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PeerJ 2022T-37 can infect grapes and other fruit trees and cause root cancer. Given the pollution and damage of chemical agents to the environment, the use of biological control...
BACKGROUND
T-37 can infect grapes and other fruit trees and cause root cancer. Given the pollution and damage of chemical agents to the environment, the use of biological control has become an important area of focus. L2 is a beneficial biocontrol strain isolated and identified in the laboratory, which has a good antibacterial effect on a variety of plant pathogens. The antibacterial metabolites of L2 were separated and purified to obtain a bioactive compound phenylacetic acid (PAA).
METHODS
The potential antibacterial mechanism of PAA against T-37 strain was determined by relative conductivity, leakage of nucleic acids, proteins, and soluble total sugars, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and reactive oxygen species (ROS).
RESULTS
PAA showed good antibacterial activity against strain T-37 with IC of 0.8038 mg/mL. Our data suggested that after treatment with PAA, the relative conductivity, nucleic acid, protein, and total soluble sugar of T-37 were increased significantly compared with the chloramphenicol treatment group and the negative treatment group. The total protein synthesis of T-37 cells was inhibited, the consumption of phosphorus decreased with the increase of incubation time, and the content of ROS was significantly higher than that in the negative treatment group. Meanwhile, the activity of two key enzymes (MDH and SDH) involved in the tricarboxylic acid cycle (TCA cycle) decreased. In addition, T-37 cells were found to be damaged by scanning electron microscopy observation. Our results showed that PAA can destroy cell membrane integrity, damage cell structures, affect cell metabolism, and inhibit protein synthesis to exert an antibacterial effect.
CONCLUSIONS
We concluded that the mechanism of action of the PAA against strain T-37 might be described as PAA exerting antibacterial activity by affecting cell metabolism, inhibiting protein synthesis, and destroying cell membrane integrity and cell ultrastructure. Therefore, PAA has a promising application prospect in the prevention and treatment of root cancer disease caused by .
Topics: Agrobacterium tumefaciens; Bacillus megaterium; Reactive Oxygen Species; Solanum lycopersicum; Anti-Bacterial Agents; Phenylacetates
PubMed: 36389424
DOI: 10.7717/peerj.14304 -
Physiological Research Dec 2023Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine...
Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain.
Topics: Humans; Rats; Animals; Hyperalgesia; Methylphenidate; Rats, Wistar; Disease Models, Animal; Neuralgia
PubMed: 38165759
DOI: 10.33549/physiolres.935215 -
Cambridge Quarterly of Healthcare... Oct 2022Pharmacological cognitive enhancement (PCE) refers to the use of pharmaceuticals to improve cognitive function when that use is not intended to prevent or treat disease....
Pharmacological cognitive enhancement (PCE) refers to the use of pharmaceuticals to improve cognitive function when that use is not intended to prevent or treat disease. Those who favour a liberal approach to PCE trust users to make informed decisions about whether enhancing is in their best interest. The author argues that making informed decisions about PCE requires a nuanced risk-benefit analysis that is not accessible to many users. Presently, the PCE use of prescription medications such as methylphenidate and modafinil is widespread but most commonly happens without medical supervision. Direct and indirect barriers generate a situation where the risks and benefits of PCE are inequitably distributed; as a result, PCE is sometimes not in the user's best interest. This is likely to also be the case for future pharmaceuticals. As a result, even if PCE pharmaceuticals were equitably distributed, its associated risks and benefits would not be. The article concludes with a discussion of the prospects of the clinical consultation on one hand, and e-health solutions on the other, in ameliorating the situation, arguing for cautious optimism.
Topics: Humans; Nootropic Agents; Methylphenidate; Cognition; Decision Making; Pharmaceutical Preparations
PubMed: 36398505
DOI: 10.1017/S096318012200041X -
The Science of the Total Environment Feb 2022Diclofenac is a pharmaceutical active compound frequently detected in wastewater and water bodies, and often reported to be persistent and difficult to biodegrade. While...
Diclofenac is a pharmaceutical active compound frequently detected in wastewater and water bodies, and often reported to be persistent and difficult to biodegrade. While many previous studies have focussed on assessing diclofenac biodegradation in nitrification and denitrification processes, this study focusses on diclofenac biodegradation in the enhanced biological phosphorus removal (EBPR) process, where the efficiency of this process for diclofenac biodegradation as well as the metabolites generated are not well understood. An enrichment of Accumulibacter polyphosphate accumulating organisms (PAOs) was operated in an SBR for over 300 d, and acclimatized to 20 μg/L of diclofenac, which is in a similar range to that observed in domestic wastewater influents. The diclofenac biotransformation was monitored in four periods of stable operation and linked to the microbial community and metabolic behaviour in each period. Nitrification was observed in two of the four periods despite the addition of a nitrification inhibitor, and these periods were positively correlated with increased diclofenac biodegradation. Interestingly, in two periods with excellent phosphorus removal (>99%) and no nitrification, different levels of diclofenac biotransformation were observed. Period 2, enriched in Accumulibacter Type II achieved more significant diclofenac biotransformation (3.4 μg/gX), while period 4, enriched in Accumulibacter Type I achieved lower diclofenac biotransformation (0.4 μg/gX). In total, 23 transformation products were identified, with lower toxicity than the parent compound, enabling the elucidation of multiple metabolic pathways for diclofenac biotransformation. This study showed that PAOs can contribute to diclofenac biotransformation, yielding less toxic transformation products, and can complement the biodegradation carried out by other organisms in activated sludge, particularly nitrifiers.
Topics: Bioreactors; Biotransformation; Diclofenac; Phosphorus; Sewage
PubMed: 34715209
DOI: 10.1016/j.scitotenv.2021.151232 -
The Science of the Total Environment Jan 2020Diclofenac, a nonsteroidal anti-inflammatory drug has turned into a contaminant of emerging concern; hence, it was included in the previous Watch List of the EU Water... (Review)
Review
Diclofenac, a nonsteroidal anti-inflammatory drug has turned into a contaminant of emerging concern; hence, it was included in the previous Watch List of the EU Water Framework Directive. This review paper aims to highlight the metabolism of diclofenac at different trophic levels, its occurrence, ecological risks, and interactive effects in the water cycle and biota over the past two decades. Increased exposure to diclofenac not only raises health concerns for vultures, aquatic organisms, and higher plants but also causes serious threats to mammals. The ubiquitous nature of diclofenac in surface water (river, lake canal, estuary, and sea) is compared with drinking water, groundwater, and wastewater effluent in the environment. This comprehensive survey from previous studies suggests the fate of diclofenac in wastewater treatment plants (WWTPs) and may predict its persistence in the environment. This review offers evidence of fragmentary available data for the water environment, soil, sediment, and biota worldwide and supports the need for further data to address the risks associated with the presence of diclofenac in the environment. Finally, we suggest that the presence of diclofenac and its metabolites in the environment may represent a high risk because of their synergistic interactions with existing contaminants, leading to the development of drug-resistant strains and the formation of newly emerging pollutants.
Topics: Biota; Diclofenac; Environmental Monitoring; Environmental Pollutants
PubMed: 31783460
DOI: 10.1016/j.scitotenv.2019.134057 -
Psychiatry Research Dec 2023This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on... (Randomized Controlled Trial)
Randomized Controlled Trial
Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.
This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).
Topics: Adult; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dialectical Behavior Therapy; Double-Blind Method; Emotions; Methylphenidate; Treatment Outcome
PubMed: 37992514
DOI: 10.1016/j.psychres.2023.115610 -
Chemico-biological Interactions Jan 2022Vicagrel, an antiplatelet drug candidate targeting platelet P2Y receptor and has finished its phase II clinical trial. The inhibition of six major cytochrome P450...
Inhibition of cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases by vicagrel in human liver microsomes: A prediction of potential drug-drug interactions.
Vicagrel, an antiplatelet drug candidate targeting platelet P2Y receptor and has finished its phase II clinical trial. The inhibition of six major cytochrome P450 enzymes (P450) (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six UDP-glucuronosyltransferases (UGT) (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) by vicagrel was evaluated using pooled human liver microsomes and specific probe substrates. Physiology-based pharmacokinetic (PBPK) simulation was further applied to predict the in vivo drug-drug interaction (DDI) potential between vicagrel and bupropion as well as S-mephenytoin. The results suggested that vicagrel inhibited CYP2B6 and CYP2C19 potently with apparent IC values of 1.6 and 2.0 μM, respectively. In terms of mode of reversible inhibition, vicagrel exhibited mixed-type inhibition of CYP2B6-catalyzed bupropion hydroxylation and noncompetitive inhibition of CYP2C19-mediated S-mephenytoin 4'-hydroxylation with K values of 0.19 μM and 1.2 μM, respectively. Vicagrel displayed profound time-dependent inhibition towards CYP2B6 with maximal rate constant of inactivation (k) and half-maximal inactivator concentration (K) values of 0.062 min and 1.52 μM, respectively. No time-dependent inhibition by vicagrel was noted for CYP2C19. For UGT, negligible to moderate inhibition by vicagrel was observed with IC values of >50.0, >50.0, 28.2, 8.7, >50.0 and 28.2 μM for UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7, respectively. In terms of mode of reversible inhibition, vicagrel exhibited mixed-type inhibition of UGT1A6-catalyzed N-Acetylserotonin β-D-glucuronidation with a K value of 5.6 μM. No time-dependent inhibition by vicagrel was noted for UGT1A6. PBPK simulation indicated that neither altered AUC nor C of bupropion and S-mephenytoin was observed in the presence of vicagrel. Our study provides inhibitory constants for future DDI prediction between vicagrel and drug substrates of CYP2B6, CYP2C19 and UGT1A6. In addition, our simulation suggests the lack of clinically important DDI between vicagrel and bupropion or S-mephenytoin.
Topics: Bupropion; Computer Simulation; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2B6 Inhibitors; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Glucuronosyltransferase; Humans; In Vitro Techniques; Kinetics; Mephenytoin; Microsomes, Liver; Phenylacetates; Platelet Aggregation Inhibitors; Thiophenes
PubMed: 34910929
DOI: 10.1016/j.cbi.2021.109775 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023To investigate the effect of sleep deprivation on the metabolism of the hippocampal region in mice.
OBJECTIVE
To investigate the effect of sleep deprivation on the metabolism of the hippocampal region in mice.
METHODS
The mice were randomly assigned to three groups, a control group, a 24-h sleep deprivation (SD) group, and a 48-h SD group. Each group had 10 mice. The sleep deprivation model was induced by the modified multiple platform method. The mice's anxiety-like behaviors were assessed with the open field test (OFT) and their depression-like behaviors were assessed with the sucrose preference test (SPT), the forced swimming test (FST), and tail suspension test (TST). High performance liquid chromatography (HPLC) was performed to determine the levels of 6 monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), gamma-aminobutyric acid (GABA), 5-dihydroxyphenylacetic acid (5-DOPAC), and homovanillic acid (HVA), and 4 amino acids, including glutamic acid (Glu), aspartic acid (Asp), serine (Ser), and taurine (Tau), in the hippocampal region. Immunofluorescence staining was performed to examine the expression of glial cells in the hippocampal region of the mice. The main indicators measured were the levels of monoamine neurotransmitters and amino acids.
RESULTS
According to the results of the behavioral analysis, in comparison with the findings for the control group, the 24-h SD mice exhibited increased consumption of sucrose in SFT, significantly decreased total immobility time in FST and TST, and increased total distance covered in OFT, while the 48-h SD mice showed decreased consumption of sucrose in SFT, prolonged total immobility time in FST and TST, and decreased total distance covered in OFT. The results of the HPLC analysis of the monoamine neurotransmitter showed that 24-h SD mice had in their hippocampal region increased levels of DA (<0.001) and NE (<0.01) and decreased levels of GABA (<0.05) in comparison with those of the control mice, while their 5-HT, 5-DOPAC, and HVA levels were not significantly different from those of the control mice. In comparison with those of the control mice, the 48-h SD mice had, in their hippocampal region, decreased levels of 5-HT and NE (all <0.05), decreased DA (<0.01), and increased level of GABA (<0.01), while the levels of 5-DOPAC and HAV were not significantly different. The 48-h SD group showed a significant decrease in the levels of Tau and Glu in comparison with those of the 24-h SD group (all <0.05). According to the results of immunofluorescence assay, there was no significant difference between the control group and the 24-h SD group in the cell count of glial fibrillary acidic protein (GFAP)-positive cells, while a decline in GFAP-positive cells in comparison with that of the control group was observed in the 48-h SD group.
CONCLUSION
SD of 24 hours may induce anxiety-like behavioral changes in mice by activating their hippocampal glial cells, upregulating the levels of 5-HT, DA, and NE, and increasing the levels of Glu and Tau in the hippocampal region. SD of 48 hours may induce depression-like behavioral changes in mice by inhibiting the activation of glial cells in the hippocampal region and regulating in the opposite direction the levels of the above-mentioned monoamine neurotransmitters and amino acids in the hippocampal region.
Topics: Mice; Animals; Sleep Deprivation; Serotonin; Amino Acids; 3,4-Dihydroxyphenylacetic Acid; Hippocampus; Dopamine; Norepinephrine; Homovanillic Acid; Neurotransmitter Agents; gamma-Aminobutyric Acid; Sucrose
PubMed: 38162057
DOI: 10.12182/20231160203 -
Molecular Genetics and Metabolism Nov 2023Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium...
Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium phenylacetate (NaPAA) are important for the management of urea cycle disorders (UCDs). Plasma concentrations of their primary metabolite, phenylacetate (PAA), as well as the ratio of PAA to phenylacetylglutamine (PAGN) are useful for guiding dosing and detecting toxicity. However, the frequency of toxic elevations of metabolites and associated clinical covariates is relatively unknown. A retrospective analysis was conducted on 1255 plasma phenylbutyrate metabolite measurements from 387 individuals. An additional analysis was also conducted on a subset of 68 individuals in whom detailed clinical information was available. In the course of these analyses, abnormally elevated plasma PAA and PAA:PAGN were identified in 39 individuals (4.15% of samples) and 42 individuals (4.30% of samples), respectively. Abnormally elevated PAA and PAA:PAGN values were more likely to occur in younger individuals and associate positively with dose of NAPBA and negatively with plasma glutamine and glycine levels. These results demonstrate that during routine clinical management, the majority of patients have PAA levels that are deemed safe. As age is negatively associated with PAA levels however, children undergoing treatment with NaPBA may need close monitoring of their phenylbutyrate metabolite levels.
Topics: Child; Humans; Phenylbutyrates; Retrospective Studies; Urea Cycle Disorders, Inborn
PubMed: 37717413
DOI: 10.1016/j.ymgme.2023.107699 -
The American Journal of Clinical... Apr 2024Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.
BACKGROUND
Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.
OBJECTIVES
This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD.
METHODS
In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR).
RESULTS
Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN.
CONCLUSIONS
We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
Topics: Child; Humans; Crohn Disease; Enteral Nutrition; Prospective Studies; Remission Induction; Microbiota; Metabolome; Butyrates; Acetates; Phenylacetates
PubMed: 38569785
DOI: 10.1016/j.ajcnut.2023.12.027