Search Results (248)

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. 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

Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article

This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we conducted a comprehensive literature review using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases. Of 30 qualifying papers ultimately reviewed, 28 reported a significant contribution of ROS to the pathogenesis of endometriosis, while two found no association. The presence of ROS in endometriosis is associated with infertility, irregular menstrual cycles, painful menstruation, and chronic pelvic discomfort. Among individual ROS types studied, hydrogen peroxide was most frequently investigated, followed by lipid peroxides and superoxide radicals. Notable polymorphisms associated with ROS in endometriosis include those for AT-rich interactive domain 1A (ARID1A) and quinone oxidoreductase 1 (NQO1) isoforms. Key enzymes for ROS scavenging and detoxification include superoxide dismutase, glutathione, and glutathione peroxidase. Effective inhibitors of ROS related to endometriosis are vitamins C and E, astaxanthin, fatty acid-binding protein 4, cerium oxide nanoparticles (nanoceria), osteopontin, sphingosine 1-phosphate, N-acetyl-L-cysteine, catalase, and a high-antioxidant diet. Elevated levels of ROS and free radicals are involved in the pathogenesis of endometriosis, suggesting that targeting these molecules could offer potential therapeutic strategies. Full article

Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, controlling the expression of genes involved in antioxidant defense, detoxification, and mitochondrial function. By inducing Nrf2 and promoting the transcription of downstream antioxidant response element (ARE)-driven genes, bardoxolone methyl enhances cellular resilience to oxidative stress and inflammation. This mechanism is central not only to its cytoprotective effects but also to its emerging role in oncology. A number of studies investigated the effects of bardoxolone methyl in several malignancies including breast cancer, lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, oral and esophageal squamous cell carcinoma, ovarian cancer and glioblastoma. Studies in the literature indicate that bardoxolone methyl exhibits anticancer activity through several mechanisms, including the suppression of cell proliferation, induction of cell cycle arrest and apoptosis, inhibition of epithelial–mesenchymal transition (EMT), and impairment of cancer cell stemness. Additionally, bardoxolone methyl modulates mitochondrial function, reduces glycolytic and oxidative phosphorylation capacities, and induces reactive oxygen species (ROS)-mediated stress responses. In this review, we summarize the available literature regarding the studies which investigated the effects of bardoxolone methyl as anticancer agent. Full article

Background: Drought stress is a major abiotic factor limiting Brassica juncea productivity, resulting in significant yield reductions. Plant Growth-Promoting Rhizobacteria (PGPR) have shown potential in enhancing drought tolerance; however, the metabolomic changes associated with their effects remain largely unexplored. This study examines the metabolic changes induced by a PGPR consortium (Enterobacter hormaechei, Pantoea dispersa, and Acinetobacter sp.) in two contrasting genotypes B. juncea (L.) Czern. ‘RH 725’ (drought tolerant) and B. juncea (L.) Czern. ‘RH-749’ (drought sensitive for drought tolerance, under both control and drought conditions. Methods: Metabolite profiling was conducted using gas chromatography-mass spectrometry (GC-MS) to identify compounds that accumulated differentially across treatments. We applied multivariate statistical methods, such as Partial Least Squares Discriminant Analysis (PLS-DA), hierarchical clustering, and pathway enrichment analysis, to explore metabolic reprogramming. Results: Drought stress induced significant changes in metabolite profile, particularly increasing the levels of osmoprotectants such as trehalose, glucose, sucrose, proline, and valine. Additionally, alterations in organic acids (malic acid and citric acid) and fatty acids (oleic acid and linoleic acid) were observed. PGPR inoculation further amplified these metabolic responses to enhance the osmotic regulation, reactive oxygen species (ROS) detoxification, and carbon-nitrogen metabolism, with RH-725 displaying a stronger adaptive response. Pathway enrichment analysis revealed that PGPR treatment significantly influenced metabolic pathways related to starch and sucrose metabolism, galactose metabolism, and amino acid biosynthesis, which play critical roles in drought adaptation. Conclusion: These findings provide insights into how PGPR contributes to stress resilience in B. juncea by modulating key biochemical pathways. This study provides new molecular insights into the known effect of PGPR for mitigating drought stress in oilseed crops. Full article

Paraquat is one of the most widely used nonselective herbicides globally. Although the emergence of weed resistance to paraquat has progressed relatively slowly since the first reported case in Japan in 1980, it has been steadily increasing. Resistance in weedy plants is predominantly associated with non-target-site resistance (NTSR), particularly via reduced uptake and translocation to target sites (i.e., chloroplasts) and/or enhanced sequestration; increased antioxidant capacity is also a common mechanism by which plants cope with various stresses, including reactive oxygen species (ROS). However, direct evidence for paraquat transport mediated by membrane transporters in weeds has not been established. Over the past decade, research, especially in model plants such as Arabidopsis thaliana, has advanced our understanding of the mechanisms underlying plant resistance to paraquat. This brief review summarized recent studies on paraquat resistance, with a particular focus on uptake, translocation, and sequestration mechanisms. For instance, three L-amino acid transporter (LAT) proteins (LAT1/3/4) and one (PDR11) belonging to the PDR (pleiotropic drug resistance) subfamily within the ABC (ATP-binding cassette) transporter family were confirmed to exhibit paraquat transporter activity; furthermore, transporters such as DTX6 (detoxification efflux carrier) can export/sequestrate paraquat inside the cell to the vacuole and apoplast, which confers stronger paraquat resistance to nearly commercial doses. In addition, the evolving perspectives in paraquat resistance research integrating big data and artificial intelligence, development of paraquat-tolerant crops, and a proposal of ryegrass (Lolium. spp.) and/or goosegrass (Eleusine indica) as a model weed species for paraquat resistance studies were also briefly discussed. Further advances in elucidating the molecular mechanisms of paraquat resistance in plants, including weeds, are anticipated. Full article

Serratia plymuthica, isolated from the midgut of Aedes aegypti, displays remarkable resilience to hemin, a toxic hemoglobin byproduct generated during blood digestion. This study explores its proteomic adaptations under oxidative stress induced by 5 mM hemin, mimicking midgut conditions. Growth assays demonstrated that S. plymuthica tolerated hemin concentrations ranging from 5 µM to 1 mM, reaching the stationary phase within approximately 10 h. Colonies exhibited morphological changes—darkened peripheries and translucent halos—suggesting heme accumulation and detoxification. Label-free quantitative proteomics identified 436 proteins, among which 28 were significantly upregulated—including universal stress proteins (USPs), ABC transporters, and flavodoxin—while 54 were downregulated, including superoxide dismutase and several ribosomal proteins. Upregulated proteins were associated with antioxidant defense, heme transport, and redox regulation, whereas downregulated proteins suggested metabolic reprogramming to conserve energy under stress. Functional enrichment analysis revealed significant alterations in transmembrane transport, oxidative stress response, and central metabolism. These findings suggest that S. plymuthica contributes to redox homeostasis in the mosquito gut by mitigating reactive oxygen species (ROS) and detoxifying excess heme, supporting its role as a beneficial symbiont. The observed stress tolerance mechanisms may influence mosquito physiology and vector competence, offering novel insights into mosquito–microbiota interactions and potential microbiota-based strategies for vector control. Full article

Drought stress limits plant survival and yield in arid regions. Uncovering the molecular mechanisms of drought tolerance is key to developing resilient crops. This study used Arabidopsis thaliana as a model to perform an in silico analysis of miRNA–mRNA interactions linked to post-transcriptional drought response. Using the MirTarget program, 274 miRNAs and 48,143 gene transcripts were analyzed to predict high-confidence miRNA–mRNA interactions based on binding free energies (−79 to −129 kJ/mole). Predicted binding sites were located in the CDS, 5′UTR, and 3′UTR regions of target mRNAs. Key regulatory interactions included ath-miR398a-c and ath-miR829-5p targeting ROS detoxification genes (CSD1, FSD1); ath-miR393a/b-5p and ath-miR167a-c-5p targeting hormonal signaling genes (TIR1, ARF6); and the miR169 family, ath-miR414, and ath-miR838 targeting drought-related transcription factors (NF-YA5, DREB1A, WRKY40). Notably, ath-miR414, ath-miR838, and the miR854 family showed broad regulatory potential, targeting thousands of genes. These findings suggest the presence of conserved regulatory modules with potential roles in abiotic stress tolerance. While no direct experimental validation was performed, the results from Arabidopsis thaliana provide a useful genomic framework for hypothesis generation and future functional studies in non-model plant species. This work provides a molecular foundation for improving drought and salt stress tolerance through bioinformatics-assisted breeding and genetic research. Full article

Salt stress severely constrains global crop productivity. However, most sweet corn cultivars exhibit weak tolerance to salt stress. In this study, two sweet corn CSSLs, salt-tolerant line D55 and salt-sensitive line D96, were selected as materials. We conducted comparative phenotyping and physiological profiling of seedlings under salinity treatment, and transcriptome analysis was carried out by sampling root tissues at 0 h, 4 h, 12 h, and 72 h post-treatment. The results indicated that D55 exhibited enhanced seedling height, root length, fresh weight, relative chlorophyll content, and antioxidant enzyme activities, while showing reduced malondialdehyde accumulation in comparison to D96. Pairwise comparisons across time points (0 h, 4 h, 12 h, 72 h) identified 6317 and 6828 differentially expressed genes (DEGs) in D55 and D96. A total of 49 shared DEGs across four time points were identified in D55 and D96, which were enriched in 12 significant Gene Ontology (GO) terms. Only eight DEGs were shared between genotypes across all comparisons. Transcriptomic analysis revealed 1281, 1946, and 1717 DEGs in genotypes D55 and D96 at 4 h, 12 h, and 72 h post-salt treatment, respectively. Genes associated with reactive oxygen species (ROS) homeostasis, phenylpropanoid metabolism, cutin, suberin and wax biosynthesis, and benzoxazinoid synthesis exhibit enhanced sensitivity in the salt-tolerant genotype D55. This leads to an enhanced ROS scavenging capacity and the establishment of a multi-layered defense mechanism. Additionally, brassinosteroid (BR), gibberellin (GA), and abscisic acid (ABA) and auxin-related genes exhibited different responses to salt stress in sweet corn. A hypothetical model, which established a multi-layered salt adaptation strategy, by integrating ROS detoxification, osmotic balance, and phytohormone signaling, was put forward. By integrating transcriptome and differential chromosomal fragment data, our findings identify 14 candidate genes for salt tolerance, providing potential ideal target genes in breeding to improve salt tolerance in sweet corn. Full article

Acrylamide (ACR), utilized as a precursor for producing polyacrylamide for water purification, has demonstrated neurotoxic properties. However, the mechanisms underlying its neurotoxicity remain inadequately understood. In this investigation, Caenorhabditis elegans were exposed to ACR at concentrations ranging from 250 to 1000 μg/mL and then their locomotor behavior, neuronal development, neurotransmitter concentrations, and gene expression profiles were assessed. Exposure to 250–1000 μg/mL ACR resulted in observable behaviors such as head swiveling and body bending, accompanied by a significant reduction in body size. Furthermore, ACR exposure caused damage to serotonergic, cholinergic, dopaminergic, and glutamatergic neuronal structures. In this context, elevated levels of serotonin, dopamine, acetylcholine, and glutamate were detected, along with notable upregulation of the expression of genes associated with neurotransmitters, including tph-1, cat-4, mod-1, mod-5, cat-1, ser-1, dat-1, dop-1, dop-3, unc-17, cho-1, eat-4, and glr-2. Moreover, ACR exposure elevated reactive oxygen species (ROS), O₂, and H₂O₂ levels while concurrently depleting glutathione (GSH), thereby compromising the antioxidant defense system. This led to a significant upsurge in the expression of genes involved in the nematode ACR detoxification pathway, specifically daf-16, skn-1, mlt-1, sod-3, gst-4, gcs-1, hsf-1, and hsp-16.2. Additionally, Spearman correlation analysis revealed a significant inverse relationship between certain neurotransmitter and antioxidant genes and locomotor activities, highlighting the role of these genes in mediating ACR-induced neurotoxicity in C. elegans. Collectively, this research enhances the understanding of the mechanisms related to ACR neurotoxicity. Full article

High concentrations of ammonia nitrogen could result in the death of aquatic animals and cause a huge economic loss in the aquaculture industry. However, the metabolic responses to acute ammonia nitrogen stress remain largely unknown in Penaeus monodon. In this study, we first investigated the histological change in tissues in Penaeus monodon under 96 h acute ammonia nitrogen stress. The result of the paraffin section showed that acute ammonia nitrogen stress induced severe epithelial detachment and lumen dilatation of the hepatopancreas, swollen and hemocyte infiltration of the gills, and mucosa exfoliation and shortened villi of the intestine in Penaeus monodon, suggesting the impairment of the normal physiological function in these tissues. We next examined the change in the metabolic product in the plasma and the enzyme activity in the hepatopancreas after ammonia nitrogen stress. Upon ammonia stress, both the concentration of ammonia and urea nitrogen significantly increased, while there was no significant increase in the concentration of uric acid, which is consistent with the results that the enzyme activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH), and aspartate transaminase (GOT) became significantly elevated and the enzyme activity of adenosine deaminase (ADA) in the purine metabolism pathway significantly decreased after ammonia stress, suggesting that shrimp could convert excessive ammonia to urea for ammonia detoxification through the ammonia–nitrogen metabolism pathways. Interestingly, we also observed a significant increase in superoxide dismutase (SOD) activity, suggesting a potential role of this antioxidant enzyme in the clearance of reactive oxygen species (ROS) induced via ammonia stress. Moreover, we found that acute ammonia nitrogen stress inhibited the enzyme activity of caspase 3 and caspase 8, suggesting an important role of apoptosis in protecting Penaeus monodon against acute ammonia stress. Overall, our findings revealed that Penaeus monodon may employ metabolic and purine pathways and undergo oxidative stress and apoptosis for ammonia detoxification under ammonia nitrogen stress, thus providing new insight into the metabolic response of shrimp to acute ammonia stress. Full article

Plants face various abiotic stresses in their natural environments that trigger the production of reactive oxygen species (ROS), leading to oxidative stress and potential cellular damage. This comprehensive review examines the interplay between plant antioxidant defense systems and ROS under abiotic stress conditions. We discuss the major enzymatic antioxidants, including superoxide dismutase, catalase, reductases, and peroxidases, as well as non-enzymatic antioxidants, such as ascorbic acid, glutathione, polyphenols, and flavonoids, which play crucial roles in ROS detoxification. This review elaborates on different types of ROS, their production sites within plant cells, and their dual role as both damaging oxidants and key signaling molecules. We discuss how various abiotic stresses—including heat, cold, drought, flooding, salinity, and heavy metal toxicity—induce oxidative stress and trigger specific antioxidant responses in plants. Additionally, the mechanisms of ROS generation under these abiotic stress conditions and the corresponding activation of enzymatic and non-enzymatic scavenging systems are discussed in detail. This review also discusses recent advances in understanding ROS signaling networks and their integration with other stress-response pathways. This knowledge provides valuable insights into plant stress-tolerance mechanisms and suggests potential strategies for developing stress-resistant crops by enhancing antioxidant defense systems. Moreover, the strategic ROS modulation through priming, exogenous antioxidants, nanoparticles, or genetic tools can enhance plant resilience. Integrating these methods with agronomic practices (e.g., irrigation management) offers a sustainable path to climate-smart agriculture. Our review reveals that ROS accumulation can be detrimental; however, the coordinated action of various antioxidant systems helps plants maintain redox homeostasis and adapt to environmental stress. Full article

Background: Sucralose and benzo(a)pyrene (B[a]P) are widespread foodborne substances known to harm human health. However, the effects of their combined exposure on kidney function remain unclear. This study aimed to investigate the mechanisms by which sucralose and B[a]P induce kidney injury through P-glycoprotein (PGP/ABCB1), a crucial protein involved in cellular detoxification. Methods: C57BL/6N mice were co-treated with sucralose and B[a]P for 90 days to evaluate their impact on kidney histopathology and function. In vitro experiments assessed cell viability, reactive oxygen species (ROS) levels, and B[a]P accumulation by flow cytometry. Molecular docking and cellular thermal shift assay (CETSA) were used to determine the binding affinity of sucralose to PGP. Furthermore, PCR, Western blotting, and immunohistochemistry were performed to analyze the expression of PGP and its upstream transcription factors. Results: Ninety days of co-exposure to sucralose and B[a]P significantly exacerbated renal dysfunction in mice, as evidenced by the elevated level of serum creatinine and urea nitrogen, which could be reverted by ROS scavenger N-acetyl cysteine (NAC). In vitro, sucralose promoted cellular accumulation of B[a]P, consequently enhancing B[a]P-induced cell growth inhibition and ROS production. Consistently, B[a]P accumulation was enhanced by PGP knockdown in both HK2 and HEK-293 cells. Mechanistically, sucralose can directly bind to PGP, competitively inhibiting its efflux capacity and increasing intracellular B[a]P retention. Prolonged co-exposure further downregulated PGP expression, possibly through the reductions of its transcriptional regulators (PXR, NRF2, and NF-κB). Conclusions: Co-exposure to sucralose and B[a]P exacerbates renal injury by impairing PGP function. Mechanistically, sucralose inhibits PGP activity, resulting in the accumulation of B[a]P within renal cells. This accumulation triggers oxidative stress and inhibits cell growth, which demonstrates that sucralose potentiates B[a]P-induced nephrotoxicity by directly inhibiting PGP-mediated detoxification pathways, thus underscoring the critical need to evaluate toxicity risks associated with combined exposure to these compounds. Full article

Gaseous chlorine dioxide (ClO₂) is a potent antimicrobial agent used to control microbial contamination in food and water. This study evaluates the bactericidal activity of gaseous ClO₂ released from a sodium chlorite (NaClO₂) pad against Campylobacter jejuni. Exposure to a low concentration (0.4 mg/L) of dissolved ClO₂ for 2 h resulted in a >93% reduction of C. jejuni, highlighting the bacterium’s extreme sensitivity to gaseous ClO₂. To elucidate the molecular mechanism of ClO₂-induced bactericidal action, transcriptomic analysis was conducted using RNA sequencing (RNA-seq). The results indicate that C. jejuni responds to ClO₂-induced oxidative stress by upregulating genes involved in reactive oxygen species (ROS) detoxification (sodB, ahpC, katA, msrP, and trxB), iron transport (ceuBCD, cfbpABC, and chuBCD), phosphate transport (pstSCAB), and DNA repair (rdgB and mutY). Reverse transcription-quantitative PCR (RT-qPCR) validated the increased expression of oxidative stress response genes but not general stress response genes (spoT, dnaK, and groES). These findings provide insights into the antimicrobial mechanism of ClO₂, demonstrating that oxidative damage to essential cellular components results in bacterial cell death. Full article