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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.

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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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]

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]

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]

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]

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]

Objective: To investigate the involvement of ferroptosis mediated by glutathione peroxidase 4 (Gpx4) in acute lung injury in rats with sepsis, as well as the intervention mechanism of curcumin (Cur). Methods: Twenty-four rats were randomly divided into three groups, with 8 rats in each group: Sham group, Sepsis group and Cur group. The rat model of acute lung injury in sepsis was established by cecal ligation and puncture (CLP). The Sham group only underwent laparotomy and closure. Both Sepsis group and Cur group underwent CLP, Cur group was injected with curcumin (200 mg/kg) intraperitoneally 1 hour after modeling, and the administration was repeated 24 hours later. The lung tissues of the rats were sampled 48 hours after surgery, and the wet/dry weight of lung tissue ratio (W/D) of lung tissues in each group was measured. Morphological changes of lung tissues were observed by HE staining. The contents of GSH, MDA, and Fe2+ and the levels of inflammatory factors including TNF-α, IL-6, and IL-1β in the lung tissues were measured using test kits. Western blot was used to detect the expressions of nuclear factor E2-related factor 2 (Nrf2) and the key regulatory protein of ferroptosis Gpx4. Apoptosis of alveolar epithelial cells was detected by TUNEL method. Ultrastructural changes of alveolar epithelial cells were observed by transmission electron microscopy. Results: Compared with the Sham group, lung tissues in the Sepsis group showed an increased W/D (P<0.05), significantly higher levels of inflammatory factors TNF-α, IL-6, and IL-1β and contents of MDA and Fe2+ (P<0.05), decreased content of GSH, up-regulated expression of Nrf2, and down-regulated expression of Gpx4 (P< 0.05), the type II alveolar epithelial cells were seen to be edematous, congested, and infiltrated with inflammatory cells via light microscopy, and ferroptosis signs such as mitochondrial crinkling, thickened bilayer membrane density, and reduced or broken cristae were seen via transmission electron microscopy. Compared with Sepsis group, lung tissues in the Cur group showed decreased W/D (P<0.05), lower levels of TNF- α, IL-6 and IL-1β, lower contents of MDA and Fe2+, increased content of GSH, down-regulated expression of Nrf2, and up-regulated expression of Gpx4 (P<0.05), the pathological changes of lung tissues were significantly reduced. Conclusion: Curcumin reduces sepsis-induced acute lung injury in rats, and the mechanism is related to inhibiting inflammatory response and GPX4-mediated ferroptosis. [ABSTRACT FROM AUTHOR]

The current research evaluated the effects of dietary hesperidin (HSP) on growth parameters, digestive enzyme activities, innate immune markers, and antioxidant responses in rainbow trout, Oncorhynchus mykiss after the 30- and 60-day feeding trial. Then, specimens were subjected to Yersinia ruckeri infection for 14 days. For this, six hundred rainbow trout juveniles (initial weight; 25.49±0.40 g) were fed with different levels of HSP including 0 (HSP0; control), 50 (HSP50), 100 (HSP100), 150 (HSP150), and 200 (HSP200) mg/kg feed. After 60 days, dietary HSP100 supplementation significantly improved growth and feed efficiency indices. The optimal dose of HSP based on the regression test for WG and FCR detected 122 and 131 mg/kg, respectively. At the end of the 30th day, dietary HSP150 supplementation markedly boosted serum lysozyme (LYZ), myeloperoxidase (MPO), complement component C3, and immunoglobulin (Ig) levels, but decreased malondialdehyde (MDA) content. In the same period, dietary administration of HSP at the different concentrations markedly increased complement component C4 (HSP150 and HSP200), superoxide dismutase (SOD), skin mucus alkaline phosphatase (ALP) (HSP100–HSP200), skin mucus LYZ and catalase (CAT) (HSP100 and HSP 150), and skin mucus Ig level (HSP50–HSP200). After 60 days, all dietary HSP supplementation significantly improved lipase, serum C3, glutathione peroxidase (GPX), and skin mucus ALP, LYZ, and Ig levels, but decreased MDA, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) values. After 60 days, dietary administration of HSP150 induced a significant discrepancy in the activity of serum LYZ, MPO, respiratory burst (RB), and lactate dehydrogenase (LDH) compared to the control group. In the same period, dietary HSP supplementation at different levels induced a remarkable increase in digestive protease activity (HSP100), serum ACH50 and CAT activities (HSP100 and HSP150), skin mucus peroxidase and serum SOD levels (HSP100–HSP200), and serum C4 value (HSP50, HSP150, and HSP200), but markedly decreased ALP activity (HSP150 and HSP200). In addition, dietary HSP supplementation, especially HSP150, markedly boosted disease resistance against Y. ruckeri infection. The current data demonstrated that the oral administration of 100–150 mg/kg HSP has a high potential to promote growth performance, disease resistance, and faster induction of immune and antioxidant responses. [ABSTRACT FROM AUTHOR]

Chemical compounds used to prevent and control fish disease often cause environmental hazards; thus, alternative approaches as new and effective strategies are needed. The current investigation was performed with the aim of exploring the effects of dietary Moldavian balm (MB, Dracocephalum moldavica L.) on the growth, immune parameters, and antioxidant status of common carp (Cyprinus carpio). Fish (n=300, w=3.80±0.02 g) in four groups in triplicates were supplemented with 0%, 0.5%, 1%, and 2% MB. After 42 days, it was found that feed supplements increased final weight (FW), weight gain (WG), and specific growth rate (SGR) and decreased the food conversion ratio (FCR) (P<0.05). In addition, fish supplemented with 2% MB significantly showed higher serum total protein (TP), alternative complement pathway (ACH50), and glutathione peroxidase (GPx) (P<0.05). The 0.5% MB-supplemented fish represented higher levels of LYZ, alkaline phosphatase (ALP), total Ig, and ACH50 in their skin mucus in comparison with the unsupplemented fish (P<0.05). The results also indicated that 2% MB resulted in a significantly higher expression level of intestinal tumor necrosis factor (TNF- α) (P<0.05); however, the level of LYZ, interleukin-1β (IL-1β), and TLRs decreased in supplemented fish. CAT and SOD expressions were increased in 0.5% MB supplement. In conclusion, MB could be recommended as an efficient feed additive to boost common carp's growth, immunity, and health status. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the effects of dietary supplementation with Lactobacillus salivarius (LS) ATCC 11741 and lutein (LU) on immunological, antioxidant, and growth responses, and resistance against Yersinia ruckeri infection in rainbow trout (Oncorhynchus mykiss). There were seven experimental diets containing un-supplemented diet (CTL), L. salivarius at 1 × 106 (LS6) and 1 × 108 (LS8) CFU/g, lutein at 50 (LU50) and 150 (LU150) mg/kg, L. salivarius at 1 × 106 CFU/g plus lutein at 50 g/kg (LS6+LU50), and L. salivarius at 1 × 108 CFU/g plus lutein at 150 g/kg (LS8+LU150). These diets were provided to the fish (N= 735; 14.0±0.38 g). After 60 days of feeding, all experimental treatments exhibited significantly higher growth performance, compared to the CTL treatment. The intestinal protease activity and the intestinal lactic acid bacteria population in the probiotic-treated fish were significantly higher than in the CTL fish. The intestinal lipase activity was only higher in the LS6+LU50 treatment, compared to the CTL treatment. Compared to the CTL treatment, the intestinal total bacterial count, and serum superoxide dismutase significantly increased in the LS6+LU50 and LS8+LU150 treatments. The serum catalase significantly increased in LU150, LS6+LU50, and LS8+LU150 treatments, and serum glutathione peroxidase significantly increased in the lutein-treated fish. All experimental treatments, particularly LS6+LU50 and LS8+LU150, had significantly lower serum malondialdehyde levels, compared to the CTL treatment. The levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase in LU50, LS6+LU50, and LS8+LU150 treatments were significantly lower than the CTL. All experimental treatments showed significantly higher serum lysozyme (LYZ), complement, blood respiratory burst activity (RB), and skin mucus alkaline phosphatase (ALP), compared to the CTL treatment. The highest serum LYZ, C4, total immunoglobulin (Ig), blood RB activity, and skin mucus peroxidase, ALP, and Ig were observed in the LS6+LU50 and LS8+LU150 treatments. All the experimental treatments, especially LS6+LU50, exhibited significantly lower mortality after the bacterial challenge compared to the CTL. In conclusion, dietary supplementation with 1 × 106 CFU/g L. salivarius and 50 mg/kg lutein can maximally improve growth performance, digestive enzymes, antioxidant parameters, immune responses, intestinal lactic acid bacteria, and resistance against yersiniosis in rainbow trout. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on brain damage induced by subarachnoid hemorrhage (SAH) in male Wistar Albino rats. Forty male Wistar Albino rats were randomly divided into 4 groups of equal size: control, SEC, SAH, and SAH + SEC. SAH was induced the SAH and SAH + SEC groups by injecting autologous blood collected from the hearts of the rats into the subarachnoid space via the foramen magnum. SEC was administered intraperitoneally once a week to the SEC and SAH + SEC groups after the surgical procedure. On the 14th day of surgery, the rats were sacrificed and their cerebral tissues were collected for biochemical analysis and histopathological examination. SAH led to changes in oxidative stress parameters by increasing malondialdehyde levels and decreasing superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. Histopathologically, cerebral tissues in the SAH groups showed alterations such as congestion and cell infiltration. Treatment with SEC significantly reduced malondialdehyde levels and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. SEC also decreased histopathological alterations in brain tissues. This study revealed that SEC (3 mg/kg) therapeutically influenced oxidative and histopathological changes in blood parameters and brain tissues caused by experimental SAH. SEC helps reduce brain damage in rats with SAH and possesses antioxidant and neuroprotective properties. Further advanced studies are needed to prove its potential benefits for humans. [ABSTRACT FROM AUTHOR]

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO3. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China. [ABSTRACT FROM AUTHOR]

Scn1b plays essential roles in the heart, where it encodes β1-subunits that serve as modifiers of gene expression, cell surface channel activity, and cardiac conductivity. Reduced β1 function is linked to electrical instability in various diseases with cardiac manifestations and increased susceptibility to arrhythmias. Recently, we demonstrated that loss of Scn1b in mice leads to compromised mitochondria energetics and reactive oxygen species (ROS) production. In this study, we examined the link between increased ROS and arrhythmia susceptibility in Scn1b−/− mice. In addition, ROS-scavenging capacity can be overwhelmed during prolonged oxidative stress, increasing arrhythmia susceptibility. Therefore, we isolated whole hearts and cardiomyocytes from Scn1b−/− and Scn1b+/+ mice and subjected them to an oxidative challenge with diamide, a glutathione oxidant. Next, we analyzed gene expression and activity of antioxidant enzymes in Scn1b−/− hearts. Cells isolated from Scn1b−/− hearts died faster and displayed higher rates of ROS accumulation preceding cell death compared with those from Scn1b+/+. Furthermore, Scn1b−/− hearts showed higher arrhythmia scores and spent less time free of arrhythmia. Lastly, we found that protein expression and enzymatic activity of glutathione peroxidase is increased in Scn1b−/− hearts compared with wild type. Our results indicate that Scn1b−/− mice have decreased capability to manage ROS during prolonged oxidative stress. ROS accumulation is elevated and appears to overwhelm ROS scavenging through the glutathione system. This imbalance creates the potential for altered cell energetics that may underlie increased susceptibility to arrhythmias or other adverse cardiac outcomes. NEW & NOTEWORTHY: Using an oxidative challenge, we demonstrated that isolated cells from Scn1b−/− mice are more susceptible to cell death and surges in reactive oxygen species accumulation. At the whole organ level, they were also more susceptible to the formation of cardiac arrhythmias. This may in part be due to changes to the glutathione antioxidant system. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stress‐related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress‐induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose‐dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcer induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazole (20 mg kg−1 day−1) group (P), LGG (3 × 108 cfu mL−1 day−1) + stress group (M1), LGG (15 × 108 mL−1 day−1) + stress group (M5) and LGG (30 × 108 mL−1 day−1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. RESULTS: Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic–pituitary–adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. CONCLUSIONS: We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress‐induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a multifactorial degenerative disease in the elder. Given the involvement of mammalian sterile 20-like kinase 1 (MST1) in PD, this article was to illustrate the mechanism of MST1 in 1-methyl-4-phenylpyridinium ion (MPP+)-induced PD cell model. Cells were treated with different concentrations of MPP+ to establish a PD cell model. Reverse transcription–quantitative polymerase chain reaction and Western blot revealed that MST1 expression and iron ion concentration increased, but cellular viability decreased with MPP+ concentration. Inhibition of MST1 decreased ferroptosis; increased cellular viability, iron ion content, and levels of glutathione peroxidase 4; and decreased reactive oxygen species and lactate dehydrogenase release. Upregulation of ferroptosis levels using ferroptosis agonist Erastin reduced the protective effect of MST1 inhibition on PD cells. Mechanistically, dual-luciferase analysis identified that miR-23b-3p targeted MST1 and inhibited its expression. Overexpression of miR-23b-3p inhibited MST1 levels, thereby reducing cellular ferroptosis and attenuating MPP+-induced cell injury. Collectively, MST1 expression increased with increasing MPP+ concentration, and miR-23b-3p targeted MST1 to reduce ferroptosis and MPP+-induced cell injury. [ABSTRACT FROM AUTHOR]

Cysteine desulfurase (NFS1) is highly expressed in a variety of tumors, which is closely related to ferroptosis of tumor cells and affects prognosis. The relationship between NFS1 and the development of gastric cancer (GC) remains unknown. Here we showed that NFS1 expression was significantly higher in GC tissues compared to adjacent normal tissues. Patients with high expression of NFS1 in GC tissues had a lower overall survival rate than those with low expression. NFS1 was highly expressed in cultured GC cells compared to normal gastric cells. Knockdown of NFS1 expression reduced the viability, migration and invasion of GC cells. In cultured GC cells, NFS1 deficiency promoted ferroptosis. Mechanistically, NFS1 inhibited ferroptosis by upregulating the signal transduction and activator of transcription 3 (STAT3) signaling pathway in cultured GC cells. NFS1 knockdown using siRNA inhibited the STAT3 pathway, reduced the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and elevated intracellular levels of reactive oxygen species (ROS), ferrous ion (Fe2+), and malondialdehyde (MDA) in cultured GC cells. A specific STAT3 activator significantly reversed the inhibitory effect of NFS1 deficiency on ferroptosis in cultured GC cells. These in vitro results were further confirmed by experiments in vivo using a mouse xenograft tumor model. Collectively, these results indicate that NFS1 is overexpressed in human GC tissues and correlated with prognosis. NFS1 inhibits ferroptosis by activating the STAT3 pathway in GC cells. These results suggest that NFS1 may be a potential prognostic biomarker and therapeutic target to treat GC. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+. Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe2+, and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe2+, and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models. [ABSTRACT FROM AUTHOR]

Cisplatin (a platinum-based drug) has chemotherapeutical potency in treating different kinds of cancer but elicits side effects of testicular dysfunction while hesperetin has antioxidant attributes against inflammation, free radicals, and apoptosis. This study investigated the likely protective property of hesperetin against cisplatin-induced testicular and epididymal toxicity. Forty mice randomly assigned into four groups of 10 animals each were administered with the appropriate regimen. Group 1 (control) received normal saline alone while group 2 received 2.5 mg/kg body weight of cisplatin only. Group 3 received 40 mg/kg body weight of hesperetin and 2.5 mg/kg body weight of cisplatin, while group 4 received only 40 mg/kg body weight of hesperetin. Hesperetin administration (orally) was for 30 consecutive days while cisplatin (intraperitoneally) was on days 5, 7, 10, 13, 17, 20, 24, and 28. Findings revealed that cisplatin decreased the activities/level of glutathione peroxidase, superoxide dismutase, reduced glutathione, nitric oxide, total thiol, testosterone, luteinizing hormone, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, sperm viability, sperm motility, and total sperm count while the abnormal sperm cells and levels of lipid peroxidation, H2O2, and inteleukin-1β were increased (P < 0.05). Furthermore, histopathological results of examined testes showed a reduction in the tube-shaped size of testes, diminished development of spermatozoa, and architectural impairment with cisplatin exposure. Contrarily, hesperetin reversed cisplatin-induced testicular and epididymal oxidative damage, suppressed steroidogenesis and spermatogenesis, and repaired the architecture of the testes. The study showed that hesperetin demonstrated multi-mechanistic protective activity against testicular dysfunction, oxidative stress, and histological damage owing to its antioxidant and steroidogenic actions. [ABSTRACT FROM AUTHOR]

This study investigated the alleviating effect of fermented ginsenosides obtained through yeast strain fermentation transformation on acute liver injury (ALI) induced by CCl4. Strains were screened for their ability to produce β-glucosidase, the transformation ability of the strain was verified by high-performance liquid chromatography, and the Saccharomyces cerevisiae strain F6 was obtained by 26S rRNA sequencing. After fermentation by F6 strain, it was found that the content of ginsenosides Re, Rb1, and Rb2 was significantly decreased (P < 0.05), and rare ginsenosides were detected, with the content of Rh4 and Rg5 reaching 2.65 mg·g−1 and 2.56 mg·g−1. We also explored the preventive effect of fermented ginsenoside extract (FGE) on ALI. Mice were evenly divided into 9 groups as follows: control group, ALI model group, positive drug bifendate group, and treatment group, which included 3 ginsenoside extract (GE) groups and 3 FGE groups (dosage of 150, 300, and 450 mg·kg−1 b.w.). The results showed that compared with the ALI model group, FGE significantly increased the levels of glutathione peroxidase, hydroperoxidase, and superoxide dismutase and also decreased the malondialdehyde level. The levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin markers were significantly reduced, and the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly decreased. Bioinformatics analysis combined with Western blot validation explored the molecular mechanism of the effect of FGE. It was found that FGE could downregulate the expression of the p-AKT/AKT and the p-mTOR/mTOR ratios. These results suggested that FGE played an alleviative role in ALI by promoting autophagy to inhibit the AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: The leaves of Perilla frutescens var. acuta (PFA) are generally reported to have antioxidant, anti-allergic, anti-inflammatory, and antitumor effects and commonly used as a traditional medicine in East Asia. This study aimed to investigate the protective effect and antioxidant activity of PFA on busulfan-induced testicular dysfunction, histological damage, oxidative stress (OS), sperm quality, and hormone levels using a mouse model. Materials and Methods: C57BL/6 male mice were divided into four groups: control, busulfan-only treated, and varying concentrations of PFA (100 and 200 mg/kg) with busulfan. In the busulfan group, 40 mg/kg of busulfan was intraperitoneally injected to induce azoospermia. Mice were orally administered PFA for 35 consecutive days after busulfan administration. Samples were collected and assessed for testis/body weight, testicular histopathology, sperm quality, serum hormone levels, and OS to evaluate the effects of PFA treatment on spermatogenesis dysfunction induced by busulfan. Results: The busulfan-induced testicular dysfunction model showed reduced testis weight, adverse histological changes, significantly decreased sex hormones and sperm quality, and attenuated OS. These results indicate that PFA treatment significantly increased testis weight, testis/body weight, epididymal sperm count, motility, and testosterone level compared with busulfan alone. PFA treatment also attenuated the busulfan-induced histological changes. Furthermore, compared with mice treated with busulfan alone, PFA supplementation upregulated the testicular mRNA expression of the antioxidant enzymes superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), with a decrease in malondialdehyde (MDA) production and an increase in SOD and GPx activities. Conclusions: This study shows that PFA exerts a protective effect against testicular damage by attenuating OS induced by busulfan. Our results suggest that PFA is a potentially relevant drug used to decrease the side effects induced by busulfan on testicular function and sperm during cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Inflammatory diseases, including psoriasis, atherosclerosis, rheumatoid arthritis, and ulcerative colitis, are characterized by persistent inflammation. Moreover, the existing treatments for inflammatory diseases only provide temporary relief by controlling symptoms, and treatments of unstable and expensive. Therefore, new therapeutic solutions are urgently needed to address the underlying causes or symptoms of inflammatory diseases. Inflammation frequently coincides with a high level of (reactive oxygen species) ROS activation, serving as a fundamental element in numerous physiological and pathological phenotypes that can result in serious harm to the organism. Given its pivotal role in inflammation, oxidative stress, and ferroptosis, ROS represents a focal node for investigating the (nuclear factor E2-related factor 2) Nrf2 pathway and ferroptosis, both of which are intricately linked to ROS. Ferroptosis is mainly triggered by oxidative stress and involves iron-dependent lipid peroxidation. The transcription factor Nrf2 targets several genes within the ferroptosis pathway. Recent studies have shown that Nrf2 plays a significant role in three key ferroptosis-related routes, including the synthesis and metabolism of glutathione/glutathione peroxidase 4, iron metabolism, and lipid processes. As a result, ferroptosis-related treatments for inflammatory diseases have attracted much attention. Moreover, drugs targeting Nrf2 can be used to manage inflammatory conditions. This review aimed to assess ferroptosis regulation mechanism and the role of Nrf2 in ferroptosis inhibition. Therefore, this review article may provide the basis for more research regarding the treatment of inflammatory diseases through Nrf2-inhibited ferroptosis. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. At the onset of lactation in dairy cows, inflammation and oxidative stress may occur and result in a risk of pathologies and lower milk yield. To propose an innovative management strategy for cows during this period, it is essential to better understand these physiological variations. Our objective was to evaluate the metabolic, redox, and immune status of 7 primiparous and 8 multiparous Holstein cows during late gestation and the first months of lactation. Blood samples were collected between 3 wk before calving until 12 wk postpartum. Milk samples were also collected, but only at the time points after calving. The metabolic (nonesterified fatty acids [NEFA], BHB, glucose, urea, calcium) and redox (reactive oxygen metabolites [ROM], oxidative stress index [OSI], glutathione peroxidase activity, vitamin E) statuses were analyzed in plasma or erythrocytes. The expression of genes related to antioxidant functions was determined in leukocytes collected from milk. For immune status, plasma cytokine levels and the production of reactive oxygen species (ROS) in classical and regulatory neutrophils were measured in 2 whole blood ex vivo challenges. The data were analyzed using a mixed model that included the fixed effects of parity and week and their interaction. Milk yield, plasma NEFA, and BHB in wk 2 and 4 after calving were higher in multiparous cows than in primiparous cows, whereas glucose and calcium tended to be lower. Plasma ROM and OSI levels in wk 8 were higher in multiparous than in primiparous cows. Multiparous cows also displayed higher glutathione peroxidase activity in erythrocytes, and antioxidant transcription factor and superoxide dismutase-1 expression levels in milk leukocytes. Moreover, multiparous cows had higher plasma concentrations of vitamin E but lower plasma levels of cytokines CXCL10, CCL2, IL1Rα, and IFNγ. Following ex vivo whole blood stimulation with Escherichia coli , lower IL1α and TNFα levels were measured in multiparous than in primiparous cows. Intracellular ROS production by neutrophils was lower in multiparous than in primiparous cows. These results thus indicated marked physiological changes in wk 8 compared with wk 2 and 4 of lactation. These differences in the physiological status of primiparous and multiparous cows offer interesting perspectives for potential dietary strategies to prevent pathologies which take account of parity and week relative to calving. [ABSTRACT FROM AUTHOR]