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Journal of Agricultural and Food... Nov 2023Silicon-containing compounds are sporadically used in crop protection and drug discovery and have demonstrated to increase the biological efficacy as well as to reduce...
Silicon-containing compounds are sporadically used in crop protection and drug discovery and have demonstrated to increase the biological efficacy as well as to reduce toxicity, improve physicochemical properties, and favorably impact the environmental profile. As part of our research, we have investigated the application of bioisosteric silicon replacements in -diamide insecticides and studied the biological activity and molecular properties of the corresponding novel compounds. At all meaningful structural elements of the -diamides, silicon-containing substituents were introduced and synthetic methodology was developed for their syntheses. As the most promising compound, silicon-containing -diamide emerged, which exhibits a very low LC value of 2.00 mg/L against and compares well to the reference compounds (LC = 0.17 mg/L) and (LC = 0.27 mg/L). Our research on silicon-containing crop protection compounds once again confirmed that the biological activity can be beneficially affected by the insertion of silicone substituents and that the introduction of well-chosen silicone motifs is an excellent strategy for agrochemical research.
Topics: Animals; Insecticides; Structure-Activity Relationship; Diamide; Silicon; Moths; Silicon Compounds; Silicones
PubMed: 37191337
DOI: 10.1021/acs.jafc.3c01342 -
Biochemical and Biophysical Research... Aug 2023As a Lepidoptera pest, Spodoptera frugiperda has become one of the major migratory pests causing significant damage to crops. It should prevent and control Spodoptera... (Review)
Review
As a Lepidoptera pest, Spodoptera frugiperda has become one of the major migratory pests causing significant damage to crops. It should prevent and control Spodoptera frugiperda with strong reproductive ability, adaptability, and migration ability, and reduce economic losses as much as possible. Chemical insecticides are mainly used in the emergency control of Spodoptera frugiperda. Diamide insecticide is a kind of pesticide that specifically targets the ryanodine receptor of Lepidopteran pests, which makes it safe, effective, targeted, and low toxicity to mammals. So, it is one of the most concerned and fastest-growing pesticide products after neonicotinoid pesticides. Intracellular Ca concentration can be regulated by ryanodine receptors, and the continuous release of Ca eventually leads to the death of pests and achieve the insecticidal effect. This review introduces in detail diamide insecticides that mainly play roles in stomach toxicity, as well as its specific target-ryanodine receptor, and analyzes how the diamide insecticide acts on the ryanodine receptor and how its mechanism of action can provide a theoretical basis for the rational use of highly effective insecticides and solve the resistance problem. Moreover, we also propose several recommendations for reducing resistance to diamide insecticides, and provide a reference for chemical control and resistance studies of Spodoptera frugiperda, which has broad development prospects in today's increasingly concerned about the ecological environment and advocating green environmental protection.
Topics: Animals; Insecticides; Ryanodine Receptor Calcium Release Channel; Diamide; Insecticide Resistance; Spodoptera; Mammals
PubMed: 37271036
DOI: 10.1016/j.bbrc.2023.05.107 -
Pharmacological Research Sep 2023In our previous multicenter study, we delineated the inherent metabolic features of colorectal cancer (CRC). Therein, we identified a member of the ectonucleotide...
In our previous multicenter study, we delineated the inherent metabolic features of colorectal cancer (CRC). Therein, we identified a member of the ectonucleotide pyrophosphatase/ phosphodiesterase family (ENPP2) as a significant differential metabolite of CRC. In this study, the role of ENPP2 in CRC has been demonstrated using established in vitro and in vivo models including ENPP2 gene knockdown, and use of the ENPP2 inhibitor, GLPG1690. We found that CRC proliferation was decreased after either ENPP2 gene knockdown or use of ENPP2 inhibitors. We further evaluated the role of GLPG1690 in AOM/DSS-induced CRC mice via intestinal barrier function, macrophage polarization, inflammatory response and microbial homeostasis. Results of immunofluorescence staining and Western blotting showed that GLPG1690 can restore gut-barrier function by increasing the expression of tight junction proteins, claudin-1, occludin and ZO-1. M2 tumor-associated macrophage polarization and colonic inflammation were attenuated after treatment with GLPG1690 using the Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) model. Moreover, 16 S rDNA pyrosequencing and metagenomic analysis showed that GLPG1690 could alleviate gut dysbiosis in mice. Furthermore, administration of GLPG1690 with antibiotics as well as fecal microbiota transplantation assays demonstrated a close link between the efficacy of GLPG1690 and the gut microbiota composition. Finally, results of metabolomic analysis implicated mainly the gut microbiota-derived metabolites of aromatic amino acids in CRC progression. These findings may provide novel insights into the development of small-molecule ENPP2 inhibitors for the treatment of CRC.
Topics: Animals; Mice; Azoxymethane; Cell Proliferation; Colitis; Colorectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Mice, Inbred C57BL; Phosphoric Diester Hydrolases
PubMed: 37524154
DOI: 10.1016/j.phrs.2023.106877 -
CNS Neuroscience & Therapeutics Nov 2023Blood-brain barrier (BBB) dysfunction is one of the hallmarks of ischemic stroke. USP14 has been reported to play a detrimental role in ischemic brain injury. However,...
AIM
Blood-brain barrier (BBB) dysfunction is one of the hallmarks of ischemic stroke. USP14 has been reported to play a detrimental role in ischemic brain injury. However, the role of USP14 in BBB dysfunction after ischemic stroke is unclear.
METHODS
In this study, we tested the role of USP14 in disrupting BBB integrity after ischemic stroke. The USP14-specific inhibitor IU1 was injected into middle cerebral artery occlusion (MCAO) mice once a day. The Evans blue (EB) assay and IgG staining were used to assess BBB leakage 3 days after MCAO. FITC-detran test was slected to examine the BBB leakage in vitro. Behavior tests were conducted to evaluate recovery from ischemic stroke.
RESULTS
Middle cerebral artery occlusion increased endothelial cell USP14 expression in the brain. Furthermore, the EB assay and IgG staining showed that USP14 inhibition through IU1 injection protected against BBB leakage after MCAO. Analysis of protein expression revealed a reduction in the inflammatory response and chemokine release after IU1 treatment. In addition, IU1 treatment was found to rescue neuronal loss resulting from ischemic stroke. Behavior tests showed a positive effect of IU1 in attenuating brain injury and improving motor function recovery. In vitro study showed that IU1 treatment could alleviate endothelial cell leakage induced by OGD in cultured bend.3 cells through modulating ZO-1 expression.
CONCLUSIONS
Our results demonstrate a role for USP14 in disrupting the integrity of the BBB and promoting neuroinflammation after MCAO.
Topics: Animals; Mice; Blood-Brain Barrier; Brain Injuries; Brain Ischemia; Endothelial Cells; Evans Blue; Immunoglobulin G; Infarction, Middle Cerebral Artery; Ischemic Stroke; Neuroinflammatory Diseases; Stroke
PubMed: 37269080
DOI: 10.1111/cns.14292 -
American Journal of Physiology.... Oct 2023Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural...
Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural compounds. We previously reported that panaxynol (PA), a bioactive component in American ginseng, possesses anticancer properties in vitro and suppresses murine colitis through its proapoptotic and anti-inflammatory properties. Because colitis is a predisposing factor of CRC and inflammation is a major driver of CRC, we sought to evaluate the therapeutic potential of PA in CRC. Azoxymethane-dextran sodium sulfate (AOM/DSS) mice (C57BL/6) were administered 2.5 mg/kg PA or vehicle 3 times/wk via oral gavage over 12 wk. PA improved clinical symptoms ( ≤ 0.05) and reduced tumorigenesis ( ≤ 0.05). This improvement may be reflective of PA's restorative effect on intestinal barrier function; PA upregulated the expression of essential tight junction and mucin genes ( ≤ 0.05) and increased the abundance of mucin-producing goblet cells ( ≤ 0.05). Given that macrophages play a substantial role in the pathogenesis of CRC and that we previously demonstrated that PA targets macrophages in colitis, we next assessed macrophages. We show that PA reduces the relative abundance of colonic macrophages within the lamina propria ( ≤ 0.05), and this was consistent with a reduction in the expression of important markers of macrophages and inflammation ( ≤ 0.05). We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions ( ≤ 0.05). These results suggest that PA is a promising therapeutic compound to treat CRC and improve clinical symptoms given its ability to inhibit macrophages and modulate the inflammatory environment in the colon. We report that panaxynol (PA) reduces colorectal cancer (CRC) by improving the colonic and tumor environment. Specifically, we demonstrate that PA improves crypt morphology, upregulates crucial tight junction and mucin genes, and promotes the abundance of mucin-producing goblet cells. Furthermore, PA reduces macrophages and associated inflammation, important drivers of CRC, in the colonic environment. This present study provides novel insights into the potential of PA as a therapeutic agent to ameliorate CRC tumorigenesis.
Topics: Mice; Animals; Disease Models, Animal; Mice, Inbred C57BL; Inflammation; Colitis; Carcinogenesis; Cell Transformation, Neoplastic; Azoxymethane; Macrophages; Colorectal Neoplasms; Mucins; Dextran Sulfate
PubMed: 37489869
DOI: 10.1152/ajpgi.00119.2023 -
Environmental Science and Pollution... May 2024The textile industry, with its extensive use of dyes and chemicals, stands out as a significant source of water pollution. Exposure to certain textile dyes, such as azo... (Review)
Review
The textile industry, with its extensive use of dyes and chemicals, stands out as a significant source of water pollution. Exposure to certain textile dyes, such as azo dyes and their breakdown products like aromatic amines, has been associated with health concerns like skin sensitization, allergic reactions, and even cancer in humans. Annually, the worldwide production of synthetic dyes approximates 7 × 10 tons, of which the textile industry accounts for over 10,000 tons. Inefficient dyeing procedures result in the discharge of 15-50% of azo dyes, which do not adequately bind to fibers, into wastewater. This review delves into the genotoxic impact of azo dyes, prevalent in the textile industry, on aquatic ecosystems and human health. Examining different families of textile dye which contain azo group in their structure such as Sudan I and Sudan III Sudan IV, Basic Red 51, Basic Violet 14, Disperse Yellow 7, Congo Red, Acid Red 26, and Acid Blue 113 reveals their carcinogenic potential, which may affect both industrial workers and aquatic life. Genotoxic and carcinogenic characteristics, chromosomal abnormalities, induced physiological and neurobehavioral changes, and disruptions to spermatogenesis are evident, underscoring the harmful effects of these dyes. The review calls for comprehensive investigations into the toxic profile of azo dyes, providing essential insights to safeguard the aquatic ecosystem and human well-being. The importance of effective effluent treatment systems is underscored to mitigate adverse impacts on agricultural lands, water resources, and the environment, particularly in regions heavily reliant on wastewater irrigation for food production.
Topics: Coloring Agents; Azo Compounds; Humans; Textile Industry; Water Pollutants, Chemical; Textiles
PubMed: 38676865
DOI: 10.1007/s11356-024-33444-1 -
Acta Neuropathologica Communications Feb 2024
Topics: Humans; Mutagens; Guam; Methylazoxymethanol Acetate; Mutagenesis; Amyotrophic Lateral Sclerosis
PubMed: 38383591
DOI: 10.1186/s40478-024-01725-y -
Journal of Natural Medicines Sep 2023Dasatinib is effective in the treatment of chronic and acute myeloid leukemia, which could cause the side effect of gastrointestinal bleeding by overdose or longtime...
Dasatinib is effective in the treatment of chronic and acute myeloid leukemia, which could cause the side effect of gastrointestinal bleeding by overdose or longtime use. Ruscogenin (RUS) from the traditional Chinese medicine Ophiopogon japonicas could protect endothelial microvascular barrier function. In this study, the therapeutic effect and underlying mechanisms of RUS were investigated on intestinal barrier dysfunction induced by dasatinib. Male C57BL/6 J mice were given three doses of dasatinib (70, 140, 210 mg/kg, ig) and RUS (3, 10, 30 μg/kg, ip) to explore the effect of dasatinib on intestinal barrier and the intervention of RUS. It was proved that dasatinib could reduce intestinal blood flow, inhibit phosphorylation of EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ErbB4)/YES-associated protein (YAP) and activation of Rho-associated coiled coil-containing protein kinase (ROCK)/phosphorylation of (myosin light chain) MLC. RUS could significantly increase intestinal blood flow, improve intestinal injury, reduce Evans blue leakage and serum content of FITC-dextran 4 kDa, and increase the expression of connexin (ZO-1, Occludin and VE-cadherin). Meanwhile, the in vitro effect of RUS (0.01, 0.1, 1 μM) on the dysfunction of the endothelial barrier was observed in dasatinib (150 nM)-pretreated HUVECs. The results showed that RUS suppressed dasatinib-induced the leakage of Evans blue, and degradation of F-actin and connexin. Furthermore, RUS could significantly increase the phosphorylation of ErbB4 at Tyr1284 site and YAP at Ser397 site, and inhibit ROCK expression and phosphorylation of MLC at Ser19 site in vivo and in vitro. In conclusion, the present research proved that RUS could suppress the side effects of dasatinib-induced intestinal barrier dysfunction by regulating ErbB4/YAP and ROCK/MLC pathways.
Topics: Male; Mice; Animals; Dasatinib; Evans Blue; Mice, Inbred C57BL; Phosphorylation; rho-Associated Kinases
PubMed: 37347409
DOI: 10.1007/s11418-023-01715-9 -
Journal of Environmental Management Dec 2023The efficiency of microbial populations in degrading refractory pollutants and the impact of adverse environmental factors often presents challenges for the biological...
The efficiency of microbial populations in degrading refractory pollutants and the impact of adverse environmental factors often presents challenges for the biological treatment of azo dyes. In this study, the genome analysis and azo dye Reactive Black 5 (RB5) degrading capability of a newly isolated strain, Shewanella sp. SR1, were investigated. By analyzing the genome, functional genes involved in dye degradation and mechanisms for adaptation to low-temperature and high-salinity conditions were identified in SR1. The addition of co-substrates, such as glucose and yeast extract, significantly enhanced RB5 decolorization efficiency, reaching up to 87.6%. Notably, SR1 demonstrated remarkable robustness towards a wide range of NaCl concentrations (1-30 g/L) and temperatures (10-30 °C), maintaining efficient decolorization and high biomass concentration. The metabolic pathways of RB5 degradation were deduced based on the metabolites and genes detected in the genome, in which the azo bond was first cleaved by FMN-dependent NADH-azoreductase and NAD(P)H-flavin reductase, followed by deamination, desulfonation, and hydroxylation mediated by various oxidoreductases. Importantly, the degradation metabolites exhibited reduced toxicity, as revealed by toxicity analysis. These findings highlighted the great potential of Shewanella sp. SR1 for bioremediation of wastewaters contaminated with azo dyes.
Topics: Biodegradation, Environmental; Azo Compounds; Shewanella; Anaerobiosis; Coloring Agents
PubMed: 37776795
DOI: 10.1016/j.jenvman.2023.119073 -
Environmental Research Aug 2023The present study identifies and analyses the degraded products of three azo dyes (Reactive Orange 16, Reactive Red 120, and Direct Red 80) and proffers their in silico...
Systematic computational toxicity analysis of the ozonolytic degraded compounds of azo dyes: Quantitative structure-activity relationship (QSAR) and adverse outcome pathway (AOP) based approach.
The present study identifies and analyses the degraded products of three azo dyes (Reactive Orange 16, Reactive Red 120, and Direct Red 80) and proffers their in silico toxicity predictions. In our previously published work, the synthetic dye effluents were degraded using an ozonolysis-based Advanced Oxidation Process. In the present study, the degraded products of the three dyes were analysed using GC-MS at endpoint strategy and further subjected to in silico toxicity analysis using Toxicity Estimation Software Tool (TEST), Prediction Of TOXicity of chemicals (ProTox-II), and Estimation Programs Interface Suite (EPI Suite). Several physiological toxicity endpoints, such as hepatotoxicity, carcinogenicity, mutagenicity, cellular and molecular interactions, were considered to assess the Quantitative Structure-Activity Relationships (QSAR) and adverse outcome pathways. The environmental fate of the by-products in terms of their biodegradability and possible bioaccumulation was also assessed. Results of ProTox-II suggested that the azo dye degradation products are carcinogenic, immunotoxic, and cytotoxic and displayed toxicity towards Androgen Receptor and Mitochondrial Membrane Potential. TEST results predicted LC50 and IGC50 values for three organisms Tetrahymena pyriformis, Daphnia magna, and Pimephales promelas. EPISUITE software via the BCFBAF module surmises that the degradation products' bioaccumulation (BAF) and bioconcentration factors (BCF) are high. The cumulative inference of the results suggests that most degradation by-products are toxic and need further remediation strategies. The study aims to complement existing tests to predict toxicity and prioritise the elimination/reduction of harmful degradation products of primary treatment procedures. The novelty of this study is that it streamlines in silico approaches to predict the nature of toxicity of degradation by-products of toxic industrial affluents like azo dyes. These approaches can assist the first phase of toxicology assessments for any pollutant for regulatory decision-making bodies to chalk out appropriate action plans for their remediation.
Topics: Adverse Outcome Pathways; Quantitative Structure-Activity Relationship; Protoporphyrinogen Oxidase; Mutagens; Azo Compounds; Coloring Agents
PubMed: 37217122
DOI: 10.1016/j.envres.2023.116142