Antioxidant Machinery Research Articles

Exogenously Applied Triacontanol Mitigates Cadmium Toxicity in Vigna radiata L. by Optimizing Growth, Nutritional Orchestration, and Metal Accumulation

Cadmium (Cd) is one of the foremost phytotoxic elements. Its proportion in agricultural soil is increasing critically due to anthropogenic activities. Cd stress is a major crop production threat affecting food security globally. Triacontanol (TRIA) is a phytohormone that promotes growth, development, and metabolic processes in plants. The current study explicates the mitigation of Cd toxicity in Vigna radiata L. (mung bean) seedlings through the application of TRIA by a seed priming technique under Cd stress. The role of TRIA in improving metabolic processes to promote Vigna radiata (mung bean, green gram) vegetative growth and performance under both stressed and unstressed conditions was examined during this study. To accomplish this, three doses of TRIA (10, 20, and 30 µmol L−1) were used to pretreat V. radiata seeds before they were allowed to grow for 40 days in soil contaminated with 20 mg kg−1 Cd. Cd stress lowered seed germination, morphological growth, and biomass in V. radiata plants. The maximum root and shoot lengths, fresh and dry weights of roots, and shoot and seed germination rates were recorded for TRIA2 compared with those of TRIA1 and TRIA3 under Cd stress. In Cd-stressed V. radiata plants, TRIA2 increased the content of chlorophyll a (2.1-fold) and b (3.1-fold), carotenoid (4.3-fold), total chlorophyll (3.1-fold), and gas exchange attributes, such as the photosynthetic rate (2.9-fold), stomatal conductance (6.0-fold), and transpiration rate (3.5-fold), compared with those in plants treated with only Cd. TRIA seed priming increased nutrient uptake (K1+, Na1+, Mg2+, and Zn2+), total phenolic content, total soluble protein content, and DPPH (2,2-diphenyl-1-picrylhydrazyl) activity. Additionally, TRIA2 significantly reduced the quantity of Cd in the plants (3.0-fold) and increased the metal tolerance index (6.6-fold) in plants contrasted with those in the Cd-treated plants. However, TRIA2 promoted plant growth and biomass production by lowering Cd-induced stress through modifying the plant antioxidant machinery and reducing oxidative stress. The improved yield characteristics of V. radiata seedlings treated with TRIA suggest that exogenous TRIA may be used to increase plant tolerance to Cd stress.

Unveiling the Link Between NADPH Oxidase 2 Activation and Mitochondrial Superoxide Formation in Leukemic Cell Killing Induced by Arsenic Trioxide.

This study focused on the interplay between NADPH oxidase 2 (NOX 2) activation and mitochondrial superoxide (mitoO2.-) formation induced by clinically relevant concentrations of arsenic trioxide (ATO; As2O3) in acute promyelocytic leukemia (APL) cells. Carefully controlled inhibitor studies and small interfering RNA mediated downregulation of p47phox (a component of the NOX 2 complex) expression demonstrated that, in an APL cell line, ATO promotes upstream NOX 2 activation critically connected with the formation of mitoO2.- and with the ensuing mitochondrial permeability transition (MPT)-dependent apoptosis. Instead, acute myeloid leukemia (AML) cell lines respond to ATO with low NOX 2 activation, resulting in a state that is non-permissive for mitoO2.- formation. Consistently, through rescue experiments, we demonstrate that pharmacological stimulation of NOX 2 overcomes resistance in these cells, thereby initiating the same cascade of downstream events observed in APL cells. As a final note, several lines of evidence, including measurement of glutathione, catalase and glutathione peroxidase levels, indicated that the antioxidant machinery was similar in APL and AML cells. The results regarding nuclear factor erythroid 2 p45-related factor 2-dependent antioxidant responses were instead of more complex interpretation as NB4 cells appeared particularly responsive to ATO. Our findings allow a novel interpretation of the interplay between NOX 2 activation and mitoO2.- formation induced by ATO, ultimately steering leukemic cells towards MPT-dependent apoptosis. These mechanistic insights provide a rationale for the disparate responses of APL and AML cells to ATO, offering potential avenues for the development of therapeutic intervention tailored to specific leukemia subtypes.

Effects of Rhizospheric Microbes, Growth Regulators, and Biochar in Modulating Antioxidant Machinery of Plants Under Stress

Effects of Rhizospheric Microbes, Growth Regulators, and Biochar in Modulating Antioxidant Machinery of Plants Under Stress

Mycorrhization and chemical seed priming boost tomato stress tolerance by shifts of primary and defence metabolic pathways.

Priming modulates plant stress responses before the stress appears, increasing the ability of the primed plant to endure adverse conditions and thrive. In this context, we investigated the effect of biological (i.e., arbuscular mycorrhizal fungi, AMF) agents and natural compounds (i.e., salicylic acid applied alone or combined with chitosan) against water deficit and salinity on a commercial tomato genotype (cv. Moneymaker). Effects of seed treatments on AMF colonization were evaluated, demonstrating the possibility of using them in combination. Responses to water and salt stresses were analysed on primed plants alone or in combination with the AMF inoculum in soil. Trials were conducted on potted plants by subjecting them to water deficit or salt stress. The effectiveness of chemical seed treatments, both alone and in combination with post-germination AM fungal inoculation, was investigated using a multidisciplinary approach that included eco-physiology, biochemistry, transcriptomics, and untargeted metabolomics. Results showed that chemical seed treatment and AM symbiosis modified the tomato response to water deficit and salinity triggering a remodelling of both transcriptome and metabolome, which ultimately elicited the plant antioxidant and osmoprotective machinery. The plant physiological adaptation to both stress conditions improved, confirming the success of the adopted approaches in enhancing stress tolerance.

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.

Investigating the potency of ethylenediurea (EDU) in alleviating the affliction of ambient ozone in heat labile tomato cultivars (Solanum lycopersicum L.).

Tomato is the second most valuable vegetable crop, and its susceptibility to tropospheric ozone (O3) varies on the cultivar. Eight tomato cultivars with documented O3 sensitivity were reevaluated using ethylenediurea (400ppm EDU) to determine the effectiveness of EDU in assessing O3 sensitivity under heavily O3-polluted tropical conditions. EDU helped in amending the growth, photosynthetic pigments, photosynthetic rate, stomatal conductance, and yield characteristics in the tomato cultivars. EDU reduced the lipid peroxidation and reactive oxygen species content, while enzymatic and non-enzymatic antioxidant responses differed across cultivars. The cultivar Superbug and Sel-7 (O3 susceptible) performed better by employing more biomass and yield and exhibiting more potent antioxidative defense machinery mainly non-enzymatic antioxidants after EDU treatment. The higher value of total antioxidative potential (TAP) in O3 susceptible cultivars suggested the adaptive resilience through EDU application against O3 stress. EDU application greatly enhanced the photosynthetic rate in O3 susceptible cultivars by increasing the stomatal conductance. Hence, both biophysical and biochemical responses were involved in protection against O3 provided by EDU. Kashi chayan and VRT02 (O3 tolerant) cultivars showed least response to EDU, due to their efficient inherent mechanisms in alleviating O3 stress. Thus, EDU may be used as an efficient biomonitoring tool against O3-sensitive cultivars.

Exploring the Potential of Bacillus subtilis IS1 and B. amyloliquificiens IS6 to Manage Salinity Stress and Fusarium Wilt Disease in Tomato Plants by Induced Physiological Responses.

The intensified concerns related to agrochemicals' ecological and health risks have encouraged the exploration of microbial agents as eco-friendly alternatives. Some members of Bacillus spp. are potential plant-growth-promoting agents and benefit numerous crop plants globally. This study aimed to explore the beneficial effects of two Bacillus strains (B. subtilis strain IS1 and B. amyloliquificiens strain IS6) capable of alleviating the growth of tomato plants against salinity stress and Fusarium wilt disease. These strains were able to significantly promote the growth of tomato plants and biomass accumulation in pot trials in the absence of any stress. Under salinity stress conditions (150 mM NaCl), B. subtilis strain IS1 demonstrated superior performance and significantly increased shoot length (45.74%), root length (101.39%), fresh biomass (62.17%), and dry biomass (49.69%) contents compared to control plants. Similarly, B. subtilis strain IS1 (63.7%) and B. amyloliquificiens strain IS6 (32.1%) effectively suppressed Fusarium wilt disease and significantly increased plant growth indices compared to the pathogen control. Furthermore, these strains increased the production of chlorophyll, carotenoid, and total phenolic contents. They significantly affected the activities of enzymes involved in antioxidant machinery and the phenylpropanoid pathway. Hence, this study effectively demonstrates that these Bacillus strains can effectively alleviate the growth of tomato plants under multiple stress conditions and can be used to develop bio-based formulations for use in the fields.

Oxidative state is associated with migration distance, but not traits linked to flight energetics

Flight can be highly energy demanding, but its efficiency depends largely on flight style, wing shape and wing loading, and a range of morphological and lifestyle adaptations that can modify the cost of sustained flight. Such behavioural and morphological adaptations can also influence the physiological costs associated with migration. For instance, during intense flight and catabolism of reserves, lipid damage induced by pro‐oxidants increases, and to keep oxidative physiological homeostasis under control, the antioxidant machinery can be upregulated. Studies on the oxidative physiology of endurance flight have produced contradictory results, making generalization difficult, especially because multispecies studies are missing. Therefore, to explore the oxidative cost of flight and migration, we used samples collected during the breeding season from 113 European bird species and explored the associations of measures of antioxidant capacity (total antioxidant status, uric acid and glutathione concentration) and oxidative damage of lipids (malondialdehyde) with variables reflecting flight energetics (year‐round or specifically during migration) using a phylogenetic framework. We found that none of the traits predicting year‐round flight energy expenditure (flight style, wing morphology and flight muscle morphology) explained any measures of oxidative state. Our results suggest that birds endure their everyday flight exercise without or with low oxidative cost. However, oxidative damage to lipids and one component of the endogenous antioxidant system (uric acid), measured after the end of spring migration on breeding adult birds, increased with migration distance. Our results suggest that migration could have oxidative consequences that might be carried over to subsequent life‐history stages (breeding).

Transcriptomic Communication between Nucleus and Mitochondria during the Browning Process of Lentinula edodes.

To explore the reason for cytoplasmic replacement's significant effect on browning, transcriptomic data of nuclear (N) and mitochondrial (M) mRNAs and long noncoding RNAs (lncRNAs) in L808 and two cytoplasmic hybrids (cybrids) (L808-A2 and L808-B) of Lentinula edodes at three different culturing times (80, 100, and 120 days) were obtained. The results showed that the expression of N and M genes and lncRNAs changed with the culture time and cytoplasmic source. Cytoplasmic replacement significantly affected some M and N genes related to the internal mechanism and external morphological characteristics of L. edodes browning. The internal browning mechanism should be the nicotinamide adenine dinucleotide phosphate (NADPH)-mediated antioxidant machinery to protect mycelia against oxidative stress induced by the generation of reactive oxygen species under light irradiation. External morphological characteristics were the changing features of brown films by melanin (an antioxidant) aggregation on the surface of the mycelia of the bag or log. Especially, some genes were related to the remodeling of the plasma membrane, extracellular enzymes of celluloses and hemicellulases, small molecules, and NADPH metabolic processes. Additionally, communication between the nucleus and mitochondria mediated by M-rps3 was reported for the first time, and it is mainly appreciated in M structural assembly, functional implementation, and cooperation with other organelles.

Cardio-Protective-Promoting Properties of Functional Foods Inducing HDL-Cholesterol Levels and Functionality

High-density lipoprotein (HDL) has been proposed to provide cardio-protective properties through the functionality of its anti-inflammatory and antioxidant enzymatic machinery. Within this article, the beneficial effects of several functional foods on HDL levels and functionality for cardio-protection are thoroughly reviewed. Emphasis is given to functional foods and their antioxidant and anti-inflammatory health-promoting effects for the cardiovascular system through their benefits on HDL, which act either solely or synergistically as an adjuvant approach with well-established anti-atherogenic therapies. Promising outcomes from both in vitro and in vivo studies in animal models and clinical trials, which outline the beneficial effects of such functional foods on HDL levels and functionality, are thoroughly discussed. The mechanisms of the obtained antioxidant, anti-inflammatory, antithrombotic, and cardio-protective effects on HDL activities of functional foods containing natural bioactives are also outlined. Limitations and future perspectives on the overall benefits that these natural bioactive compounds exert as important ingredients in functional foods to induce HDL-related benefits and to strengthen cardiovascular health are also discussed.

Overexpression of SIMK in menadione-treated alfalfa enhances antioxidant machinery and leads to oxidative stress resistance

Mitogen-activated protein kinases (MAPKs) transduce stress and developmental signals related to the production of reactive oxygen species (ROS). Alfalfa (Medicago sativa L.) is a valuable forage and human nutrition crop, however, the involvement of MAPKs in plant resistance to oxidative stress is poorly understood in this species. Therefore, we elucidated the role of STRESS-INDUCED MAPK (SIMK) in alfalfa response to menadione, a compound inducing ROS generation, exploiting transgenic alfalfa lines with contrasting SIMK abundance. SIMK was activated by short-term menadione treatment and relocated from the nucleus to the cytoplasm. Proteomic analysis revealed that menadione caused changes in the abundance of proteins involved in metabolism, oxidative stress, biotic stress response, detoxification of carbonyl species, glutathione homeostasis, chloroplast protein turnover, photosynthesis, and membrane trafficking. Genetic manipulations of SIMK altered the abundance of proteins involved in mitochondrial and chloroplast protein import and processing, as well as GLUTATHIONE S-TRANSFERASES (GSTs). Increased GST abundance and activity in roots, and modifications in mitochondrial and chloroplast protein turnover might be responsible for the elevated oxidative stress resistance of alfalfa line overexpressing SIMK. This was supported by the reduced ROS levels in this line. These results reveal a complex nature of plant stress response and suggest a new role of SIMK in the alfalfa resistance to menadione-induced oxidative stress.

Pretreatment with aqueous Moringa oleifera Lam. leaf extract prevents cadmium-induced hepatotoxicity by improving cellular antioxidant machinery and reducing cadmium accumulation

Cadmium (Cd) is a highly harmful pollutant that poses a serious threat to human health. The liver is the primary organ for Cd accumulation, and Cd-induced hepatotoxicity has been shown to be strongly correlated with an oxidative imbalance in hepatocytes. Our previous studies in the eukaryotic model organism Saccharomyces cerevisiae revealed that not only co-treatment but also pretreatment with aqueous Moringa oleifera Lam. leaf extract (AMOLE) effectively mitigated Cd toxicity by reducing intracellular Cd accumulation and Cd-mediated oxidative stress. In this study, we therefore investigated the preventive effect of AMOLE against Cd toxicity in human HepG2 hepatocytes. The results showed that, similar to the case of the yeast model, pretreatment with AMOLE prior to Cd exposure also significantly inhibited Cd-induced oxidative stress in HepG2 cells. Untargeted LC-MS/MS-based metabolomic analysis of AMOLE revealed that its major phytochemical constituents were organic acids, particularly phenolic acids and carboxylic acids. Additionally, DPPH-HPTLC fingerprints suggested that quercetin and other flavonoids possibly contribute to the antioxidant activities of AMOLE. Based on our findings, it appears that pretreatment with AMOLE prevented Cd-induced hepatotoxicity via three possible mechanisms: i) direct elimination of free radicals by AMOLE antioxidant compounds; ii) upregulation of antioxidant defensive machinery (GPx1, and HO-1) via Nrf2 signaling cascade to improve cellular antioxidant capacity; and iii) reduction of intracellular Cd accumulation, probably by suppressing Cd uptake. These data strongly suggest the high potential of AMOLE for clinical utility in the prevention of Cd toxicity.

Redox Status as a Key Driver of Healthy Pancreatic Beta-Cells.

Redox status plays a multifaceted role in the intricate physiology and pathology of pancreatic beta-cells, the pivotal regulators of glucose homeostasis through insulin secretion. They are highly responsive to changes in metabolic cues where reactive oxygen species are part of it, all arising from nutritional intake. These molecules not only serve as crucial signaling intermediates for insulin secretion but also participate in the nuanced heterogeneity observed within the beta-cell population. A central aspect of beta-cell redox biology revolves around the localized production of hydrogen peroxide and the activity of NADPH oxidases which are tightly regulated and serve diverse physiological functions. Pancreatic beta-cells possess a remarkable array of antioxidant defense mechanisms although considered relatively modest compared to other cell types, are efficient in preserving redox balance within the cellular milieu. This intrinsic antioxidant machinery operates in concert with redox-sensitive signaling pathways, forming an elaborate redox relay system essential for beta-cell function and adaptation to changing metabolic demands. Perturbations in redox homeostasis can lead to oxidative stress exacerbating insulin secretion defect being a hallmark of type 2 diabetes. Understanding the interplay between redox signaling, oxidative stress, and beta-cell dysfunction is paramount for developing effective therapeutic strategies aimed at preserving beta-cell health and function in individuals with type 2 diabetes. Thus, unraveling the intricate complexities of beta-cell redox biology presents exciting avenues for advancing our understanding and treatment of metabolic disorders.

Protocatechuic Acid from Euonymus alatus Mitigates Scopolamine-Induced Memory Impairment in Mice.

The increasing prevalence of age-related neurodegenerative disorders owing to the aging population worldwide poses substantial challenges. This study investigated the neuroprotective effects of protocatechuic acid (PCA), a compound found in various fruits, vegetables, and grains, using a scopolamine-induced hypomnesia mouse model. Six-week-old male C57BL/6J mice were orally administered PCA at doses of 10 and 100 mg/kg body weight per day for two weeks, along with intraperitoneal injections of scopolamine. Learning and memory abilities were assessed using the passive avoidance, Morris water maze, and Y-maze behavioral assays. Biochemical analyses evaluated the levels of oxidative stress markers, including 8-hydroxydeoxyguanosine (8-OHdG) in the blood and malondialdehyde (MDA) in the brain, as well as phase II antioxidant proteins in the hippocampus. Histological examination was conducted to determine hippocampal integrity. Our results demonstrated that PCA administration at 10 mg/kg body weight per day or higher for two weeks (i) significantly ameliorated scopolamine-induced learning and memory impairments, as evidenced by improved performance in behavioral tasks, (ii) reduced plasma 8-OHdG levels and cerebral MDA levels in a dose-dependent manner, (iii) increased antioxidant protein expressions in the hippocampal tissue, and (iv) mitigated histological damage in the hippocampal region of the brain. These findings suggest that oral administration of PCA provides neuroprotective effects against oxidative stress-induced learning and memory impairments, possibly through upregulating antioxidant machinery. Therefore, PCA may serve as a promising dietary supplement for mitigating cognitive deficits associated with neurodegenerative diseases.

Boosting banana resilience: Calcium supplementation enhances osmolyte and secondary metabolites production and strengthens the antioxidant machinery in drought and cold-exposed banana plants

Banana (Musa spp.) is a vital tropical fruit crop cultivated worldwide and is known for its nutritional value. The cultivation of bananas is often challenged by environmental stresses such as cold and drought, which can adversely affect plant productivity. In response to these challenges, plants deploy adaptive mechanisms to mitigate the impacts of environmental stresses. Calcium (Ca2+), recognized as a universal second messenger, is pivotal in cellular responses to hormones, pathogens, and stress factors. This study explores the potential of exogenous calcium supplementation as a cost-effective and promising solution, influencing metabolic activities and signal transductions in plants. To investigate the defensive role of Ca2+ supplementation in banana plants subjected to drought (200 mM Mannitol) and cold (14 °C) stress, comprehensive analyses were conducted to elucidate the mechanism underlying Ca2+-mediated stress tolerance. The plants were treated with mannitol, cold or Hoagland, and then supplemented with CaCl2 (15 mM). Exogenous Ca2+ treatment significantly increased the proline content and maintained water balance and cellular stability. Additionally, it enhanced the production of protective secondary metabolites and activated key antioxidant enzymes, countering oxidative stress. Molecular analysis revealed an upregulation of calcium-binding proteins involved in stress response, while Ca2+ treatment reduced lipid peroxidation, as indicated by lower malondialdehyde (MDA) levels, signifying improved membrane integrity and reduced oxidative damage. These findings underscore the protective impact of exogenously supplied calcium, offering insights for sustainable strategies to enhance banana resilience in the face of environmental challenges and climate change.

Ethylene Is Crucial in Abscisic Acid-Mediated Modulation of Seed Vigor, Growth, and Photosynthesis of Salt-Treated Mustard.

The current study explored the differential interaction between ethylene (ET) and abscisic acid (ABA) in relation to salt stress in mustard (Brassica juncea L.) plants. Significant reductions in seed germination, growth, and photosynthesis were observed with 100 mmol NaCl. Among the cultivars tested, the Pusa Vijay cultivar was noted as ET-sensitive. Pusa Vijay responded maximally to an application of 2.0 mmol ethephon (Eth; 2-chloethyl phosphonic acid-ethylene source), and exhibited the greatest growth, photosynthesis, activity of 1-aminocyclopropane carboxylic acid (ACC) synthase (ACS), and ET evolution. Notably, Eth (2.0 mmol) more significantly improved the seed germination percentage, germination and vigor index, amylase activity, and reduced H2O2 content under salt stress, while ABA (25 µmol) had negative effects. Moreover, the individual application of Eth and ABA on Pusa Vijay under both optimal and salt-stressed conditions increased the growth and photosynthetic attributes, nitrogen (N) and sulfur (S) assimilation, and antioxidant defense machinery. The addition of aminoethoxyvinylglycine (0.01 µmol AVG, ET biosynthesis inhibitor) to ABA + NaCl-treated plants further added to the effects of ABA on parameters related to seed germination and resulted in less effectiveness of growth and photosynthesis. In contrast, the effects of Eth were seen with the addition of fluoridone (25 µmol Flu, ABA biosynthesis inhibitor) to Eth + NaCl. Thus, it can be suggested that ET is crucial for alleviating salt-induced inhibition in seed germination, growth, and photosynthesis, while ABA collaborated with ET to offer protection by regulating nutrient assimilation and enhancing antioxidant metabolism. These findings provide insight into the complex regulatory processes involved in ET-ABA interaction, enhancing our understanding of plant growth and development and the mitigation of salt stress in mustard. It opens pathways for developing hormonal-based strategies to improve crop productivity and resilience, ultimately benefiting agricultural practices amidst a challenging environment.

Elucidating PAR1 as a therapeutic target for delayed traumatic brain injury: Unveiling the PPAR-γ/Nrf2/HO-1/GPX4 axis to suppress ferroptosis and alleviate NLRP3 inflammasome activation in rats

Repetitive traumatic brain injury (RTBI) is acknowledged as a silent overlooked public health crisis, with an incomplete understanding of its pathomechanistic signaling pathways. Mounting evidence suggests the involvement of thrombin and its receptor, the protease-activated receptor (PAR)1, in the development of secondary injury in TBI; however, the consequences of PAR1 modulation and its impact on ferroptosis-redox signaling, and NLRP3 inflammasome activation in RTBI, remain unclear. Further, the utilitarian function of PAR1 as a therapeutic target in RTBI has not been elucidated. To study this crosstalk, RTBI was induced in Wistar rats by daily weight drops on the right frontal region for five days. Three groups were included: normal control, untreated RTBI, and RTBI+SCH79797 (a PAR1 inhibitor administered post-trauma at 25 μg/kg/day). The concomitant treatment of PAR1 antagonism improved altered behavior function, cortical histoarchitecture, and neuronal cell survival. Moreover, the receptor blockade downregulated mRNA expression of PAR1 but upregulatedthat of the neuroprotective receptor PPAR-γ. The anti-inflammatory impact of SCH79797 was signified by the low immune expression/levels of NF-κB p65,TNF-α, IL-1β, and IL-18. Consequently, the PAR1 blocker hindered the formation of inflammasome components NLRP3, ASC, and activated caspase-1. Ultimately, SCH79797 treatment abated ferroptosis-dependent iron redox signaling through the activation of the antioxidant Nrf2/HO-1 axis and its subsequent antioxidant machinery (GPX4, SOD) to limit lipid peroxidation, iron accumulation, and transferrin serum increment. Collectively, SCH79797 offered putative preventive mechanisms against secondary RTBI consequences in rats by impeding ferroptosis and NLRP3 inflammasome through activating the PPAR-γ/Nrf2 antioxidant cue.

Enhancing the Storage Longevity of Apples: The Potential of Bacillus subtilis and Streptomyces endus as Preventative Bioagents against Post-Harvest Gray Mold Disease, Caused by Botrytis cinerea.

Gray mold, caused by Botrytis cinerea Pers. Fr., is one of the most vital plant diseases, causing extensive pre- and post-harvest losses in apple fruits. In the current study, we isolated and identified two potential endophytic bioagents, Bacillus subtilis and Streptomyces endus. Both bioagents exhibited a potent fungistatic effect against B. cinerea under both in vitro and in planta conditions. Moreover, two experiments were carried out; (i) the first experiment was conducted at room temperature after artificial inoculation with B. cinerea to monitor the progression of the infection and the corresponding biochemical responses of the apples. Our in vivo findings showed that the treated B. cinerea-infected apple fruits with the cell-free bacterial filtrate of B. subtilis and S. endus (dipping or wrapping) significantly reduced the rotten area of the treated apple at room temperature. Additionally, B. subtilis and S. endus enhanced the enzymatic (POX and PPO) and non-enzymatic (phenolics and flavonoids) antioxidant defense machinery in treated apples. (ii) The second experiment focused on the preventive effects of both bioagents over a 90-day storage period at 1 °C of healthy apples (no artificial inoculation). The application of both bacterial filtrates prolonged the storage period, reduced the relative weight loss, and maintained high-quality parameters including titratable acidity, firmness, and total soluble solids of apple fruits under cold storage at 1 °C. The Kaplan-Meier analysis of rotten apples over 90 days during cold storage showed that the treated apples lasted longer than the non-treated apples. Moreover, the lifespan of apple fruits dipped in the culture filtrate of B. subtilis, or a fungicide, was increased, with no significant differences, compared with the non-treated apples. The current results showed the possibility of using both bioagents as a safe and eco-friendly alternative to chemical fungicides to control gray mold disease in apples.

Chitosan-fulvic acid nanoparticles enhance drought tolerance in maize via antioxidant defense and transcriptional reprogramming.

Nanoparticles are promising alternatives to synthetic fertilizers in the context of climate change and sustainable agriculture. Maize plants were grown under gradient concentrations (50 μM, 100 μM, 200 μM, 500 μM, and 1 mM) of chitosan (Ch), fulvic acid (FA) or chitosan-fulvic acid nanoparticles (Ch-FANPs). Based on the overall phenotypic assessment, 100 μM was selected for downstream experiments. Maize plants grown under this optimized concentration were thereafter subjected to drought stress by water withholding for 14 days. Compared to the individual performances, the combined treatment of Ch-FANPs supported the best plant growth over chitosan, fulvic acid, or sole watered plants and alleviated the adverse effects of drought by enhancing root and shoot growth, and biomass by an average 20%. In addition, Ch-FANPs-treated plants exhibited a significant reduction in hydrogen peroxide (H2O2) content (~10%), with a concomitant increase in ascorbate peroxidase (APX) activity (>100%) while showing a reduced lipid peroxidation level observed by the decrease in malondialdehyde (MDA) content (~100%) and low electrolyte leakage level. Furthermore, chlorophyll content increased significantly (>100%) in maize plants treated with Ch-FANPs compared to Ch or FA and control in response to drought. The expression of drought-induced transcription factors, ZmDREB1A, ZmbZIP1, and ZmNAC28, and the ABA-dependent ZmCIPK3 was upregulated by Ch-FANPs. Owing to the above, Ch-FANPs are proposed as a growth-promoting agent and elicitor of drought tolerance in maize via activation of antioxidant machinery and transcriptional reprogramming of drought-related genes.

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms observed in cancer therapy. In this review, we outline the contribution of antioxidant systems to therapeutic resistance. We detail the fundamental constituents of these systems, encompassing the central regulatory mechanisms involving transcription factors (of particular importance is the KEAP1/NRF2 signaling axis), the molecular effectors of antioxidants, and the auxiliary systems responsible for NADPH generation. Furthermore, we present recent clinical trials based on targeted antioxidant systems for the treatment of cancer, assessing the potential as well as challenges of this strategy in cancer therapy. Additionally, we summarize the pressing issues in the field, with the aim of illuminating a path toward the emergence of novel anticancer therapeutic approaches by orchestrating redox signaling.