Search Results (698)

Mycotoxin contamination in agricultural products poses severe global health risks, with ochratoxins (particularly OTA and OTB) exhibiting marked nephrotoxicity and classified as Group 2B carcinogens by IARC. Conventional physical/chemical detoxification methods often impair food nutritional quality, highlighting the need for enzymatic alternatives. Herein, we systematically investigated the degradation mechanisms of ochratoxin A (OTA) and ochratoxin B (OTB) using Pleurotus ostreatus dye-decolorizing peroxidase (PoDyP4) coupled with redox mediators. Remarkably, hydroxybenzotriazole (HBT) enhanced degradation efficiency 26.7-fold for OTA and 10.6-fold for OTB compared to mediator-free systems, establishing it as the optimal catalytic enhancer. Through LC-MS/MS analysis, we identified five key degradation products, including 6-OH-OTA and OTB-quinone, elucidating a putative oxidative degradation pathway. In vitro cytotoxicological evaluation in HK-2 cells demonstrated that PoDyP4-treated ochratoxins significantly attenuated cytotoxicity, reducing malondialdehyde (MDA) levels by 48.7% (OTA) and 42.3% (OTB) (p < 0.01) and suppressing ROS generation. Molecular docking revealed strong binding affinities between PoDyP4 and ochratoxins, with calculated binding energies of −7.6 kcal/mol (OTA) and −8.6 kcal/mol (OTB), stabilized by hydrogen bond networks (1.9–3.4 Å). These findings position PoDyP4 as a promising biocatalyst for mycotoxin mitigation in food systems, offering a sustainable alternative to traditional detoxification methods. Full article

Copper (Cu) is an essential micronutrient for plants, playing a crucial role in various physiological and molecular processes. Excess Cu induces oxidative stress and disrupts cellular functions, while Cu deficiency causes chlorosis and poor pollen development, thereby reducing crop yields. However, the molecular and evolutionary mechanisms of Cu tolerance and homeostasis remain unclear in the plant kingdom. In this review, we discuss the uptake, transport, and detoxification of Cu through high-affinity Cu transporters (COPTs). Additionally, we update recent studies on maintaining Cu balance by mediating the root exudation of organic acids (e.g., citrate and proline), xylem/phloem loading, cell wall binding, vacuolar sequestration, redistribution, and the activity of antioxidant enzymes (e.g., SOD, CAT, and APX). Furthermore, tissue-specific expression analyses reveal that COPT genes exhibit distinct spatial regulation in the roots and leaves, which are the primary sites of Cu transport and detoxification. Overall, our review highlights the critical roles of COPT gene families and detoxification pathways in maintaining Cu homeostasis in plants. Future research should focus on genetic engineering approaches to enhance Cu tolerance, optimize Cu distribution in grains, and mitigate soil contamination risks. By clarifying these mechanisms, we can develop strategies to sustain crop production under increasing Cu stress, thereby ensuring food security and human health. Full article

Alzheimer’s disease is the most common form of dementia, yet current treatments only offer symptomatic relief, with little preventative, therapeutic, or disease-modifying properties. As a result, there has been growing interest in targeting various disease mechanisms. One promising target is soluble epoxide hydrolase (sEH), an enzyme found in many organs, playing an important role in metabolism and detoxification. In the brain, sEH is mainly present in astrocytes, oligodendrocytes, and neuronal cell bodies, with higher concentrations in the cerebral cortex and striatum. The main function of sEH is the hydrolysis of epoxyeicosatrienoic acids (EETs), which are important anti-inflammatory molecules derived from arachidonic acid. Deletion of EPHX2, the encoding gene of sEH, maintains EET levels in the brain and helps mitigate inflammation. Multiple studies have found links between sEH function, inflammation, and neurodegeneration in Alzheimer’s disease. Several compounds, including TPPU, benzohomoadamantane derivatives, and natural products, have shown significant beneficial effects, including reduction of amyloid-beta plaques, tau fibrils, and inflammation, while improving cognition and neuronal structure and function. sEH inhibitors have also been explored for their potential in the management of Parkinson’s disease, vascular dementia, stroke, and other neurodegenerative conditions. Although these preclinical findings are promising, efficacy and safety concerns still need to be addressed, and further clinical trials are needed to translate these therapeutic agents into clinical practice. Full article

Microbial reduction in hexavalent chromium (Cr(VI)) is a well characterized bioremediation strategy, yet the mechanistic diversity among bacterial taxa necessitates detailed investigations into strain-specific pathways. Here, we report the isolation and characterization of Bacillus safensis BSF-4, a halophilic bacterium derived from saline-alkali soil, which demonstrates efficient Cr(VI) reduction capacity. Physiological assays showed that BSF-4 achieved 89.15% reduction of 20 mg/L Cr(VI) within 72 h, with Cr(III) identified as the primary extracellular end product. Resting cell assays and subcellular fractionation analyses confirmed that Cr(VI) reduction predominantly occurs in the extracellular milieu. X-ray photoelectron spectroscopy (XPS) further revealed soluble Cr(III) complexed with extracellular polymeric substances (EPS). Transcriptomic profiling indicated upregulation of membrane-associated transport systems (facilitating Cr(VI) exclusion) and quorum sensing (QS) pathways (mediating adaptive stress responses). These findings highlight a dual mechanism: (1) extracellular enzymatic reduction mediated by EPS-bound redox proteins, and (2) intracellular detoxification via QS-regulated defense pathways. Collectively, Bacillus safensis BSF-4 exhibits robust Cr(VI) reduction capacity under saline conditions, positioning it as a promising candidate for bioremediation of Cr(VI)-contaminated saline soils and aquatic ecosystems. Full article

Background/Objectives: Nutrigenomics explores how dietary components influence genome function, especially via epigenetic mechanisms like DNA methylation. A key challenge is identifying healthy food-derived molecules capable of counteracting epigenetic damage from harmful dietary elements. Pistachio nuts (Pistacia vera L.), particularly the Bronte variety from Sicily, are rich in antioxidant polyphenols. In this study we used a methylomic approach to assess the nutrigenomic potential of a hydrophilic extract from Bronte pistachio (BPHE) in a model of human intestinal epithelium, as well as its capacity to modulate arsenic (As)-induced epigenotoxicity. Methods: BPHE was obtained via ethanol/water Soxhlet extraction. CaCo-2 cells were treated with BPHE, alone and after exposure to sodium arsenite. The methylation pattern of the genomic DNA was assessed by methylation-sensitive arbitrarily primed PCR and the methylomic signature was defined by Next-generation bisulfite sequencing. Results: BPHE alone did not alter DNA methylation pattern but, at the highest dose, modulated the changes induced by As. The identification of differentially methylated gene promoters in cell treatment vs. untreated controls revealed that BPHE and As primarily induced hyper-methylation, with a synergistic effect when combined. In particular, all the treatments increased methylation levels of gene categories such as pseudogenes, key genes of specific pathways, genes for zinc-finger proteins, homeobox proteins, kinases, antisense RNA, and miRNA. Notably, in co-treatment with As, BPHE promoted hypo-methylation of genes involved in tumor suppression, detoxification, mitochondrial function, and cell division. Conclusions: These findings suggest that Bronte pistachio polyphenols may epigenetically steer gene expression toward a protective profile, reducing risks of genomic instability and disease. This supports their potential as nutraceuticals to counter harmful epigenetic effects of toxic food components like arsenic. Full article

Gastrointestinal (GI) cancers represent a major global health burden. Among them, colorectal cancer (CRC) is the most common type, followed by esophagus, stomach, liver, and pancreatic cancer. Since disturbance of the gut microbiota has been directly associated with the development of severe health issues, including cancer, probiotic administration may induce dysbiosis reversion and ameliorate carcinogenesis. Therefore, manipulation of the gut microbiota composition based on probiotic utilization has gradually attained scientific interest as a potent therapeutic modality for GI cancers. This review aims to synthesize the current in vitro and in vivo evidence on probiotics’ effectiveness in GI cancer chemoprevention and treatment. It also provides a classification of the fundamental anticancer features of probiotics, including antiproliferation and cell death induction, anticarcinogenic compound production, reduction in chemotherapy-related toxicity, gut microbiota modulation, intestinal barrier improvement, antioxidant activity, immunomodulatory/anti-inflammatory effects, and carcinogen detoxification. Finally, it underscores the future perspectives and challenges of probiotic administration to individuals. In this regard, it emphasizes the exploitation of advanced encapsulation techniques and the development of novel genetically engineered probiotics and next-generation probiotics as feasible ways to improve their bioavailability, ensure their targeted delivery, and eliminate their mild side effects to the host’s health. Full article

The natural resistance-associated macrophage proteins (NRAMPs) gene family represents a group of membrane transporter proteins with wide distribution in plants. This family of membrane transporters plays a pivotal role in mediating plant responses to metal stress by coordinating ion transport processes and maintaining cellular metal homeostasis, thereby effectively mitigating the detrimental effects of metal ion stress on plant growth and development. This study conducted a comprehensive genome-wide analysis of the NRAMP gene family in A. tauschii using integrated bioinformatics approaches, as well as the expression pattern when exposed to heavy metal-induced stress. By means of phylogenetic investigation, eleven AetNRAMP proteins were categorized into five distinct subgroups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the majority of NRAMP genes exhibited marked differential expression patterns under specific stress treatments. Subsequently, yeast cells were employed to validate the functions of AetNRAMP1 and AetNRAMP3. It was confirmed that AetNRAMP1 functioned in copper transport, and AetNRAMP3 showed an increase in its expression level under manganese stress. These findings establish a molecular foundation for elucidating the functional specialization of NRAMP gene family members in A. tauschii’s heavy metal detoxification pathways, providing critical genetic evidence for their stress-responsive regulatory networks. Nevertheless, significant knowledge gaps persist regarding its functions in A. tauschii. Research on metal stress resistance in this wheat progenitor species may establish a theoretical foundation for enhancing wheat tolerance and developing improved cultivars. Full article

Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus that has a lethal effect on many species of Sphingidae pests. DnCPV-23 can replicate in Spodoptera frugiperda Sf9 cells, but the replication characteristics of the virus in this cell line are still unclear. To determine the replication characteristics of DnCPV-23 in Sf9 cells, uninfected Sf9 cells and Sf9 cells at 24 and 72 h after DnCPV-23 infection were collected for transcriptome analysis. Compared to uninfected Sf9 cells, a total of 188 and 595 differentially expressed genes (DEGs) were identified in Sf9 cells collected at 24 hpi and 72 h, respectively. KEGG analyses revealed that 139 common DEGs in two treatment groups were related to nutrition and energy metabolism-related processes, cell membrane integrity and function-related pathways, detoxification-related pathways, growth and development-related pathways, and so on. We speculated that these cellular processes might be manipulated by viruses to promote replication. This study provides an important basis for further in-depth research on the mechanism of interaction between viruses and hosts. It provides additional basic information for the future exploitation of DnCPV-23 as a biological insecticide. Full article

Powdery mildew (PM), caused by Sphaerotheca phaseoli, severely threatens mungbean (Vigna radiata) productivity and quality, yet the molecular basis of resistance remains poorly defined. This study employed transcriptome profiling to compare defense responses in a resistant genotype, SUPER5, and a susceptible variety, CN84-1, following pathogen infection. A total of 1755 differentially expressed genes (DEGs) were identified, with SUPER5 exhibiting strong upregulation of genes encoding pathogenesis-related (PR) proteins, disease resistance proteins, and key transcription factors. Notably, genes involved in phenylpropanoid and flavonoid biosynthesis, pathways associated with antimicrobial compound and lignin production, were markedly induced in SUPER5. In contrast, CN84-1 showed limited activation of defense genes and downregulation of essential regulators such as MYB14. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the involvement of plant–pathogen interaction pathways, MAPK signaling, and reactive oxygen species (ROS) detoxification in the resistant response. Quantitative real-time PCR validated 11 candidate genes, including PAL3, PR2, GSO1, MLO12, and P21, which function in pathogen recognition, signaling, the biosynthesis of antimicrobial metabolites, the production of defense proteins, defense regulation, and the reinforcement of the cell wall. Co-expression network analysis revealed three major gene modules linked to flavonoid metabolism, chitinase activity, and responses to both abiotic and biotic stresses. These findings offer valuable molecular insights for breeding PM-resistant mungbean varieties. Full article

Cadmium (Cd) toxicity destroys plant cells and affects plant growth and development. Due to its unique metallic properties, selenium (Se) has been shown to be effective in antioxidants, cellular immunity, and heavy metal detoxification. When Se and Cd are present together in plants, they antagonize. However, the mechanism of action of the two in the rice cell wall remains to be clarified. In this study, we analyzed the mechanism of Cd detoxification by rice (Oryza sativa L.) cellular polysaccharides mediated by Se, using the cell wall as an entry point. Proteomic and transcriptomic analyses revealed that “Glycosyl hydrolases family 17”, “O-methyltransferase”, and “Polygalacturonase” protein pathways were significantly expressed in the cell wall. The most abundant enzymes involved in polysaccharide biosynthesis were found, including bglB, otsB, HK, PFP, ADH1, and ALDH, which resulted in the synthetic pathway of polysaccharide formation in the rice cell wall. Finally, the essential genes/proteins, such as protein Os03g0170500, were identified. The study showed that Se inhibits Cd uptake and transport when Se (1 mg/kg) is low relative to Cd (3 mg/kg), has little inhibitory effect, and even promotes Cd (3 mg/kg) uptake when Se (5 mg/kg) is relatively high. Full article

Green tea, derived from the unoxidized leaves of Camellia sinensis (L.) Kuntze, is one of the least processed types of tea and is rich in antioxidants and polyphenols. Among these, catechins—particularly epigallocatechin gallate (EGCG)—play a key role in regulating cell signaling pathways associated with various chronic conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic diseases, and cancer. This review presents a comprehensive analysis of recent clinical studies focused on the therapeutic benefits and potential risks of interventions involving green tea extracts or EGCG. A systematic literature survey identified 17 relevant studies, classified into five key areas related to catechin interventions: toxicity and detoxification, drug pharmacokinetics, cognitive functions, anti-inflammatory and antioxidant properties, and obesity and metabolism. Findings from these clinical studies suggest that the health benefits of green tea catechins outweigh the potential risks. The review highlights the importance of subject genotyping for enzymes involved in catechin metabolism to aid in interpreting liver injury biomarkers, the necessity of assessing drug–catechin interactions in clinical contexts, and the promising effects of topical EGCG in reducing inflammation. This analysis underscores the need for further research to refine therapeutic applications while ensuring the safe and effective use of green tea catechins. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl₂-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI. Full article

Glycoside hydrolase family 1 (GH1) enzymes are essential for plant cell wall digestion and the detoxification of plant metabolites in insects, yet their evolutionary history in Lepidoptera remains unresolved. This study systematically identified GH1 genes across 61 Lepidopteran genomes and analyzed their evolutionary dynamics. In addition, the expression profiles of GH1 genes in the silkworm (Bombyx mori) across various developmental stages and tissues were related to their evolutionary histories. A total of 996 GH1 genes were annotated and classified into 11 groups, with each showing distinct species diversity. Gene duplication and loss analysis revealed frequent duplications and losses during Lepidoptera evolution; these duplications primarily originated through tandem and dispersed duplications and were located in syntenic regions. Transcriptomic analysis of the silkworm revealed that the groups and duplications of GH1 genes were correlated to their expression patterns, with high expression in the larval midgut and fat body. These findings suggest that GH1 gene duplications and losses and expression have played a significant role in Lepidopteran adaptation to diverse host plants. Overall, this study provides comprehensive insights into the evolutionary trajectories of GH1 genes, highlighting their potential contribution to insect–plant interactions in Lepidoptera. Full article

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has re-emerged, causing widespread outbreaks and a significant clinical burden. Despite advances in virology, the molecular mechanisms governing CHIKV’s interaction with host cells remain poorly understood. In this study, we aimed to identify novel host protein interactors of the CHIKV nonstructural protein 3 (nsP3), a critical component of the viral replication complex, using mass spectrometry-based proteomic profiling in liver-derived Huh7 cells. Co-immunoprecipitation followed by LC-MS/MS identified a wide array of host proteins associated with nsP3, revealing 52 proteins classified as high-confidence (FDR of 1%, and unique peptides > 2) CHIKV-specific interactors. A bioinformatic analysis using STRING and Cytoscape uncovered interaction networks enriched in metabolic processes, RNA processing, translation regulation, cellular detoxification, stress responses, and immune signaling pathways. A subcellular localization analysis showed that many interactors reside in the cytosol, while others localize to the nucleus, nucleolus, and mitochondria. Selected novel host protein interactions were validated through co-immunoprecipitation and immunofluorescence assays. Our findings provide new insights into the host cellular pathways hijacked by CHIKV and highlight potential targets for therapeutic intervention. This is the first report mapping direct nsP3–host protein interactions in Huh7 cells during CHIKV infection. Full article