87,655 results match your criteria cytochromes p450


Detection of the First Epoxyalcohol Synthase/Allene Oxide Synthase (CYP74 Clan) in the Lancelet (, Chordata).

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, P.O. Box 30, 420111 Kazan, Russia.

The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher's) lancelet (, Chordata) was biochemically characterized in the present work. Read More

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Potential Cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments.

Crit Rev Oncol Hematol 2021 Apr 27:103342. Epub 2021 Apr 27.

Sorbonne Université, INSERM CIC Paris-Est, AP-HP, ICAN, Pitié-Salpêtrière Hospital, Department of Pharmacology, F-75013, Paris, France.

Herbs, food and dietary supplements (HFDS), can interact significantly with anticancer drug treatments via cytochrome p450 isoforms (CYP) CYP3A4, CYP2D6, CYP1A2, and CYP2C8. The objective of this review was to assess the influence of HFDS compounds on these cytochromes. Interactions with CYP activities were searched for 189 herbs and food products, 72 dietary supplements in Web of Knowledge® databases. Read More

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In Silico Prediction of Drug-Drug Interactions Mediated by Cytochrome P450 Isoforms.

Pharmaceutics 2021 Apr 13;13(4). Epub 2021 Apr 13.

Laboratory of Structure-Function Based Drug Design, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str. 10, bldg. 8, 119121 Moscow, Russia.

Drug-drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and include an assessment of the DDIs potential mediated by inhibition or induction of the most important drug-metabolizing cytochrome P450 isoforms. Our study was dedicated to creating a computer model for prediction of the DDIs mediated by the seven most important P450 cytochromes: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. Read More

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Pharmacogenetic and Pharmacokinetic Assays from Saliva Samples Can Guarantee Personalized Drug Prescription.

Braz Dent J 2021 Jan-Feb;32(1):3-8

Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.

Saliva is widely used for clinical and laboratory analysis. This study proposed to use DNA extracted from saliva for genotyping and pharmacokinetics of piroxicam. A fast and efficient genotyping method was used to determine relevant allelic variants of CYP2C9 (*2 and *3), since genetic factors can influence in non-steroidal anti-inflammatory drugs (NSAIDs) metabolization. Read More

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Conversion of five proluciferin esters by human cytochrome P450 enzymes.

Biotechnol J 2021 Apr 28:e2100007. Epub 2021 Apr 28.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China.

Background: Probe substrates are an important tool for activity monitoring of human drug metabolizing enzymes such as cytochromes P450 (CYPs).

Brief Methods: In the present study we have tested human CYPs for metabolization of five proluciferin ester substrates which had previously only been known to be hydroxylated by CYP26A1.

Major Results: It was found that these substrates were converted by another 21 human CYPs, which belong to the CYP families 1 to 4, 7, and 26. Read More

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Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient's lung cells.

Sci Rep 2021 04 21;11(1):8570. Epub 2021 Apr 21.

Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum, India.

Although a defective vitamin D endocrine system has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D endocrine system and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D endocrine system in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Read More

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Optimisation of Cytochrome P450 BM3 Assisted by Consensus-Guided Evolution.

Appl Biochem Biotechnol 2021 Apr 16. Epub 2021 Apr 16.

Department of Chemical Engineering, Université Laval, Québec, Québec, G1V 0A6, Canada.

Cytochrome P450 enzymes have attracted much interest over the years given their ability to insert oxygen into saturated carbon-hydrogen bonds, a difficult feat to accomplish by traditional chemistry. Much of the activity in this field has centered on the bacterial enzyme CYP102A1, or BM3, from Bacillus megaterium, as it has shown itself capable of hydroxylating/acting upon a wide range of substrates, thereby producing industrially relevant pharmaceuticals, fine chemicals, and hormones. In addition, unlike most cytochromes, BM3 is both soluble and fused to its natural redox partner, thus facilitating its use. Read More

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Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase.

Nat Commun 2021 04 15;12(1):2260. Epub 2021 Apr 15.

Department of Chemistry & Nanoscience Centre, University of Copenhagen, Copenhagen Ø, Denmark.

Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natural product biosynthesis in plants. The mechanisms underlying POR-mediated CYP metabolism remain poorly understood and to date no ligand binding has been described to regulate the specificity of POR. Read More

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Recent Advances in Computational Metabolite Structure Predictions and Altered Metabolic Pathways Assessment to Inform Drug Development Processes.

Drug Metab Rev 2021 Apr 12:1-37. Epub 2021 Apr 12.

Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, California 94143, United States.

Many drug candidates fail during preclinical and clinical trials due to variable or unexpected metabolism which may lead to variability in drug efficacy or adverse drug reactions. The drug metabolism field aims to address this important issue from many angles which range from the study of drug-drug interactions, pharmacogenomics, computational metabolic modeling, and others. This manuscript aims to provide brief but comprehensive manuscript summaries highlighting the conclusions and scientific importance of seven exceptional manuscripts published in recent years within the field of drug metabolism. Read More

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Amphipol-facilitated Elucidation of the Functional Tetrameric Complex of Full-length Cytochrome P450 CYP2B4 and NADPH-Cytochrome-P450 Oxidoreductase.

J Biol Chem 2021 Apr 8:100645. Epub 2021 Apr 8.

Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI, 48109, USA. Electronic address:

Interactions of membrane-bound mammalian cytochromes P450 (CYPs) with NADPH-cytochrome P450 oxidoreductase (POR), which are required for metabolism of xenobiotics, are facilitated by membrane lipids. A variety of membrane mimetics, such as phospholipid liposomes and nanodiscs, have been used to simulate the membrane to form catalytically active CYP:POR complexes. However, the exact mechanism(s) of these interactions are unclear, due to the absence of structural information of full-length mammalian CYP:POR complexes in membranes. Read More

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High temperature stress induces expression of CYP450 genes and contributes to insecticide tolerance in Liriomyza trifolii.

Pestic Biochem Physiol 2021 May 10;174:104826. Epub 2021 Mar 10.

College of Horticulture and Plant Protection & Institute of Applied Entomology, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, China. Electronic address:

Liriomyza trifolii is an invasive leafminer fly that inflicts damage on many horticultural and vegetable crops. In this study, the effects of elevated temperatures on L. trifolii tolerance to insecticides abamectin (AB), monosultap (MO) and a mixture of abamectin and monosultap (AM) were firstly investigated, then five CYP450 genes (LtCYPs) were cloned, and expression patterns and NADPH cytochrome C reductase (NCR) activity in L. Read More

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Chlorpyrifos alters expression of enzymes involved in vitamin D synthesis in skin cells.

Pestic Biochem Physiol 2021 May 27;174:104812. Epub 2021 Feb 27.

Department of Molecular Biology and Translational Research, Institute of Rural Health, Lublin, Poland. Electronic address:

Skin acts as a mechanical barrier between human body and environment. Epidermal cells are regularly exposed to many physiological and environmental stressors, such as pesticides, like chlorpyrifos (CPS). It is recognised that CPS may affect metabolism of other exo- and endogenous substances by affecting enzyme activity and expression. Read More

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Effects of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 enzyme activities in rats.

J Tradit Chin Med 2021 04;41(2):284-292

College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.

Objective: To investigate the efficacy of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 (CYP450) enzyme activities in rats.

Methods: A cocktail strategy was followed to evaluate the influence of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on the activities of CYP450 isoforms (CYP1A2, CYP3A4, CYP2E1, CYP2C19, CYP2C9, CYP2D6), which were determined by changes in the pharmacokinetic parameters of six probe drugs, theophylline, dapsone, chlorzoxazone, omeprazole, tolbutamide and dextromethorphan. Study groups included, Control group (CG), Tianma (Rhizoma Gastrodiae) group (TM), Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) group (GT) and Tianma Gouteng (Gastrodia Uncaria) group (TMGT). Read More

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Toxicity Assessment of Transfluthrin, Benzyl Butyl Phthalate, and 17β-Estradiol on the Primary Fibroblast of the Striped Field Mouse, Apodemus agrarius.

J Environ Pathol Toxicol Oncol 2021 ;40(2):65-79

Department of Laboratory Animal Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.

Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius. Read More

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The oxysterome and its receptors as pharmacological targets in inflammatory diseases.

Br J Pharmacol 2021 Apr 5. Epub 2021 Apr 5.

Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 1200, Bruxelles, Belgium.

Oxysterols have gained attention over the last decades and are now considered as full-fledged bioactive lipids. The study of their levels in several diseases, (e.g. Read More

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Efficacy and Effect of Inhaled Adenosine Treatment in Hospitalized COVID-19 Patients.

Front Immunol 2021 18;12:613070. Epub 2021 Mar 18.

Section of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Lack of specific antiviral treatment for COVID-19 has resulted in long hospitalizations and high mortality rate. By harnessing the regulatory effects of adenosine on inflammatory mediators, we have instituted a new therapeutic treatment with inhaled adenosine in COVID-19 patients, with the aim of reducing inflammation, the onset of cytokine storm, and therefore to improve prognosis. The use of inhaled adenosine in COVID19 patients has allowed reduction of length of stay, on average 6 days. Read More

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Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Institute of Pharmacology, University of Bern, Inselspital, INO-F, 3010 Bern, Switzerland.

Acetaminophen (APAP) is one of the most commonly used analgesic and anti-pyretic drugs, and APAP intoxication is one of the main reasons for liver transplantation following liver failure in the Western world. While APAP poisoning ultimately leads to liver necrosis, various programmed cell death modalities have been implicated, including ER stress-triggered apoptosis. The BCL-2 family member BOK (BCL-2-related ovarian killer) has been described to modulate the unfolded protein response and to promote chemical-induced liver injury. Read More

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Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl and TAA-Induced Liver Fibrosis in Mice.

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. Read More

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Electromagnetic Field (EMF) Radiation Alters Estrogen Release from the Pig Myometrium during the Peri-Implantation Period.

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10-719 Olsztyn, Poland.

An electromagnetic field (EMF) may affect the functions of uterine tissues. This study hypothesized that EMF changes the estrogenic activity of pig myometrium during the peri-implantation period. Tissue was collected on days 15-16 of the gestation and incubated in the presence of EMF (50 and 120 Hz, 2 and 4 h). Read More

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Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response.

Int J Mol Sci 2021 Mar 10;22(6). Epub 2021 Mar 10.

Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech Republic.

Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). Read More

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Bioluminescence Measurement of Time-Dependent Dynamic Changes of CYP-Mediated Cytotoxicity in CYP-Expressing Luminescent HepG2 Cells.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago 683-8503, Tottori, Japan.

We sought to develop a cell-based cytotoxicity assay using human hepatocytes, which reflect the effects of drug-metabolizing enzymes on cytotoxicity. In this study, we generated luminescent human hepatoblastoma HepG2 cells using the mouse artificial chromosome vector, in which click beetle luciferase alone or luciferase and major drug-metabolizing enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) are expressed, and monitored the time-dependent changes of CYP-mediated cytotoxicity expression by bioluminescence measurement. Real-time bioluminescence measurement revealed that compared with CYP-non-expressing cells, the luminescence intensity of CYP-expressing cells rapidly decreased when the cells were treated with low concentrations of aflatoxin B1 or primaquine, which exhibits cytotoxicity in the presence of CYP3A4 or CYP2D6, respectively. Read More

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Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges.

Int J Mol Sci 2021 Mar 14;22(6). Epub 2021 Mar 14.

Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Read More

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Exploring the Use of Serum-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Hepatic Cytochromes P450 and Organic Anion Transporting Polypeptides.

Clin Pharmacol Ther 2021 Apr 1. Epub 2021 Apr 1.

College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.

Liver-derived small extracellular vesicles (sEVs), prepared from small sets of banked serum samples using a novel two-step protocol, were deployed as liquid biopsy to study the induction of cytochromes P450 (CYP3A4, CYP3A5, and CYP2D6) and organic anion transporting polypeptides (OATP1B1 and OATP1B3) during pregnancy (nonpregnant (T0), first, second, and third (T3) trimester women; N = 3 each) and after administration of rifampicin (RIF) to healthy male subjects. Proteomic analysis revealed induction (mean fold-increase, 90% confidence interval) of sEV CYP3A4 after RIF 300 mg × 7 days (3.5, 95% CI = 2. Read More

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Roles of CYP3A4, CYP3A5 and CYP2C8 drug-metabolizing enzymes in cellular cytostatic resistance.

Chem Biol Interact 2021 May 26;340:109448. Epub 2021 Mar 26.

Division of Biochemical Toxicology, National Center for Toxicological Research/U.S. FDA, 3900 NCTR Road, Jefferson, AR, 72079, USA.

Metabolic deactivation by cytochrome P450 (CYP) is considered a potential mechanism of anticancer drug resistance. However, this hypothesis is predominantly based on indirect pieces of evidence and/or is influenced by interfering factors such as the use of multienzymatic models. Thus, an experimental approach for its verification is needed. Read More

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Knockdown of CYP4PR1, a cytochrome P450 gene highly expressed in the integument tissue of Triatoma infestans, increases susceptibility to deltamethrin in pyrethroid-resistant insects.

Pestic Biochem Physiol 2021 Mar 21;173:104781. Epub 2021 Jan 21.

Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT La Plata Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de La Plata (UNLP), La Plata 1900, Argentina. Electronic address:

Metabolic resistance to chemical insecticides implies a greater capacity to detoxify insecticides due to an increase in the expression of genes and/or in the activity of enzymes related to detoxification metabolism. The insect integument is known to participate as the cuticular penetration factor of resistance, but recently this tissue was also linked with metabolic resistance due to P450-dependent detoxification in the Chagas disease vector Triatoma infestans. The objectives of this study were i) to name and classify all P450s known to date in T. Read More

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Combined over-expression of two cytochrome P450 genes exacerbates the fitness cost of pyrethroid resistance in the major African malaria vector Anopheles funestus.

Pestic Biochem Physiol 2021 Mar 9;173:104772. Epub 2021 Jan 9.

LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaoundé, Cameroon; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, L35QA Liverpool, UK. Electronic address:

Metabolic resistance driven by multiple P450 genes is worsening insecticide resistance in malaria vectors. However, it remains unclear whether such multiple over-expression imposes an additive fitness cost in the vectors. Here, we showed that two highly over-expressed P450 genes (CYP6P9a and CYP6P9b) combine to impose additive fitness costs in pyrethroid-resistant Anopheles funestus. Read More

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Mechanistic insights into the CYP2C19 genetic variants prevalent in the Indian population.

Gene 2021 Jun 23;784:145592. Epub 2021 Mar 23.

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India. Electronic address:

Purpose: CYP2C19 metabolizes the antiplatelet and antiepileptic drugs. Any alteration in CYP2C19 activity might influence the therapeutic efficacy. The objective of this study was to identify CYP2C19 variants prevalent in Indians and perform their in silico characterization. Read More

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Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium.

Biomed Environ Sci 2021 Mar;34(3):192-202

Immunotoxicology Group, Department of Ecology, Institute for Biological Research 'Siniša Stanković'- National Institute of Republic of Serbia, University of Belgrade, 142 Bulevar despota Stefana, Belgrade 11000, Serbia.

Objective: To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).

Methods: The effect of Cd on AhR activation ( and mRNA expression) was examined in lung leukocytes of Cd-exposed rats (5 and 50 mg/L, 30 d orally) and by leukocyte exposure. The involvement of AhR signaling in the effects of Cd on the interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) lung leukocyte response was investigated using the receptor antagonist CH-223191. Read More

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Simulation of Ligand Transport in Receptors Using CaverDock.

Methods Mol Biol 2021 ;2266:105-124

Institute of Computer Science, Masaryk University, Brno, Czech Republic.

Interactions between enzymes and small molecules lie in the center of many fundamental biochemical processes. Their analysis using molecular dynamics simulations have high computational demands, geometric approaches fail to consider chemical forces, and molecular docking offers only static information. Recently, we proposed to combine molecular docking and geometric approaches in an application called CaverDock. Read More

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Non-target Site Herbicide Resistance Is Conferred by Two Distinct Mechanisms in Black-Grass ().

Front Plant Sci 2021 3;12:636652. Epub 2021 Mar 3.

Agriculture, School of Natural, and Environmental Science, Newcastle University, Newcastle upon Tyne, United Kingdom.

Non-target site resistance (NTSR) to herbicides in black-grass () results in enhanced tolerance to multiple chemistries and is widespread in Northern Europe. To help define the underpinning mechanisms of resistance, global transcriptome and biochemical analysis have been used to phenotype three NTSR black-grass populations. These comprised NTSR1 black-grass from the classic Peldon field population, which shows broad-ranging resistance to post-emergence herbicides; NTSR2 derived from herbicide-sensitive (HS) plants repeatedly selected for tolerance to pendimethalin; and NTSR3 selected from HS plants for resistance to fenoxaprop--ethyl. Read More

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