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Journal of Hazardous Materials Jun 2023Methomyl is a widely used carbamate pesticide, which has adverse biological effects and poses a serious threat to ecological environments and human health. Several...
Methomyl is a widely used carbamate pesticide, which has adverse biological effects and poses a serious threat to ecological environments and human health. Several bacterial isolates have been investigated for removing methomyl from environment. However, low degradation efficiency and poor environmental adaptability of pure cultures severely limits their potential for bioremediation of methomyl-contaminated environment. Here, a novel microbial consortium, MF0904, can degrade 100% of 25 mg/L methomyl within 96 h, an efficiency higher than that of any other consortia or pure microbes reported so far. The sequencing analysis revealed that Pandoraea, Stenotrophomonas and Paracoccus were the predominant members of MF0904 in the degradation process, suggesting that these genera might play pivotal roles in methomyl biodegradation. Moreover, five new metabolites including ethanamine, 1,2-dimethyldisulfane, 2-hydroxyacetonitrile, N-hydroxyacetamide, and acetaldehyde were identified using gas chromatography-mass spectrometry, indicating that methomyl could be degraded firstly by hydrolysis of its ester bond, followed by cleavage of the C-S ring and subsequent metabolism. Furthermore, MF0904 can successfully colonize and substantially enhance methomyl degradation in different soils, with complete degradation of 25 mg/L methomyl within 96 and 72 h in sterile and nonsterile soil, respectively. Together, the discovery of microbial consortium MF0904 fills a gap in the synergistic metabolism of methomyl at the community level and provides a potential candidate for bioremediation applications.
Topics: Humans; Methomyl; Biodegradation, Environmental; Pesticides; Bacteria; Soil; Metabolic Networks and Pathways; Microbial Consortia
PubMed: 37003005
DOI: 10.1016/j.jhazmat.2023.131287 -
Metabolites Aug 2023Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the...
Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the n-methyl carbamate class, including methomyl. Here, we investigate the liver and systemic metabolic effects of methomyl in a mouse model. We hypothesize that methomyl exposure will disrupt xenobiotic and intermediary metabolism and promote hepatic steatosis in mice. Male C57BL/6 mice were exposed daily to 0-5 mg/kg methomyl for 18 days. Mice were fed water and regular chow diet ad libitum. Metabolic phenotyping was performed, and tissue samples were collected. Effects were generally greatest at the highest methomyl dose, which induced . Methomyl decreased whole body weight while the liver:body weight and testes:body weight ratios were increased. Hepatic steatosis increased while plasma LDL decreased. Fasting blood glucose and the glucose tolerance test area under the curve decreased along with hepatic glycogen stores. Methomyl, however, did not increase liver oxidative stress or injury. Collectively, these data demonstrate that methomyl disrupts hepatic xenobiotic and intermediary metabolism while increasing the testes:body weight ratio, suggesting that it may be an endocrine disrupting chemical. Besides methomyl's known action in cholinesterase inhibition, it may be involved in aryl hydrocarbon receptor activation. The potential impact of n-methyl carbamate insecticides on metabolic health and diseases, including toxicant-associated steatotic liver disease (TASLD), warrants further investigation.
PubMed: 37623845
DOI: 10.3390/metabo13080901 -
Pakistan Journal of Biological Sciences... Jan 2021<b>Background and Objective:</b> Effect of some compounds such as Plant extracts (Techno oil and Berna Star), natural origin compounds (Top-nine, Repcar and...
<b>Background and Objective:</b> Effect of some compounds such as Plant extracts (Techno oil and Berna Star), natural origin compounds (Top-nine, Repcar and Chitosan 5%) and classical chemical pesticides (methomyl and lambda-cyhalothrin) were studied against the terrestrial snail <i>Massylaea vertmiculata</i> using the bait technique. Material and Methods: LC<sub>50</sub> of the each tested compound of natural compounds were estimated after 14 days of treatment, while LC<sub>50</sub> of pesticide were evaluated after 72 hrs of treatment. The impact of LC<sub>50 </sub>of each tested compound on some biochemical parameters, total protein content, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity were determined 48 hrs post treatment. <b>Results:</b> The results revealed that the methomyl and lambda-cyhalothrin were the most effective compounds against test land snails, followed by Repcar, Top-nine and Techno oil, while Berna Star and Nema Ultra Chem come in the last rank. The pesticide compound methomyl was the most toxic one against the tested terrestrial snail species, while the Chitosan 5% was the least toxic one. The results showed that all tested compounds caused fluctuated effect whether increasing or decreasing on all the studies parameters such as total protein content, ALP and ACP activity as well. However, the Techno oil and the Berna Star caused sever decreasing on total protein content and ACP, followed by Top-nine, Repcar, Chitosan 5% (Nema Ultra Chem) and plant extracts. <b>Conclusion:</b> The both tested natural compounds and plant extracts recorded satisfying results compared with methomyl and lambda-cyhalothrin effect and that can be used in the pest controlling programs against terrestrial snails to reduce the environmental pollution.
Topics: Animals; Gastropoda; Plant Extracts; Toxicological Phenomena
PubMed: 34842373
DOI: 10.3923/pjbs.2021.1040.1047 -
Insects Jul 2020Until recently, the Old World bollworm (OWB) (Hübner) and the corn earworm (Boddie) (Lepidoptera: Noctuidae) were geographically isolated. Both species are major...
Until recently, the Old World bollworm (OWB) (Hübner) and the corn earworm (Boddie) (Lepidoptera: Noctuidae) were geographically isolated. Both species are major pests of agricultural commodities that are known to develop insecticide resistance, and they now coexist in areas where invaded the Americas. This is the first study to compare the susceptibility of the two species to conventional insecticides. The susceptibility of third instar and larvae to indoxacarb, methomyl, spinetoram, and spinosad was determined using a diet-overlay bioassay in a quarantine laboratory in Puerto Rico. Mortality was assessed at 48 h after exposure for up to eight concentrations per insecticide. Spinetoram exhibited the highest acute toxicity against , with a median lethal concentration (LC) of 0.11 µg a.i./cm, followed by indoxacarb and spinosad (0.17 µg a.i./cm for both) and methomyl (0.32 µg a.i./cm). Spinetoram was also the most toxic to (LC of 0.08 µg a.i./cm), followed by spinosad (0.17 µg a.i./cm) and methomyl (0.18 µg a.i./cm). Indoxacarb was the least toxic to . , with an LC of 0.21 µg a.i./cm. These findings could serve as a comparative reference for monitoring the susceptibility of and to indoxacarb, methomyl, spinetoram, and spinosad in Puerto Rico, and may facilitate the detection of field-selected resistance for these two species and their potential hybrids in areas recently invaded by .
PubMed: 32664300
DOI: 10.3390/insects11070431 -
Insects Nov 2022A resistant strain (MRS) of was cultured by continuous selection with malathion for over 40 generations. The MRS exhibited 32.7-fold resistance to malathion compared to...
A resistant strain (MRS) of was cultured by continuous selection with malathion for over 40 generations. The MRS exhibited 32.7-fold resistance to malathion compared to the susceptible strain (MSS) and 13.5-fold, 2.9-fold and 4.8-fold cross-resistance for omethoate, methomyl and beta-cypermethrin, respectively. However, no cross-resistance was found to imidacloprid in this resistant strain. The realized heritability for malathion resistance was 0.02. Inhibitors of esterase activity, both triphenyl phosphate (TPP) and S,S,S,-tributyl phosphorotrithioate (DEF) as synergists, exhibited significant synergism to malathion in the MRS strain, with 11.77-fold and 5.12-fold synergistic ratios, respectively, while piperonyl butoxide (PBO) and diethyl maleate (DEM) showed no significant synergism in the MRS strain. The biochemical assay indicated that carboxylesterase activity was higher in MRS than in MSS. These results suggest that the increase in esterase activity might play an important role in resistance to malathion. Imidacloprid could be used as an alternative for malathion in the management of wheat aphid resistance.
PubMed: 36421946
DOI: 10.3390/insects13111043 -
Journal For Immunotherapy of Cancer Apr 2024Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene...
BACKGROUND
Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy.
METHOD
200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy.
RESULTS
After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041).
CONCLUSION
Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted.
STATEMENT
The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.
Topics: Humans; B7-H1 Antigen; Biomarkers; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Metabolomics; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38641349
DOI: 10.1136/jitc-2023-008190 -
Analytical and Bioanalytical Chemistry Feb 2022The existence of pesticide residues in the hydrosphere, biosphere, and anthroposphere can cause acute or chronic diseases and deteriorate the environment. Therefore,...
The existence of pesticide residues in the hydrosphere, biosphere, and anthroposphere can cause acute or chronic diseases and deteriorate the environment. Therefore, efficient detection of pesticide residues is of great significance to prevent food poisoning, control food pollution, and protect human lives by recognizing their distribution and concentration. Herein, a novel smartphone-coupled three-layered paper-based microfluidic chip is proposed as a facile platform to detect the pesticides. The stereoscopic capillary-driven fluid transport is enabled by the three-layered microfluidic chip configuration. The detection mechanism is based on the enzyme inhibition reaction and the chromatic reaction. The detection results are obtained by a smartphone and figured out by colorimetric quantitative analysis. Taking advantages of the above merits, we demonstrate the utilization of this smartphone-coupled three-layered paper-based microfluidic chip for the effective analysis of typical pesticides (profenofo and methomyl). The linear ranges of profenofo and methomyl are 0.27-2.1 μmol L and 0.14-1.85 μmol L, respectively. The corresponding limits of detection in the chips are 55 nM and 34 nM, respectively. The paper-based chips are also highly cost-effective with a total cost of 0.082 ¥ per piece. It can be anticipated that this technique will open new avenues for the mass fabrication of paper-based microfluidic chips and provide state-of-the-art methods in the field of analytical chemistry.
Topics: Colorimetry; Lab-On-A-Chip Devices; Paper; Pesticides; Smartphone
PubMed: 35059790
DOI: 10.1007/s00216-021-03839-x -
Chemosphere Apr 2020Reactive oxygen species (ROS) including singlet oxygen (O) and hydroxylradicals (OH) photogenerated in natural waters play important roles in indirect photolysis of...
Reactive oxygen species (ROS) including singlet oxygen (O) and hydroxylradicals (OH) photogenerated in natural waters play important roles in indirect photolysis of man-made pollutants. This study was conducted to investigate how the generation of these two ROS influences the degradation of two highly toxic insecticides (methomyl and carbaryl) in river water. To accomplish this, the reaction rate constants of O and OH with carbaryl and methomyl were determined; the degradation rate constants of the tested insecticides in ultrapure water (direct photolysis) and in river water in the presence and absence of O and OH scavengers were also measured. The rate constants for the reaction of OH with carbaryl and methomyl were found to be (14.8 ± 0.64) × 10 and (4.68 ± 0.52) × 10 M s, respectively. The reaction rate constant of O with carbaryl (2.98 ± 0.10) × 10 M s, was much higher than that of methomyl (<10 M s). Indirect photolysis by OH accounted for 63% and 62%, while O accounted for 26% and 30% and direct photolysis accounted for 1.4% and 7% of methomyl and carbaryl degradation, respectively. The high degradation rate in river water demonstrated by both insecticides suggests that indirect photolysis mediated by OH is an important means of their degradation in river water. In addition, kinetic calculations of OH-mediated degradation rate constants of the compounds agrees with their experimentally-determined values thereby confirming the importance of OH towards their degradation.
Topics: Carbaryl; Fresh Water; Hydroxyl Radical; Kinetics; Methomyl; Photolysis; Reactive Oxygen Species; Rivers; Singlet Oxygen; Water Pollutants, Chemical
PubMed: 31790988
DOI: 10.1016/j.chemosphere.2019.125464 -
Human & Experimental Toxicology Apr 2018In this study, we developed a serum and urine metabolomic method based on gas chromatography-mass spectrometry (GC-MS) combination with biomedical results to evaluate...
In this study, we developed a serum and urine metabolomic method based on gas chromatography-mass spectrometry (GC-MS) combination with biomedical results to evaluate the effect of vitamin E treatment on methomyl poisoning rats. The rats were divided into three groups: the control group, methomyl poisoning group, and vitamin E treatment group. Partial least squares discriminate analysis (PLS-DA) showed that methomyl poisoning induced metabolic perturbations. Compared to the control group, based on the urinary metabolomics data, the level of ribitol, l-proline, xylitol, hydrocinnamic acid, 11-cis-octadecenoic acid, octadecanoic acid, and hexadecanoic acid of methomyl poisoning group increased, while the level of 2,3,4-trihydroxybutyric acid, ethanimidic acid, pantothenic acid, and retinoic acid decreased. Vitamin E pretreatment effectively normalized the levels of metabolites in rat urine in vitamin E treatment group. There was no significant difference in rat plasma metabolomic data after acute methomyl poisoning. The results indicate that metabolomic method based on GC-MS may be useful to elucidate the vitamin E treatment for methomyl poisoning.
Topics: Animals; Biomarkers; Cholinesterase Inhibitors; Discriminant Analysis; Gas Chromatography-Mass Spectrometry; Least-Squares Analysis; Male; Metabolomics; Methomyl; Poisoning; Rats, Sprague-Dawley; Vitamin E
PubMed: 28425351
DOI: 10.1177/0960327117705428 -
Chemosphere Dec 2016Male tilapia were exposed to sub-lethal methomyl concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 d, and were subsequently cultured in methomyl-free water for...
Male tilapia were exposed to sub-lethal methomyl concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 d, and were subsequently cultured in methomyl-free water for 18 d. Relative transcript abundance of steroidogenic genes involved in the HPGL axis of male tilapia was examined at 30 d in the exposure test and at 18 d in the recovery test. The results revealed that low concentrations of methomyl (0.2 and 2 μg/L) did not cause significant changes in gene mRNA levels in the HPGL axis of male tilapia; thus, we considered 2 μg/L concentrations as the level that showed no apparent adverse endocrine disruption effects. However, higher concentrations of methomyl (20 and 200 μg/L) disrupted the endocrine system and caused significant increase in the levels of GnRH2, GnRH3, ERα, and ERβ genes in the hypothalamus, GnRHR and FSHβ genes in the pituitary, CYP19a, FSHR, and ERα genes in the testis, and VTG and ERα genes in the liver, and significantly decreased the levels of LHR, StAR, 3β-HSD, and ARα genes in the testis and LHβ gene in the pituitary, leading to changes in sex steroid hormone and vitellogenin levels in the serum and ultimately resulting in reproductive dysfunction in male tilapia. The recovery tests showed that the toxicity effect caused by 20 μg/L methomyl was reversible; however, the toxicity effect at 200 μg/L of methomyl was irreversible after 18 d. Therefore, we concluded that 200 μg/L was the threshold concentration for methomyl-induced irreversible endocrine disruption in male tilapia.
Topics: Animals; Dose-Response Relationship, Drug; Endocrine Disruptors; Gonadal Steroid Hormones; Hypothalamo-Hypophyseal System; Liver; Male; Methomyl; Testis; Tilapia; Transcription, Genetic; Vitellogenins; Water Pollutants, Chemical
PubMed: 27643660
DOI: 10.1016/j.chemosphere.2016.09.024