Superoxide Dismutase Research Articles

Abstract 4136786: Prediabetes increases platelet activation and thrombotic susceptibility via mitochondrial oxidants

Recent studies suggest that prediabetes is not only a prelude to diabetes, but also is an independent risk factor for cardiovascular thrombotic events in young and aged people. However, the mechanisms that may promote platelet activation and thrombosis during prediabetes have not been studied. We hypothesized that in prediabetes, dysregulation of electron transfer and accumulation of mitochondrial oxidants promotes platelet activation and thrombosis, and that aging exacerbates the phenotype. We recruited young (18-50 year) and middle-aged (51-64 year) Veterans with prediabetes and age- and BMI- matched healthy Veterans. Compared to healthy cohort, platelets from prediabetes exhibited enhanced agonist induced platelet activation, mitochondrial oxidants, membrane potential and thrombus formation ex vivo in both young and middle-aged cohorts to a similar extent. Preincubation of platelets with either a mitochondria targetable superoxide dismutase (SOD) mimetic or MitoQ (transfers electrons from Complex I/II to complex III to lower superoxide generation within mitochondria), rescued the prothrombotic phenotype. We confirmed these platelet phenotypes in C57BL6/J mice fed high fat (HF) diet for 2 weeks (model of early diabetes). Importantly, HF-fed mice showed increased susceptibility to carotid artery and pulmonary thrombosis in vivo . Pharmacological treatment of HF-fed mice with SOD-mimetic or MitoQ, or genetic overexpression of catalase within mitochondria, rescued the prothrombotic state. This is the first report showing platelet hyperactivity and enhanced thrombotic susceptibility in prediabetes. Further, our findings suggest that enhanced mitochondrial oxidants due to the premature electron escape contribute to the phenotype. Our data imply a therapeutic potential of SOD-mimetic and MitoQ in lowering thrombotic burden in prediabetes.

Characterization and Bioactive Metabolite Profiling of Streptomyces sp. Y009: A Mangrove-Derived Actinomycetia with Anticancer and Antioxidant Potential

Microorganisms from poorly explored environments are promising sources for the development of novel drugs. In our continuous efforts to screen for mangrove actinomycetes that produce metabolites with potential pharmaceutical applications, Streptomyces sp. Y009 was isolated from mangrove sediments in Guangxi, China. The phenotypic, physiological, biochemical, and phylogenetic characteristics of this strain were investigated. Analysis of phylogenetic and 16S rRNA gene sequences showed that it had the highest sequence similarity to Streptomyces thermolilacinus NBRC 14274 (98.95%). Further, the Y009 extract exhibited antioxidant activity, as indicated by DPPH and superoxide dismutase assays. The extract showed broad-spectrum and potent anticancer potential against six human cancer cell lines, with IC50 values ranging from 5.61 to 72.15 μg/mL. Furthermore, the selectivity index (SI) demonstrated that the Y009 extract exhibited less toxicity toward normal cell lines in comparison to the lung cancer cell line (A549) and hepatoma cell line (HepG2). GC–MS analysis revealed that the extract contained some biologically important secondary metabolites, mainly cyclic dipeptides and esters, which might be responsible for the antioxidant and anticancer properties. 3-Isobutylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione (28.32%) was the major chemical compound available in the extract. The effect on cancer cells was then confirmed using nuclear staining and in silico docking. This study suggests that further exploration of the bioactive compounds of the newly isolated strain may be a promising approach for the development of novel chemopreventive drugs.

Ginsenoside-Enriched Extract from Black Ginseng Anti-Fatigue Effects by Improving Antioxidant Capacity and Mitochondrial Function

In this study, we investigated the anti-fatigue effects of black ginseng ginsenosides using exercise performance tests, serum analyses, and gene expression profiling. No significant differences in dietary intake or body weight were observed between groups. The low-dose black ginseng (LBG) group showed no significant improvements in swimming and rotating rod tests. In contrast, the medium (MBG)- and high-dose (HBG) groups showed notable increases in swimming time and significant improvements in the rotating rod test. All treatment groups exhibited longer running times, particularly the HBG group. Serum analysis revealed increased muscle and hepatic glycogen, catalase, and lactate dehydrogenase levels in the MBG and HBG groups, whereas lactate, lipid peroxide, and superoxide dismutase levels were decreased. Additionally, gene expression analysis showed significant upregulation of key antioxidant and mitochondrial function genes, including those encoding cationic amino acid transporter 2, stearoyl-CoA desaturase-2, nuclear respiratory factor 1, nuclear factor erythroid 2-related factor 2, mitochondrial transcription factor A, cytochrome c oxidase II, and NADH–ubiquinone oxidoreductase core subunit 1, particularly in the HBG group, indicating enhanced antioxidant capacity and improved mitochondrial function. These findings suggested that black ginseng ginsenosides effectively mitigated fatigue.

Increased Circulating Extracellular Superoxide Dismutase Attenuates Platelet-Neutrophil Interactions

Increased Circulating Extracellular Superoxide Dismutase Attenuates Platelet-Neutrophil Interactions

Impact of accelerated aging on seed quality, seed coat physical structure and antioxidant enzyme activity of Maize (Zea mays L.)

Aging induces many deteriorative changes to seeds during storage like protein degradation, enzyme inactivation and loss of membrane integrity. In this study, we investigate the impact of accelerated aging on seed quality, seed coat physical structure and antioxidant enzyme activity of maize. Three genotypes African Tall, MAH 14-5 and a local landrace were selected and artificially aged for 96 and 120 h. The aging process led to a decrease in germination, vigour, and total dehydrogenase in seeds, while the electrical conductivity of seed leachates increased, indicating a decline in seed quality. Additionally, there was a variation in the microsculpture pattern of seed coats between genotypes. There was an accumulation of damage on the seed coat surface as the seeds aged and higher damage occurred in African Tall followed by MAH 14-5 and local landrace. Higher catalase, superoxide dismutase, peroxidase and polyphenol oxidase activity were reported in the seed coat of Local landrace and MAH 14-5 that resisted aging and deterioration while, lower catalase, superoxide dismutase, peroxidase and polyphenol oxidase activity was reported in African Tall seed coat that deteriorated during aging. Decrease antioxidant activity in aged seeds might be a possible cause of seed deterioration due to the accumulation of free radicals. Thus, these results clearly show the influence of seed coat structure and antioxidant activity on seed quality during aging.

Evaluate the effect of exercise core strength training on antioxidant enzyme activity in women from a biomechanical perspective

At present, the incidence rate of chronic diseases is increasing year by year. A variety of antioxidant enzymes in the human body, such as Superoxide Dismutase (SOD), Nitric Oxide Synthase (NOS), Glutathione Peroxidase (GSH Px), Malonic Dialdehyde (MDA) and Catalase (CAT), help to inhibit the generation of oxygen free radicals and play a certain role in preventing the occurrence of chronic diseases. The research on the activity of antioxidant enzymes and the delivery of antioxidant drugs has gradually become the focus of relevant scholars. The physical quality of women is lower than that of men, so it is of great practical significance to study the antioxidant enzyme activity of women. Therefore, this paper explores the influence of exercise core strength training on women’s antioxidant enzyme activity from a biomechanical perspective and concludes that core strength training can improve female students’ SOD content level by 2.58%, and can improve female students’ NOS content level, GSH-Px content level, and MDA content level. Sports core strength training has a positive impact on women’s antioxidant enzyme activity.

Metabolic Response of Laboratory Rats to Extreme Hyperthermia

The dynamics of basic parameters of metabolism and lipid peroxidation in the blood serum of rats was studied during the formation of a state of hyperthermia (exposure to air at a temperature of +40 °C for 60 min). It was found that the albumin/globulin ratio, uric acid, cholesterol, triglycerides, blood electrolytes, as well as the activity of the enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, superoxide dismutase, glutathione peroxidase under short-term heat exposure did not have statistically significant differences from the values in the state of normothermia. The level of lipid hydroperoxides and reduced glutathione changes significantly already during the mobilization phase of thermoregulatory mechanisms. The dynamics of these indicators are stable, which allows these indicators to be correlated with hyperthermia itself.

Therapeutic potential of mackerel-derived peptides and the synthetic tetrapeptide TVGF for sleep disorders in a light-induced anxiety zebrafish model

IntroductionAnxiety-like insomnia is a known risk factor for the onset and worsening of certain neurological diseases, including Alzheimer’s disease. Due to the adverse effects of current anti-insomnia medications, such as drug dependence and limited safety, researchers are actively exploring natural bioactive compounds to mitigate anxiety-like insomnia with fewer side effects. Mackerel (Pneumatophorus japonicus), a traditional Chinese medicine, is known for its tonic effects and is commonly used to treat neurasthenia. The use of mackerel protein extract has been shown to effectively improve symptoms of light-induced anxiety-like insomnia in a zebrafish model.MethodsThis study examines the effects of mackerel bone peptides (MW < 1 kDa, MBP1) and the synthetic peptide Thr-Val-Gly-Phe (TVGF) on light-induced anxiety-like insomnia in zebrafish. The evaluation is conducted through behavioral observation, biochemical marker analysis, and gene transcriptome profiling.ResultsMBP1 significantly alleviated abnormal hyperactivity and restored neurotransmitter levels (dopamine and γ-aminobutyric acid) to normal. Moreover, it mitigated oxidative stress by reducing reactive oxygen species production and malonaldehyde levels, while enhancing antioxidant enzyme activities (superoxide dismutase and catalase). This was further attributed to the regulation of lipid accumulation and protein homeostasis. Furthermore, MBP1 ameliorated sleep disturbances primarily by restoring normal expression levels of genes involved in circadian rhythm (per2 and sik1) and visual function (opn1mw2, zgc:73075, and arr3b). Molecular docking analysis indicated that TVGF exhibited good affinity for receptors linked to sleep disturbances, including IL6, HTR1A, and MAOA. TVGF exhibited sedative effects in behavioral assays, mainly mediated by regulating the normal expression of genes associated with circadian rhythm (cry1bb, cry1ba, per2, per1b and sik1), visual function (opn1mw1, gnb3b, arr3b, gnat2), purine metabolism (pnp5a), and stress recovery (fkbp5).DiscussionThese findings suggest that MBP1 and TVGF could be promising therapies for light-induced anxiety-like insomnia in humans, offering safer alternatives to current medications. Additionally, the regulation of genes related to circadian rhythm and visual perception may be a key mechanism by which MBP1 and TVGF effectively relieve anxiety-like insomnia.

Evaluation of Gender-Specific Variation in Lead-induced Nephrotoxicity in Wistar Rats

The kidney is sensitive to heavy metals because of its intensive metabolic activity and multiple functions namely those of excretion and pollutants concentration. The study aimed to evaluate the gender-specific variation in lead-induced nephrotoxicity in Wistar rats. 10 male and 10 female Wistar rats (180-220g) were each divided into 2 groups (n=5 each): Control (M), Lead alone (M), Control (F), Lead alone (F). Male and female rats of the experimental groups were administered a daily dose of 100 mg/kg/bw of lead acetate dispersed in distilled water for 21 days. All rats were anesthetized and sacrificed 24 hours after the last administration. Blood samples were collected via cardiac puncture for biochemical analysis, kidney tissues were harvested, homogenized, and analyzed for antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and lipid peroxidation (measured by malondialdehyde levels). Results indicated a significantly (p<0.01) lower weight gain in the lead-only female (F) group compared to the lead-only male (M) group. Lead acetate exposure caused oxidative damage, evidenced by significantly reduced antioxidant enzyme levels and increased lipid peroxidation in both male and female groups, with the effects being more pronounced in females (p<0.05). Serum creatinine and Urea levels in the lead alone (M) and lead alone (F) group were increased when compared to their respective control groups (p<0.05) however serum creatinine was significantly (p<0.001) higher in lead alone (F) than lead alone (M). The electrolyte function increased significantly in this study (p<0.05) when compared with their control groups. Sodium ion in lead alone (F) increased significantly (p<0.01) when compared to lead alone (M). The study concludes that lead exposure induced nephrotoxicity in both male and female rats, but more significantly pronounced in females than the males. This increased severity may have been mediated by the higher lead-induced oxidative stress observed in the female rats compared to males.

Antioxidant System of Scutellum During Germination and Early Growth of Maize Seedlings

Maize is among the world’s three most important cereals because it is used for human consumption and agricultural feed. The embryo in monocotyledons contains a cotyledon that is the scutellum, which in Chalqueño maize constitutes approximately 80% of the embryo’s mass. The activation of metabolism during germination is accompanied by the production of reactive oxygen species, which must be maintained at a low level to avoid damage. Little is known about the oxidative state of the scutellum, but it is important to understand the control of oxidative stress during the final phase of germination and the embryo–seedling transition. Among the enzymes involved are class III peroxidase (POX), catalase (CAT), and superoxide dismutase (SOD), which were observed in the scutella of isolated imbibed embryos between 0 and 36 h. The activity of SOD fluctuated over a baseline value. The activity of class III POX was greater than that of CAT, showing differences between them in germination and postgermination. The activities of CAT and POX increased during germination (0 to 18 h), stabilized towards the final phase of germination (18 to 24 h), and then increased again in postgermination (24 to 36 h). The POX activity is a biochemical marker of the scutellum metabolism and marks the transition from germination to the embryo–seedling transition.

Moisturizing and antioxidant factors of skin barrier restoring cream with shea butter, silkflo and vitamin E in human keratinocyte cells

AbstractObjectiveMoisturizers are integral to daily skincare routines, reflecting the increasing trend among people towards cosmetic products, particularly for skin care. They significantly contribute to preserving skin health, particularly by regulating the epidermal barrier and moisture levels within the skin. This study aims to explore the moisturizing and antioxidant effect of skin barrier restoring cream Moiz MM (MZ) with shea butter, silkflo and vitamin E by investigating its protective effect against oxidative stress‐induced cellular damage and therapeutic mechanisms in human keratinocytes cells (HaCaT).MethodsThe in vitro antioxidant activity of MZ was evaluated by DPPH, ABTS and NO assays. For the cell culture study, HaCaT cells were cultured and stimulated using H2O2 and then treated with different concentrations of MZ. Then, it was subjected to DCFH‐DA staining, reverse transcriptase PCR and western blot analysis for the evaluation of various skin‐moisture‐related components in human keratinocyte cells. Type I procollagen was examined using ELISA technique.ResultsThe results highlighted that oxidative stress in HaCaT cells decreased type I procollagen synthesis, while MZ treatment significantly increased the synthesis. Moreover, the viability of HaCaT cells was not affected in the presence of MZ, which demonstrates its non‐toxic effect. Furthermore, MZ can counteract H2O2‐mediated oxidative stress by enhancing the antioxidant enzyme activity such as superoxide dismutase and catalase, and decrease reactive oxygen species generation in skin cells. Additionally, MZ greatly promotes hyaluronic acid production by enhancing the expression of the hyaluronic acid synthase‐1 gene and Aquaporin 3 protein.ConclusionThis study suggests that MZ has the potential to serve as a moisturizing and antioxidant skincare formula.

THE EFFECT OF NF-ΚB ON THE INTENSITY OF OXIDATIVE STRESS IN THE CEREBRAL CORTEX OF RATS UNDER THE COMBINED INFLUENCE OF THE LIGHT-DARK CYCLE, SYSTEMIC INFLAMMATORY RESPONSE, AND SODIUM GLUTAMATE ADMINISTRATION

To date, scientists have confirmed the link between the development of oxidative stress and disruptions in the light regime, as well as the systemic inflammatory response. The impact of monosodium glutamate on increasing oxidative damage to rat brain tissue has also been identified. The aim of this study was to investigate the role of the transcription factor NF-κB by examining the effect of its inhibitor, ammonium pyrrolidinedithiocarbamate, on the development of oxidative stress in the cerebral hemispheres of rats, in combination with acute desynchronosis, systemic inflammatory response, and monosodium glutamate administration. The study was conducted on 45 white Wistar rats weighing 150-200 g, divided into three groups: control (n=15), a group subjected to a combination of acute desynchronosis, systemic inflammatory response, and sodium glutamate administration (n=15), and a group exposed to the combination of acute desynchronosis, systemic inflammatory response, and received sodium glutamate and pyrrolidinedithiocarbamate (n=15). To induce acute desynchronosis, the rats were initially kept under a regular light-dark cycle (12 hours of light, 12 hours of darkness) for 3 weeks, followed by a shift in the light-dark phases by 6 hours back over the next 3 days. The systemic inflammatory response was modeled through intraperitoneal administration of Salmonella typhi lipopolysaccharide. During the first week, lipopolysaccharide was administered three times at a dose of 0.4 μg per 1 kg of body weight, and during the following seven weeks, it was given once a week. Sodium glutamate, at a dose of 30 mg/kg, dissolved in 0.5 ml of distilled water, was administered intragastrically for 20 days. The NF-kB activation inhibitor ammonium pyrrolidinedithiocarbamate (Sigma-Aldrich, Inc., USA) was administered at a dose of 76 mg/kg three times a week for 20 days. In a 10% homogenate of the cerebral hemispheres, the following were measured: the rate of superoxide anion radical production, the content of thiobarbituric acid-reactive substances (TBARS), the increase in these parameters, as well as the activity of catalase and superoxide dismutase. Administration of pyrrolidinedithiocarbamate in combination with acute desynchronosis, systemic inflammatory response, and sodium glutamate reduced the rate of basic superoxide anion radical production by 10%, NADPH-induced production by 17.6%, NADH-induced production by 13%, reduced the concentration and growth of TBC-active products by 6.6% and 14.6%, respectively, increased the activity of superoxide dismutase by 35.2%, catalase by 10.5% compared to the group exposed to the combination of acute desynchronosis, systemic inflammatory response, and sodium glutamate administration. Conclusion. The administration of pyrrolidinedithiocarbamate in combination with a systemic inflammatory response, acute desynchronosis and the action of sodium glutamate reduces the production of the superoxide anion radical, the concentration and increase in TBC-active products, enhances antioxidant protection that indicates the possible influence of the nuclear factor NF-κB on the development of oxidative processes in the cerebral hemispheres of rats.

Exogenous nitric oxide extends longevity in cut Lilium tigrinum flowers by orchestrating biochemical and molecular aspects

Senescence represents a developmentally orchestrated and precisely regulated cascade of events, culminating in the abscission of plant organs and ultimately leading to the demise of the plant or its constituent parts. In this study, we observed that senescence in cut Lilium tigrinum flowers is induced by elevated ABA levels and the hyperactivation of lipoxygenase (LOX) activity. This cascade increased ROS concentrations, heightened oxidative damage, and disrupted cellular redox equilibrium. This was evidenced by elevated lipid peroxidation, attenuated antioxidant machinery, and reduced membrane stability index (MSI). Despite its known role in delaying flower senescence, the specific biochemical and molecular mechanisms by which nitric oxide (NO) regulates senescence in cut L. tigrinum flowers are not fully elucidated. Specifically, the interactions between NO signaling and ABA metabolism, the regulation of protease activity, and the influence of NO-mediated ROS scavenging, senescence-associated gene expression requires further exploration. Exogenous application of sodium nitroprusside (SNP), a source of NO, mitigated senescence in L. tigrinum cut flowers by upregulating the activity of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and reducing the LOX activity, an indicator of lipid peroxidation. SNP treatment also downregulated the relative expression of senescence-associated gene (SAG12),lipoxygenase 1 (LOX1), and abscisic aldehyde oxidase 3 (AAO3). NO also upregulated defender against apoptotic death 1 (DAD1) expression correlated with minimized protease activity and reduced α-amino acid content in SNP-treated tepals. This regulation was accompanied by increased contents of sugars, proteins and phenols and reduced abscisic acid content, which collectively delayed the senesecence and enhanced the longevity of L. tigrinum cut flowers. This study demonstrates that exogenous SNP application can effectively mitigate senescence in cut L. tigrinum flowers by modulating antioxidant enzyme activities, reducing oxidative stress, and regulating the expression of key senescence-associated genes. This study unravels the complex molecular networks involved in NO-mediated senescence delay, which may lead to the development of innovative approaches for improving flower longevity.

TMET-16. GABA PRODUCTION INDUCED BY IMIPRIDONES IS A TARGETABLE AND IMAGEABLE METABOLIC ALTERATION IN DIFFUSE MIDLINE GLIOMAS

Abstract Diffuse midline gliomas (DMGs) are lethal brain tumors in children. The imipridones ONC201 and ONC206 have emerged as promising therapies for DMG patients, but efficacy as monotherapy is limited. Another hurdle is the lack of biomarkers that report on drug-target engagement at an early timepoint after treatment. Here, using 1H-magnetic resonance spectroscopy (1H-MRS), which is a non-invasive method of quantifying metabolite pool sizes, we show that imipridones induce accumulation of gamma-aminobutyric acid (GABA) in patient-derived (BT245, SF8628) and syngeneic (26-B7, 26-C2) cells. Importantly, in vivo1H-MRS detects a significant increase in GABA within a week of ONC206 treatment, when anatomical alterations are absent, in mice bearing orthotopic BT245, SF8628 or 26-B7 xenografts. Mechanistic studies show that imipridones activate the mitochondrial protease ClpP and upregulate the stress-responsive transcription factor ATF4. ATF4, in turn, upregulates glutamate decarboxylase, the enzyme that synthesizes GABA, and downregulates GABA transaminase, which degrades GABA, leading to GABA accumulation in DMG cells and orthotopic tumors. Since GABA is known to regulate oxidative stress signaling and since imipridones induce oxidative stress, we assessed whether GABA influences oxidative stress in DMG cells. Our studies indicate that GABA induces expression of superoxide dismutase (SOD1), which scavenges superoxide radicals and, thereby, curbs apoptosis induced by imipridones. The biological effects of GABA are mediated via signaling cascades triggered by GABA receptors and we find that GABA acts in an autocrine manner via the GABAB receptor to upregulate SOD1. Importantly, the clinically translatable GABAB receptor antagonist SGS742 and the SOD1 inhibitor ATN-224 exacerbate oxidative stress and synergistically induce apoptosis in combination with imipridones in DMG cells. Furthermore, SGS742 is brain-penetrant and potentiates ONC206-induced apoptosis in mice bearing orthotopic SF8628 xenografts in vivo. Collectively, we identify GABA as a unique metabolic adaptation to imipridones that can be leveraged for imaging drug-target engagement and for enhancing response to therapy. Clinical translation of our studies will enable precision therapy and imaging for DMG patients.

Investigating the Effects of Gossypetin on Cardiovascular Function in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats

Gossypetin (GTIN) is a naturally occurring flavonoid recognised for its pharmacological properties. This study examined the effects of GTIN on cardiovascular function in a diet-induced pre-diabetic rat model, which has not been previously studied. Pre-diabetes was induced using a high-fat high-carbohydrate (HFHC) diet supplemented with 15% fructose water for 20 weeks. Thereafter, the pre-diabetic animals were sub-divided into five groups (n = 6), where they were either orally treated with GTIN (15 mg/kg) or metformin (MET) (500 mg/kg), both in the presence and absence of dietary intervention for 12 weeks. The results demonstrated that the pre-diabetic (PD) control group exhibited significantly higher plasma triglyceride, total cholesterol, low-density lipoprotein and very low-density lipoprotein levels, along with decreased high-density lipoprotein (HDL) levels in comparison to the non-pre-diabetic (NPD) group. This was accompanied by significantly higher mean arterial pressure (MAP), body mass index (BMI), waist circumference (WC) and plasma endothelial nitric oxide (eNOS) levels in PD control. Additionally, there were increased heart malondialdehyde levels, reduced heart superoxide dismutase and glutathione peroxidase activity as well as increased plasma interleukin-6, tumour necrosis factor alpha and c-reactive protein levels present in the PD control group. Notably, both GTIN-treated groups showed significantly reduced plasma lipid levels and increased HDL, as well as decreases in MAP, BMI, WC and eNOS levels in comparison to PD control. Additionally, GTIN significantly decreased heart lipid peroxidation, enhanced antioxidant activity and decreased plasma inflammation markers. These findings may suggest that GTIN administration in both the presence and absence of dietary intervention may offer therapeutic potential in ameliorating cardiovascular disturbances associated with the PD state. However, future studies are needed to determine the physiological mechanisms by which GTIN improves cardiovascular function in the PD state.

Foliar application of Verticillium dahliae Aspf2‐like protein improved the heat tolerance of creeping bentgrass by regulating photosynthetic and antioxidant capabilities

AbstractContinuous high ambient temperature in hot summer months leads to a sharp decline in turf quality of cool‐season turfgrass. Verticillium dahliae Aspf2‐like protein (VDAL) is a secretory protein of V. dahliae that can improve crop yield and resistance to disease, but its role in improving heat tolerance of cool‐season turfgrass has not been reported so far. The objectives of this study were to explore the effect and mechanism of foliar application of VDAL on improving heat tolerance in cool‐season creeping bentgrass (Agrostis stolonifera) and to further examine the advantage of foliar spraying with VDAL in mitigating summer bentgrass decline (SBD) in the US transition zone or other regions with similar climate. The results demonstrated that the optimal dose of VDAL for improving thermotolerance of two creeping bentgrass cultivars (heat‐tolerant 13 M and heat‐sensitive Seaside II) was screened as 0.2 g L−1 based on analyses of chlorophyll content, photochemical efficiency of PSII, and cell membrane stability under controlled heat stress conditions. Foliar application of the optimal dose of VDAL significantly restricted chlorophyll loss under heat stress and also alleviated heat‐induced declines in net photosynthetic rate, transpiration rate, stomatal conductance, and water use efficiency. In addition, overaccumulations of superoxide anion radical and hydrogen peroxide could be significantly alleviated by the exogenous application of VDAL through improving the activity of antioxidant enzymes including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase in two cultivars. A further 2‐year field trial showed that foliar application of VDAL improved turf quality, chlorophyll content, photochemical efficiency, and cell membrane stability of the two cultivars during hot summer months of 2022 and 2023. The results indicate that the appropriate dose of VDAL plays a positive role in photosynthetic performance and antioxidant capacity for thermotolerance of creeping bentgrass, and foliar application of VDAL could be considered an effective approach for alleviating SBD.

The effect of methylphenidate on the reproductive function of female rats

AbstractAimResearch on the effects of methylphenidate on female fertility is limited. This study evaluated the effects of methylphenidate on reproductive function, oxidants, antioxidants, proinflammatory cytokines, prolactin, and cortisol in female rats.MethodsForty‐eight albino Wistar female rats were divided into four groups consisting of 12 rats, which were given pure water orally once daily for 7 days (HG‐1), 10 mg/kg methylphenidate orally once daily for 7 days (MP‐1), pure water orally once daily for 30 days (HG‐2), and 10 mg/kg methylphenidate orally once daily for 30 days (MP‐2). At the end of the treatment periods, tail vein blood was collected from six rats per group for prolactin and cortisol determination. Subsequently, euthanasia was performed and the ovaries were removed. Ovaries were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin‐1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α), and immunohistochemically. For breeding, the remaining six rats were mated with male rats for 1 month. Rats that failed to give birth were classed as infertile.ResultsA comparison of MP‐1 and MP‐2 groups to healthy controls revealed an elevation in MDA and corticosterone levels, and a decline in tGSH, SOD, and CAT levels (p < 0.001). Methylphenidate did not affect prolactin, IL‐1β, and TNF‐α levels (p > 0.05). MP‐1 and MP‐2 exhibited immunopositivity for 8‐hydroxy‐2'‐deoxyguanosine (8‐OHDG). MP‐2 rats developed 66.7% infertility while MP‐1, HG‐1, and HG‐2 rats did not.ConclusionIn ovaries, methylphenidate caused oxidative stress, but did not induce inflammation. Long‐term use of methylphenidate caused increased cortisol levels and infertility.

Effect of dietary Anabaena supplementation on nutrient utilization, metabolism and oxidative stress response in Catla catla fingerlings

A 60-day feeding trial was conducted to evaluate the effects of dietary Anabaena blue-green algae (ABGA) meal on the growth performance, digestibility, and physio-metabolic responses of Catla catla fingerlings (initial average weight 9.45 ± 0.15 g). Six iso-nitrogenous (30% crude protein) and iso-caloric (378.09 Kcal. digestible energy/100 g) diets were formulated: a control diet (A0, 0% ABGA) and five experimental diets with varying ABGA inclusion levels (A3: 3%, A6: 6%, A9: 9%, A12: 12%, A15: 15%). The results demonstrated that there were no significant differences (P > 0.05) in percentage weight gain (PWG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) among the experimental groups. Additionally, dietary ABGA did not significantly affect (P > 0.05) body carcass composition among different groups. However, amylase activity significantly decreased (P < 0.05) in the A12 and A15 fed groups, whereas lipase and protease activities remained insignificant (P > 0.05) across all groups. Notably, oxidative stress responses (SOD; superoxide dismutase and CAT; catalase), carbohydrate metabolic enzymes (LDH; lactate dehydrogenase and MDH; malate dehydrogenase), and serum glucose levels increased significantly (P < 0.05) with higher ABGA inclusion. Conversely, serum albumin content significantly decreased (P < 0.05) in the ABGA-fed groups. There were no significant differences (P > 0.05) observed in serum total protein, albumin/globulin (A/G) ratio, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities among the experimental groups. Hematological parameters revealed that RBC (red blood cell) count, hemoglobin (Hb) concentration, and packed cell volume (PCV) significantly decreased (P < 0.05), while WBC (white blood cell) count significantly (P < 0.05) increased with higher dietary ABGA inclusion. In conclusion, the inclusion of dietary ABGA up to 15% did not impair nutrient utilization and supported normal growth performance in C. catla fingerlings. However, higher inclusion levels may have a detrimental effect on their growth, nutrient utilization, and physio-metabolic responses.

Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models

Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation.

Tanshinone IIA inhibits the apoptosis process of nerve cells by upshifting SIRT1 and FOXO3α protein and regulating anti- oxidative stress molecules and inflammatory factors in Cerebral Infarction Model

: Background as a prevalent cerebrovascular disorder, cerebral infarction (CI) has garnered extensive attention globally due to its high incidence and substantial fatality rate. Ischemia-reperfusion injury (IRI) exacerbates not only neuronal demise but also amplifies neural functional impairment. Tanshinone IIA (Tan IIA) has been identified to confer protection against IRI, yet the precise underlying mechanisms remain elusive. This work aimed to delve into the mechanistic role of Tan IIA in CI, with the goal of furnishing more distinct theoretical substantiation for its clinical application. Methods initially, a middle cerebral artery embolization model group (MCAO) model was established, followed by the categorization of rats into distinct groups based on different administration modes. Therapeutic effects were evaluated through indices including mortality rate, cerebral tissue water content, CI proportion, and neural functional scoring. Meanwhile, cellular apoptosis rates in hippocampal and cortical tissues, as well as levels of oxidative stress molecules (OSM), Sirtuin 1 (SIRT1), Forkhead box O3 (FOXO3α), and inflammatory factors, were examined to explore the mechanism of action. Results this work revealed that within varying doses of Tan IIA groups, as dosage escalated, mortality rate, cerebral edema severity, CI proportion, and neural functional scoring gradually diminished. Notably, the 35 mg/kg dose group exhibited the most significant reductions, with decreases of 74.9%, 12.7%, 47.5%, and 54% respectively. Cellular apoptosis rates in hippocampal and cortical tissues displayed a stepwise descending trend, with the 35 mg/kg dose group showcasing the largest reduction. SIRT1 and FOXO3α proteins exhibited a steady increase, with the 35 mg/kg dose group manifesting respective elevations of 87.9% and 65.5%, the highest among all groups. Antioxidant molecules glutathione (GSH) and superoxide dismutase (SOD) contents progressively increased, whereas malondialdehyde (MDA) and nitric oxide (NO) content decreased. The 35 mg/kg dose group recorded the highest increments of 49.1% and 58.1% for GSH and SOD content, while achieving the greatest reductions of 55.6% and 56.2% for MDA and NO content. Expression of inflammatory factors, namely tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), gradually declined, with reductions of 42.1%, 32.2%, and 29.1% respectively in the 35 mg/kg dose group, exhibiting drastic differences (P < 0.05). Conclusion In conclusion, this research elucidates that Tan IIA improves cerebral edema and neural function by elevating intracellular expression of SIRT1 and FOXO3α proteins, modulating OSM and inflammatory factors. These findings yielded robust experimental support for the potential use of Tan IIA as a therapeutic agent for CI.