Search Results (1,717)

Background/Objectives: Manganese (Mn) is a neurotoxic trace element whose excessive accumulation in the brain can induce hippocampal damage via oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. This study investigated whether honokiol (HNK) and its liposomal nanoformulation (HNK-LNPs) can ameliorate Mn-induced hippocampal neurotoxicity by modulating key antioxidant and mitochondrial regulatory pathways. Methods: Male Wistar rats were subjected to Mn exposure to induce hippocampal neurotoxicity and were treated with HNK or HNK-LNPs. We assessed oxidative status via NRF2/HO-1 signaling, antioxidant defenses (glutathione, GPx, SOD, CAT), and oxidative indices (ROS, MDA). Neuroinflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, Iba-1), mitochondrial respiratory chain function and ATP levels, SIRT1/PGC-1α signaling, and neurotransmitter homeostasis were evaluated. We analyzed apoptosis using Bax, Bcl-2, caspase-3, and cytochrome c, along with histopathological and ultrastructural examination of the hippocampus. Results: Mn exposure was associated with NRF2/HO-1 downregulation, depleted endogenous antioxidants, increased ROS and MDA levels, and increased NF-κB–driven neuroinflammation and microglial Iba-1 expression. Mn was further associated with reduced ATP synthesis, dysregulation of SIRT1/PGC-1α signaling, and disrupted neurotransmitter balance, with a pro-apoptotic shift (elevated Bax, caspase-3, cytochrome c; reduced Bcl-2) and neuronal degeneration. Co-treatment with HNK, and more prominently with HNK-LNPs, was associated with reversing these alterations, restoring antioxidant and mitochondrial pathways, dampening inflammatory cascades, normalizing neurotransmitters, and favoring neuronal survival, with many indices approaching control values and consistently surpassing free HNK. Conclusions: Liposomal encapsulation significantly enhances honokiol’s neuroprotection against Mn-induced hippocampal neurotoxicity, likely via improved CNS bioavailability and coordinated modulation of NRF2/HO-1 and SIRT1/PGC-1α pathways. These findings support HNK-LNPs as a promising multi-mechanistic therapeutic strategy for metal-induced and related neurotoxic brain disorders. Full article

Parkinson’s disease (PD) is widely regarded as a disorder of dopaminergic neurons that involves mitochondrial dysfunction, impaired mitophagy, and oxidative stress. However, the nature and significance of skeletal muscle pathology remain unclear. In this study, we used Caenorhabditis elegans, which lack muscle stem cells in adulthood, to examine the effects of PDR-1/Parkin deficiency on mitochondrial homeostasis and motor function under conditions where muscle regeneration does not occur. Silencing of pdr-1 attenuated age-related mitochondrial fragmentation in body-wall muscle cells but was associated with later impairments in locomotor activity and loss of nuclear GFP signals, suggesting progressive muscle cell damage. By day 2 of adulthood, mitochondrial reactive oxygen species (mtROS) levels were elevated in muscle cells subjected to pdr-1 RNAi, and in the pdr-1(gk448) mutant this mtROS elevation was accompanied by a reduction in mitochondrial membrane potential (ΔΨm). In vivo imaging further revealed elevated mitochondrial Ca²⁺ levels ([Ca²⁺]_mito) in PDR-1-deficient muscle cells. Moreover, the mtROS increase associated with PDR-1 deficiency was suppressed in mcu-1 mutants. These findings support a model in which MCU-1-dependent elevation of [Ca²⁺]_mito contributes to oxidative mitochondrial defects in PDR-1/Parkin-deficient muscle. Full article

Pseudomonas syringae pv. actinidiae (Psa) is the most destructive pathogen of kiwifruit, and the absence of curative measures makes the management of Psa-induced kiwifruit bacterial canker (KBC) particularly challenging. Elettaria cardamomum produces an essential oil (CAR) rich in bioactive compounds with demonstrated potential to act directly against Psa, but its mechanisms of action remain insufficiently explored. Here, we investigated CAR’s mode of action in plants with established mild KBC symptoms, and assessed its potential as a plant elicitor. In the in planta assay, CAR application (0.1% w/v, applied 7 days after inoculation) reduced KBC symptoms, with the strongest effect observed 14 days after treatment (DAT). However, CAR did not significantly affect oxidative stress biomarkers, antioxidant system, pigments and primary metabolism, or the expression of target genes related to systemic acquired resistance or salicylic acid and jasmonic acid pathways. For instance, Psa inoculation significantly upregulated PR1 (≈5.4-fold) and PR5 (≈4.3–5.5-fold), irrespective of CAR application. Complementary in vitro assays revealed a transient, phase-dependent antimicrobial activity of CAR: although the effect disappeared by 32 h in liquid-phase assay and no inhibition was observed under vapor-phase exposure, a strong reduction in Psa viable cells (79.7%) was observed after 8 h exposure in the liquid phase. This study demonstrates that CAR exerts a direct, albeit transient, antibacterial effect against Psa, conferring curative activity when applied to plants with mild KBC symptoms. Consequently, repeated applications may be required to maintain disease suppression, as CAR does not appear to induce a sustained preventive defense response in the host. Full article

Currently, effective disease-modifying treatments for Parkinson’s disease (PD) remain lacking. Although exercise has been confirmed to exert neuroprotective effects against PD, its specific molecular mechanisms remain unclear. In particular, the causal role of the Nuclear Factor E2-related Factor 2 (Nrf2)–antioxidant response element (ARE) signaling axis in this process has not been clearly elucidated. This study aimed to provide direct causal evidence that regular treadmill exercise protects the substantia nigra pars compacta (SNc)–striatal dopaminergic system by activating the Nrf2-ARE pathway. The results showed that exercise significantly improved motor function deficits in PD mice, preserved the number of TH-positive neurons, and restored striatal dopamine homeostasis. Mechanistically, exercise activated the Nrf2-ARE pathway, thereby inhibiting the accumulation of mitochondrial ROS (mtROS) and the activation of pro-inflammatory amoeboid microglia in the substantia nigra. Crucially, the improvements in behavioral, neuropathological, and neurochemical indicators induced by exercise were completely reversed, returning to levels comparable to those in the sedentary model group. In conclusion, this study provides clear pharmacological evidence that the neuroprotective effect of regular treadmill exercise against chronic PD strictly depends on the Nrf2-ARE pathway. These findings indicate that Nrf2 is a key mechanistic node linking exercise and neuroprotection, providing reliable preclinical evidence for Nrf2-targeted disease-modifying strategies in PD rehabilitation. Full article

Cancer metastasis, characterized by the dissemination of malignant cells from the primary tumor to distant organs, remains the leading cause of cancer-related mortality in solid tumors. In colorectal cancer (CRC), increasing attention has been directed toward therapeutic strategies aimed at suppressing cancer cell migration and invasion rather than solely reducing tumor mass, giving rise to the concept of migrastatic therapies. In the present study, green-synthesized silver nanoparticles (AgNPs), previously obtained using aqueous extracts of Filipendula ulmaria (L.) Maxim. and Salvia verticillata L., were evaluated for their antimigratory and anti-inflammatory potential in human colorectal carcinoma HCT-116 cells. Treatment with AgNPs induced considerable perturbations in cellular redox homeostasis, as evidenced by increased intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH), and nitric oxide (NO) levels. These redox alterations were accompanied by a significant inhibition of cancer cell migration, together with reduced expression of matrix metalloproteinases MMP-2 and MMP-9, key mediators of extracellular matrix remodeling associated with tumor progression. AgNP exposure was associated with activation of the cytoprotective transcription factor Nrf-2 and suppression of the pro-inflammatory NF-κB/COX-2 signaling axis, indicating coordinated modulation of redox-sensitive pathways linked to tumor cell motility and inflammatory responses. Collectively, these findings demonstrate that green-synthesized AgNPs derived from F. ulmaria and S. verticillata exert multi-level regulatory effects on redox balance, inflammatory signaling, and migration-associated molecular markers in colorectal cancer cells. This study supports their potential as promising migrastatic nanocarriers for further investigation in colorectal cancer research. Full article

Drought and salinity are major abiotic stresses that severely constrain plant growth and agricultural productivity. Histidine kinases (HKs), as key components of the plant two-component system (TCS), play crucial roles in environmental signal perception and adaptive responses. In this study, we functionally characterized a sweet potato (Ipomoea batatas L.) HK gene, IbHK1a, and investigated its role in drought and salt stress tolerance. Expression analysis revealed that IbHK1a is predominantly expressed in root tissues, particularly in storage and fibrous roots, indicating its potential involvement in stress sensing and adaptation. Subcellular localization demonstrated that the IbHK1a protein is localized to the plasma membrane, suggesting a role in external signal perception. To elucidate its biological function, IbHK1a was heterologously overexpressed in Arabidopsis thaliana. Transgenic plants exhibited significantly enhanced tolerance to drought and salt stress, as evidenced by higher seed germination rates, improved primary root growth, reduced leaf wilting, and increased survival rates compared with wild-type (WT) plants. Physiological analyses showed that IbHK1a overexpression led to increased activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), accompanied by reduced accumulation of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂) and malondialdehyde (MDA). Consistently, leaf histochemical staining confirmed lower ROS accumulation in transgenic plants under stress conditions. In sweet potato, overexpression of IbHK1a in transgenic hairy roots enhanced tolerance to drought and salinity, whereas RNA interference lines displayed increased sensitivity, further confirming its positive regulatory role. Additionally, protein interaction analysis indicated that IbHK1a interacts with Arabidopsis histidine phosphotransferase proteins (AHPs), suggesting its involvement in conserved TCS-mediated phosphorelay signaling pathways. Functional complementation analysis demonstrated that IbHK1a partially rescues the stress-sensitive phenotype of the AHK1 mutant, indicating functional conservation with Arabidopsis AHK1. Collectively, these findings demonstrate that IbHK1a positively regulates drought and salt stress tolerance by enhancing antioxidant defense and ROS homeostasis. Its interaction with AHPs and partial complementation of the ahk1 mutant further support its involvement in the conserved TCS phosphorelay pathway. These results establish IbHK1a as an important component of abiotic stress responses and a potential genetic target for improving drought and salinity tolerance in sweet potato. Full article

Peritoneal dialysis (PD) is an effective renal replacement therapy; however, its long-term use is limited by the detrimental effects of glucose-based PD fluids on the peritoneal membrane, contributing to fibrosis and ultrafiltration failure. Previous studies have demonstrated that high-glucose exposure promotes oxidative DNA damage through upregulation of thioredoxin-interacting protein (TXNIP) expression, resulting in reduced thioredoxin (Trx) activity. This study investigated strategies to reduce oxidative stress in human peritoneal mesothelial cells exposed to high glucose concentrations. TXNIP expression, Trx activity, intracellular oxidative stress levels, and oxidative DNA damage were analyzed. High-glucose exposure caused a dose-dependent increase in TXNIP expression, a 5–15% reduction in Trx activity, and increased intracellular oxidative stress levels and oxidative DNA damage. Pre-treatment with the ROS scavenger N-acetylcysteine (NAC) reduced these effects. These findings demonstrate that glucose-induced TXNIP upregulation disrupts cellular redox homeostasis, resulting in increased intracellular oxidative stress and oxidative damage. Antioxidant compounds may therefore represent promising therapeutic strategies to protect the peritoneal membrane and improve long-term outcomes in PD. Full article

Climate change is increasing the frequency and severity of abiotic stresses, including drought, salinity, waterlogging, and temperature extremes, thereby threatening the productivity and quality of Brassica crops. This review synthesizes recent progress in abiotic stress tolerance from physiological, genetic, epigenetic, and multi-omics perspectives, with an emphasis on how mechanistic discoveries can be translated into breeding decisions. We first outline the signaling hierarchy that links stress perception at the plasma membrane and cell wall interface to Ca²⁺ signaling, MAPK cascades, hormone crosstalk, osmotic adjustment, ROS homeostasis, and metabolic reprogramming. We then examine the genetic architecture of stress tolerance through QTL mapping, GWAS, and functional genomics, highlighting how allopolyploidy, subgenome specialization, homoeologous gene divergence, and alternative splicing create both opportunities and complications for Brassica improvement. We further evaluate how transcriptomic, epigenomic, metabolomic, and microbiome-related data are revealing regulatory complexity but remain underused for prediction and causal inference. Major bottlenecks include the inefficient conversion of association signals into validated functional markers, the descriptive rather than predictive use of multi-omics datasets, limited mechanistic understanding of combined stresses, and insufficient field validation across genetic backgrounds. Finally, we discuss integrated breeding strategies, including marker-assisted selection, genomic selection, genome editing, wild germplasm utilization, microbiome-assisted approaches, and synthetic biology. By connecting stress biology with translational breeding, this review provides a framework for developing climate-resilient Brassica cultivars. Full article

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), severely restricts the sustainable development of the kiwifruit industry. Screening stable resistant germplasm and establishing efficient disease resistance evaluation methods are core prerequisites for breeding resistant cultivars. In this study, 86 Actinidia accessions were systematically assessed for Psa susceptibility over three consecutive years using the reported detached shoot inoculation assay. Seven representative accessions with contrasting resistance phenotypes, namely ‘Cuiyu’, ‘Chuhong’, ‘Jinmei’, ‘Hongyang’, ‘Cuixiang’, ‘Avfs08’, and ‘G3’, were selected to measure the activities of four defense-related enzymes post Psa inoculation to dissect the physiological mechanisms driving divergent Psa resistance in kiwifruit. Lesion lengths across years exhibited a significant positive correlation, demonstrating that this inoculation method delivers repeatable, genetically stable phenotypic data with limited environmental interference. Two accessions belonging to A. valvata and A. eriantha exhibited stable high resistance via synergistic biochemical defenses. By contrast, the widely grown cultivar ‘Hongyang’ was highly susceptible, while moderately resistant materials such as ‘Cuiyu’ and ‘Yannong 3’ were discovered within the inherently susceptible species A. chinensis. Highly resistant accessions rapidly induced coordinated increases in SOD and PAL activity at 24 h post inoculation to maintain ROS homeostasis and lignin biosynthesis, whereas susceptible accessions displayed chaotic, ineffective enzymatic stress responses. Temporal synergy of PAL and POD may act as the key defensive regulatory mode. This study uncovered substantial interspecific variation in Psa resistance across Actinidia germplasm, identified elite donors with stable resistance, and elucidated the physiological mechanisms of kiwifruit resistance to Psa. These findings provided a theoretical foundation and valuable germplasm for subsequent resistance gene mining and disease resistance breeding. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, pancreatic β-cell dysfunction, and dysregulated glucose and lipid metabolism. Sustained hyperglycemia and hyperlipidemia promote excessive reactive oxygen species (ROS) production, antioxidant defense depletion, and chronic low-grade inflammation, thereby aggravating insulin signaling impairment, β-cell injury, and diabetes-related complications. Although current glucose-lowering therapies have improved glycemic control, weight management, and cardiorenal outcomes, oxidative stress and inflammation remain incompletely addressed in many individuals with T2DM. Curcumin, a natural polyphenol derived from Curcuma longa L., exhibits antioxidant, anti-inflammatory, lipid-regulating, insulin-sensitizing, and tissue-protective activities. Evidence suggests that curcumin may alleviate T2DM-associated oxidative stress by suppressing ROS generation, reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, modulating the advanced glycation end-product/receptor for advanced glycation end-product (AGE/RAGE) axis, activating nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling, preserving mitochondrial homeostasis, and protecting β-cells. It may also inhibit nuclear factor-κB (NF-κB) and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signaling, decrease pro-inflammatory cytokines and C-reactive protein (CRP), improve metabolic tissue inflammation, and attenuate gut-derived inflammation by regulating gut microbiota and intestinal barrier function. However, current clinical evidence mainly supports modest improvements in metabolic, inflammatory, oxidative stress-related, and selected complication-related biomarkers rather than definitive disease-modifying outcomes. Moreover, formulation heterogeneity, low bioavailability, limited pharmacokinetic reporting, and insufficient long-term endpoint data remain major translational barriers. This review summarizes the molecular mechanisms, clinical evidence, formulation-dependent interpretation, safety considerations, and translational limitations of curcumin as a candidate adjunctive intervention for T2DM, rather than as a replacement for evidence-based antidiabetic therapy. Full article

Superoxide dismutase 2 (SOD2), a key mitochondrial antioxidant enzyme, is essential for maintaining cellular redox homeostasis by scavenging superoxide radicals. While viruses often induce oxidative stress, the specific role of SOD2 in antiviral defense remains unclear. Here, we report that vaccinia virus (VACV) infection triggers mitochondrial and cellular reactive oxygen species (ROS) and selectively upregulates SOD2, but not SOD1. Genetic knockout of SOD2 exacerbated mitochondrial ROS (mtROS) accumulation and significantly enhanced VACV replication and spread, resulting in larger viral plaques. Conversely, SOD2 overexpression constrained plaque formation and suppressed viral dissemination. Mechanistically, the antiviral function of SOD2 does not strictly rely on its enzymatic activity or mitochondrial targeting, as neither the deacetylation-mimicking mutant nor the mutant lacking the mitochondrial localization signal peptide appreciably impaired its antiviral potency. Furthermore, in a rabbit model, local overexpression of human SOD2 attenuated the poxvirus lesion formation. Our findings unveil an important yet easily overlooked role of SOD2 in antiviral defense and posit it as a promising candidate for the development of host-directed therapeutics against poxviruses. Full article

Bergapten is a plant-derived linear furanocoumarin widely distributed in Rutaceae and Apiaceae species and increasingly recognized for its multifunctional anticancer potential. This review critically synthesizes current evidence on bergapten’s biosynthesis, physicochemical and pharmacokinetic properties, anti-inflammatory and antioxidant pharmacodynamics, and mechanistic antitumor activity, highlighting its translational relevance within pharmaceutical development. Preclinical studies across diverse malignancies demonstrate pleiotropic anticancer effects. Mechanistically, bergapten activates mitochondrial apoptosis via Bax/Bcl-2 modulation and caspase cascades, induces cell cycle arrest through p53–p21 signaling, and suppresses PI3K/Akt/mTOR and NF-κB pathways. Additional effects include PTEN-mediated autophagy induction, interference with metabolic reprogramming, reversal of multidrug resistance through ABC transporter modulation, and context-dependent photoactivated cytotoxicity. Beyond direct tumor cell targeting, bergapten attenuates pro-inflammatory mediators and regulates redox homeostasis through downregulation of NOX4-derived ROS and activation of Nrf2-driven antioxidant defenses, addressing the redox–inflammatory axis implicated in carcinogenesis. Despite promising mechanistic depth, clinical translation is limited by incomplete human pharmacokinetic data and poor aqueous solubility. Nanotechnology-enabled delivery systems and structural derivatives offer strategies to enhance bioavailability and therapeutic index. Overall, bergapten emerges as a systems-level phytochemical candidate warranting further translational investigation in oncology. Full article

Soil microorganisms are essential for nutrient cycling, plant productivity, and soil health, yet the relative importance of land-use and soil depth in shaping agricultural microbiomes remains poorly understood. This study investigated soil microbial communities across uncultivated land, alfalfa fields, crop systems (feed corn and sweet corn), and orchard systems (walnut and quince) in the Hajdúnánás region of Hungary using shotgun metagenomic sequencing and soil physicochemical analyses. Microbial alpha diversity showed limited variation among land-use systems but declined significantly with soil depth in both bacterial (Kruskal–Wallis, p = 0.00054) and fungal (p = 0.00051) communities. Beta diversity analyses identified soil depth as the primary driver of microbial community composition in both bacterial (R² = 0.305, p = 0.001) and fungal (R² = 0.277, p = 0.001) communities. In contrast, land-use significantly influenced only fungal community composition (R² = 0.250, p = 0.005). Fungal alpha diversity showed significant negative relationships with soil pH and CaCO₃, whereas bacterial diversity exhibited only weak correlations. Crop soils contained the highest numbers of unique bacterial and fungal taxa. Functional analyses revealed significant differences in nutrient cycling, plant-growth-related, decomposition, and environmental adaptation functions among land-use systems. In crop soils, topsoil communities were enriched in oxidative stress-related pathways involved in reactive oxygen species detoxification (ROS), redox homeostasis, and stress regulation, whereas subsoil communities showed a greater representation of antioxidant metabolite production functions. Co-occurrence network analyses indicated greater connectivity in perennial systems, particularly alfalfa soils. Analyses of bacterial and fungal species with reported phytopathogenic potential identified stable cores of phytopathogenic species across agricultural systems, with soil pH emerging as the strongest environmental factor associated with the abundance of phytopathogenic species. Overall, soil depth was the primary driver of bacterial and fungal community assembly, whereas land-use primarily shaped fungal community composition and influenced ecological functions, microbial interaction networks, and the distribution of phytopathogenic species. Full article

While individual Si-nutrient interactions have been reviewed separately, a comparative analysis of multiple Si-element interactions remains lacking. This review compares current knowledge on co-application of Si with selenium (Se), sulphur (S), zinc (Zn) and iron (Fe), focusing on stress tolerance, nutrient homeostasis, physiological responses, secondary metabolism and agronomic relevance. The evidence indicates that combining Si with these elements helps maintain reactive oxygen species (ROS) homeostasis, strengthen antioxidant defenses, stabilize photosynthetic function and improve nutrient uptake, translocation and use efficiency. Responses depend on plant species, nutrient form, application strategy and environmental conditions; at the metabolic level, Si-based combinations affect the synthesis of phenolic compounds, amino acids and sulphur-containing metabolites. Si-Se and Si-Fe proved most effective under heavy-metal stress, through regulation of metal transport, detoxification and sequestration, and Si-S and Si-Zn under drought, salinity and nutrient-deficient conditions, by enhancing osmotic adjustment, nutrient-use efficiency, ionic homeostasis and photosynthetic performance. Agronomically, these interactions can increase crop productivity, nutritional value and biofortification potential, and mitigate toxic-element accumulation in edible parts. Knowledge gaps remain regarding molecular regulation, variability among species and environments, and the long-term effectiveness of nanoparticle formulations. Since most evidence comes from hydroponic, pot and greenhouse studies, standardized field experiments are needed to assess agronomic relevance. Full article

Esophageal cancer is a common malignancy of the upper gastrointestinal tract that is associated with high incidence and mortality rates. Radiotherapy constitutes a cornerstone therapeutic modality for esophageal cancer. In radiotherapy, ionizing radiation is used to eliminate tumor cells through direct DNA damage and indirect reactive oxygen species (ROS)-mediated effects. However, clinical outcomes are frequently limited by interpatient heterogeneity and intrinsic tumor radioresistance. This review systematically describes the determinants of radiosensitivity in esophageal cancer within the established radiobiological framework of the “6Rs”: DNA damage repair (Repair), which is mediated by γ-H2AX phosphorylation, PARP family enzymes, and nonhomologous end joining (NHEJ) and homologous recombination (HR) pathways; cell cycle redistribution (Redistribution), which is regulated by G1/S and G2/M checkpoint dynamics; tumor repopulation (Repopulation), which is driven by cancer stem cell activity during fractionated treatment; reoxygenation (Reoxygenation), which is modulated through HIF-1α signaling and ROS homeostasis; intrinsic radiosensitivity (Radiosensitivity), which reflects interindividual and histopathological variability; and reactivation of antitumor immune responses (Reactivation), which enhances efficacy by remodeling the tumor immune microenvironment. Furthermore, regulated cell death mechanisms, including ferroptosis, autophagy, and apoptosis, significantly modulate radiotherapeutic responses. Elucidating these interconnected mechanisms provides a robust theoretical foundation for developing targeted interventions, identifying predictive biomarkers, and advancing precision radiotherapy strategies to optimize clinical outcomes for patients with esophageal cancer. Full article