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关键词:'36541'
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Dennis J Pelletier et al.
Journal of chemical information and modeling, 47(3), 1196-1205 (2007-04-13)
The identification of phospholipidosis (PPL) during preclinical testing in animals is a recognized problem in the pharmaceutical industry. Depending on the intended indication and dosing regimen, PPL can delay or stop development of a compound in the drug discovery process.
Casey E Hughes et al.
Cell, 180(2), 296-310 (2020-01-25)
Mitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we
Carolina Torres-Rojas et al.
Toxicological sciences : an official journal of the Society of Toxicology, 176(1), 137-146 (2020-04-16)
Paraquat (PQ) is an herbicide used in many countries, including the United States. It is also implicated as a risk factor for sporadic Parkinson's disease, especially in those living in agricultural areas and drinking well water. Studies linking PQ to
Arun Kumar Yadawa et al.
Pesticide biochemistry and physiology, 153, 106-115 (2019-02-13)
Paraquat (PQ) is a herbicide and well characterized pneumotoxicant which is also known to induce neurodegeneration in organisms. Aim of this study was to investigate the effect of PQ on hypothalamic - pituitary - adrenal (HPA) axis. PQ was administered
Naomi L Kruhlak et al.
Toxicology mechanisms and methods, 18(2-3), 217-227 (2008-01-01)
ABSTRACT Drug-induced phospholipidosis (PL) is a condition characterized by the accumulation of phospholipids and drug in lysosomes, and is found in a variety of tissue types. PL is frequently manifested in preclinical studies and may delay or prevent the development
Iratxe Estibariz et al.
mBio, 11(4) (2020-08-28)
Multiple studies have demonstrated rapid bacterial genome evolution during chronic infection with Helicobacter pylori In contrast, little was known about genetic changes during the first stages of infection, when selective pressure is likely to be highest. Using single-molecule, real-time (SMRT)
Sasha De Henau et al.
Developmental cell, 53(3), 263-271 (2020-04-11)
Symmetry breaking is an essential step in cell differentiation and early embryonic development. However, the molecular cues that trigger symmetry breaking remain largely unknown. Here, we show that mitochondrial H2O2 acts as a symmetry-breaking cue in the C. elegans zygote. We
Jasmina Zivanovic et al.
Cell metabolism, 30(6), 1152-1170 (2019-11-19)
Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure
Natalia Moskal et al.
Nature communications, 11(1), 88-88 (2020-01-05)
The accumulation of damaged mitochondria causes the death of dopaminergic neurons. The Parkin-mediated mitophagy pathway functions to remove these mitochondria from cells. Targeting this pathway represents a therapeutic strategy for several neurodegenerative diseases, most notably Parkinson's disease. We describe a
Isabella Zafra et al.
microPublication biology, 2021 (2021-03-11)
Saul-Wilson Syndrome is an ultra-rare skeletal syndrome caused by a mutation in the COG4 gene resulting in a glycine-to-arginine substitution at amino acid position 516. The COG4 gene encodes one of 8 subunits of the conserved oligomeric Golgi complex. Using
Reece J Knippel et al.
Cell host & microbe, 28(3), 411-421 (2020-06-12)
Clostridioides difficile infection of the colon leads to severe inflammation and damage to the gastrointestinal epithelium due to the production of potent toxins. This inflammatory tissue damage causes the liberation of high concentrations of host heme at infection sites. Here
Michał Turek et al.
EMBO reports, 22(8), e52071-e52071 (2021-07-22)
Organismal functionality and reproduction depend on metabolic rewiring and balanced energy resources. However, the crosstalk between organismal homeostasis and fecundity and the associated paracrine signaling mechanisms are still poorly understood. Using Caenorhabditis elegans, we discovered that large extracellular vesicles (known
Rikke Illum Høgh et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(11), 15531-15546 (2020-10-01)
SCFAs are primarily produced in the colon by bacterial fermentation of nondigestible carbohydrates. Besides providing energy, SCFAs can suppress development of colon cancer. The mechanism, however, remains elusive. Here, we demonstrate that the SCFA propionate upregulates surface expression of the
Hongying Fu et al.
Nature communications, 11(1), 1050-1050 (2020-02-28)
Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers
Inhibition of c-Src protects paraquat induced microvascular endothelial injury by modulating caveolin-1 phosphorylation and caveolae mediated transcellular permeability
Yu H and Qing H
Environmental Toxicology and Pharmacology, 52, 62-68 (2017)
Nigel Greene et al.
Chemical research in toxicology, 23(7), 1215-1222 (2010-06-18)
Drug-induced liver injury is a major issue of concern and has led to the withdrawal of a significant number of marketed drugs. An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential
Sean Ekins et al.
Drug metabolism and disposition: the biological fate of chemicals, 38(12), 2302-2308 (2010-09-17)
Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds
Marion Robin et al.
Autophagy, 15(5), 771-784 (2018-12-20)
The tumor suppressor TP53/p53 is a known regulator of apoptosis and macroautophagy/autophagy. However, the molecular mechanism by which TP53 regulates 2 apparently incompatible processes remains unknown. We found that Drosophila lacking p53 displayed impaired autophagic flux, higher caspase activation and
Kriti Chaplot et al.
Disease models & mechanisms, 12(2) (2019-01-13)
Familial amyotrophic lateral sclerosis (ALS) is an incurable, late-onset motor neuron disease, linked strongly to various causative genetic loci. ALS8 codes for a missense mutation, P56S, in VAMP-associated protein B (VAPB) that causes the protein to misfold and form cellular
Vijaya Bharathi Srinivasan et al.
Antimicrobial agents and chemotherapy, 53(12), 5312-5316 (2009-09-23)
In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of Acinetobacter baumannii was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned abeS gene in hypersensitive
Nonthakorn Beatrice Apirajkamol et al.
Ecology and evolution, 10(12), 5680-5693 (2020-07-02)
Stress is a widespread phenomenon that all organisms must endure. Common in nature is oxidative stress, which can interrupt cell homeostasis to cause cell damage and may be derived from respiration or from environmental exposure through diet. As a result
Julia M D Grandjean et al.
ACS chemical biology, 14(4), 784-795 (2019-03-02)
Cellular proteostasis is maintained by stress-responsive signaling pathways such as the heat shock response (HSR), the oxidative stress response (OSR), and the unfolded protein response (UPR). Activation of these pathways results in the transcriptional upregulation of select subsets of stress-responsive
Hiroki Nagai et al.
Genes to cells : devoted to molecular & cellular mechanisms, 25(5), 343-349 (2020-02-23)
Reactive oxygen species (ROS) often injure intestinal epithelia that cause loss of damaged cells, which is mainly repaired by proliferation of intestinal stem cells (ISCs). To maintain the homeostatic state, coordination of sensing of the ROS injury and the subsequent
Diego Herrero et al.
Redox biology, 22, 101156-101156 (2019-03-10)
Adult progenitor cells reside in specialized microenvironments which maintain their undifferentiated cell state and trigger regenerative responses following injury. Although these environments are well described in several tissues, the cellular components that comprise the cardiac environment where progenitor cells are
Fukai Liu et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(1), e21273-e21273 (2020-12-29)
Numerous studies have confirmed that prenatal or early postnatal exposure to pesticides can lead to functional deficits in the developing brain. This study aimed to investigate whether combined exposure to paraquat (PQ) and maneb (MB) during puberty could cause permanent
Min Huang et al.
Neurotoxicity research, 37(4), 913-925 (2019-12-21)
Paraquat (PQ), a widely characterized neurotoxicant, has been generally accepted as one of the environmental factors in the etiology of Parkinson's disease (PD). Despite the direct evidence that PQ could induce inflammatory responses in central nervous system, the putative adverse
Victor Girard et al.
Scientific reports, 10(1), 20023-20023 (2020-11-20)
Glial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD). Using a data-mining approach
Chung-Yang Kao et al.
PLoS genetics, 16(6), e1008868-e1008868 (2020-06-25)
Parkinson's disease (PD) is a neurodegenerative disorder featuring progressive loss of midbrain dopaminergic (DA) neurons that leads to motor symptoms. The etiology and pathogenesis of PD are not clear. We found that expression of COUP-TFII, an orphan nuclear receptor, in
Veronica Diez et al.
Communications biology, 4(1), 151-151 (2021-02-03)
Upon exposure to excessive reactive oxygen species (ROS), organismal survival depends on the strength of the endogenous antioxidant defense barriers that prevent mitochondrial and cellular deterioration. Previously, we showed that glycolic acid can restore the mitochondrial membrane potential of C.
Field Dissiation Kinetics of Paraquat in Acid Soil as Function of Concentration and its Residues in Tea Leaves
Janaki.P and Chinnusamy.C
Asian Journal of Chemistry, 28, 1639-1639 (2016)
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