Article
Oncology
Emma C. Hulshof, Mirjam de With, Femke M. de Man, Geert-Jan Creemers, Birgit A. L. M. Deiman, Jesse J. Swen, Saskia Houterman, Stijn L. W. Koolen, Sander Bins, Anna M. J. Thijs, Marjan M. J. Laven, Anke M. Hovels, Saskia A. C. Luelmo, Danny Houtsma, Katerina Shulman, Howard L. McLeod, Ron H. N. van Schaik, Henk-Jan Guchelaar, Ron H. J. Mathijssen, Hans Gelderblom, Maarten J. Deenen
Summary: This study aimed to determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan. The results showed that UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Sangeeta Shrestha Sharma, Shishir Sharma, Jie Zhao, Matthias Bureik
Summary: Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are important human drug metabolizing enzymes, and this study explores their mutual interactions. The study used recombinant co-expression of 19 human UGTs with CYP enzymes in yeast and found that UGT co-expression had a significant effect on P450 activity in most cases. The study also observed varying degrees of influence of CYP co-expression on UGT activity.
Article
Microbiology
Saurav Howlader, Min-Jung Kim, M. Rasheduzzaman Jony, Nguyen Phuoc Long, Yong-Soon Cho, Dong-Hyun Kim, Jae-Gook Shin
Summary: This study characterized the metabolic pathways and enzymes responsible for the metabolism of clofazimine in human liver microsomes. Eight metabolites, including oxidative metabolites, glucuronide conjugates, and sulfate conjugates, were identified. CYP1A2 and CYP3A were involved in the formation of oxidative metabolites, while UGT1A1, 1A3, 1A4, 1A9, and 2B4 were involved in the formation of glucuronide conjugates of oxidative metabolites of clofazimine.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Plant Sciences
Seth A. Strom, Aaron G. Hager, Jeanaflor Crystal T. Concepcion, Nicholas J. Seiter, Adam S. Davis, James A. Morris, Shiv S. Kaundun, Dean E. Riechers
Summary: The resistance of waterhemp to the herbicide S-metolachlor involves a combination of Phase I and Phase II metabolic activities, specifically the O-demethylation reaction conferring resistance. Greater activities of GSTs and P450s were observed in resistant populations compared to sensitive populations, leading to increased metabolism of S-metolachlor and the formation of resistant metabolites.
PLANT AND CELL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kai Lu, Yimin Li, Yibei Cheng, Wenru Li, Yuanyuan Song, Rensen Zeng, Zhongxiang Sun
Summary: Increased production of detoxification enzymes is a primary mechanism for insecticide resistance in crop pests. This study identified the NR2E nuclear receptor HR83 as critical for chlorpyrifos resistance in brown planthoppers, regulating the expression of detoxification genes. Knockdown of HR83 led to decreased resistance to chlorpyrifos and reduced expression of multiple detoxification genes, essential for the resistance of BPH to chlorpyrifos. This research suggests that regulation of detoxification genes may be an ancestral function of the NR2E nuclear receptor subfamily.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Viatcheslav Mordvinov, Maria Pakharukova
Summary: This article discusses the structure and functional significance of the xenobiotic-metabolizing system in trematodes, emphasizing the importance of understanding this system for finding new targets for antiparasitic therapy, understanding the adaptation mechanisms and drug resistance development in parasites, and discovering new anthelmintics.
Article
Biochemistry & Molecular Biology
Xuegao Wei, Jinyu Hu, Jing Yang, Cheng Yin, Tianhua Du, Mingjiao Huang, Buli Fu, Peipan Gong, Jinjin Liang, Shaonan Liu, Hu Xue, Chao He, Yao Ji, He Du, Rong Zhang, Chao Wang, Junkai Li, Xin Yang, Youjun Zhang
Summary: The study found that a differentially expressed gene CYP6DB3 is involved in the resistance of B. tabaci to neonicotinoid insecticides. The expression of CYP6DB3 was up-regulated in resistant strains compared to susceptible strains. Knocking down CYP6DB3 expression increased the sensitivity of B. tabaci to thiamethoxam and imidacloprid, while overexpression of CYP6DB3 gene reduced the toxicity of these insecticides. Additionally, CYP6DB3 was found to metabolize imidacloprid. This research provides important insights into the role of cytochrome P450s in insecticide resistance and the development of new pest resistance management strategies.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Genetics & Heredity
Saket Chandra, Ramon G. Leon
Summary: This study explored four gene groups involved in non-target-site resistance (NTSR), identified their sequences and analyzed their upstream promoter sequences and functions. Additionally, the 3D structure of NTSR enzymes was predicted and substrate recognition sites were identified. These findings can be utilized for the development of innovative weed control techniques.
Article
Agriculture, Multidisciplinary
Marcelo R. A. De Figueiredo, Hamlin Barnes, Claudia M. Boot, Ana Beatriz T. B. De Figueiredo, Scott J. Nissen, Franck E. Dayan, Todd A. Gaines
Summary: Amaranthus tuberculatus, a waterhemp plant species resistant to 2,4-dichlorophenoxyacetic acid (2,4-D), has been found to possess rapid metabolic detoxification ability. Through a novel detoxification mechanism, resistant plants hydroxylate 2,4-D into a less toxic metabolite, while susceptible plants conjugate 2,4-D to aspartate. This evolution of detoxification reactions in resistant plants allows for more efficient detoxification of 2,4-D.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jiang Zhu, Ruinan Qu, Yawei Wang, Ruoyao Ni, Kai Tian, Chan Yang, Mei Li, Michael Kristensen, Xinghui Qiu
Summary: Many insect species have developed various resistance mechanisms in response to insecticide selection. This study focuses on understanding the molecular mechanisms of P450-mediated insecticide resistance using the house fly. The results highlight the common involvement of the CncC pathway in adaptive evolution and provide evidence for parallel evolution in P450-mediated insecticide resistance.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Agriculture, Multidisciplinary
Carlos A. G. Rigon, Luan Cutti, Guilherme M. Turra, Enrico Z. Ferreira, Christian Menegaz, Walker Schaidhauer, Franck E. Dayan, Todd A. Gaines, Aldo Merotto
Summary: Herbicide mixtures are commonly used to control a wide range of weeds, including those resistant to specific herbicides. However, the impact of mixtures on the evolution of herbicide resistance through enhanced metabolism is not well understood. In this study, the effects of a fenoxaprop-p-ethyl and imazethapyr mixture on herbicide resistance evolution in Echinochloa crus-galli were evaluated. Results showed that recurrent selection with the mixture led to decreased control and increased resistance to several herbicides. Additionally, it was found that the main contributor to decreased control was fenoxaprop. This study highlights the need for using fully recommended herbicide rates in mixtures to reduce the risk of resistance evolution.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jaromir Petrtyl, Karel Dvorak, Jan Stritesky, Martin Lenicek, Alena Jiraskova, Vaclav Smid, Martin Haluzik, Radan Bruha, Libor Vitek
Summary: The study revealed dysregulated bilirubin metabolism in NAFLD patients, likely due to increased oxidative stress, with no effect on NAFLD development from major functional variants in the HMOX1 or UGT1A1 gene promoters.
Article
Environmental Sciences
Diana Dimunova, Petra Matouskova, Martina Navratilova, Linh Thuy Nguyen, Martin Ambroz, Ivan Vokral, Barbora Szotakova, Lenka Skalova
Summary: This study found that the environmental circulation of veterinary anthelmintics may contribute to drug resistance in parasitic nematodes, as it improves their ability to deactivate the drugs.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Biochemistry & Molecular Biology
Patrick Maada Ngegba, Gaofeng Cui, Yun Li, Guohua Zhong
Summary: Spodoptera frugiperda is a major agricultural pest that threatens global food security. It is highly polyphagous, migratory, and fecund, making its management challenging. The insecticide chlorantraniliprole is commonly used to control S. frugiperda, but its overuse poses health risks, resistance development, toxicity to beneficial insects, and environmental contamination. This study investigates the synergistic effects of camptothecin with chlorantraniliprole in managing S. frugiperda resistance and associated challenges.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Natalie Jakobs, Esra Yilmaz, Juergen Kruecken
Summary: The number of reported cases of macrocyclic lactones (ML) resistance is increasing in livestock hosts. Studies have suggested the involvement of cytochrome P450s (Cyps) enzymes in ML resistance in the parasitic nematode Haemonchus contortus. However, there is a lack of functional data regarding the individual contribution of these enzymes to resistance or substrate specificity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Nicholas Graves, Vivek P. Venu, Bryan G. Yipp, Bjorn Petri, Simon Hirota, John Gilleard, Derek M. McKay, Fernando Lopes
JOURNAL OF INNATE IMMUNITY
(2019)
Article
Biotechnology & Applied Microbiology
Stephen R. Doyle, Christopher J. R. Illingworth, Roz Laing, David J. Bartley, Elizabeth Redman, Axel Martinelli, Nancy Holroyd, Alison A. Morrison, Andrew Rezansoff, Alan Tracey, Eileen Devaney, Matthew Berriman, Neil Sargison, James A. Cotton, John S. Gilleard
Article
Ecology
Susannah Gold, Charlotte E. Regan, Philip D. McLoughlin, John S. Gilleard, Alastair J. Wilson, Jocelyn Poissant
INTERNATIONAL JOURNAL FOR PARASITOLOGY-PARASITES AND WILDLIFE
(2019)
Article
Parasitology
Carly D. Barone, Janneke Wit, Eric P. Hoberg, John S. Gilleard, Dante S. Zarlenga
VETERINARY PARASITOLOGY
(2020)
Article
Parasitology
Julie Sanchez, Guha Dharmarajan, Melissa M. George, Cassan Pulaski, Adrian J. Wolstenholme, John S. Gilleard, Ray M. Kaplan
VETERINARY PARASITOLOGY
(2020)
Article
Parasitology
Emma A. Borkowski, Jacob Avula, Niel A. Karrow, Paula Menzies, William Sears, Elizabeth M. Redman, Brandon N. Lillie, John S. Gilleard, Andrew S. Peregrine
VETERINARY PARASITOLOGY
(2020)
Article
Parasitology
Emma A. Borkowski, Elizabeth M. Redman, Rebecca Chant, Jacob Avula, Paula Menzies, Niel A. Karrow, Brandon N. Lillie, William Sears, John S. Gilleard, Andrew S. Peregrine
VETERINARY PARASITOLOGY
(2020)
Article
Parasitology
Umer Chaudhry, E. M. Redman, Ray Kaplan, Thomas Yazwinski, Neil Sargison, John S. Gilleard
VETERINARY PARASITOLOGY
(2020)
Article
Parasitology
Melissa M. George, Adriano F. Vatta, Sue B. Howell, Bob E. Storey, Ciaran J. McCoy, Adrian J. Wolstenholme, Elizabeth M. Redman, John S. Gilleard, Ray M. Kaplan
Summary: The study successfully replaced a population of Haemonchus contortus resistant to multiple anthelmintics with a susceptible isolate, but resistance re-emerged within a short period of time. Genetic changes may have contributed to this reversion.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Infectious Diseases
Maria A. Santa, Andrew M. Rezansoff, Rebecca Chen, John S. Gilleard, Marco Musiani, Kathreen E. Ruckstuhl, Alessandro Massolo
Summary: The study found Echinococcus multilocularis is expanding its distribution in North America and the European-type haplotype is prevalent in western Canada, increasing the risk of human infection. Deep amplicon sequencing is a valuable tool for detecting co-infections and assessing the distribution of different haplotypes. The study highlights the importance of next-generation sequencing technologies for understanding the geographic expansion patterns of the parasite.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Parasitology
Pablo D. Jimenez Castro, Abhinaya Venkatesan, Elizabeth Redman, Rebecca Chen, Abigail Malatesta, Hannah Huff, Daniel A. Zuluaga Salazar, Russell Avramenko, John S. Gilleard, Ray M. Kaplan
Summary: Ancylostoma caninum infections in greyhound dogs in the USA exhibit high levels of multiple-drug resistance, with a high prevalence and infection intensity observed within the greyhound population.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Microbiology
Roz Laing, Stephen R. Doyle, Jennifer McIntyre, Kirsty Maitland, Alison Morrison, David J. Bartley, Ray Kaplan, Umer Chaudhry, Neil Sargison, Andy Tait, James A. Cotton, Collette Britton, Eileen Devaney
Summary: Through crossbreeding and gene expression analysis, we have identified certain genes associated with ivermectin resistance and proposed a novel mechanism that allows resistant worms to survive treatment. This is crucial for understanding ivermectin resistance and response to treatment in parasitic helminths.
Article
Veterinary Sciences
Jennifer McIntyre, Laura Miskell, Eric R. Morgan, Fiona Lovatt, Roz Laing
Summary: This study investigated the use and effectiveness of moxidectin against gastrointestinal nematodes among Scottish sheep farmers. The results showed that although the majority of farmers used moxidectin, there was variation in their knowledge levels, and most farmers did not consistently follow the guidelines for sustainable control of parasites.
Article
Parasitology
Alistair Antonopoulos, Stephen R. Doyle, David J. Bartley, Alison A. Morrison, Ray Kaplan, Sue Howell, Cedric Neveu, Valentina Busin, Eileen Devaney, Roz Laing
Summary: Haemonchus contortus is a parasitic nematode that infects small ruminants and causes health issues and economic losses in the livestock industry. The treatment for this parasite primarily relies on broad-spectrum anthelmintics, but resistance has emerged. Levamisole (LEV) is an important treatment option, as resistance to LEV is less common. Genetic variation at the acr-8 locus has been implicated in LEV resistance.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Biology
Stephen R. Doyle, Alan Tracey, Roz Laing, Nancy Holroyd, David Bartley, Wojtek Bazant, Helen Beasley, Robin Beech, Collette Britton, Karen Brooks, Umer Chaudhry, Kirsty Maitland, Axel Martinelli, Jennifer D. Noonan, Michael Paulini, Michael A. Quail, Elizabeth Redman, Faye H. Rodgers, Guillaume Salle, Muhammad Zubair Shabbir, Geetha Sankaranarayanan, Janneke Wit, Kevin L. Howe, Neil Sargison, Eileen Devaney, Matthew Berriman, John S. Gilleard, James A. Cotton
COMMUNICATIONS BIOLOGY
(2020)