Search Results (2,855)

Imidazole is, from a structural point of view, a heterocycle consisting of three C atoms and two N atoms, belonging to the class of diazoles, having two N atoms at the first and third positions in the aromatic ring. Being a polar and ionizable aromatic compound, it has the role of improving the pharmacological properties of lead molecules, thus being used to optimize their solubility and bioavailability. Imidazole is a constituent of many important biological compounds, like histidine, histamine, and purine compounds, the most widespread heterocyclic compound in nature. In current practice, substituted imidazole derivatives play a major role in antifungal, antibacterial, anti-inflammatory, CNS active compounds, antiprotozoal, as well as anticancer therapy. Thus, imidazole derivatives have demonstrated significant anticancer activities by inhibiting the key metabolic pathways essential for tumor cell growth and survival. Nitroimidazoles, for instance, have been employed as hypoxia-directed therapeutic agents, targeting oxygen-deprived tumor tissues, while mercaptopurine derivatives are well-established in oncological treatments. Structural modifications of the imidazole nucleus have led to the novel compounds exhibiting increased selective cytotoxicity against cancer cells, while sparing normal healthy cells. In accordance with what has been stated, this review highlights recent research on the medicinal and pharmaceutical interest of novel imidazole derivatives, emphasizing their potential in the development of new drugs. Full article

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies. Full article

Objectives: This study aims to explore the therapeutic effect and mechanism of stir-roasted deer velvet antler with ghee (ZLR) on Non-Alcoholic Fatty Liver Disease (NAFLD). Methods: This study used proteomics to analyze the protein composition of roasted deer antler velvet. It established a high-fat diet (HFD)-induced NAFLD rat model and evaluated the therapeutic effects of different dosage groups, including liver injury, oxidative stress, glucose metabolism, steatosis, and insulin homeostasis (via fasting glucose tolerance). Transcriptomics explored the mechanism. Gene expression and Western blot detected lipid metabolism-related gene expression. In vivo experiments validated that ZLR-containing serum alleviates NAFLD and reduces reactive oxygen species levels. Results: The results indicated that ZLR could significantly reduce the body weight, liver weight and degree of hepatic steatosis in HFD rats, improve glycolipid metabolism and insulin sensitivity, and alleviate oxidative stress damage. The mechanism involves activating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor (AMPK/PPAR) signaling pathway, regulating the expression of lipid metabolism-related genes, promoting fatty acid oxidation, and reducing fat deposition. The results of in vitro experiments show that ZLR-containing serum can effectively reduce lipid droplet production in liver cells and effectively alleviate oxidative stress damage in liver cells. Conclusions: The traditional Chinese medicine processed product ZLR can regulate lipid metabolism in the body and alleviate the degree of NAFLD by activating the AMPK and PPAR signaling pathways. It provides new ideas for the clinical treatment of NAFLD Full article

Disulfiram (DSF) is a well-established inhibitor of aldehyde dehydrogenases (ALDHs) and an FDA-approved drug for chronic alcoholism. DSF has gained attention as a versatile scaffold for drug repurposing. Its metabolite, diethyldithiocarbamate (DDTC), mediates multiple biological effects via metal chelation and covalent modification of key cysteine residues. Beyond its established anticancer properties, DSF modulates cancer stem cells, reactive oxygen species, proteasome function, and drug-resistance pathways. It also shows promise in metabolic disorders, including type 2 diabetes and obesity, by targeting enzymes such as fructose-1,6-bisphosphatase and α-glucosidase, and influences energy expenditure and autophagy. DSF exhibits antimicrobial and antiparasitic activity, enhances antibiotic efficacy against multidrug-resistant bacteria, and demonstrates antischistosomal and anti-Trichomonas effects, while also providing radioprotective benefits. The clinical translation of DSF is limited by poor solubility, rapid metabolism, and off-target effects; consequently, the development of DSF analogs has become a major focus. Structural optimization has yielded derivatives with improved selectivity, stability, solubility, and target specificity, enabling precise modulation of key enzymes while reducing adverse effects. A key structure-based strategy involves introducing bulkier substituents to exploit differences in ALDH active-site architecture and achieve target selectivity. This concept is exemplified by compounds (1) and (2), in which bulky substituents confer selective inhibition of ALDH1A1 while sparing ALDH2. This review provides a comprehensive overview of DSF analogs, their molecular mechanisms, and therapeutic potential, highlighting their promise as multifunctional agents for cancer, metabolic disorders, infectious diseases, and radioprotection. Full article

Silver nanoparticles (AgNPs) have been widely employed across various industrial, medical, and consumer applications due to their unique biocidal properties, raising concerns about their potential impact on biota such as planktonic microinvertebrates, which, in turn, necessitates the rapid development of in vivo nanotoxicological bioassays. Here, we combined physicochemical particle characterization with organismal responses to assess the in vivo nanotoxicity of chemically synthesized AgNPs in the marine rotifer Brachionus plicatilis (Ploimida, Brachionidae). Particles were fully characterized by dynamic light scattering (hydrodynamic diameter and polydispersity), zeta potential, transmission electron microscopy, and UV–Vis spectroscopy in both stock and exposure media. Rotifers were exposed to low AgNP concentrations: 0 (control), 2, and 20 µg/L. After a 24 h exposure, in vivo metabolic activity was quantified via resazurin reduction. Reactive oxygen species (ROS) were measured using the fluorescent probe H₂DCF-DA (excitation 485 nm, emission 530 nm), quantified by fluorimeter and fluorescence microscopy. Results showed that AgNP exposure decreased ROS levels at both tested concentrations, a finding that can be linked to reduced aerobic metabolic activity in the rotifers. These findings demonstrate that B. plicatilis provides a rapid and sensitive in vivo toxicity assessment that integrates metabolic and ROS endpoints for nano-ecotoxicity evaluations. Full article

Sustained abiotic stress severely impairs fruit crop growth and development. As plants’ primary environmental sensing organ, fruit tree roots experience disrupted morphogenesis and physiological functions, reducing yield, lowering fruit quality, and threatening orchard ecosystem stability. Abiotic stress is diverse: water deficit from drought, extreme temperature fluctuations, and salinization-induced ion imbalance, heavy metal accumulation, or nutrient disorders. Its complexity requires synergistic and crosstalk regulation of multiple root-specific signaling modules and pathways in root stress perception and transduction. When responding to stress, roots activate hormone, reactive oxygen species (ROS), and calcium ion (Ca²⁺) signaling. These pathways mediate early stress recognition and regulate downstream gene expression and physiological metabolic reprogramming via transcription factors (TFs) and other regulators, determining stress tolerance and adaptability. Using typical abiotic stresses as models, this review outlines the composition, activation mechanisms, specificity, and synergistic effects of root-specific signaling modules/pathways, along with modern biotechnologies for decoding these modules and current research limitations, aiming to reveal the root signal network’s integration mode. Full article

Asparagine synthetase (AS) is a key enzyme in plant nitrogen metabolic network. Beyond its canonical role as a major nitrogen transport and storage molecule, asparagine also serves critical functions in plant immunity and tolerance to environmental stresses. This review systematically summarizes the characteristics of the core AS-mediated asparagine biosynthesis pathway and two other minor pathways in plants. It details the distribution of the AS gene family, protein structure, and evolutionary classification. The mechanisms governing AS expression are analyzed, revealing tissue-specific patterns and precise regulation by nitrogen availability, abiotic stresses, and exogenous hormones, mediated through an interactive network of cis-acting elements and transcription factors. Furthermore, the biological functions of AS are multifaceted: it influences plant biomass and nitrogen use efficiency by regulating nitrogen uptake, transport, and recycling during growth and development; it contributes to abiotic stress tolerance by synthesizing asparagine to maintain cellular osmotic balance and scavenge reactive oxygen species; and it indirectly enhances antibacterial and antiviral capacity by activating the SA signaling pathway and modulating programmed cell death. Current knowledge gaps remain regarding the crosstalk between AS-mediated signaling pathways, the upstream transcriptional regulatory network, and the balance between nitrogen utilization and disease resistance in crop breeding. Future research aimed at addressing these questions will provide a theoretical foundation and molecular targets for improving crop nitrogen use efficiency and breeding resistant cultivars. Full article

Hypoxia is a common feature of inflamed and ischemic tissues and represents an important regulatory signal for innate immune cells. The master regulator of this response is hypoxia-inducible factor-1α (HIF-1α), a transcription factor whose stabilization and activity are tightly regulated by the presence of oxygen, inflammatory signaling, and cellular metabolism. Monocytes, key players in innate immunity, rapidly sense oxygen deprivation and display specific responses during acute hypoxia, primarily aimed at adapting and maintaining cellular homeostasis. Unlike macrophages, in which HIF-1α activity is known, the mechanisms regulating HIF-1α stabilization, subcellular localization, and transcriptional activity in circulating monocytes remain incompletely elucidated. Recent studies indicate that acute hypoxia primarily triggers post-translational stabilization of HIF-1α, calcium- and PKC-dependent signaling, metabolic reprogramming, and early inflammatory responses, while transcriptional activation of HIF-1α may require additional inflammatory or stress-related signals. Furthermore, extensive crosstalk between HIF-1α and NF-κB integrates hypoxic and inflammatory signals, modulating cytokine production, cell migration, and survival. Epigenetic regulators can also modulate these responses and contribute to hypoxia-induced trained immunity. In this review, we summarize current knowledge of the mechanisms controlling the stabilization, localization, and function of HIF-1α in human monocytes and monocyte–macrophages during acute hypoxia, highlighting the key differences between these cell types and discussing their implications for inflammation, tissue homeostasis, and disease. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Psychological stress is increasingly investigated as a potentially modifiable factor in male infertility, in part through oxidative stress. This narrative review synthesizes mechanistic and translational evidence linking stress-related neuroendocrine activation and coping behaviors with redox imbalance in the male reproductive tract. Chronic activation of the hypothalamic–pituitary–adrenal axis and sympathetic outflow elevates glucocorticoids and catecholamines. In controlled animal stress paradigms, this is accompanied by suppression of the hypothalamic–pituitary–gonadal axis and by immune and metabolic changes that favor reactive oxygen species generation. The resulting oxidative stress may reduce Leydig cell steroidogenesis, impair testicular and epididymal function, and induce lipid peroxidation, mitochondrial dysfunction, and sperm DNA fragmentation. In such models, these lesions, together with apoptosis of germ and supporting cells, are associated with lower sperm concentration, reduced motility, compromised viability, and diminished fertilizing potential. Overall, preclinical animal studies using defined stress paradigms provide experimental evidence consistent with causal effects of stress on oxidative injury and reproductive impairment in preclinical settings. Human studies linking perceived stress, anxiety/depression, and disturbed sleep to adverse semen parameters and oxidative biomarkers are summarized. However, the human evidence is predominantly associative, and the available studies are cross sectional and remain vulnerable to residual confounding and reverse causality. Potential effect modifiers, including smoking, alcohol use, and circadian disruption, are also discussed as contributors to heterogeneity across clinical studies. Standardized assessment of stress biology and redox status, longitudinal designs aligned with spermatogenic timing, and well-powered intervention trials are needed to define dose–response relationships and support individualized prevention and care. Full article

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

Background/Objectives: Oats and oat bran are rich in polyphenols and soluble fiber, which are metabolized by gut microbiota into bioactive compounds. Previous studies identified ursodeoxycholic acid (UDCA), 3-(3-hydroxyphenyl)propionic acid (3-HPP), and avenanthramide C (AVC) as key microbial metabolites with protective effects against colitis. Methods: This study aimed to elucidate their antioxidant and anti-inflammatory activities and underlying mechanisms using LPS-induced RAW 264.7 macrophages and AAPH-induced oxidative stress in zebrafish embryos. All three metabolites significantly reduced intracellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-6, TNF-α). They also restored mitochondrial membrane potential and enhanced superoxide dismutase (SOD) activity. Results:In vivo, treatment improved zebrafish survival, normalized SOD activity to 76–89% of control levels, and decreased ROS and MDA by 2.4 to 3.8 fold, with UDCA showing the greatest efficacy. Molecular docking revealed strong binding affinities to Keap1, particularly UDCA, which interacted with residues Met577, Ala440, Val532, and Val486. qRT-PCR further demonstrated downregulation of Keap1 and upregulation of Nrf2 and SOD, indicating activation of the Keap1-Nrf2 pathway. Conclusions: Collectively, these findings show that oats and bran-derived microbial metabolites exert potent antioxidant and anti-inflammatory effects via modulation of the Keap1-Nrf2 axis. Among the metabolites, UDCA exhibited the strongest biological activity at equivalent concentrations. This study provides mechanistic insight into how microbiota-derived oat metabolites contribute to redox balance and immune regulation, supporting their potential as functional components in dietary strategies for managing oxidative stress-related inflammatory diseases. Full article

Background: Black spot disease severely constrains Chinese cabbage production. Methods: To elucidate the defence mechanisms underlying this response, transcriptomic and metabolomic profiles were analysed in leaves of the Chinese cabbage line 904B at 24 h post-inoculation (hpi) with Alternaria brassicicola. In parallel, gene silencing and overexpression were conducted for BraPBL, an RLCK family member in Chinese cabbage. Results: The Chinese cabbage line 904B exhibited marked suppression of cytokinin and auxin signalling, coupled with enhanced expression of genes involved in ethylene and jasmonic acid signalling. Multiple secondary metabolites exhibited differential changes, specifically the sterol compound 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol was significantly upregulated in the treatment group. These metabolites were primarily enriched in the indole alkaloid metabolism and glycerolipid metabolism pathways. Concurrently, BraPBL exhibits increasing expression with prolonged infection. BraPBL overexpression enhances resistance to black spot disease, whereas silencing reduces resistance. Subcellular localization confirmed BraPBL at the plasma membrane. Overexpression of BraPBL upregulates the reactive oxygen species-related gene RBOH and the signal transduction-related gene MEKK1, whilst simultaneously activating the JA pathway. Conclusions: Overall, 904B activates defence-related hormones while suppressing growth and development-related hormones during early infection. Secondary metabolites, particularly the sterol compound 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol, play key roles in defence, and BraPBL functions as a black spot disease–related defence gene in Chinese cabbage. Full article

With intensifying global climate change and human activities, and with regional topography interactions, soil and water salinization has intensified, posing major ecological and environmental challenges worldwide. Here, we integrated histology, transmission electron microscopy, RNA sequencing (RNA-seq) and data-independent acquisition (DIA)-based proteomics to profile hepatopancreas responses of Exopalaemon carinicauda during acute sulfate stress (≤48 h). Sulfate exposure disrupted tubular architecture and organelle integrity, consistent with early cellular injury. Multi-omics analyses revealed metabolic reprogramming marked by suppressed glycolysis (e.g., HK2, ENO) and enhanced oxidative phosphorylation (e.g., ATP5F1B), together with activation of calcium signaling (e.g., SLC8A1, ADCY9) and reinforcement of antioxidant/one-carbon and glucose-branch pathways (e.g., SHMT2, PGAM2). These coordinated transcript–protein changes indicate a shift from rapid cytosolic ATP supply to mitochondrial ATP production while buffering Ca²⁺ overload and reactive oxygen species. Collectively, our results delineate the physiological and molecular adjustments that enable E. carinicauda to cope with sulfate conditions and provide mechanistic targets for selective breeding and water-quality management in saline–alkaline aquaculture. Full article

Sorghum (Sorghum bicolor L.) is a vital crop for both grain production and forage, playing a critical role in ensuring global food security and sustainable livestock production. Drought stress represents one of the most severe abiotic constraints in sorghum cultivation, adversely affecting plant growth and development, and ultimately leading to significant reductions in yield and quality. Melatonin has emerged as a multifaceted plant growth regulator that enhances plant growth and confers tolerance to various abiotic stresses. It actively participates in regulating key physiological processes, including seed germination, seedling establishment, cellular development, and metabolic homeostasis. This review synthesizes current knowledge on the impacts of drought stress on sorghum growth and physiological metabolism, with a specific focus on the protective role of melatonin under water-deficit conditions. The underlying physiological and molecular mechanisms are comprehensively discussed, encompassing ion homeostasis, nutrient metabolism, reactive oxygen species (ROS) scavenging, photosynthetic efficiency, energy metabolism, phytohormone crosstalk, signal transduction, and associated gene expression. Finally, we outline future research directions to advance our understanding of melatonin-mediated drought tolerance in sorghum, providing insights for breeding drought-resilient varieties and developing high-yielding cultivation strategies. Full article