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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.

Supplementing with antioxidants may be one of the most efficient means of minimizing oxidative stress during workouts in obese individuals. The aim of this study is to identify the results after twelve weeks of CrossFit workouts combined with Spinach thylakoid extract on the levels of insulin resistance (insulin and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]), fasting blood sugar (FBS), malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), and superoxide dismutase (SOD), glutathione peroxidase (GPx) in obese males. Sixty-eight males with an average age of 27 ± 8 yrs and a BMI of 32.6 ± 2.6 kg.m− 2 were randomly split into four groups each consisting of seventeen individuals. : control group (CG), supplement group (SG), training group (TG), and training + supplement group (TSG). After initial assessments, the two training groups (TG and TSG) started on a 12 weeks of the CrossFit workouts program involving three sessions per week each lasting up to 60 min. Participants in supplement groups ingested 30 min before lunch, 5 gof Spinach thylakoid extract per day or one sachet of raw corn starch in the control group. Baseline and post-intervention measurements were performed 48 h pre- and post-last session, respectively. The findings revealed noteworthy relationships between the exercise groups and timefor TAC, SOD, GPx, MDA, CK, and LDH (p < 0.001, ES: 0.88, 0.88, 0.8, 0.4, 0.7, and 0.7, respectively). In addition, there were statistically significant differences among study groups after attending the intervention program in TAC (ES: 0.88), SOD (ES: 0.92), GPX (ES: 0.85), MDA (ES: 0.5), CK (ES: 0.7) and LDH (ES: 0.8). The effect sizes of insulin (0.77), glucose (0.21), and HOMA-IR (0.44) varied significantly (p < 0.05) among the groups. The results demonstrated that CrossFit workouts for 12 weeks combined with Spinach thylakoid extract in men with obesity may prevent oxidative damage caused by obesity and CrossFit workouts. [ABSTRACT FROM AUTHOR]

AbstractMultiple myeloma (MM), a malignant plasma cell disorder, remains incurable due to inevitable chemo-resistance development, including carfilzomib (CFZ) leading to relapse and poor patient outcomes. Therefore, new treatment strategies, including using FDA-approved alcohol deterrent disulfiram (DSF) are under investigation. The present study investigated the effect of DSF on ferroptosis and CFZ resistance in MM cells. Our findings indicate that DSF increases the production of cytosolic and mitochondrial reactive oxygen species, and causes a loss of mitochondrial Δψ and an elevation in lipid peroxidation in MM cells. DSF treatment in MM cell lines led to the significant downregulation of ferroptotic genes, including glutathione peroxidase 4. Moreover, ferroptosis inhibitor liproxstatin-1rescued DSF-induced ferroptosis by promoting glutathione peroxidase 4 upregulation. DSF alone overcomes CFZ resistance through lipid peroxidation elevation and acts synergistically with CFZ in CFZ-resistant MM cell lines. Our results suggest that DSF is a promising anti-myeloma agent for overcoming CFZ resistance in MM through ferroptosisinduction. [ABSTRACT FROM AUTHOR]

The research investigated the nutritional physiology effect of ginseng saponins on Litopenaeus vannamei (L. vannamei) under low-fishmeal diets. In total, five experimental groups were arranged, with 21% fishmeal (high-fishmeal) serving as the positive control (PC), 11% fishmeal (low-fishmeal) serving as the negative control (NC), and 11% fishmeal serving as the addition in all three other groups. Similarly, ginseng saponins (GSP, purity of 2%) were added in the order of 0.1%, 0.3%, and 0.5% (GSP0.1, GSP0.3, and GSP0.5), with an 8-week growth cycle. Both GSP0.1 and GSP0.3 showed significantly higher growth performance (final body weight, FBW; weight gain rate, WGR; specific growth rate, SGR) than the NC group, but significantly lower growth performance than the PC group (P <0.05). However, it was found that there was no significant difference in the body composition of the whole shrimp between the experimental groups. Compared to the PC group, the GSP0.3 group exhibited significantly elevated levels of antioxidant enzymes, total antioxidant capacities (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) (P <0.05). Additionally, significant differences were observed between the PC and GSP0.3 groups regarding the expression levels of sod , cat , and gsh-px (P<0.05). And there was a better morphological organization of shrimp hepatopancreas in the GSP0.3 group than in all other groups. In comparison with the PC group, there was no significant difference in shrimp survival rates after ammonia nitrogen stress with ginseng saponins added (P >0.05). Whereas, in terms of the relative expression levels of the corresponding genes, in shrimp of the GSP0.3 group, the relative expression of antioxidant-related genes sod , cat , and gsh-px were significantly higher than that of the PC group (P <0.05). Caspase3 and p53 , along with bcl-2 and bax , were found to be significantly more expressed in shrimp of the GSP0.3 group than in all other groups (P <0.05). These findings imply that in addition to improving growth performance, adding ginseng saponins at a concentration of 11% fishmeal could improve the antioxidant capacity of L. vannamei as well as its resistance to stress. Therefore, ginseng saponins can be utilized as a functional additive to increase L. vannamei growth performance, enhance antioxidant capacity, and reduce stress in low-fishmeal diets, 0.3% of ginseng saponins is optimal. [ABSTRACT FROM AUTHOR]

ABSTRACT Bivalve mollusks frequently experience salinity fluctuations that may drive oxidative stress (OS) in the organism. Here we investigated OS markers and histopathological changes in gills and hemolymph of Mediterranean mussels Mytilus galloprovincialis Lamarck, 1819 exposed to a wide range of salinities (6, 10, 14, 24, and 30 ppt). Mussels were captured at the shellfish farm with the salinity 18 ppt and then exposed to hypo‐ and hypersaline conditions in the laboratory. Indicators of redox balance in hemocytes (intracellular reactive oxygen species (ROS) levels, DNA damage) and gills (thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The effect of salinity stress on microstructure of gills has been evaluated as well. The results revealed induction of OS in tissues and cells of mussels for both experimental increase and decrease salinity modelings. Hemocytes showed higher sensitivity to osmotic stress compared to gills. In gills TBARS were stable in all experimental groups and PC increased only at salinity 6 ppt. The activity of SOD, CAT and GPx in gills decreased only in mussels acclimated to salinity 24 ppt and further salinisation up to 30 ppt was associated with the recovery of the activity of all enzymes. Major histopathological changes in gills upon salinity fluctuations included inflammatory reactions, circulatory alterations, regressive and progressive changes. Our findings clearly indicate that salinity fluctuations promote OS at cellular and tissue level and also affect microstructure of gills in mussels. The results provide new insights into the mechanisms of osmotic stress in bivalves. [ABSTRACT FROM AUTHOR]

Background: Indian meal moth (Plodia interpunctella) is a significant pest infesting stored grains, particularly maize. Over time, synthetic insecticides have been employed to control insect. The residual effects posed on non-target organisms have called for replacement of synthetic insecticides with botanicals. This study therefore aimed at comparing the insecticidal consistency and oxidative stress invoked by dichlorvos (DDVP) and the oil extract of ginger (Zingiber officinale) on Indian meal moth infesting maize. Disinfested maize grains were treated with DDVP and ginger oil extract separately. Adults P. interpunctella were introduced to the treated grains daily using complete replacement method. The percentage mortality was calculated daily for 10 d. Furthermore, the oxidative stress caused by DDVP and ginger oil extract on the moth was evaluated by measuring the level of some oxidative stress biomarkers such as glutathione S-transferase, superoxide dismutase, glutathione peroxidase (GPx), and catalase (CAT) activity in the exposed insects. Results: Preliminary results indicated that both DDVP and ginger oil extract exhibited insecticidal properties against Indian meal moth infesting maize. However, the insecticidal (active) period of ginger oil extract was found to be longer than that of DDVP. Nevertheless, DDVP provoked greater oxidative stress in the exposed moth. Conclusions: Ginger oil extract and DDVP show potential for controlling Indian meal moth infestations in stored maize. Yet, ginger oil offers a longer-lasting effect on pest suppression and control. Consequently, it could be a replacement or synergistic insecticide with DDVP to provide ecofriendly insecticide application. [ABSTRACT FROM AUTHOR]

Background: Triptolide (TP), a principal active substance from Tripterygium wilfordii, exhibits various pharmacological effects. However, its potential hepatotoxicity has always been a significant concern in clinical applications. Purpose: This research aimed to explore the involvement of ferroptosis in TP-mediated hepatic injury and the underlying mechanisms. Methods: In this study, in vitro and in vivo experiments were involved. Hepatocyte damage caused by TP was evaluated using MTT assays, liver enzyme measurement and H&E staining technique. Ferroptosis was assessed by measuring iron level, lipid peroxide, glutathione (GSH), mitochondrial morphology and the key protein/mRNA expression implicated in ferroptosis. To verify the contribution of ferroptosis to TP-induced liver damage, the ferroptosis inhibitor Ferrostatin-1 (Fer-1) and a plasmid for overexpressing glutathione peroxidase 4 (GPX4) were employed. Subsequently, nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice and Nrf2 overexpression plasmid were utilized to investigate the underlying mechanisms. Nontargeted lipidomics was used to analyze lipid metabolism in mouse liver. Moreover, the cellular thermal shift assay (CETSA), cycloheximide (CHX) and MG132 treatments, and immunoprecipitation (IP) assays were applied to validate the binding of TP to Nrf2 and their interactions. Results: TP triggered ferroptosis in hepatocytes, as indicated by iron accumulation and lipid peroxidation. Ferroptosis was responsible for TP-induced hepatic injury. During the process of TP-induced liver damage, the Nrf2 signaling pathway was significantly suppressed. Notably, the deletion of Nrf2 in mice aggravated the extent of liver injury and ferroptosis associated with TP, whereas enhancing Nrf2 expression in cells significantly reduced TP-induced ferroptosis. Additionally, dysregulation of lipid metabolism was associated with TP-induced liver injury. TP may directly bind to Nrf2 and enhance its degradation through the ubiquitin–proteasome pathway, thereby inhibiting or reducing Nrf2 expression. Conclusion: In summary, the suppression of Nrf2 by TP facilitated the occurrence of ferroptosis, resulting in liver damage. [ABSTRACT FROM AUTHOR]

Introduction: In Japan, the importance of medical checkups for pet dogs is increasing. In this study, we retrospectively explored the effects of age on plasma biomarkers in healthy small dogs that underwent medical checkups. Methods: Based on the modified American Animal Hospital Association Canine Life Stage Guidelines, 52 healthy small dogs were divided into 3 groups according to their life stage: young adult (1–4 years old), mature adult (5–11 years old), senior (12–15 years old). None of the dogs were obese. Plasma was collected from animals that underwent medical checkups at Muromi Animal Hospital (Fukuoka, Japan). Plasma glucose, triglyceride (TG), total protein, blood urea nitrogen (BUN), creatinine, total cholesterol, and albumin concentrations; alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase (ALP) activities; c-reactive protein (CRP), non-esterified fatty acid, malondialdehyde (MDA), serum amyloid A (SAA), insulin, and adiponectin (ADN) concentrations; glutathione peroxidase (GPx), superoxide dismutase (SOD), malate dehydrogenase (MDH), and lactate dehydrogenase (LDH) activities; and M/L ratio (MDH/LDH) were examined. Changes in the abovementioned plasma biomarker levels were compared between canines in different life stages. Results: Plasma ADN concentrations and GPx, SOD, and MDH activities significantly decreased with age, whereas plasma ALP, BUN, TG, and MDA concentrations gradually increased. Plasma SAA levels measured by the latex agglutination method in 51 of the 52 small dogs that underwent medical checkups were below the detection limit. Conclusion: Plasma ADN concentrations, GPx, SOD activity, and BUN levels may be important biomarkers for clarifying the effect of age in healthy dogs that undergo medical checkups. However, plasma SAA values obtained by the latex agglutination method were not considered an age-related inflammation marker for healthy dogs. [ABSTRACT FROM AUTHOR]

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro , accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Ferroptosis plays a crucial role in the progression of postmenopausal osteoporosis. Anemarrhena asphodeloides Bunge/ Phellodendron chinense C.K. Schneid (AA/PC) is the core herb pair in traditional Chinese medicines formulae for postmenopausal osteoporosis treatment. However, the synergistic effects, and mechanisms, of AA/PC on alleviating ferroptosis and postmenopausal osteoporosis remain unclear. Methods: The goal herein was to analyze the effective ingredients and molecular mechanisms of AA/PC in the treatment of osteoporosis through serum pharmacochemistry, network pharmacology, metabolomics analysis, and pharmacodynamics evaluation. A bilateral ovariectomized (OVX) mouse model was established. Results and Discussion: Micron-scale computed tomography analysis showed that AA/PC increased bone mineral density in OVX mice. The effects of AA/PC were better than AA or PC alone on inhibiting the bone resorption marker nuclear factor of activated T-cells 1. Furthermore, five absorbable compounds were detected in serum: mangiferin, magnoflorine, berberine, timosaponin BIII, and timosaponin AIII. Network pharmacology showed these compounds had close relationship with seven ferroptosis targets. Importantly, compared with AA or PC alone, the AA/PC herb pair exerted better effects on regulating crucial ferroptosis pathways, including the system xc-/glutathione/glutathione peroxidase 4, transferrin receptor/ferritin, and acyl-CoA synthetase long chain family member 4/polyunsaturated fatty acids signaling pathways. These results indicate that AA/PC exerts synergistic effects on regulating glutathione synthesis, iron homeostasis, and lipid metabolism in ferroptosis. This work lays the foundation for further development and use of AA/PC herb pair for preventing and treating postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood. Purpose: This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue. Materials and methods: UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin–eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking. Results: The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways. Conclusions: RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment. [ABSTRACT FROM AUTHOR]

A 30‐day research was carried out to examine the impacts of dietary taurine (Tau) on ovaries maturation and physiological responses of Penaeus vannamei female brooders (29.4 ± 0.2 g). A basal diet (497 g kg−1 protein and 140 g kg−1 lipid) was administered with graded levels of Tau ranging from 0 (control) to 2, 4, 6, 8, and 10 g kg−1. A total of 180 shrimp brooders were stocked into 18 250 L black circular polyethylene tanks. Female (n = 5) and male (n = 5) shrimps were stocked in each tank and supplied with seawater (35.2 ± 3.1 g L−1 salinity, 28.9 ± 1.4°C) and the experimental feeds were offered to shrimp twice a day at 5% of their biomass. Supplementing diet with 4–8 g Tau kg−1 reduced latency period after eye stalk ablation to spawning (5–6 days) that was associated with higher hepatopancreatic and gonadosomatic (except for 8 g Tau kg−1 diet) indices (p < 0.05). With 10 g Tau kg−1 diet hepatopancreas glutathione peroxidase activity and total antioxidant capacity increased and catalase activity increased by 6 g Tau kg−1 diet. Supplementing diet with Tau‐enhanced bile‐salt dependent lipase activity in the gut. Docosahexaenoic acid and Tau levels were elevated in the ovaries with the increment of dietary Tau level (p < 0.05). Plasma total protein, calcium, cholesterol, and high‐density lipoprotein increased with inclusion of 6–10 g Tau kg−1 diet. The transcription levels of vitellogenin, insulin-like growth factor II, superoxide dismutase, prophenoloxidase, and lysozyme genes transcription levels were upregulated in the hepatopancreas of shrimp brooders fed 6–10 g Tau kg−1 diet (p < 0.05). It seems that Tau at 4–8 g kg−1 diet by modulating lipid metabolism, antioxidant capacity, and immunocompetence can improve maturation and health status of P. vannamei brooders. [ABSTRACT FROM AUTHOR]

To assay new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we carried out a descriptive cross-sectional study. We recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C); among them, 22 presented MVC. Peripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO), nitrite levels in plasma (NOx). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to the CG. The DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased expression of miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive values for vascular complications presence: (1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484 (Exp(B) = 0.926, chi2 = 34.093, p < 0.001; AUC = 0.913). (2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484 (Exp(B) = 0.958, Chi2 = 33.863, p < 0.001; AUC = 0.938). Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values (Exp(B) = 0.528, p = 0.024, Chi2 = 28.214, AUC = 0.904) than classical variables (Exp(B) 0.462, p = 0.007, Chi2 = 18.814, AUC = 0.850). miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies. [ABSTRACT FROM AUTHOR]

Environmental concerns have consistently been a focal point for the scientific community. Pollution is a critical ecological issue that poses significant threats to human health and agricultural production. Contamination with heavy metals and pesticides is a considerable concern, a threat to the environment, and warrants special attention. In this study, we investigated the significant issues arising from sub-chronic exposure to imidacloprid (IMI), mercury (Hg), and cadmium (Cd), either alone or in combination, using zebrafish (Danio rerio) as an animal model. Additionally, we assessed the potential protective effects of polyfloral honey enriched with natural ingredients, also called honey formulation (HF), against the combined sub-chronic toxic effects of the three contaminants. The effects of IMI (0.5 mg·L−1), Hg (15 μg·L−1), and Cd (5 μg·L−1), both individually and in combination with HF (500 mg·L−1), on zebrafish were evaluated by quantifying acetylcholinesterase (AChE) activity, lipid peroxidation (MDA), various antioxidant enzyme activities like superoxide dismutase and glutathione peroxidase (SOD and GPx), 2D locomotor activity, social behavior, histological and immunohistochemical factors, and changes in body element concentrations. Our findings revealed that all concentrations of pollutants may disrupt social behavior, diminish swimming performances (measured by total distance traveled, inactivity, and swimming speed), and elevate oxidative stress (OS) biomarkers of SOD, GPx, and MDA in zebrafish over the 21-day administration period. Fish exposed to IMI and Hg + Cd + IMI displayed severe lesions and increased GFAP (Glial fibrillary acidic protein) and S100B (S100 calcium-binding protein B) protein expression in the optic tectum and cerebellum, conclusively indicating astrocyte activation and neurotoxic effects. Furthermore, PCNA (Proliferating cell nuclear antigen) staining revealed reduced cell proliferation in the IMI-exposed group, contrasting with intensified proliferation in the Hg + Cd group. The nervous system exhibited significant damage across all studied concentrations, confirming the observed behavioral changes. Moreover, HF supplementation significantly mitigated the toxicity induced by contaminants and reduced OS. Therefore, the exposure to chemical mixtures offers a more complete picture of adverse impacts on aquatic ecosystems and the supplementation with bioactive compounds can help to reduce the toxicity induced by exposure to environmental pollutants. [ABSTRACT FROM AUTHOR]

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis. MDH2 knock-down enhances RSL3-induced intracellular reactive oxygen species, free iron ions and lipid per-oxides levels, leading to HCC ferroptotic cell death which is rescued by ferrostatin-1 and iron chelator deferiprone. Importantly, the inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity dependent on glutathione peroxidase 4 (GPX4), an enzyme responsible for scavenging lipid peroxides, which is stabilized by MDH2 in HCC. The protein expressions of MDH2 and GPX4 are positively correlated with each other in HCC cell lines. Furthermore, through our UALCAN website analysis, we found that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combi-nation with ferroptosis inducers for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Mitochondrial damage and associated oxidative stress are considered to be major contributory factors in cardiac pathology. One of the most potent naturally occurring antioxidants is taxifolin, especially in its water-soluble form. Herein, the effect of a 14-day course of the peroral application of the water-soluble taxifolin (aqTAX, 15 mg/kg of body weight) on the progression of ultrastructural and functional disorders in mitochondria and the heart's electrical activity in a rat model of myocardial injury induced with isoprenaline (ISO, 150 mg/kg/day for two consecutive days, subcut) was studied. The delayed ISO-induced myocardial damage was accompanied by an increase in the duration of RR and QT intervals, and long-term application of aqTAX partially restored the disturbed intraventricular conduction. It was shown that the injections of ISO lead to profound ultrastructural alterations of myofibrils and mitochondria in cardiomyocytes in the left ventricle myocardium, including the impairment of the ordered arrangement of mitochondria between myofibrils as well as a decrease in the size and the number of these organelles per unit area. In addition, a reduction in the protein level of the subunits of the respiratory chain complexes I-V and the activity of the antioxidant enzymes catalase, glutathione peroxidase, and Mn-SOD in mitochondria was observed. The application of aqTAX caused an increase in the efficiency of oxidation phosphorylation and a partial restoration of the morphometric parameters of mitochondria in the heart tissue of animals with the experimental pathology. These beneficial effects of aqTAX are associated with the inhibition of lipid peroxidation and the normalization of the enzymatic activities of glutathione peroxidase and Mn-SOD in rat cardiac mitochondria, which may reduce the oxidative damage to the organelles. Taken together, these data allow one to consider this compound as a promising cardioprotector in the complex therapy of heart failure. [ABSTRACT FROM AUTHOR]

Excess oxidative stress and inadequate antioxidant capacities are critical features in the development of hepatocellular carcinoma. This study aimed to determine whether supplementation with glutathione (GSH) and/or selenium (Se), as antioxidants, attenuates diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. C57BL/6J male mice were randomly assigned to control, DEN, DEN + GSH, DEN + Se, and DEN + GSH + Se groups for 20 weeks. Daily supplementation with GSH and/or Se commenced in the first experimental week and continued throughout the study. DEN was administered in weeks 2–9 and 16–19 of the experimental period. DEN administration induced significant pathological alterations of hepatic foci, evidenced by elevated levels of liver function, accompanied by high malondialdehyde (MDA) levels; low GSH levels; and glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Supplementation with GSH and Se significantly ameliorated liver pathological changes, reducing liver function and MDA levels while increasing GSH levels and GPx, GR, and GST activities. Notably, combined supplementation with GSH and Se more effectively increased the GSH/glutathione disulfide ratio and GPx activity than individual supplementation. Supplementation with GSH and Se attenuated liver injury in DEN-induced hepatocarcinogenic mice by enhancing GSH and its related antioxidant capacities, thereby mitigating oxidative damage. [ABSTRACT FROM AUTHOR]

The objectives of this study were to identify factors associated with the relative change in prepartum DMI (RCDMI) of 273 cows fed individually, evaluate the performance of linear models to estimate RCDMI using different classes of predictors, and characterize the implications of RCDMI to transition metabolism, health, and subsequent milk production. Two periods of interest were established. Period 1 comprised d −21 to −12 relative to calving, when DMI was stable. Period 2 comprised d −4 to −1, when average DMI was distinctly declined. The RCDMI from period 1 to 2 was calculated as a percentage value, which ranged from −75% to 15% and averaged −18.1% (± 15.0%). Season, parity, body fatness, body weight, milk production in the previous lactation and at dry-off, and length of dry period were associated with RCDMI and explained 11% of the variation in all cows, and 19% when only parous cows were considered. Performance of linear models to predict RCDMI was improved when data on rumination and physical activities and target blood metabolites were added. The adjusted R2 increased to values between 0.45 and 0.55, and selected models performed consistently in cross-validation analyses. To evaluate the implications of RCDMI, cows were ranked within parity according to RCDMI and classified into terciles as large decline (LDec), moderate decline (MDec), or small decline (SDec). By design, DMI did not differ between tercile groups in period 1 (13.3 ± 0.2 kg/d), but differed substantially in period 2 (LDec = 8.8; MDec = 11.2; SDec = 12.7 ± 0.2 kg/d), creating important differences in RCDMI among groups (LDec = −33.8; MDec = −16.2; SDec = −3.4% ± 0.8%). At enrollment, cows in the LDec and MDec groups were heavier (LDec = 788; MDec = 775; SDec = 750 ± 7 kg), and the proportion of cows with BCS >3.5 was higher in LDec (LDec = 63%; MDec = 47%; SDec = 38%). An interaction between group and time was observed for postpartum DMI, which started lower in LDec than in SDec cows, equaled by the end of transition, and inverted at wk 13 and 14 after calving. Yields of ECM were greater in LDec than in SDec cows, and both groups did not differ from MDec (LDec = 41.0; MDec = 40.3; SDec = 39.0 ± 0.5 kg/d). The LDec cows had decreased energy balance and greater concentrations of nonesterified fatty acids, β-hydroxybutyrate, and aspartate aminotransferase in serum, and greater glutathione peroxidase activity in plasma than SDec cows. Larger declines in prepartum DMI were also associated with increased risk for postpartum disease, although the associations were only weak to moderate. In conclusion, a large decline in prepartum DMI of cows fed ad libitum was associated with important adjustments in the energy metabolism and antioxidants activities, and greater milk production in the subsequent lactation. These findings indicate that feed intake decline close to parturition is likely a normal response to physiological adaptations at the onset of lactation when cows are fed ad libitum. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is an obligate human neurotoxicant ubiquitously produced and found in foods processed at high temperature. There is an increasing public health concern regarding its probable carcinogenic potential. Its prevailing toxicity mechanism is oxidative inflammation and apoptosis. Herein, we explored whether thymoquinone (TQ), a bioactive quinone in Nigella sativa seed, could mitigate ACR-induced cerebellar toxicity in rats. Our study design featured four rat groups: control, TQ (5 mg/kg bw), ACR (50 mg/kg bw), and TQ + ACR (5 mg/kg + 50 mg/kg). After 14 days of respective treatments, cerebellar homogenate was used to estimate acetylcholinesterase activity (AchE) activity, antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), malondialdehyde (MDA), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-4, and IL-10), nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), caspase-3, and caspase-9. The level of DNA damage by fragmentation and histopathological lesions was also determined in the cerebellum. The rat exposure to ACR caused significant decreases in the cerebellar activities of AchE, CAT, SOD, and GPx, IL-4, IL-10, and expression of Nrf2, whereas the levels of MDA, IL-6, TNF-α, caspase-3, and caspase-9 were prominently increased compared with the control. ACR induced significant DNA fragments and cerebellar lesions when compared with the control. Contrarily, TQ treatment inhibited the depression of CAT, SOD, and GPx activities and reversed the MDA level and expression of Nrf2/NF-κB, cytokines, and caspases. These effects were confirmed by reduced DNA damage and cerebellar histopathological lesions in comparison with the ACR. TQ afforded neuroprotection via its antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats. [ABSTRACT FROM AUTHOR]

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]

MicroRNAs have been shown to play a critical role in lung inflammatory diseases. Here, we report that knocking out miR‐144/451 in mice exacerbates lipopolysaccharide (LPS)‐induced lung inflammation. The lung inflammation in mice was induced by intratracheal instillation of LPS. Loss‐of‐function experiments demonstrated that miR‐144/451 gene knockout (KO) increased LPS‐induced lung inflammation and oxidant stress compared with wild‐type (WT) mice, as manifested by increased total bronchoalveolar lavage fluid cells and neutrophil counts, elevated TNF‐α and IL‐6 levels in bronchoalveolar lavage fluid, enhanced myeloperoxidase activity, and reduced catalase and glutathione peroxidase activity in lung tissues. We also found that LPS significantly decreased miR‐451 expression in lung tissues and macrophages; while miR‐451 overexpression in LPS‐induced RAW264.7 cells remarkably reduced TNF‐α and IL‐6 levels as well as reactive oxygen species (ROS) production, suggesting a feedback loop might exist in inflammatory cells. Rac1 mRNA and protein levels were downregulated in miR‐451‐overexpressed RAW264.7 cells. Ex vivo stimulation experiments, performed using alveolar macrophages isolated from miR‐144/451 KO mice, confirmed that Rac1 inhibitor alleviated levels of TNF‐α and ROS in response to LPS stimulation compared with WT controls. Luciferase reporter assay demonstrated that STAT‐3 is a direct target of miR‐451. STAT‐3 protein levels were elevated in miR‐144/451 KO macrophages. LPS treatment also resulted in higher phosphorylation levels of STAT‐3 in macrophages from KO mice than in WT cells. Our study identified miR‐144/451 as an anti‐inflammatory factor in LPS‐induced lung inflammation that acts by downregulating Rac1 and STAT‐3. [ABSTRACT FROM AUTHOR]

Fagopyrum dibotrys is a herbal plant. Selenium (Se) is a beneficial element for plants; selenium nanoparticles (SeNPs) are gaining importance in food and agriculture due to their low toxicity and high activity. This study revealed that foliar application of SeNPs enhanced superoxide dismutase, glutathione peroxidase, and peroxisome activities and significantly enhanced the flavonoid compound content in F. dibotrys. SeNPs with a concentration of 5.0 mg L−1 also promoted the growth of F. dibotrys. The foliar application of SeNPs could be absorbed by pores in leaves of F. dibotrys and mainly transformed to selenomethionine (32.5–43.2%) and selenocysteine (23.4–38.4%) in leaves and tubers of F. dibotrys. Consequently, this study offers a profound understanding of plants' uptake and biotransformation of SeNPs. Furthermore, the findings of this study have suggested that SeNPs can be applied to improve the quantity and quality of the herbal plant of F. dibotrys. [ABSTRACT FROM AUTHOR]

Drought is one of the most important abiotic factors limiting plant productivity. Although the aromatic plants of the Lamiaceae family often grow in arid regions, drought tolerance varies greatly among the different species of this family. The effect of induced drought stress can be reduced by the application of selenium. The current study aims to compare the growth and biochemical responses of three species of the Lamiaceae family (hyssop, salvia, and oregano) to drought stress and the possibility of reducing the effect of stress in these plants by foliar treatment with selenium. Drought stress reduced the fresh and dry biomass of hyssop (by 35% and 15%), salvia (by 45% and 41%), and oregano (by 51% and 32%). Se treatment did not affect the growth of plants under drought stress, but it improved relative water content in hyssop and salvia under moderate drought conditions. A reduction in the content of chlorophyll a and chlorophyll b (in hyssop and salvia). In addition, an increase in the content of hydrogen peroxide (in oregano and salvia), malondialdehyde, and proline in plants cultivated under drought conditions was observed. Se treatment led to reduced levels of hydrogen peroxide and malondialdehyde, along with an increase in chlorophyll a content (in hyssop and oregano) and proline content. The response of the antioxidant system depended on the plant species. Hyssop exhibited a significant increase in glutathione peroxidase, superoxide dismutase, and peroxidase activities. Oregano showed enhanced catalase activity. Salvia experienced a sharp increase in ascorbic acid content. Se treatment stimulated the accumulation of phenolic compounds and increased glutathione peroxidase activity in all studied species. [ABSTRACT FROM AUTHOR]

Pericarp browning and fruit decay severely reduce the postharvest quality of litchi. Improving the antioxidant capacity of the fruit is an effective way to solve these problems. In our study, the appropriate zinc oxide nanoparticles (ZnO NPs) treatment and its mechanism of action on the storability of litchi was investigated. Litchi fruit was soaked in a 100 mg·L−1 ZnO NPs suspension, water, and 500 mg·L−1 prochloraz for 2 min, respectively. The results showed that the ZnO NPs treatment delayed pericarp browning and decay in litchi fruit and was more effective than prochloraz treatment. The ZnO NPs-treated fruit showed significantly increased contents of total anthocyanin, total phenols, and activities of DPPH scavenging, superoxide dismutase, and glutathione peroxidase, as well as the lowest activities of polyphenol oxidase and laccase. ZnO NPs generated hydrogen peroxide and superoxide anion radicals, which were beneficial in slowing down the decay and inducing antioxidant capacity. However, these reactive oxygen species also consumed catalase, peroxidase, glutathione, and glutathione peroxidase. This means that litchi should be treated with an appropriate concentration of ZnO NPs. We concluded that treatment with a 100 mg·L−1 ZnO NPs suspension could induce antioxidant capacity, which is a promising and effective method to maintain the postharvest quality of litchi. [ABSTRACT FROM AUTHOR]

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Gemcitabine (GEM) is a first-line treatment for pancreatic ductal adenocarcinoma (PDAC) patients, causing side effects and poor overall survival. Eighty percent of patients often develop resistance rapidly to GEM. Developing therapeutic approaches and increasing sensitivity to gemcitabine in PDAC has become one of the challenges in cancer research. We synthesized GEM-loaded NPs prepared with a method that combines ultrasonication and ionotropic gelation to overcome GEM-related limitations in PDAC. CFPAC-1 cells were treated with increased concentrations of GEM, empty chitosan, and GEM-loaded NPs (0.66, 1.32, 2.64, 5.32 µg/ml) for up to 48 h. Empty chitosan NPs did not show toxicity on L929 cells. Antioxidant enzyme activities, including glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), and glutathione peroxidase (GPx), significantly reduced in GEM-loaded NPs compared to the GEM associated with increased oxidative stress, PPP, and glycolysis. Bcl-xL, NOXA/mcl-1, and Ca2+ levels significantly increased in GEM-loaded NP-administered cells compared to the GEM and control groups. In contrast, JNK, p38, STAT3, Akt, and CREB levels significantly decreased in the GEM-loaded NP group, addressing enhanced apoptotic response compared to the GEM alone. Increased ferroptosis activity in GEM-loaded NP-administered groups has been validated via decreased antioxidant enzyme activities, increased cytosolic Fe, Zn, Mg, and Mn levels, and reduced GPx activity compared to the GEM and control groups. For the first time in the literature, we showed biocompatible GEM-loaded NPs enhanced apoptotic and ferroptotic response in CFPAC-1 cells via downregulation of antioxidant, glycolysis, and PPP metabolism compared to the GEM alone. [ABSTRACT FROM AUTHOR]

Fruits and vegetables are laden with antioxidants and have been used to quench reactive oxygen species. The combination of two or more fruits and vegetables to produce smoothies is expected to yield a synergistic effect that could further improve functionality. This study investigated the antioxidative and blood glucose-lowering potentials of smoothies made from selected fruits and vegetables as well as their effect on the expression of pro-inflammatory genes in streptozotocin-induced diabetic Wistar rats. Standard procedures were used for the in vitro antioxidant determination while pancreas tissue was excised for molecular study. The inclusion of beetroot increased the total phenolic contents by 30-50% while the flavonoid content was increased by more than 3-fold. Similarly, smoothies with beetroot and bitter gourd exhibited stronger free radical scavenging abilities as shown by DPPH (1, 1- diphenyl-2-picrylhydrazyl), ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), Nitric oxide (NO) scavenging ability, metal chelation (Fe2+) and ferric reducing antioxidant properties (FRAP) compared to the sample devoid of the duo. The blood glucose levels of the rats fed the smoothie were significantly lowered with a similar trend in the animals that were administered metformin. The smoothies significantly (p<0.05) reduced the malondialdehyde (MDA) content thus reducing lipid peroxidation in the animals. The endogenous antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the pancreas were all significantly (p<0.05) increased when the animals were fed smoothies. The expression of pro-inflammatory genes, IL-1β, IL-6 and TNF-α, was down-regulated in the animals fed with smoothies. The findings showed that the smoothies made from the combination have the potential for managing type-2 diabetes mellitus. [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 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]

Nonmetal‐containing peroxidase enzymes, including glutathione peroxidase (GPx), and peroxiredoxins, control cellular redox levels by catalyzing the reduction of H2O2. The remarkably higher reactivity of GPx enzyme as compared to the fully dissociated synthetic selenolate/thiolate molecule is probably due to the dual‐attack on the peroxide bond (HO1−O2H) by the enzyme; The first one is a nucleophilic attack of the selenolate/thiolate moiety to O1 atom and the second attack at the O2 atom of the peroxide bond by the acidic “parked proton” from Trp or His residue present at the enzyme's active site, leading to the facile cleavage of O−O bond. Herein, we report two synthetic compounds (1 and 2), having a selenolate (Se−) and a proton donor (imidazolium or −COOH group) moieties, which showed excellent GPx‐like activity via dual‐attack on the peroxide bond. The combined effect of selenolate moiety that donates electrons to the antibonding (σ*) orbital of O1−O2 bond and the imidazolium or carboxylic acid moiety at the side chain that forms a strong H‐bonding with the O2 atom facilitates O−O bond cleavage of H2O2 more efficiently. 1 and 2 exhibit remarkable ability in protecting Cu(I)‐complex [TpmCu(CH3CN)]+ (9) against H2O2 by acting as a sacrificial antioxidant, thereby preventing metal‐mediated ROS production. [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]