"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Combined application of the endophyte Bacillus K1 and sodium dehydroacetate alleviates postharvest gray mold in grapes.

Botrytis cinerea, which causes postharvest gray mold, is a primary pathogen that limits grape shelf-life and consumption and causes substantial yield loss worldwide. The combined use of biocontrol agents and food additives has attracted increasing interest. The effects of combined treatment with the endophyte Bacillus subtilis K1 and sodium dehydroacetate (SD) on the occurrence of gray mold and maintenance of grape fruit quality were studied. Treatment with a K1 suspension (1 × 108 CFU/ml) combined with 0.32 g/L SD resulted in markedly improved control of B. cinerea on grapes. The disease incidence and severity in the groups treated with K1 alone or in combination with SD were significantly lower than those in the control groups (P < 0.05) when the mixtures were applied 2 h after pathogen inoculation. Moreover, application of the mixture could maintain the appearance, firmness, total soluble solid (TSS) content and titratable acidity (TA) of grape fruit. Furthermore, the combination triggered increases in the activities of defense-related enzymes such as peroxidase (POD), phenylalanine ammonia lyase (PAL), catalase (CAT), superoxide dismutase (SOD) and polyphenol oxidase (PPO). Additionally, it could increase the vitamin C content. Thus, appropriate combinations of biocontrol agents and chemical reagents can provide effective protection against postharvest decay.

Exploration of uricase-like activity in Pd@Ir nanosheets and their application in relieving acute gout using self-cascade reaction.

Gout, marked by the deposition of sodium urate crystals in joints and peripheral tissues, presents a considerable health challenge. Recent research has shown a growing interest in nanozyme-based treatments for gout. However, literature on nanozymes that combine uricase-like (UOX) activity for uric acid (UA) degradation with catalase (CAT)-like activity for H2O2 elimination through a self-cascade reaction is limited. Herein, we discovered that two-dimensional Pd@Ir nanosheets (NSs) exhibit UOX and CAT activities effectively. Notably, we observed a size-dependent effect of Pd@Ir on activation energy during UA degradation, with the larger Pd@Ir NSs demonstrating a lower energy barrier. The 46-nm Pd@Ir had activation energy as low as 35.9 kJ/mol, surpassing the efficiency of natural bacterial uricase and most reported nanozymes. Through a tandem self-cascade reaction of Pd@Ir, UA was effectively degraded via UOX activity, while the byproduct H2O2 was simultaneously eliminated by CAT-like activity. Cell experiments revealed that Pd@Ir protect normal cells from oxidative stress and promote cell proliferation, demonstrating an excellent self-cascade effect. Additionally, Pd@Ir substantially alleviated gout symptoms in monosodium urate-induced acute gout mice without causing toxic effects on biological organs and tissues. This study opens new avenues for using nanozyme-based cascade reaction systems in the treatment of metabolic diseases.

Effects of long-term Tai Chi vs. aerobic exercise on antioxidant activity and cognitive function in individuals with Parkinson's disease.

An imbalance between the generation of reactive oxygen species and the body's antioxidant defense mechanisms is closely related to the development and progression of Parkinson's disease (PD). Considering that physical exercise is a potential therapeutic intervention for modulating oxidative stress markers and cognitive function in PD, the primary purpose of this study was to compare the effects of different long-term exercise modalities on antioxidants and cognitive performance in patients with PD. In addition, the secondary purpose was to explore whether changes in the levels of these biochemical markers are associated with alterations in cognitive performance pre- and post-intervention. In all, 61 participants were randomly divided into the aerobic exercise (AE, n=20), Tai Chi exercise (TCE, n=21), or control (n=20) group. Blood samples were collected before and after a 12-week intervention period for the analysis of antioxidant markers [leukocyte 8-hydroxydeoxyguanosine (8-OHdG), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), oxidized glutathione (GSSG), superoxide dismutase (SOD), and uric acid (UA)]. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Although no significant changes were observed in the activity of 8-OhdG, GSH-Px, GSSG, GSH:GSSG ratio, SOD, and cognitive performance in the AE and TCE groups, the 12-week AE intervention led to a significant increase in CAT and GSH levels, along with a significantly decrease in UA levels among individuals with PD. Conversely, the TCE intervention resulted in a significant increase in GSH levels. However, SOD activity and MMSE scores were significantly decreased after 12 weeks in the control group. The correlations between changes in MMSE scores and changes in the levels of GSH and UA prior to and after the intervention reached significance in the AE group. Thus, long-term AE and TCE might serve as effective strategies for reducing oxidative damage and preserving cognitive function in PD, with AE exhibiting greater benefits compared with TCE. These findings hold potential clinical relevance as complementary measures to standard medical treatments and alternative therapies, such as antioxidant supplements and dietary adjustments, particularly for individuals in the early stages of PD.

Novel catalytic behavior of defective nanozymes with catalase-mimicking characteristics for the degradation of tetracycline.

Although nanozymes have shown significant potential in wastewater treatment, enhancing their degradation performance remains challenging. Herein, a novel catalytic behavior was revealed for defective nanozymes with catalase-mimicking characteristics that efficiently degraded tetracycline (TC) in wastewater. Hydroxyl groups adsorbed on defect sites facilitated the in-situ formation of vacancies during catalysis, thereby replenishing active sites. Additionally, electron transfer considerably enhanced the catalytic reaction. Consequently, numerous reactive oxygen species (ROS) were generated through these processes and subsequent radical reactions. The defective nanozymes, with their unique catalytic behavior, proved effective for the catalytic degradation of TC. Experimental results demonstrate that •OH, •O2-, 1O2 and e- were the primary contributors to the degradation process. In real wastewater samples, the normalized degradation rate constant for defective nanozymes reached 26.0 min-1 g-1 L, exceeding those of other catalysts. This study reveals the new catalytic behavior of defective nanozymes and provides an effective advanced oxidation process for the degradation of organic pollutants.

CuO nanoparticles for glioma treatment in vitro and in vivo.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

Methyl jasmonate effects on Lactuca serriola L.: Antioxidant defense and bioactive compound changes.

The effect of methyl jasmonate (MeJA) foliar spray on the activity of antioxidant enzymes-Superoxide dismutase (SOD), Catalase (CAT), Ascorbate peroxidase (APX), and Guaiacol peroxidase (GPX)-along with assessments of total phenolic and flavonoid contents and antioxidant activity (IC50), was examined in Prickly lettuce (Lactuca serriola L.). The study involved treating plants with three MeJA solutions (0, 200, and 400 µM) and harvesting samples at four distinct time intervals. Varied MeJA concentrations and time intervals resulted in a substantial increase in the activity of all the antioxidant enzymes investigated in this study. Both concentration levels and time courses exhibited progressive outcomes. Moreover, MeJA treatment led to elevated levels of total phenolic and flavonoid contents, reaching peaks of 17.02 (mg GAL/g DW) and 8.3 (mg QUE/g DW), respectively, particularly in response to the 400 µM concentration. However, the total flavonoid content did not show any significant variation between the two concentrations. Based on the half-maximal inhibitory concentration (IC50) values, the antioxidant activity in MeJA-treated plants was found to be lower compared to the controls. However, our findings suggest that, under specific conditions discussed in this study, MeJA has the potential to enhance the nutritional value of L. serriola.

Revisiting the activity of two poly(vinyl chloride)- and polyethylene-degrading enzymes.

Biocatalytic degradation of non-hydrolyzable plastics is a rapidly growing field of research, driven by the global accumulation of waste. Enzymes capable of cleaving the carbon-carbon bonds in synthetic polymers are highly sought-after as they may provide tools for environmentally friendly plastic recycling. Despite some reports of oxidative enzymes acting on non-hydrolyzable plastics, including polyethylene or poly(vinyl chloride), the notion that these materials are susceptible to efficient enzymatic degradation remains controversial, partly driven by a general lack of studies independently reproducing previous observations. Here, we attempt to replicate two recent studies reporting that deconstruction of polyethylene and poly(vinyl chloride) can be achieved using an insect hexamerin from Galleria mellonella (so-called "Ceres") or a bacterial catalase-peroxidase from Klebsiella sp., respectively. Reproducing previously described experiments, we do not observe any activity on plastics using multiple reaction conditions and multiple substrate types. Digging deeper into the discrepancies between the previous data and our observations, we show how and why the original experimental results may have been misinterpreted.

Improved longevity of actomyosin in vitro motility assays for sustainable lab-on-a-chip applications.

In the in vitro motility assay (IVMA), actin filaments are observed while propelled by surface-adsorbed myosin motor fragments such as heavy meromyosin (HMM). In addition to fundamental studies, the IVMA is the basis for a range of lab-on-a-chip applications, e.g. transport of cargoes in nanofabricated channels in nanoseparation/biosensing or the solution of combinatorial mathematical problems in network-based biocomputation. In these applications, prolonged myosin function is critical as is the potential to repeatedly exchange experimental solutions without functional deterioration. We here elucidate key factors of importance in these regards. Our findings support a hypothesis that early deterioration in the IVMA is primarily due to oxygen entrance into in vitro motility assay flow cells. In the presence of a typically used oxygen scavenger mixture (glucose oxidase, glucose, and catalase), this leads to pH reduction by a glucose oxidase-catalyzed reaction between glucose and oxygen but also contributes to functional deterioration by other mechanisms. Our studies further demonstrate challenges associated with evaporation and loss of actin filaments with time. However, over 8 h at 21-26 °C, there is no significant surface desorption or denaturation of HMM if solutions are exchanged manually every 30 min. We arrive at an optimized protocol with repeated exchange of carefully degassed assay solution of 45 mM ionic strength, at 30 min intervals. This is sufficient to maintain the high-quality function in an IVMA over 8 h at 21-26 °C, provided that fresh actin filaments are re-supplied in connection with each assay solution exchange. Finally, we demonstrate adaptation to a microfluidic platform and identify challenges that remain to be solved for real lab-on-a-chip applications.

Functional characterization of extracellular and intracellular catalase-peroxidases involved in virulence of the fungal wheat pathogen Zymoseptoria tritici.

Understanding how pathogens defend themselves against host defence mechanisms, such as hydrogen peroxide (H2O2) production, is crucial for comprehending fungal infections. H2O2 poses a significant threat to invading fungi due to its potent oxidizing properties. Our research focuses on the hemibiotrophic fungal wheat pathogen Zymoseptoria tritici, enabling us to investigate host-pathogen interactions. We examined two catalase-peroxidase (CP) genes, ZtCpx1 and ZtCpx2, to elucidate how Z. tritici deals with host-generated H2O2 during infection. Our analysis revealed that ZtCpx1 was up-regulated during biotrophic growth and asexual spore formation in vitro, while ZtCpx2 showed increased expression during the transition from biotrophic to necrotrophic growth and in-vitro vegetative growth. Deleting ZtCpx1 increased the mutant's sensitivity to exogenously added H2O2 and significantly reduced virulence, as evidenced by decreased Septoria tritici blotch symptom severity and fungal biomass production. Reintroducing the wild-type ZtCpx1 allele with its native promoter into the mutant strain restored the observed phenotypes. While ZtCpx2 was not essential for full virulence, the ZtCpx2 mutants exhibited reduced fungal biomass development during the transition from biotrophic to necrotrophic growth. Moreover, both CP genes act synergistically, as the double knock-out mutant displayed a more pronounced reduced virulence compared to ΔZtCpx1. Microscopic analysis using fluorescent proteins revealed that ZtCpx1 was localized in the peroxisome, indicating its potential role in managing host-generated reactive oxygen species during infection. In conclusion, our research sheds light on the crucial roles of CP genes ZtCpx1 and ZtCpx2 in the defence mechanism of Z. tritici against host-generated hydrogen peroxide.

Next generation preservation solution using synthetic enzymes added to polyhemoglobin to protect warm ischemic human hepatocytes and cardiomyocytes.

This study investigates the potential improvement of polyhemoglobin's protective properties by the addition of 3 synthetic enzymes (neo-carbonic anhydrase, neo-catalase and neo-superoxide dismutase) to polyhemoglobin after 90 and 180 min of warm in-vitro ischemia (100% Nitrogen at 37 °C). Following the warm ischemic shock, cell cultures were subjected to various treatment solutions: Controls; PolyHb; 3 neoenzymes; PolyHb + 3 neoenzymes; PolyHb + 2 neoenzymes. The cultures were then incubated (Oxygen, 5% CO2 at 37 °C) for 24 h followed by several analyses. Compared to polyhemoglobin alone, this novel solution containing polyhemoglobin + 3 neoeznymes significantly increased the viability, cell growth, albumin production, protection against oxidative stress and cellular injury of human hepatocytes. Moreover, this also protects the viability of human cardiomyocytes. These findings suggest that it could be useful as a pre-transplant cell/organ preservation solution which, in the long-term, could contribute to the development of blood substitutes.

LSU family members and NBR1 are novel factors that contribute to homeostasis of catalases and peroxisomes in Arabidopsis thaliana.

The short coiled-coil LSU (RESPONSE TO LOW SULFUR) proteins are linked to sulfur metabolism and have numerous protein partners. However, most of these partners lack direct links to sulfur metabolism, and the role of such interactions remains elusive. Here, we confirmed LSU binding to Arabidopsis catalase (CAT) and revealed that NBR1, a selective autophagy receptor, strongly interacts with LSU1 but not with CAT. Consequently, we observed the involvement of autophagy but not NBR1 in CAT removal. The lsu and nbr1 mutants differed from the wild-type plants in size and the number of yellow fluorescent protein (YFP)-CAT condensates, the number of peroxisomes, and photosynthetic pigments levels in the presence and absence of stress. We conclude that LSU family members and NBR1 contribute directly or indirectly to CAT and peroxisome homeostasis, and the overall fitness of plants. Our structural models of CAT-LSU complexes show at least two regions of interaction in CAT, one of which is at the N-terminus. Indeed, the N-terminally truncated variants of CAT2 and CAT3 interact more weakly with LSU1 than their full-length variants, but the extent of reduction is higher for CAT2, suggesting differences in recognition of CAT2 and CAT3 by LSU1.

Hepatitis B Virus X Protein Induces Reactive Oxygen Species Generation via Activation of p53 in Human Hepatoma Cells.

Hepatitis B virus (HBV), particularly through the HBx protein, induces oxidative stress during liver infections. This study reveals that HBx increases reactive oxygen species (ROS) via two distinct mechanisms. The first mechanism is p53-independent, likely involving mitochondrial dysfunction, as demonstrated by elevated ROS levels in p53-deficient Hep3B cells and p53-knocked-down HepG2 cells after HBx expression or HBV infection. The increase in ROS persisted even when p53 transcriptional activity was inhibited by pifithrin-α (PFT-α), a p53 inhibitor. The second mechanism is p53-dependent, wherein HBx activates p53, which then amplifies ROS production through a feedback loop involving ROS and p53. The ability of HBx to elevate ROS levels was higher in HepG2 than in Hep3B cells. Knocking down p53 in HepG2 cells lowered ROS levels, while ectopic p53 expression in Hep3B cells raised ROS. HBx-activated p53 downregulated catalase and upregulated manganese-dependent superoxide dismutase, contributing to ROS amplification. The transcriptional activity of p53 was crucial for these effects, as cells with a p53 R175H mutation or those treated with PFT-α generated less ROS. Additionally, HBx variants with Ser-101 increased p53 and ROS levels, whereas variants with Pro-101 did not. These dual mechanisms of HBx-induced ROS generation are likely significant in the pathogenesis of HBV and may contribute to liver diseases, including hepatocellular carcinoma.

Assessment of the impact of smoke from thermal destruction of materials of different origins on soil health.

The results of the study of the influence of smoke from the thermal destruction of materials of vegetable and synthetic origin on the enzymatic activity of ordinary chernozem are presented. The decrease of activity of investigated indicators (catalase, peroxidase, polyphenol oxidase, invertase) from thermal destruction of pine sawdust, straw, coniferous and leaf fall, peat, and materials based on polystyrene, rubber, and polyvinyl chloride was revealed. A significant decrease in the activity of soil enzymes after exposure to gaseous products of combustion during 15-60 min of soil fumigation was found. Oxidoreductases turned out to be the most sensitive to smoke. Smoke from peat burning has minimal inhibitory effect, activity of catalase after 30 min of fumigation decreased only by 15%, and peroxidase and polyphenol oxidase - by 8 and 12%. While the activity of the same enzymes when exposed to smoke from thermal degradation of rubber-based materials decreased by 16-42%, and polyvinyl chloride - by 29-73%, to a lesser extent from polystyrene (decrease by 7-29%). All obtained data on changes in the enzymatic activity of soils are reliable with the level of statistical significance p < 0.05.

Impact of smokeless tobacco on psychological and oxidative stress in unemployed indian youth.

In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chronic exposure results in various adverse health outcomes. This study examines the impact of chronic nicotine consumption on cellular oxidative stress and psychological stress, and their correlation with Homocysteine (Hcy) levels in unemployed tobacco consumers. This case-control study included 156 healthy, educated, unemployed male volunteers aged 20-40 years, divided into nicotine-addicted (n = 80) and non-addicted (n = 76) groups. Psychological stress was assessed using perceived stress scales (PSS) and coping self-efficacy (CSE) scales. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase, were measured. Hcy levels were quantified using high-performance liquid chromatography (HPLC). Nicotine-addicted participants exhibited significantly higher perceived stress (p = 0.0001) and lower coping self-efficacy (p = 0.0001) compared to non-addicted individuals. MDA levels in erythrocytes were significantly increased (p = 0.0006), while SOD (p = 0.0001) and Catalase (p = 0.02) activities were significantly decreased in the addicted group. Nicotine intake influenced Hcy concentrations, with 55% of addicted individuals falling into moderate, 27.5% into intermediate, and 7.5% into severe Hcy categories. Chronic nicotine intake also reflected the hematological parameters (WBCs, RBCs, HGB, and Platelets). Chronic tobacco consumption induces oxidative stress and perceived psychological stress, leading to elevated Hcy levels in nicotine consumers. The study highlights the detrimental effects of nicotine addiction on cellular defensive mechanisms, emphasizing the need for targeted interventions to address this growing health issue among unemployed Indian youth.

The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster.

Histone acylation plays a pivotal role in modulating gene expression, ensuring proper neurogenesis and responsiveness to various signals. Recently, the evolutionary conserved YAF9, ENL, AF9, TAF41, SAS5 (YEATS) domain found in four human paralogs, has emerged as a new class of histone acylation reader with a preference for the bulkier crotonyl group lysine over acetylation. Despite advancements, the role of either histone crotonylation or its readers in neurons remains unclear. In this study, we employed Drosophila melanogaster to investigate the role of ENL/AF9 (dENL/AF9) in the nervous system. Pan-neuronal dENL/AF9 knockdown not only extended the lifespan of flies but also enhanced their overall fitness during aging, including improved sleep quality and locomotion. Moreover, a decreased activity of dENL/AF9 in neurons led to an up-regulation of catalase gene expression which combined with reduced levels of malondialdehyde (MDA) and an enhanced tolerance to oxidative stress in aging flies. This study unveiled a novel function of histone crotonylation readers in aging with potential implications for understanding age-related conditions in humans.

Novel Antioxidant Peptides from Fermented Whey Protein by Lactobacillus rhamnosus B2-1: Separation and Identification by in Vitro and in Silico Approaches.

Whey is a byproduct of the dairy industry and is rich in protein. To enhance the significance of such byproducts and find efficacious antioxidants for combating oxidative stress, this study reported on the preparation, purification, and identification of novel peptides with antioxidant activities from whey protein metabolites following fermentation by Lactobacillus rhamnosus B2-1. The isolation and identification processes involved macroporous adsorption resin column chromatography, gel filtration column chromatography, and liquid chromatography-tandem mass spectrometry. Therein, three novel antioxidant peptides (PKYPVEPF, LEASPEVI, and YPFPGPIHNS) were selected to be synthesized, and they demonstrated remarkable antioxidant activities in vitro chemical assays. PKYPVEPF, LEASPEVI, and YPFPGPIHNS (100 µg/mL) displayed a notable cytoprotective impact on HepG2 cells under oxidative stress induced by H2O2, increasing the cell viability from 49.02 ± 3.05% to 88.59 ± 10.49%, 82.38 ± 19.16%, and 85.15 ± 7.19%, respectively. Moreover, the peptides boosted the activities of catalase and superoxide dismutase in damaged cells and reduced reactive oxygen species levels. The molecular docking studies highlighted that these antioxidant peptides efficiently bound to key amino acids in the Kelch domain of Keap1, thereby preventing the interaction between Keap1 and Nrf2. In conclusion, PKYPVEPF, LEASPEVI, and YPFPGPIHNS demonstrated substantial antioxidant activity, suggesting their potential for widespread application as functional food additives and ingredients.

Bioaccumulation, transformation and toxicity of imidacloprid and dinotefuran in Eisenia fetida under single and binary exposure scenarios.

Earthworms (Eisenia fetida) were exposed to individual and binary mixture of imidacloprid (IMI) and dinotefuran (DIN) at 0.05 and 0.5 mg/kg for 28 days to investigate their bioaccumulation, transformation and toxicity. IMI was more easily absorbed by earthworms than DIN, and worms didn't accumulate or generate toxic metabolites. The obvious accumulation of neonicotinoids during later period caused significant neural dysfunction, especially when exposed to high-concentration IMI. Meanwhile, oxidative stress indicated by decreased SOD/CAT activity (33.2 %-68.1 %) and increased MDA (38.4 %-55.0 %) was induced by binary exposure with high-concentration IMI. By contrast, coelomocytes responded earlier and more strongly than oxidative responses. Coelomocytes' viability and mitochondrial membrane potential were inhibited (23.6 %-91.7 %) mainly by IMI and binary exposure. Coelomocytes' lactate dehydrogenase activity exerted a fluctuating pattern, suggesting irregular disturbance on cellular functions. This study highlights the role of coelomocytes and the need to consider binary/multiple scenarios and transformation of neonicotinoids in their risk assessment to earthworms.

Nitric Oxide-Dependent Regulation of Oxygen-Related Processes in a Rat Model of Lead Neurotoxicity: Influence of the Hypoxia Resistance Factor.

BACKGROUND/AIMS: Lead exposure is known to induce oxidative stress and neurotoxicity. Nitric oxide (NO) plays an important role in modulating oxidative stress, with L-arginine as a precursor of NO and Nω-nitro-L-arginine (L-NNA) as an inhibitor of NO synthase, an enzyme that catalyses the production of nitric oxide (NO) from L-arginine. METHODS: This study investigated the differential effects of L-arginine and L-NNA on markers of oxidative stress and biochemical changes in brain tissue from rats with different levels of resistance to hypoxia exposed to lead nitrate. Rats with either low or high resistance to hypoxia were exposed to lead nitrate (oral 3.6 mg lead nitrate/kg b.w. per day for 30 days) and treated with L-arginine (600 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate) or L-NNA (35 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate). Brain tissue samples were analysed for lipid peroxidation, oxidative modification of proteins, and activity of antioxidant enzymes, including superoxide dismutase, catalase, glutathione reductase, and peroxidase, and total antioxidant status (TAS). We also examined the biomarkers of biochemical pathways involving the activity of alanine and aspartate aminotransferases, succinate dehydrogenase (SDH), and α-ketoglutarate dehydrogenase (KGDH). In addition, the trend observed was supported by assessments of the acetylcholine levels and acetylcholinesterase activity (ACh-AChE system) in brain tissue. RESULTS: In rats with low resistance to hypoxia, the L-arginine treatment significantly reduced lipid peroxidation and oxidative protein modification but increased antioxidant enzyme activity, suggesting a protective effect against lead-induced oxidative stress. Conversely, in rats with high resistance to hypoxia, L-NNA had a protective effect, reducing lead-induced oxidative damage and decreasing lipid peroxidation, whereas L-arginine exacerbated oxidative stress and impaired antioxidant defences. These findings were supported by corresponding changes in the acetylcholine-acetylcholinesterase system, reflecting the observed patterns of lead-induced oxidative stress and neurotoxicity. The study shows that L-arginine exerts a protective effect by reducing lead-induced oxidative damage via an improvement in TAS. Our study shows that lead nitrate exposure significantly increases ala-nine and aspartate aminotransferase activity in brain tissue, with L-arginine exacerbating and L-NNA reversing this effect. The lead nitrate exposure also affected the activities of SDH and KGDH, which are important for cellular energy production and hypoxia resistance, with L-arginine altering SDH activity depending on the level of resistance and L-NNA enhancing both SDH and KGDH activities. These trends were further validated by alterations in the ACh-AChE system, highlighting the differential role of NO-dependent mechanisms in modulating lead-induced neurotoxicity based on hypoxia resistance. CONCLUSION: These findings suggest potential targeted therapeutic strategies based on the oxidative stress profile and highlight the potential of nitric oxide system modulators in counteracting lead-induced biochemical alterations and the dynamics of the ACh-AChE system depending on the individual physiological reactivity of organisms.

Extraction, Characterization, and Antioxidant Activity of Eucommia ulmoides Polysaccharides.

Herein, the ultrasound-assisted extraction conditions affecting the yield of EUPS (Eucommia ulmoides polysaccharide) were analyzed using a Box-Behnken response surface design. The alleviation effect of EUPS on diquat-induced oxidative stress in mice was also studied. A maximum EUPS yield of 2.60% was obtained under the following optimized conditions: an extraction temperature of 63 °C, extraction time of 1 h, and ratio of liquid to raw materials of 22:1. EUPS exhibited strong 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging ability (87.05%), 2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical-scavenging ability (101.17%), and hydroxyl radical-scavenging ability (62.92%). The administration of EUPS increased the activities of superoxide dismutase, catalase, and glutathione peroxidase and decreased malondialdehyde levels in the livers of mice exposed to diquat. EUPS may inhibit the downregulation of NAD(P)H:quinoneoxidoreductase 1 and heme oxygenase 1 mRNA expression in the livers of diquat-administered mice through the Nrf2-Keap1 signaling pathway. Moreover, the abundance of Firmicutes and Ligilactobacillus was enhanced, whereas that of Helicobacter decreased in the gut of the remaining groups of mice compared with that of the diquat-treated mice. Therefore, EUPS exhibited an antioxidant effect and improved oxidative stress and intestinal flora abundance in mice.