Search Results (454)

Glucosinolates are secondary metabolites of the Brassicales, playing a role in plant protection and as health-promoting compounds. Here, Na₂SO₄ was used to modulate the aliphatic glucosinolate content in different organs of Eruca sativa Mill. In flowers, which accumulate the highest amount of glucosinolates, Na₂SO₄ increased the concentration of glucoraphanin, in roots of glucoerucin and in apical leaves it doubled the amount of dimeric 4-mercaptobutyl glucosinolate. The biosynthetic gene Branched-Chain Aminotransferase 4 was also induced in roots at the highest salt concentration, while in leaves all tested genes biosynthetic genes were downregulated or unaffected. Cytochromes P450 83A1 monooxygenase was downregulated at the highest salt concentration in all organs. Overall, E. sativa is a reliable source of glucosinolates, which can be modulated with Na₂SO₄. Full article

Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4. Full article

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

This study investigated the physiological regulatory mechanisms by which exogenous trehalose intake enhances the adaptation of the global stored-grain pest T. castaneum to high-concentration carbon dioxide (CO₂) stress. By supplementing exogenous trehalose under high-CO₂ controlled atmosphere stress, we measured the activities of key detoxification enzymes (e.g., carboxylesterase and cytochrome P450) and the levels of carbohydrate substances (e.g., glycogen, glucose, and trehalose). The results demonstrated that trehalose feeding significantly alleviated CO₂ induced mortality in T. castaneum and prolonged their survival time. In terms of detoxification metabolism, a trehalose-rich diet significantly reduced the activities of cytochrome P450 and carboxylesterase, while the glucose content in the beetles decreased markedly. These findings indicate that trehalose accumulation mitigates physiological damage caused by high-CO₂ stress in T. castaneum. Furthermore, exogenous trehalose intake did not disrupt carbohydrate metabolic homeostasis in the beetles, as trehalase activity and the levels of various carbohydrates remained relatively stable. This study elucidates the role of trehalose metabolism in T. castaneum’s adaptation to high-CO₂ environments, providing a theoretical foundation for optimizing controlled atmosphere grain storage technology and developing novel pest control strategies. Full article

The aim of this study was to determine whether a low dose of zearalenone (ZEN) affects the mRNA expression of the CYP1A1 (P450 cytochrome) and GSTπ1 (glutathione S-transferase) genes in the large intestine of pre-pubertal gilts. Materials: Control (C) group gilts (n = 18) received a placebo. Experimental (E) group gilts (n = 18) were orally administered 40 μg ZEN/kg body weight (BW) each day before morning feeding for 42 days. Three animals from each group were sacrificed each week of the study. Tissue samples were collected from the medial parts of the ascending colon and the descending colon on six dates. Results: Zearalenone concentrations were multiple times higher in the last three weeks of exposure, and ZEN metabolites were not detected. In phase I, CYP1A1 mRNA expression in the ascending colon was suppressed in the final three weeks of exposure, which substantially increased the ZEN concentration in the descending colon. In phase II, ZEN levels were high in the descending colon due to CYP1A1 suppression in the ascending colon. Consequently, the phase II detoxification processes could not take place due to the absence of a substrate. Conclusion: This study demonstrated that low-dose ZEN mycotoxicosis disrupts the expression of the CYP1A1 and GSTπ1 genes, which co-participate in the enzymatic biotransformation of ZEN in both examined sections of the large intestine. The above could have contributed to increased ZEN accumulation in the mucosa of the descending colon in the last three weeks of exposure. Full article

Bombyx mori, a key lepidopteran model with economic importance, is highly susceptible to environmental heavy metal pollution. This study investigated the mechanisms of Pb toxicity and the associated detoxification and metabolic defense responses in silkworms, employing transcriptome sequencing, enzyme activity assays, and histopathological analysis. Pb exposure caused significant histopathological changes and apoptosis in the fat body, marked by structural disorganization, swollen adipocytes, and degraded extracellular matrix. Molecular analysis showed activation of antioxidant defenses, with superoxide dismutase (SOD) and catalase (CAT) activities significantly elevated (p < 0.05), while peroxidase (POD) activity declined (p < 0.05). Levels of malondialdehyde (MDA) and glutathione (GSH) also decreased. In detoxification responses, carboxylesterase (CarE) activity was reduced, whereas cytochrome P450 (P450) and glutathione S-transferase (GST) activities increased (p < 0.05). Transcriptome sequencing revealed 1,418 differentially expressed genes (DEGs), with notable upregulation of key detoxification genes (p < 0.05), including six cytochrome P450s (CYPs), five uridine diphosphate-glycosyltransferases (UGTs), three glutathione S-transferases (GSTs), and six ATP-binding cassette transporters (ABCs). KEGG enrichment analysis highlighted the involvement of these DEGs in drug metabolism, glutathione metabolism, and ABC transporter pathways (p < 0.05). Functional validation showed that knocking down Cap ‘n’ Collar C (CncC) significantly suppressed key detoxification genes (CYP18A1, CYP332A1, GSTd3, GSTt1, UGT33D8; p < 0.05). qRT-PCR and Western blot analyses confirmed that the Caspase-3 pathway mediates Pb-induced apoptosis, with increased cleaved Caspase-3 and Caspase-4 levels following CncC silencing. Overall, our findings elucidate the mechanisms of Pb toxicity in silkworms and identify CncC as a critical regulator of detoxification and defense against heavy metal stress in lepidopteran insects. Full article

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption—traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)—has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury. Full article

Fluorinated xenobiotics, such as per- and polyfluoroalkyl substances (PFAS), fluorinated pesticides, and pharmaceuticals, are extensively used across industries, but their extreme persistence, driven by the high carbon–fluorine (C–F) bond dissociation energy (~485 kJ/mol), poses serious environmental and health risks. These compounds have been detected in water, soil, and biota at concentrations from ng/L to µg/L, leading to widespread contamination and bioaccumulation. Traditional remediation approaches are often costly (e.g., EUR >100/m³ for advanced oxidation), energy-intensive, and rarely achieve complete degradation. In contrast, microbial defluorination offers a low-energy, sustainable alternative that functions under mild conditions. Microorganisms cleave C–F bonds through reductive, hydrolytic, and oxidative pathways, mediated by enzymatic and non-enzymatic mechanisms. Factors including electron donor availability and oxygen levels critically influence microbial defluorination efficiency. Microbial taxa, including bacteria, fungi, algae, and syntrophic consortia, exhibit varying defluorination capabilities. Metagenomic and microbial ecology studies continue to reveal novel defluorinating organisms and metabolic pathways. Key enzymes, such as fluoroacetate dehalogenases, cytochrome P450 monooxygenases, reductive dehalogenases, peroxidases, and laccases, have been characterised, with structural and mechanistic insights enhancing the understanding of their catalytic functions. Enzyme engineering and synthetic biology tools now enable the optimisation of these enzymes, and the design of microbial systems tailored for fluorinated compound degradation. Despite these advances, challenges remain in improving enzyme efficiency, broadening substrate specificity, and overcoming physiological constraints. This review emphasises the emerging promise of microbial defluorination as a transformative and green solution, uniquely integrating recent multidisciplinary findings to accelerate the development of sustainable microbial defluorination strategies for effective remediation of fluorinated xenobiotics. Full article

The bird cherry-oat aphid Rhopalosiphum padi (L.) poses a significant threat to wheat production, resulting in substantial yield reductions. Abamectin and acetamiprid are frequently utilized for management. This study assessed the sublethal effects of abamectin and acetamiprid on R. padi through life table analysis and enzyme activity assays. At 24 h, the LC₁₀ and LC₃₀ values for abamectin to R. padi were 0.063 mg/L and 0.252 mg/L, respectively, while, for acetamiprid, the corresponding values were 0.065 and 0.293 mg/L. The results indicated that exposure to sublethal concentrations of abamectin (AB-LC₁₀) extended the longevity of R. padi F₀ generation, while acetamiprid (AC-LC₁₀ and AC-LC₃₀) decreased it. Furthermore, the fecundity of the F₀ generation was significantly reduced following exposure to AB-LC₃₀, AC-LC₁₀ and AC-LC₃₀. In the F₁ generation, exposure to sublethal concentrations of acetamiprid negatively impacted on R. padi, as evidenced by a significant reduction in longevity; fecundity and population parameters (R₀, r, λ, s_xj, l_x, l_xm_x, v_xj and e_xj). Conversely, sublethal concentrations of abamectin did not significantly affect these parameters. Additionally, population projections revealed a significantly smaller total population size of R. padi in the acetamiprid-exposed group compared to both the abamectin-exposed and control groups. Except these population-level effects, the activities of detoxification enzymes, including cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CarE), changed differently after treatments. These results suggest that sublethal concentrations of acetamiprid, but not abamectin, significantly inhibit the population growth of R. padi. These insights are crucial for R. padi control and facilitate the development of effective control strategies that take into account these sublethal effects in integrated pest management strategies targeting R. padi. Full article

Alveolar echinococcosis (AE) is a chronic and potentially fatal zoonotic parasitic disease that seriously affects the host’s health. It is caused by the proliferation of Echinococcus multilocularis larvae within the liver. Due to its long incubation period following host infection, early diagnosis of the disease is currently not feasible. Treatment options are extremely limited, with the only choice being curative surgical resection combined with benzimidazole medication. Thus, the development of early, rapid, and minimally invasive diagnostic methods is crucial for enhancing patient prognosis. This study conducted proteomic and metabolomic analyses of protein and metabolite changes in the serum of a treatment group and control group, aiming to compare the differences between them. Overall, 22 proteins showed significant differences between the treatment and control groups, primarily involved in carbohydrate metabolism, lipid metabolism, and amino acid metabolism. The upregulation of genes related to immune response and enhanced glycolysis were observed, possibly associated with the reproduction of E. multilocularis in the liver. A total of 182 metabolites were screened to distinguish between the treatment group and control group. A significant increase in the cytochrome P450 (cP450) metabolite of arachidonic acid indicated signs of renal and splenic involvement in the treatment group. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted a strong association between amino acid metabolism and the development of AE. The observed changes in amino acid levels may provide nutrients that facilitate E. multilocularis colonization and contribute to the pathogenesis of AE. In summary, by investigating the different characteristics of the AE and control group through proteomic (n = 4/group/time point) and metabolomic (n = 8/group/time point) analyses, potential serum biomarkers for diagnosing mice with AE were identified. Full article

Aroma composition serves as a pivotal quality determinant in table grapes (Vitis vinifera). While the cytochrome P450 enzyme CYP76F14 is implicated in aroma biosynthesis, its functional role in grape berries remains uncharacterized. A comparative analysis of three aroma-distinct cultivars—Muscat type ‘Irsai Oliver’, Neutral type ‘Yanhong’, and Berry-like type ‘Venus Seedless’—revealed cultivar-specific linalool accumulation patterns. ‘Irsai Oliver’ exhibited sustained linalool biosynthesis from the fruit set through to maturity (from Stage 1 to Stage 5), with concentrations peaking at Stage 3 (veraison phase) and remaining elevated until harvest, surpassing the other two cultivars. Transcriptional profiling demonstrated that the CYP76F14 expression exhibited a similar trend with the accumulation of linalool levels, showing a higher expression in ‘Irsai Oliver’ across the developmental stages. A structural analysis identified 12 divergent residues in the ‘Irsai Oliver’ CYP76F14 variant, including E378 and T380 within the conserved substrate recognition site. The site-directed mutagenesis of these residues (CYP76F14-E378G/T380A) reduced the catalytic efficiency by 68–72% compared to the wild-type (in vitro LC-MS/MS assays), confirming their functional significance. This work reveals that cytochrome P450 CYP76F14 mediates the conversion of its substrate linalool in table grape berries, especially of Muscat type grapes, and proposes the CYP76F14 polymorphic variants as molecular markers for aroma-type breeding. The identified catalytic residues (E378/T380) provide targets for enzymatic engineering to modulate the terpenoid profiles in Vitis species. Full article

Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut–liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome–mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies—ranging from NAD⁺ repletion and probiotics to fecal microbiota transplantation—that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease. Full article

The xeno-fungusphere, a novel microbial ecosystem formed by integrating exogenous fungi, indigenous soil microbiota, and electroactive microorganisms within microbial fuel cells (MFCs), offers a transformative approach for agricultural remediation and medicinal plant conservation. By leveraging fungal enzymatic versatility (e.g., laccases, cytochrome P450s) and conductive hyphae, this system achieves dual benefits. First, it enables efficient degradation of recalcitrant agrochemicals, such as haloxyfop-P, with a removal efficiency of 97.9% (vs. 72.4% by fungi alone) and a 27.6% reduction in activation energy. This is driven by a bioelectric field (0.2–0.5 V/cm), which enhances enzymatic activity and accelerates electron transfer. Second, it generates bioelectricity, up to 9.3 μW/cm², demonstrating real-world applicability. In medicinal plant soils, xeno-fungusphere MFCs restore soil health by stabilizing the pH, enriching dehydrogenase activity, and promoting nutrient cycling, thereby mitigating agrochemical-induced inhibition of secondary metabolite synthesis (e.g., ginsenosides, taxol). Field trials show 97.9% herbicide removal in 60 days, outperforming conventional methods. Innovations, such as adaptive electrodes, engineered strains, and phytoremediation-integrated systems, have been used to address soil and fungal limitations. This technology bridges sustainable agriculture and bioenergy recovery, offering the dual benefits of soil detoxification and enhanced crop quality. Future IoT-enabled monitoring and circular economy integration promise scalable, precision-based applications for global agroecological resilience. Full article

Food components and herbal substances can inhibit or enhance the therapeutic effects of drugs, thus influencing their efficacy and safety. As relatively little in known of these interactions, the aim of this review is to shed further light on the potentially dangerous influences that food and herbs may have on cytochrome P450 enzyme (CYP) and monoamine oxidase (MAO) activity in the first stage of drug biotransformation. The review includes documented cases in which such interactions have led to health complications in patients. For example, fruit juices, such as grapefruit juice, cranberry juice, and pomegranate juice, have been found to interact with drugs, and to particularly inhibit CYP450 activity, and commonly used herbs are known to inhibit (e.g., Astragalus membranous) or induce (e.g., Hypericum perforatum) CYP enzymes involved in drug metabolism. CYP is also induced by polycyclic aromatic hydrocarbons (PAHs), found in grilled meat and tobacco smoke. The paper also discusses the toxic effects of tyramine, present in inter alia blue cheese, resulting from interactions with MAO-metabolised drugs. Most importantly, while the quantity of food and herbs consumed plays a significant role in the described drug interactions, it is possible for toxic effects to be observed even after the consumption of relatively small amounts. Patients are encouraged to consult a healthcare provider about any potential drug interactions that may occur when starting a new medication. Full article