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Sensors (Basel, Switzerland) Jan 2024A spectral image analysis has the potential to replace traditional approaches for assessing plant responses to different types of stresses, including herbicides, through...
A spectral image analysis has the potential to replace traditional approaches for assessing plant responses to different types of stresses, including herbicides, through non-destructive and high-throughput screening (HTS). Therefore, this study was conducted to develop a rapid bioassay method using a multi-well plate and spectral image analysis for the diagnosis of herbicide activity and modes of action. Crabgrass (), as a model weed, was cultivated in multi-well plates and subsequently treated with six herbicides (paraquat, tiafenacil, penoxsulam, isoxaflutole, glufosinate, and glyphosate) with different modes of action when the crabgrass reached the 1-leaf stage, using only a quarter of the recommended dose. To detect the plant's response to herbicides, plant spectral images were acquired after herbicide treatment using RGB, infrared (IR) thermal, and chlorophyll fluorescence (CF) sensors and analyzed for diagnosing herbicide efficacy and modes of action. A principal component analysis (PCA), using all spectral data, successfully distinguished herbicides and clustered depending on their modes of action. The performed experiments showed that the multi-well plate assay combined with a spectral image analysis can be successfully applied for herbicide bioassays. In addition, the use of spectral image sensors, especially CF images, would facilitate HTS by enabling the rapid observation of herbicide responses at as early as 3 h after herbicide treatment.
Topics: Herbicides; Plants; Glyphosate; Biological Assay; Plant Weeds
PubMed: 38339634
DOI: 10.3390/s24030919 -
ChemistryOpen Feb 2024Dynamic control of the motion in a catenane remains a big challenge as it requires precise design and sophisticated well-organized structures. This paper reports the...
Dynamic control of the motion in a catenane remains a big challenge as it requires precise design and sophisticated well-organized structures. This paper reports the design and synthesis of a donor-acceptor [2]catenane through mechanical interlocking, employing a crown ether featuring two dibenzylammonium salts on its side arms as the host and a cyclobis(paraquat-p-phenylene) (CBPQT ⋅ 4PF ) ring as the guest molecule. By addition of external acid or base, the catenane can form self-complexed or decomplexed compounds to alter the cavity size of the crown ether ring, consequently affecting circumrotation rate of CBPQT ⋅ 4PF ring of the catenane. This study offers insights for the design and exploration of artificial molecular machines with intricate cascading responsive mechanisms.
PubMed: 38333963
DOI: 10.1002/open.202300304 -
Scientific Reports Feb 2024Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating...
Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating neurodegenerative diseases. However, the underlying mechanism on longevity is uncertain. In this study, we investigated the effect of magnolol on the lifespan of Caenorhabditis elegans and explored the mechanism. The results showed that magnolol treatment significantly extended the lifespan of nematode and alleviated senescence-related decline in the nematode model. Meanwhile, magnolol enhanced stress resistance to heat shock, hydrogen peroxide (HO), mercuric potassium chloride (MeHgCl) and paraquat (PQ) in nematode. In addition, magnolol reduced reactive oxygen species and malondialdehyde (MDA) levels, and increased superoxide dismutase and catalase (CAT) activities in nematodes. Magnolol also up-regulated gene expression of sod-3, hsp16.2, ctl-3, daf-16, skn-1, hsf-1, sir2.1, etc., down-regulated gene expression of daf-2, and promoted intranuclear translocation of daf-16 in nematodes. The lifespan-extending effect of magnolol were reversed in insulin/IGF signaling (IIS) pathway-related mutant lines, including daf-2, age-1, daf-16, skn-1, hsf-1 and sir-2.1, suggesting that IIS signaling is involved in the modulation of longevity by magnolol. Furthermore, magnolol improved the age-related neurodegeneration in PD and AD C. elegans models. These results indicate that magnolol may enhance lifespan and health span through IIS and sir-2.1 pathways. Thus, the current findings implicate magnolol as a potential candidate to ameliorate the symptoms of aging.
Topics: Animals; Longevity; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Hydrogen Peroxide; Antioxidants; Heat Shock Transcription Factors; Insulin; Oxidative Stress; Forkhead Transcription Factors; Biphenyl Compounds; Lignans
PubMed: 38326350
DOI: 10.1038/s41598-024-53374-9 -
JNMA; Journal of the Nepal Medical... Sep 2023Paraquat emerges as a formidable medical dilemma in Southeast Asia, its toxic effects attributed to the generation of free radicals and oxidative stress, with a specific...
UNLABELLED
Paraquat emerges as a formidable medical dilemma in Southeast Asia, its toxic effects attributed to the generation of free radicals and oxidative stress, with a specific predilection for diverse tissues, most notably the lungs. The scarcity of effective treatment modalities in resource-constrained settings magnifies the magnitude of the paraquat poisoning predicament. This report outlines the successful management of a 25-year-old man who ingested a lethal dose of paraquat. The patient presented solely with dysphagia devoid of accompanying symptoms, regardless of ingesting a fatal quantity of paraquat. The diagnosis was made based on history and a thorough clinical examination. Early, aggressive treatment with pulse therapy of steroids and antioxidants led to unexpected and quirky recovery. The case stresses the importance of prompt management and highlights the need for more research and public education to prevent future cases.
KEYWORDS
antioxidants; case reports; corrosive; paraquat; steroids.
Topics: Male; Humans; Adult; Paraquat; Lung; Treatment Outcome; Steroids; Poisoning
PubMed: 38289798
DOI: 10.31729/jnma.8263 -
Clinical and Experimental Emergency... Jan 2024Following the 2011 ban on paraquat sales, South Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning....
Following the 2011 ban on paraquat sales, South Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning. Traditionally, paraquat and diquat, alongside several highly toxic organophosphates, carbamates, and organochlorine insecticides, have been recognized as culprits in causing fatalities among patients with acute pesticide poisoning. However, despite global efforts to curtail the use of these highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles. Understanding the clinical progression of these pesticides is paramount for physicians and toxicologists, as it holds the potential to enhance patient prognoses in cases of acute poisoning. This review aims to address the persistence of such highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
PubMed: 38286498
DOI: 10.15441/ceem.23.167 -
Molecular Vision 2023Inflammation and oxidative stress contribute to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell-penetrating peptide from the kinase...
PURPOSE
Inflammation and oxidative stress contribute to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell-penetrating peptide from the kinase inhibitory region of an intracellular checkpoint inhibitor suppressor of cytokine signaling 3 (R9-SOCS3-KIR) peptide for its ability to blunt the inflammatory or oxidative pathways leading to AMD.
METHODS
We used anaphylatoxin C5a to mimic the effect of activated complement, lipopolysaccharide (LPS), and tumor necrosis factor alpha (TNFα) to stimulate inflammation and paraquat to induce mitochondrial oxidative stress. We used a human retinal pigment epithelium (RPE) cell line (ARPE-19) as proliferating cells and a mouse macrophage cell line (J774A.1) to follow cell propagation using microscopy or cell titer assays. We evaluated inflammatory pathways by monitoring the nuclear translocation of NF-κB p65 and mitogen-activated protein kinase p38. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to evaluate the induction of inflammatory markers. In differentiated ARPE-19 monolayers, we evaluated the integrity of tight junction proteins through microscopy and the measurement of transepithelial electrical resistance (TEER). We used intraperitoneal injection of sodium iodate in mice to test the ability of R9-SOC3-KIR to prevent RPE and retinal injury, as assessed by fundoscopy, optical coherence tomography, and histology.
RESULTS
R9-SOCS3-KIR treatment suppressed C5a-induced nuclear translocation of the NF-kB activation domain p65 in undifferentiated ARPE-19 cells. TNF-mediated damage to tight junction proteins in RPE, and the loss of TEER was prevented in the presence of R9-SOCS3-KIR. Treatment with the R9-SOCS3-KIR peptide blocked the C5a-induced expression of inflammatory genes. The R9-SOCS3-KIR treatment also blocked the LPS-induced expression of interleukin-6, MCP1, cyclooxygenase 2, and interleukin-1 beta. R9-SOCS3-KIR prevented paraquat-mediated cell death and enhanced the levels of antioxidant effectors. Daily eye drop treatment with R9-SOCS3-KIR protected against retinal injury caused by i.p. administration of sodium iodate.
CONCLUSIONS
R9-SOCS3-KIR blocks the induction of inflammatory signaling in cell culture and reduces retinal damage in a widely used RPE/retinal oxidative injury model. As this peptide can be administered through corneal instillation, this treatment may offer a convenient way to slow down the progression of ocular diseases arising from inflammation and chronic oxidative stress.
Topics: Humans; Animals; Mice; Lipopolysaccharides; Paraquat; Retina; Oxidative Stress; Retinal Diseases; Macular Degeneration; Peptides; Inflammation; Tight Junction Proteins; Cytokines; Iodates
PubMed: 38264613
DOI: No ID Found -
Biomedicines Dec 2023Club cells have a distinct role in the epithelial repair and defense mechanisms of the lung. After exposure to environmental pollutants, during chronic exposure, the... (Review)
Review
Club cells have a distinct role in the epithelial repair and defense mechanisms of the lung. After exposure to environmental pollutants, during chronic exposure, the secretion of club cells secretory protein (CCSP) decreases. Exposure to occupational hazards certainly has a role in a large number of interstitial lung diseases. According to the American Thoracic Society and the European Respiratory Society, around 40% of the all interstitial lung disease is attributed to occupational hazards. Some of them are very well characterized (pneumoconiosis, hypersensitivity pneumonitis), whereas others are consequences of acute exposure (e.g., paraquat) or persistent exposure (e.g., isocyanate). The category of vapors, gases, dusts, and fumes (VGDF) has been proven to produce subclinical modifications. The inflammation and altered repair process resulting from the exposure to occupational respiratory hazards create vicious loops of cooperation between epithelial cells, mesenchymal cells, innate defense mechanisms, and immune cells. The secretions of club cells modulate the communication between macrophages, epithelial cells, and fibroblasts mitigating the inflammation and/or reducing the fibrotic process. In this review, we describe the mechanisms by which club cells contribute to the development of interstitial lung diseases and the potential role for club cells as biomarkers for occupational-related fibrosis.
PubMed: 38255185
DOI: 10.3390/biomedicines12010078 -
Journal of Parkinson's Disease 2024Pre-clinical studies suggest that c-Abl activation may play an important role in the etiology of Parkinson's disease, making c-Abl an important target to evaluate for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pre-clinical studies suggest that c-Abl activation may play an important role in the etiology of Parkinson's disease, making c-Abl an important target to evaluate for potential disease-modification.
OBJECTIVE
To assess safety, tolerability, and pharmacokinetics of the c-Abl inhibitor risvodetinib (IkT-148009) in healthy subjects and participants with Parkinson's disease.
METHODS
Part 1 (single ascending dose (SAD)) and Part 2 (7-day multiple ascending dose (MAD)) studies were in healthy volunteers. Participants were randomized 3 : 1 across 9 SAD doses and 3 MAD doses of risvodetinib (IkT-148009) or placebo. Part 3 was a MAD study conducted at two doses in 14 participants with mild-to-moderate PD (MAD-PD). Primary outcome measures were safety, tolerability and pharmacokinetics. Exploratory outcomes in PD participants included clinical measures of PD state, GI function, and cerebrospinal fluid (CSF) concentration.
RESULTS
108 patients were treated with no dropouts. The SAD tested doses ranging from 12.5 to 325 mg, while the MAD tested 25 to 200 mg and MAD-PD tested 50 to 100 mg in Parkinson's participants. All active doses had a favorable safety profile with no clinically meaningful adverse events. Single dose pharmacokinetics were approximately linear between 12.5 mg and 200 mg for both Cmax and AUC0 - inf without distinction between healthy volunteers and participants with PD. Exposures at each dose were high relative to other drugs in the same kinase inhibitor class.
CONCLUSIONS
Risvodetinib (IkT-148009) was well tolerated, had a favorable safety and pharmacology profile over 7-day dosing, did not induce serious adverse events and did not appear to induce deleterious side-effects in participants administered anti-PD medications.
Topics: Aged; Humans; Area Under Curve; Healthy Volunteers; Parkinson Disease
PubMed: 38251063
DOI: 10.3233/JPD-230319 -
Antioxidants (Basel, Switzerland) Jan 2024In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single...
In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., and ) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.
PubMed: 38247491
DOI: 10.3390/antiox13010067 -
Biomedicine & Pharmacotherapy =... Feb 2024Pulmonary fibrosis is the result of dysfunctional repair after lung tissue injury, characterized by fibroblast proliferation and massive extracellular matrix...
Pulmonary fibrosis is the result of dysfunctional repair after lung tissue injury, characterized by fibroblast proliferation and massive extracellular matrix aggregation. Once fibrotic lesions develop, effective treatment is difficult, with few drugs currently available. Here, we identified a short cyclic decapeptide RL-RF10 derived from frog skin secretions as a potential novel lead molecule for the amelioration of pulmonary fibrosis. In vivo experiments indicated that RL-RF10 treatment ameliorated lung histopathological damage and fibrogenesis after paraquat (PQ) induction in a concentration-dependent manner. On day 7, bronchoalveolar lavage fluid assays performed on mice showed that RL-RF10 exerted anti-inflammatory effects by decreasing the expression of inflammation-related factors, including transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α, in lung tissue. In addition, RL-RF10 down-regulated the levels of collagen I, collagen III, and vimentin, while increasing the expression of E-cadherin to inhibit epithelial-mesenchymal transition. Further research demonstrated that the SMAD2/3 signaling pathway, which is strongly linked to TGF-β1, played a critical function in enhancing the pulmonary fibrosis relief achieved by RL-RF10. Both in vivo and in vitro assays showed that RL-RF10 treatment led to a significant reduction in the phosphorylation levels of SMAD2 and SMAD3 following PQ induction. Overall, we investigated the protective effects and underlying mechanisms of the RL-RF10 peptide against pulmonary fibrosis and demonstrated its potential as a novel therapeutic drug candidate for the treatment of pulmonary fibrotic diseases.
Topics: Mice; Animals; Pulmonary Fibrosis; Paraquat; Transforming Growth Factor beta1; Collagen; Lung Injury; Amphibians; Epithelial-Mesenchymal Transition
PubMed: 38244328
DOI: 10.1016/j.biopha.2024.116184