Mechanism Of Toxicity Research Articles

The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.

The pervasiveness and mortality associated with methamphetamine abuse have doubled during the past decade, suggesting a possible worldwide substance use crisis. Epitomizing the pathophysiology and toxicology of methamphetamine abuse proclaims severe signs and symptoms of neurotoxic and neurobehavioral manifestations in both humans and animals. Most importantly, chronic use of this drug enhances the probability of developing neurodegenerative diseases manifolds. Parkinson's disease is one such neurological disorder, which significantly and evidently not only shares a number of toxic pathogenic mechanisms induced by methamphetamine exposure but is also interlinked both structurally and genetically. Methamphetamine-induced neurodegeneration involves altered dopamine homeostasis that promotes the aggregation of α-synuclein protofibrils in the dopaminergic neurons and drives these neurons to make them more vulnerable to degeneration, as recognized in Parkinson's disease. Moreover, the pathologic mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation and decreased neurogenesis detected in methamphetamine abusers dramatically resemble to what is observed in Parkinson's disease cases. Therefore, the present review comprehensively cumulates a holistic illustration of various genetic and molecular mechanisms putting across the notion of how methamphetamine administration and intoxication might lead to Parkinson's disease-like pathology and Parkinsonism.

Adsorption of Pb(II) and Cd(II) on Modified Coal Gasification Slag: Competitive Adsorption, Leaching Toxicity, and Adsorption Mechanism

AbstractTo remove heavy metals from wastewater, coal gasification slag (CGS) was prepared as an adsorbent. Five modified materials were created, including HF‐CGSC, KOH‐HCl‐CGS, and three KOH‐CGS variants with different mass ratios. The adsorption tests showed KOH‐CGS (0.25) had the best efficiency for Pb(II) and Cd(II) via spontaneous chemisorption. Kinetic, thermodynamic, and 13C NMR analyses indicated that adsorption involved pore adsorption, functional group coordination, and π‐π interactions. Competitive adsorption results showed minimal interaction between Pb and Cd. Leaching tests confirmed the process's environmental safety. This study suggests new approaches for using coal gasification slag in wastewater treatment.

Baseline Sensitivity and Toxicity Mechanisms of Prochloraz to Alternaria alternata Strains Associated with Maize Leaf Blight in Heilongjiang Province in China.

Alternaria species are fungal pathogens that can infect maize, causing leaf blight disease and significant economic losses. This study aimed to determine the baseline sensitivity to prochloraz of A. alternata isolates obtained from diseased maize leaves collected from Heilongjiang Province by assessing the half-maximal effective concentration (EC50) values. The EC50 values of prochloraz ranged from 0.0550 to 2.3258 μg/ml, with an average of 0.9995 ± 0.5192 μg/ml. At EC50 (1.2495 μg/ml) and 2EC50 (2.4990 μg/ml), prochloraz increased the number of mycelial offshoots, disrupted the cell membrane integrity of conidia and mycelia, and resulted in a reduced ergosterol content in the mycelia. Prochloraz significantly affected the mycelial cell membrane permeability and increased the malondialdehyde content and superoxide dismutase activity. No cross-resistance was detected between prochloraz and other fungicides. These data demonstrate that prochloraz is a promising fungicide for managing maize leaf blight caused by A. alternata and provide novel insights into understanding the mechanism of prochloraz toxicity against A. alternata isolates.

Time-course analysis of the transcriptome of Arabidopsis thaliana leaves under high-concentration ammonium sulfate treatment

ABSTRACT Ammonium fertilization is of great interest for future agriculture, as unlike nitrate, ammonium use efficiency does not decrease in C3 plants, even in environments with elevated CO2 concentrations. However, excess ammonium often results in toxic effects such as growth suppression and chlorosis, i.e. ammonium toxicity. The addition of nitrate, a major source of nitrogen commonly found in soils, has been shown to alleviate these toxic effects. Understanding the mechanisms of ammonium toxicity in the presence of nitrate is crucial for the effective use of ammonium fertilizers in crop cultivation. To elucidate these responses, a time-course analysis of the transcriptome was performed on A. thaliana leaves treated with high concentrations of ammonium sulfate in the presence of sufficient nitrate. The expression of nitrate-inducible genes tended to be downregulated by the treatment. The expression of genes relating to abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and membrane trafficking was upregulated, whereas that of photosynthesis-, auxin-, and cytokinin-related genes involved in growth and development was downregulated. The induction of many osmotic stress-responsive genes and nitric oxide (NO)-inducible genes suggests the involvement of osmotic stress and NO signaling in the response. This study provides a novel and comprehensive overview of transcriptional changes occurring in response to high ammonium sulfate concentrations with sufficient nitrate, and sheds light on potential pathways involved in ammonium toxicity under these conditions.

Effects of Decabromodiphenyl Ethane and Cadmium Coexposure on Their Bioaccumulation, Oxidative Stress, Root Metabolism, and Rhizosphere Soil Microorganisms in a Soil-Rice System.

Decabromodiphenyl ethane (DBDPE) and cadmium (Cd) are typical pollutants in e-waste, seriously threatening crop growth. This study investigated the bioaccumulation and toxicity mechanisms of DBDPE and Cd in a soil-rice system. The results showed that 50 mg/kg DBDPE could reduce the level of accumulation of Cd in rice roots. DBDPE and Cd induced the antioxidant system (SOD, POD, and MDA) in rice seedlings. The combined exposure reduced the contents of carbohydrates, lipids, amino acids, and organic acids. Phenylalanine and phenylpropanoid metabolisms were identified as the key detoxification metabolic pathways under combined exposure. DBDPE and Cd disrupted the functional cycling of carbon and nitrogen in rhizosphere soil, while Gemmatimonadetes, Actinobacteria, and Bacteroidetes were the key bacterial groups responding to DBDPE and Cd stress. This work provides data for the toxicity risk evaluation of DBDPE and Cd combined exposure to food crops.

Investigating antioxidant effects of hamamelitannin-conjugated zinc oxide nanoparticles on oxidative stress-Induced neurotoxicity in zebrafish larvae model.

An excessive amount of reactive oxygen species triggers oxidative stress, leading to an imbalance in cellular homeostasis. Antioxidant therapy is an effective tool for lowering the oxidative stress and associated ailments. Recently, green nano-based drug formulations have demonstrated promising antioxidant activity and neutralizing oxidative stress. In this study, a tannin molecule Hamamelitannin (HAM), was utilized to synthesize zinc oxide nanoparticles HAM-ZnO NPs, to mitigate oxidative stress and associated ailments . The HAM-ZnO NPs were synthesized and characterized by XRD, SEM, and FTIR. The antioxidant potentials of HAM-ZnO NPs were analyzed by in vitro antioxidant assays. Zebrafish embryos and larvae were used as in-vivo models to assess the toxicity and antioxidant protective mechanism. Hydrogen peroxide (1mM) was employed to induce oxidative stress and treated with HAM-ZnO NPs to study the cognitive impairment and antioxidant enzyme levels. Levels of reactive oxygen species and cell death due to oxidative stress induction were studied by 2',7'-dichlorodihydrofluorescein diacetate and Acridine orange staining methods. Additionally, expression of Antioxidant genes such as SOD, CAT, GPx, and GSR were studied. . HAM-ZnO NPs exhibited a spherical morphology and size ranges between 48 and 53nm. In vitro antioxidant studies revealed the antioxidant properties of HAM-ZnO NPs. Furthermore, in vivo studies indicated that HAM-ZnO NPs don't possess any cytotoxic effects in zebrafish larvae at concentrations between (5-25µg/ml), The study also observed that HAM-ZnO NPs significantly reduced Hydrogen Peroxide-induced stress and increased antioxidant activity in zebrafish larvae. Also, the antioxidant gene expression was upregulated in the HAM-ZnO NPs zebrafish larvae. Findings in this study showed that HAM-ZnO NPs might be a potential intervention for diseases linked to oxidative stress.

Citreoviridin induces apoptosis through oxidative damage and inflammatory response in PC-12 cells.

Citreoviridin (CIT) is a mycotoxin produced by various fungi. Although CIT has been reported to cause neurotoxicity, the molecular mechanism is poorly understood. Therefore, the aim of this study was to investigate the effects and molecular mechanisms of CIT in neurotoxicity. Different concentrations of CIT were treated to rat pheochromocytoma (PC-12 cells), and oxidative stress parameters, cytokine levels, and cell apoptosis were evaluated. CIT treatment (5 and 10μM) significantly induced PC-12 cell apoptosis and increased lactate dehydrogenase activity. Additionally, CIT treatment induced oxidative stress, as evidenced by a significant increase in intracellular levels of reactive oxygen species, malondialdehyde, and superoxide dismutase and a decrease in glutathione activity. Moreover, CIT treatment induced an inflammatory response, as evidenced by a significant increase in the intracellular levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1-beta in PC-12 cells. Furthermore, quantitative PCR and western blotting showed that CIT treatment increased both the protein and mRNA expression of GADD45α and p21 in PC-12 cells, suggesting that CIT may induce apoptosis by inhibiting cell cycle, blocking cell growth, and damaging DNA. Conclusively, this study contributes the understanding the toxicity mechanisms of CIT to nerve cells.

Spherical covalent-organic framework-assisted laser desorption ionization mass spectrometry reveals the promotional effect of triphenyl phosphate on breast cancer in mice

Triphenyl phosphate (TPP), a wide-used organophosphate flame retardants (OPFRs), is suspected to be a risk factor for the female-specific cancers, but underlying toxicity mechanisms of environmentally relevant dose exposure remain unclear. Herein, a strategy of spherical covalent organic framework (TPB-BPTP-COF)-assisted laser desorption ionization mass spectrometry (LDI-MS), which benefited from fast analysis speed, facile sample preprocessing, and high throughput, was proposed for unveiling the biomarkers of breast cancer (BC) and the relationship between TPP exposure and progression of BC in mice by serum metabolism analysis. The results displayed that 13 metabolites associated with BC development were up-regulated in experimental group versus healthy control mice. Moreover, long-term exposure to environmentally relevant doses of TPP was found to promote BC, mainly by affecting glycolysis/gluconeogenesis, pyrimidine metabolism, pantothenic acid and CoA biosynthesis, and β-alanine metabolism. This work proved the potential application of COFs as LDI-MS substrates in analyzing complex biological samples, and also revealed the risk of long-term low-dose exposure to TPP in the development of BC.

Environmentally Persistent Free Radicals stimulate CYP2E1-mediated generation of reactive oxygen species at the expense of substrate metabolism.

Environmentally persistent free radicals (EPFRs) are a recently recognized component of particulate matter that cause respiratory and cardiovascular toxicity. The mechanism of EPFR toxicity appears to be related to their ability to generate reactive oxygen species (ROS), causing oxidative damage. EPFRs were shown to affect P450 function, inducing the expression of some forms through the Ah receptor. However, another characteristic of EPFRs lies in their ability to inhibit P450 activities. CYP2E1 is one of the P450s that is inhibited by EPFR (MCP230) exposure. As CYP2E1 is also known to generate ROS, it is important to understand the ability of EPFRs to influence the function of this enzyme and to identify the mechanisms involved. CYP2E1 was shown to be inhibited by EPFRs, and to a lesser extent by non-EPFR particles. As EPFR-mediated inhibition was more robust at subsaturating NADPH-cytochrome P450 reductase (POR) concentrations, disruption of POR·CYP2E1 complex formation and electron transfer were examined. Surprisingly, neither complex formation nor electron transfer between POR and CYP2E1 were inhibited by EPFRs. Examination of ROS production showed that MCP230 generated a greater amount of ROS than the non-EPFR CuO-Si. When a POR/CYP2E1-containing reconstituted system was added to the pollutant-particle systems there was a synergistic stimulation of ROS production. The results indicate that EPFRs cause inhibition of CYP2E1-mediated substrate metabolism, yet do not alter electron transfer and actually stimulate ROS generation. Taken together, the results are consistent with EPFRs affecting CYP2E1 function by inhibiting substrate metabolism and increasing the generation of ROS. Significance Statement Environmentally persistent free radicals affect CYP2E1 function by inhibition of monooxygenase activity. This inhibition is not due to disruption of the POR·CYP2E1 complex or inhibition of electron transfer, but due to uncoupling of NADPH and oxygen consumption from substrate metabolism to the generation of ROS. These results show that EPFRs block the metabolism of foreign compounds, and also synergistically stimulate the formation of reactive oxygen species that lead to oxidative damage within the organism.

Multi-omics profiling reveals the molecular mechanisms of H2O2-induced detrimental effects on Thamnaconus septentrionalis

BackgroundHydrogen peroxide (H2O2), a novel water treatment agent, can be used for disinfection, water quality adjustment, and disease prevention, while excessive H2O2 can injure farm animals, even leading to death. Hydrogen peroxide is a recommended disinfectant and bactericide for treating gill diseases and vibriosis in the greenfin horse-faced filefish Thamnaconus septentrionalis. However, its cumulative effect, toxic molecular mechanism and relevant signal transduction/metabolic networks in marine fishes are largely unknown.ResultsWe employed a multi-omics approach to investigate the detrimental effects of 50 mg/L H2O2 exposure (2 h/d) on filefish for 2 d, 4 d, and 6 d. Transcriptome sequencing showed that differentially expressed genes (DEGs) were mainly classified into functions such as signal transduction, nervous system, liver and bile acid metabolism, energy metabolism, cell adhesion and communication, inflammation and immune response. Metabolomic analysis found that the significantly changed metabolites (SCMs) were involved in phenylalanine metabolism, inflammatory mediator regulation, linoleic acid metabolism, and necroptosis. The main SCMs were cholic acid, carnitine C12:1, dimethylmalonic acid, glutamic acid, L-lactic acid, shikimic acid, 2-methylsuccinic acid, and others. Moreover, H2O2-induced oxidative stress also disturbs the balance of the gut microbiota, altering the microbial composition and affecting digestive processes.ConclusionsIntegrated multiomics analysis revealed that H2O2-induced detrimental impacts include mucosal damage, inflammatory and immune responses, altered energy metabolism, and gut microbiota disorders. These findings offer novel insights into the harmful effects and signal transduction/metabolic pathways triggered by H2O2 exposure in marine fishes.

Integration of transcriptomics, gut microbiota, and physiology reveals the toxic response of bensulfuron-methyl in Procambarus clarkii

Bensulfuron-methyl (BSM) enters the environment through agricultural practices, posing a threat to the health of aquatic organisms. Currently, the toxic mechanisms of BSM on crayfish (Procambarus clarkii) have not been thoroughly investigated. In this study, crayfish were exposed to BSM solutions at concentrations of 0, 5, and 10 mg/L for 48 h. The study integrated physiological, gut microbiota, and transcriptomic analyses to investigate the mechanisms of action. BSM exposure induced oxidative stress responses in crayfish, resulting in changes in superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH) activity, and malondialdehyde (MDA) levels. Exposure to BSM caused damage to the intestinal tissues, reduced gut microbiota diversity, increased the abundance of harmful bacteria, and led to intestinal dysfunction. Analysis of the hepatopancreas revealed significant tissue damage. Transcriptomic data indicated that BSM affects the growth of crayfish through genes related to immune response (SLC17A5, CTSD, CTSB, NFKBIA, Mincle). The lysosomal pathway and NF-κB pathway were notably affected. This study analyzed the negative impacts of BSM on crayfish from various levels and provided detailed data to enhance our understanding of the toxic mechanisms of BSM in aquatic organisms.

Potential toxic effects linked to taurine interactions with alkanolamines and diisopropylamine

Diisopropylamine (DIPA), aminomethyl propanol (AMP), amino ethoxy ethanol (AEE), diethanolamine (DEA), ethanolamine (EA), pyridine (PYR) and methyl diethanolamine (MDEA) are used for carbon capture and to sweeten sour gas, and are found in groundwater. They are also used in cosmetic products. Taurine is abundant in the body, with key biological functions linked to its charged SO groups. Interactions between SO and amines have not been studied, but can strongly affect the biological function of taurine. Fourier transform infrared spectroscopy indicates SO…HN hydrogen bonding between taurine and DIPA, AMP, AEE, DEA, EA and MDEA. These interactions induce the formation of hydrophobic amine-taurine clusters, thus decreasing amine miscibility in water, as revealed by light scattering. This effect is most marked for DIPA, leading to turbid mixtures indicative of micron-sized droplets. PYR and taurine likely interact via S…N bonding. This study offers insights regarding potential mechanisms of amine toxicity to humans.Graphical

Investigate the binding of pesticides with the TLR4 receptor protein found in mammals and zebrafish using molecular docking and molecular dynamics simulations.

The widespread use of pesticides poses significant threats to both environmental and human health, primarily due to their potential toxic effects. The study investigated the cardiovascular toxicity of selected pesticides, focusing on their interactions with Toll-like receptor 4 (TLR4), an important part of the innate immune system. Using computational tools such as molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA), density functional theory (DFT) calculations, and ADME analysis, this study identified C160 as having the lowest binding affinity (-8.2kcal/mol), followed by C107 and C165 (-8.0kcal/mol). RMSD, RMSF, Rg, and hydrogen bond metrics indicated the formation of stable complexes between specific pesticides and TLR4. PCA revealed significant structural changes upon ligand binding, affecting stability and flexibility, while DFT calculations provided information about the stability, reactivity, and polarity of the compounds. ADME studies highlighted the solubility, permeability, and metabolic stability of C107, C160, and C165, suggesting their potential for bioavailability and impact on cardiovascular toxicity. C107 and C165 exhibit higher bioactivity scores, indicating favourable absorption, metabolism, and distribution properties. C165 also violated rule where molecular weight is greater than 500g/mol. Further, DFT and NCI analysis of post MD conformations confirmed the binding of ligands at the binding pocket. The analysis shed light on the molecular mechanisms of pesticide-induced cardiovascular toxicity, aiding in the development of strategies to mitigate their harmful effects on human health.

Difenoconazole Induced Damage of Bovine Mammary Epithelial Cells via ER Stress and Inflammatory Response.

Difenoconazole (DIF) is a fungicide used to control various fungi. It is absorbed on the surface of different plants and contributes significantly to increased crop production. However, DIF is reported to exhibit toxicity to fungi and to aquatic plants, fish, and mammals, including humans, causing adverse effects. However, research on the impact of DIF on the mammary epithelial cells of herbivorous bovines is limited. DIF-induced damage and accumulation in the mammary glands can have direct and indirect effects on humans. Therefore, we investigated the effects and mechanisms of DIF toxicity in MAC-T cells. The current study revealed that DIF reduces cell viability and proliferation while triggering apoptotic cell death through the upregulation of pro-apoptotic proteins, including cleaved caspase 3 and Bcl-2-associated X protein (BAX), and the downregulation of leukemia type 2 (BCL-2). DIF also induced endoplasmic reticulum (ER) stress by increasing the expression of genes or proteins of Bip/GRP78, protein disulfide isomerase (PDI), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and endoplasmic reticulum oxidoreductase 1 Alpha (ERO1-Lα). We demonstrated that DIF induces mitochondria-mediated apoptosis in MAC-T cells by activating ER stress pathways. This cellular damage resulted in a significant increase in the expression of inflammatory response genes and proteins, including cyclooxygenase 2 (COX2), transforming growth factor beta 3 (TGFB3), CCAAT enhancer binding protein delta (CEBPD), and iNOS, in DIF-treated groups. In addition, spheroid formation by MAC-T cells was suppressed by DIF treatment. Our findings suggest that DIF exposure in dairy cows may harm mammary gland function and health and may indirectly affect human consumption of milk.

Resmethrin disrupts mitochondria-associated membranes and activates endoplasmic reticulum stress, leading to proliferation inhibition in cultured mouse Leydig and Sertoli cells

Resmethrin, a pyrethroid pesticide used to control insects, is toxic to non-target organisms and other mammals. However, little is known about the reproductive toxicity of resmethrin in the testes, or its mechanism of toxicity. In this study, we investigated the testicular toxicity of resmethrin on mouse Leydig (TM3) and Sertoli (TM4) cells, focusing on the mitochondria and endoplasmic reticulum (ER). We found that resmethrin inhibited proliferation and cell cycle progression and disrupted mitochondrial membrane potential (MMP; ΔΨ) in TM3 and TM4 cells. In particular, resmethrin exposure significantly reduced the expression of mitochondria-associated membranes (MAMs) proteins, such as Vapb, Vdac, and Grp75, in both cell lines. Resmethrin also disrupts calcium homeostasis in the mitochondrial matrix and cytoplasm. In addition, resmethrin activates oxidative stress-mediated ER stress signals. Finally, we confirmed that 4-PBA, an ER stress inhibitor, restored the growth of TM3 and TM4 cells, which was decreased by resmethrin. Therefore, we confirmed that resmethrin hampered MAMs and activated ER stress, thus suppressing TM3 and TM4 cell proliferation.

Enhancing Animal Nutritional Security Through Biofortification in Forage Crops: A Comprehensive Review

Livestock nutrition is crucial for sustaining the health and productivity of farm animals, which are a cornerstone of the global food supply. Proper nutrition ensures that animals receive the necessary nutrients for essential bodily functions, growth, reproduction and lactation. Tailored, balanced diets that cater to the specific nutritional needs of different livestock species and their developmental stages also boost reproductive performance, leading to higher birth rates and healthier offspring. Conversely, inadequate nutrition can lead to stunted growth, diminished productivity, and increased vulnerability to diseases, ultimately resulting in significant economic losses. Nutritional imbalances among animals, especially in dairy goats and cattle, pose a significant challenge in livestock management. These disorders result from inadequate or imbalanced nutrient intake, leading to a range of metabolic and health issues. Fodders are essential to livestock nutrition, providing a balanced diet that supports overall animal health, growth and productivity. They are primary sources of energy, with grasses and cereals supplying carbohydrates needed for maintenance and production activities. Leguminous fodders like alfalfa and clover are rich in protein and crucial for muscle development, milk production and growth. Additionally, green fodders offer vital vitamins (A, D, E, K) and minerals such as calcium and phosphorus, which are necessary for various metabolic functions. The high fibre content in fodders aids in proper digestion and prevents digestive disorders. Overall, the review highlights the impact of various nutrient deficiencies on livestock, including the effects of anti-nutritional factors and the mechanisms of nitrate, oxalate and prussic acid toxicity in animals. It underscores the importance of agronomic bio fortification as a promising strategy to enhance the nutritional quality of fodder crops, thereby improving animal health and welfare, while also contributing to food security and sustainable agriculture.

Biotechnological potential of silver nanoparticles synthesized by green method to control phytopathogenic bacteria: contributions from a proteomic analysis.

Silver nanoparticles (AgNPs) synthesized through green synthesis routes are widely used as antimicrobial agents due to their advantages such as biocompatibility, stability, sustainability, speed and cost-effectiveness. Although AgNPs appear to be more potent than silver ions, the mechanisms related to their antibacterial activity are not yet fully understood. The most common proposed mechanism of AgNPs' toxicity so far is the release of silver ions and/or specific functions of the particles. In this context, the present study aimed to investigate the mechanisms of action of AgNPs synthesized using noni fruit peels (Morinda citrifolia) against the phytopathogen Xanthomonas campestris pv. campestris (Xcc) through proteomics. Xcc was treated with AgNPs (32 µM), AgNO3 (32 µM), or received no treatment (Ctrl - control condition), and its proteomic response was comprehensively characterized to elucidate the antimicrobial mechanisms of AgNPs in the phytopathogenic microorganism. A total of 352 differentially abundant proteins were identified. Most proteins were regulated in the AgNPs × Ctrl and AgNPs × AgNO3 comparisons/conditions. When Xcc treated with 32 µM AgNPs were compared to controls, the results showed 134 differentially abundant proteins, including 107 increased and 27 decreased proteins. In contrast, when Xcc treated with 32 µM AgNO3 were compared to Ctrl, the results showed only 14 differentially abundant proteins, including 10 increased proteins and 4 decreased proteins. Finally, when Xcc treated with 32 µM AgNPs were compared to Xcc treated with 32 µM AgNO3, the results showed 204 differentially abundant proteins, including 75 increased proteins and 129 decreased proteins. Gene ontology enrichment analysis revealed that most of the increased proteins were involved in important biological processes such as metal ion homeostasis, detoxification, membrane organization, metabolic processes related to amino acids and carbohydrates, lipid metabolic processes, proteolysis, transmembrane transport, and others. The AgNPs used in this study demonstrated effective antimicrobial activity against the phytopathogenic bacteria Xcc. Furthermore, the obtained results contribute to a better understanding of the mechanisms of action of AgNPs in Xcc and may aid in the development of strategies to control Xcc in brassica.

Biological exposure to microplastics and nanoplastics and plastic additives: impairment of glycolipid metabolism and adverse effects on metabolic diseases.

Microplastics and nanoplastics (M-NPs) are widespread pollutants in the environment, posing growing risks to human health and garnering increasing concern from researchers. Due to their small particle size, ease of adsorption, and resistance to degradation, M-NPs can retain and migrate in the environment for long-term periods. Upon entering organisms, M-NPs have been reported to cause inflammation and oxidative stress and result in abnormalities in glycolipid metabolism. Furthermore, research suggests that exposure to M-NPs may act as a causative agent for metabolic and cardiovascular diseases such as diabetes, obesity, and atherosclerosis. This paper aims to review the consequences of exposure to M-NPs on animal and cellular glycolipid metabolism and discusses the disruption of gut microbial homeostasis and the subsequent emergence of insulin resistance. PPAR signaling pathway activation after exposure to M-NPs was found to lead to increased hepatic fat accumulation and impaired lipid metabolism. Additionally, the paper highlights how M-NPs exacerbate the progression of obesity and diabetes in patients, induce damage to vascular endothelial cells, trigger oxidative stress, and contribute to the development of atherosclerosis. Despite the growing concern, the toxicity and molecular mechanism of M-NPs on glycolipid metabolism remain understudied, and effective methods for removing plastic pollutants deposited in the body are yet to be established. These findings provide valuable insights for future research in this field.

Role of AhR-Hsp90-MDM2-mediated VDR ubiquitination in PM2.5-induced renal toxicity

Background and objectivesThe kidney is a primary target for the accumulation of particulate matter (PM2.5). This study aimed to investigate PM2.5-induced renal toxicity mechanisms, focusing on the aryl hydrocarbon receptor (AhR)-Hsp90-MDM2 axis and its impact on vitamin D receptor (VDR) ubiquitination. MethodsPM2.5's role in activating the AhR and its downstream pathways was investigated using in vitro and in vivo models. Renal damage and therapeutic effects in PM2.5-exposed and paricalcitol-treated mice were evaluated using weight measurements, histopathology, and scanning electron microscopy. AhR, Hsp90, and VDR localization and expression in renal cells were assessed using FISH and Western blot. Protein interactions were examined using co-immunoprecipitation. Differentially expressed gene (DEG) analysis of GEO datasets was used to identify related proteins and genes. ResultsPM2.5 exposure caused significant renal damage in mice, including increased serum creatinine, albuminuria, and histopathological deterioration, which were alleviated by paricalcitol. PM2.5 induced the nuclear translocation of AhR and Hsp90 and reduced nuclear VDR expression; paricalcitol reversed these effects. Immunohistochemistry confirmed these findings. PM2.5 upregulated the NLRP3/caspase-1/IL-1β/IL-18 axis, which was reversed by paricalcitol treatment. Inhibition of Hsp90 increased nuclear VDR expression through MDM2 mediation. DEG analysis identified VDR-regulated genes; PM2.5 increased the mRNA levels of IL-6, IL-2, and CXCL8, which were downregulated by Hsp90 and MDM2 inhibitors, with VDR agonists further decreasing these levels. ConclusionThis study reveals a novel mechanism of PM2.5-induced renal toxicity through the AhR-Hsp90-MDM2 axis, promoting VDR ubiquitination and degradation and increasing inflammation. These findings provide a foundation for future studies and lay the groundwork for developing targeted interventions to mitigate the public health impact of PM2.5 exposure.

Soybean Agglutinin Induced Apoptotic Effects by Down-Regulating ANXA2 Through FAK Pathway in IPEC-J2 Cells.

Soybean agglutinin (SBA) is an anti-nutritional factor in soybean, possesses toxic effects by binding to intestinal epithelial cells, and finally interferes the digestion and absorption of nutrients in humans and animals. Annexin A2 (ANXA2) is one of the SBA-specific binding proteins in intestinal epithelial cells and participates in multiple cellular biological processes. However, whether SBA affects apoptosis through ANXA2 and its apoptosis-related pathway remains unclear. IPEC-J2 is an ideal model to study human intestinal health. Therefore, this study aims to investigate the effects of ANXA2 on SBA-induced intestinal epithelial cell apoptosis and the related pathway mechanism using IPEC-J2 as a cell model. The results showed that SBA induced the apoptosis through FAK signal pathway and decreased the gene and protein expressions of ANXA2 in IPEC-J2. The expression of ANXA2 protein had a negative correlation with the apoptosis rates, and a positive correlation with the expression of FAK protein and FAK pathway downstream proteins. In conclusion, SBA induced apoptosis of IPEC-J2 cells by downregulating the expression of ANXA2, which activated the FAK pathway. These findings highlight the toxic mechanism of SBA, which will provide basis for studying the toxicity mechanisms of other food-derived anti-nutrients and provide a new perspective for human gastrointestinal health and related cancer treatment.