for measuring GPx activity. The efficiency of the new protocol was validated by comparing GPx activity in matched samples using the Bland–Altman plot analysis and reference methods. The new protocol was just as accurate as the reference one, with a correlation coefficient of 0.9991. [ABSTRACT FROM AUTHOR]

Nanozymes, serving as synthetic alternatives to natural enzymes, offer several benefits including cost-effectiveness, enzyme-like catalytic abilities, enhanced stability, adjustable catalytic activity, easy recyclability, mild reaction conditions, and environmental friendliness. Nonetheless, the ongoing quest to develop nanozymes with enhanced activity and to delve into the catalytic mechanism remains a challenge. In our research, we effectively developed Au@CuO nanocomposites (Au@CuO Nc), replicating the functions of four enzymes found in nature: peroxidase (POD), catalase (CAT), glutathione peroxidase (GPx), and oxidase (OXD). The catalytic efficiency of Au@CuO Nc for TMB oxidation (oxTMB) was approximately 4.8 times greater than that of plain Cu2O cubes, attributed to the synergistic catalytic impact between the Au element and Cu2O within Au@CuO Nc. Mechanistic studies revealed that the novel Au@CuO Nc nanozyme greatly enhances the decomposition of H2O2 to reactive oxygen species (ROS) intermediates (˙OH, ˙O2− and 1O2), resulting in increased POD-like activity of the single-component Cu2O cubes. When an antioxidant like TA was added to the chromogenic system, it converted oxTMB into a colorless form of TMB, enabling further evaluation of TA. Hence, a colorimetric sensor was developed for the rapid and precise quantitative measurement of TA, demonstrating strong linearity between 0.3 and 2.4 μM and featuring a low detection threshold of 0.25 μM. Moreover, this sensor was effectively utilized for the assessment of TA in actual tea samples. This work innovatively proposes a simplified and reliable strategy for the advanced design of highly effective Cu-based nanozymes, enhancing enzyme-like reactions for simultaneous, on-site colorimetric probing of antioxidants. [ABSTRACT FROM AUTHOR]

The identification of optimal candidate genes from large-scale blood transcriptomic data is crucial for developing targeted assays to monitor immune responses. Here, we introduce a novel, optimized large language model (LLM)-based approach for prioritizing candidate biomarkers from blood transcriptional modules. Focusing on module M14.51 from the BloodGen3 repertoire, we implemented a multi-step LLM-driven workflow. Initial high-throughput screening used GPT-4, Claude 3, and Claude 3.5 Sonnet to score and rank the module's constituent genes across six criteria. Top candidates then underwent high-resolution scoring using Consensus GPT, with concurrent manual fact-checking and, when needed, iterative refinement of the scores based on user feedback. Qualitative assessment of literature-based narratives and analysis of reference transcriptome data further refined the selection process. This novel multi-tiered approach consistently identified Glutathione Peroxidase 4 (GPX4) as the top candidate gene for module M14.51. GPX4's role in oxidative stress regulation, its potential as a future drug target, and its expression pattern across diverse cell types supported its selection. The incorporation of reference transcriptome data further validated GPX4 as the most suitable candidate for this module. This study presents an advanced LLM-driven workflow with a novel optimized scoring strategy for candidate gene prioritization, incorporating human-in-the-loop augmentation. The approach identified GPX4 as a key gene in the erythroid cell-associated module M14.51, suggesting its potential utility for biomarker discovery and targeted assay development. By combining AI-driven literature analysis with iterative human expert validation, this method leverages the strengths of both artificial and human intelligence, potentially contributing to the development of biologically relevant and clinically informative targeted assays. Further validation studies are needed to confirm the broader applicability of this human-augmented AI approach. [ABSTRACT FROM AUTHOR]

Background: Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. Methods: Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. Results: Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. Conclusion: These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD. [ABSTRACT FROM AUTHOR]

In recent years, there has been extensive research within the scientific community on deep eutectic systems due to their remarkable versatility in solubilizing diverse substances and serving as effective solvents in catalytic processes. While initially regarded as non-toxic, a comprehensive toxicological assessment is essential to comprehend their behavior within organisms. In this study, seven distinct systems, composed of N,N,N-triethyl-N-(2,3-dihydroxypropyl)ammonium chloride (N00Cl) and glycerol-derived ethers with alkyl chains of varying lengths (100, 200, 3F00, 300, 3i00, and 400), in a 1:2 molar ratio were investigated for their aquatic toxicity in shrimp (Palaemon varians). The assessment involved analyzing oxidative stress biomarkers such as glutathione S-transferase, glutathione peroxidase, catalase, superoxide dismutase, total antioxidant capacity (TAC), and lipoperoxidation (MDA content). Results show an odd–even effect for LC50 values being N00Cl-300, the system showing higher values. Regarding oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidant capacity in the organisms has been observed, suggesting significant toxicity to shrimps due to the changes in oxidative stress biomarkers at high concentrations. However, at 100 mg/l all systems can be considered environmentally safe, and no negative impacts are expected on aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Objective To investigate the efiect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ierroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase (PI3K) /protein kinase B ( Akt) signaling pathway. Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control, low-oxygen intervention, and Jiawei Ditan Decoction intervention groups using the random number table method, with 10 rats per group. The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling, with 8 h of intervention daily. Gavage administration was performed before and after daily intervention. The intervention group received a dosage of 16. 38 g/kg Jiawei Ditan Decoction, whereas the other two groups received normal saline. The experimental intervention period was 12 weeks. Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue. Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes. Biochemical detection was used to measure the Fe2+ and malondialdehyde ( MDA ) content in myocardial tissue. Phosphorylated-phosphoinositide 3-kinase ( p-PI3K), PI3K, phosphorylated-protein kinase B ( p-Akt), Akt, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 ( GPX4), nuclear factor erythroid 2-related factor 2 ( Nrf2), and acyl-coenzyme A synthetase long-chain family member 4 ( ACSL4) protein expression in myocardial tissue were measured using western blotting. The rat cardiomyocyte cell line, H9c2, was cultured in high glucose Dulbecco's Modified Eagle Medium, and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction. The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction. The cells were divided into the normoxic, erastin, and erastin + Jiawei Ditan Decoction intervention groups, and p-Akt and GPX4 protein expression was measured using western blotting. p-PI3K and GPX4 protein expression were detected in the normoxic, low-oxygen intervention 12 h, and low-oxygen intervention 12 h + 740Y-P groups. The p-PI3K, PI3K, p-Akt, Akt, and GPX4 protein expression was detected in the normoxic, low-oxygen intervention 6 h, low-oxygen intervention 12 h, low-oxygen intervention 12 h + Jiawei Ditan Decoction low-dose, low-oxygen intervention 12 h + Jiawei Ditan Decoction medium-dose, and low-oxygen intervention 12 h + Jiawei Ditan Decoction high-dose groups (drug concentrations of 5, 10, and 20 g/L, respectively). Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered, with increased mitochondrial membrane density, ruptured cristae, and vacudar degeneration compared with those in the normal control group. The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater, and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group, and no apparent swelling was observed. Compared with the normal control group, the low-oxygen intervention group showed an increase in the MDA and Fe2+ content, a decrease in the p-PI3K/PI3K and p-Akt/Akt values, decreased SLC7A11, GPX4, and Nrf2 expression, and increased ACSL4 expression ( P <0.05). Compared with the low-oxygen intervention group, the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+ content, an increase in the p-PI3K/PI3K and p-Akt/Akt values, increased SLC7A11, GPX4, and Nrf2 expression, and decreased ACSL4 expression ( P <0.05). Jiawei Ditan Decoction contained DL-stachydrine, D-( +) -malicacid, adenosine, etc. The cell survival rate of the 10. 00 g/L group increased (P<0.05) compared to that of the Jiawei Ditan Decoction 0, 1.25, 2.50, 5. 00, and 20. 00 g/L groups. Compared with the normoxic group, p-Akt and GPX4 expression decreased in the erastin group (P<0.05) ； compared with the erastin group, the erastin + Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression ( P<0. 05). Compared with the normoxic group, p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group ( P<0. 01) ； compared with the low-oxygen intervention 12 h group, the low-oxygen intervention 12 h + 740Y-P group showed increased p-PI3K and GPX4 expression ( P<0. 05). Compared with the normoxic group, GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups ( P < 0. 05) ; compared with the low-oxygen intervention 6 h and 12 h groups, the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h + Jiawei Ditan Decoction low, medium, and high-dose groups ( P<0. 05). GPX4 expression was also increased ( P<0. 05). Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ierroptosis in rats by regulating the PI3K/Akt signaling pathway, thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats. [ABSTRACT FROM AUTHOR]

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)‐induced arthritis in rats was investigated. The extract was characterized using liquid chromatography–electrospray mass spectrometry (LC‐ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor‐alpha (TNF‐α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF‐α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE‐treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of maternal exposure to polystyrene plastic particles of 5 µm, 0.5 µm, and 0.05 µm on the growth and development of mammalian placenta and its underlying mechanisms. Methods Pregnant mice were administered 50 mg/kg of polystyrene particles of 5 µm, 0.5 µm, and 0.05 µm via oral gavage throughout the gestation period until one day before delivery. After dissection, placental tissues were collected for weighing, counting, and histopathological examination using HE staining. The oxidative stress levels in placental tissues were quantitatively analyzed using kits for malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The expression levels of apoptosis-related proteins in placental tissues were determined using Western blotting. Results Compared to the control group, there were no significant effects on the body weight of pregnant mice (F=2.564, P>0.05), number of embryo implantations (F=0.319, P>0.05), and placental weight (F=1.225, P>0.05) in the 5 |m, 0.5 |m, and 0.05 |m groups; however, the uterine surfaces in the 0.05 | m group appeared pale in some areas. HE staining results indicated that the placental layers in the 0.5 µm and 0.05 µm groups had indistinct boundaries and a loose cell distribution. The area proportion of the labyrinth layer in the 0.05 |m group significantly decreased (F=13.77, P<0.01), accompanied by edema and vacuolar changes. Exposure to 0.5 µm and 0.05 µm polystyrene particles significantly increased MDA levels in placental tissues (F= 6.211, P<0.01) while decreasing the activities of SOD (F=9.853, P<0.01), GSH-Px (F=9.071, P<0.01), and CAT (F=7.168, P< 0.01), with the 0.05 |m group showing the most pronounced differences. Western blot analysis revealed that the expression levels of Cleaved Caspase-3 (F=16.05, P<0.01) and Bax (F=10.80, P<0.01) proteins were increased, while the expression level of Bcl-2 (F=10.66, P<0.01) was decreased in the 0.5 µm and 0.05 µm groups compared to the control group. Conclusion Polystyrene plastic particles induce developmental and reproductive dysfunction in mouse placental tissues through oxidative stress-mediated activation of the Bcl-2/Caspase-3 signaling pathway, with nanoparticles exhibiting stronger toxic effects. [ABSTRACT FROM AUTHOR]

The study evaluated the effect of a commercial polyphenol (ELIFE®) on the growth performance and antioxidant defense system of Penaeus vannamei juveniles. The study was completely randomized with three experimental groups and eight repetitions, divided into two 28-day phases. The experimental groups consisted of different dietary inclusion levels of ELIFE® (0.0, 0.5, and 1.0 g kg−1). Five shrimps were stocked in each experimental unit. Growth performance, oxidative stress, and enzymatic activity in shrimp hepatopancreas were assessed. In Phase 1, shrimp fed ELIFE®, regardless of inclusion level, displayed higher specific growth rate, final weight, and final length than the control group. In Phase 2, shrimp fed 1.0 g kg−1 ELIFE® showed higher final biomass and SGR than all other experimental groups; they also displayed increased reduced glutathione and glutathione-S-transferase activities. In both test phases, shrimp fed 1.0 g kg−1 ELIFE® presented increased glutathione reductase activity compared to all other experimental groups. In both test phases, shrimp fed ELIFE®, regardless of inclusion level, exhibited increased glutathione peroxidase activity compared to control groups. Thus, ELIFE® enhanced the antioxidant defense system of P. vannamei and led to better shrimp performance and survival. This study recommends dietary supplementation with 1.0 g kg−1 ELIFE® for P. vannamei juveniles. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte‐specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. Methods: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno‐associated virus 9 (AAV9)‐mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis‐related parameters were assessed. Dual‐luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. Results: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. Conclusions: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis. [ABSTRACT FROM AUTHOR]

The damage of the diabetic visual pathway is one of the main causes of blindness in diabetic patients. Visual pathways include anatomic parts from the retina to the occipital lobe. This study investigated the involvement of ferroptosis, a planned cell death brought on by the buildup of free iron in cells, in the impairment of visual pathways in diabetes mellitus. Streptozotocin (STZ) was used to construct a diabetic rat model. Pathological and ultrastructural changes of the occipital lobe, retina, and optic nerve were observed by Hematoxylin–Eosin (HE) staining and transmission electron microscopy (TEM). The expressions of Neuronal nuclei (NeuN), Glial fibrillary acidic protein (GFAP), and Glutathione Peroxidase 4 (GPX4) in the occipital lobe and retina were detected by immunofluorescence, and Western Blotting was used to identify the NeuN GFAP and GPX4 expressions in the occipital lobe. Iron content in the occipital lobe and retina was detected by Iron Assay Kit. The success rate of the diabetic rat model was 93.3%. In the diabetic group, the cells of the occipital lobe and retina were arranged disorderly, and the boundaries were unclear. The membrane of the occipital lobe, retina, and optic nerve was broken, some vacuoles were observed, mitochondrial morphology was changed, swelling was observed, and the mitochondrial ridge disappeared. There was a large increase in GFAP expression and iron concentration and a significant decrease in the expression of NeuN, and GPX4 in the retina and occipital lobe. Ferroptosis plays an important role in visual pathway damage in diabetes, and GPX4 regulates this process. [ABSTRACT FROM AUTHOR]

Oxidative stress caused by reactive oxygen species (ROS) is inevitable for all aerobic microorganisms as ROS are the byproducts of aerobic respiration. For gut pathogens, ROS are an integrated part of colonization resistance which protects the host against bacteria invasion. Alkyl hydroperoxide reductase (AhpR) and organic hydroperoxide resistance (Ohr) proteins are considered as the main enzymes responsible for the degradation of organic peroxides (OPs) in most bacteria. To elucidate how enteric pathogen Yersinia pseudotuberculosis YPIII deals with oxidative stress induced by OPs, we performed transcriptomic analysis and identified the OP scavenging system, which is composed of glutathione peroxidase (Gpx), thiol peroxidase (Tpx), and AhpR. Gpx serves as the main scavenger of OPs, and Tpx assists in the degradation of OPs. Transcriptional factor OxyR regulates Gpx expression, suggesting that OxyR is the regulator mediating the cellular response to OPs. Although AhpR has little influence on OP degradation, its deletion would greatly impair the scavenging ability of OPs in the absence of gpx or tpx. In addition, we found that catalase KatG and KatE are responsive to OPs but do not participate in the removal of OPs. IMPORTANCE In bacteria, oxidative stress caused by ROS is a continuously occurring cellular response and requires multiple genes to participate in this process. The elimination of OPs is mainly dependent on AhpR and Ohr protein. Here, we carried out transcriptomic analysis to search for enzymes responsible for the removal of organic peroxides in Yersinia pseudotuberculosis. We found that Gpx was the primary OP scavenger in bacteria, which was positively regulated by the oxidative stress regulator OxyR. The OP scavenging system in Y. pseudotuberculosis was composedof Gpx, Tpx, and AhpR. OxyR is the critical global regulator mediating gene expression involved in OPs and H2O2 stress. These findings suggest that Y. pseudotuberculosis has a unique defense system in response to oxidative stress. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common chronic autoimmune disease with synovitis as its pathological basis and erosive arthritis as its main symptom. Pathogenesis of RA is complex, combination of genetic factors, environmental factors, immune cells, cytokines and autoantibodies causes joint injury, bone destruction and multi-system disease of RA. However, the above mechanisms can not fully explain the poor prognosis, high disability rate and poor clinical treatment effect of RA. Therefore, exploring new pathogenesis and therapeutic targets of RA is the focus of RA research. In recent years, with the deepening of RA research, it has been found that there is a new form of cell death in pathological process of RA, namely ferroptosis. Ferroptosis is a type of cell death caused by inhibition of glutathione peroxidase activity and accumulation of lipid reactive oxygen species. Previous studies have confirmed the close correlation between RA and ferroptosis, this paper mainly explores ferroptosis-related signal pathways that affect the change and development of RA disease from the perspective of regulating the main signal pathways of ferroptosis, so as to find new therapeutic targets for RA and new therapeutic ideas for research. [ABSTRACT FROM AUTHOR]