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Analytical Methods : Advancing Methods... Jan 2023The continuing threats of military conflicts and terrorism may involve the misuse of chemical weapons. The present study aims to use environmental samples to find...
The continuing threats of military conflicts and terrorism may involve the misuse of chemical weapons. The present study aims to use environmental samples to find evidence of the release of such agents at an incident scene. A novel approach was developed for identifying protein adducts in plants. Basil (), bay laurel leaf () and stinging nettle () were exposed to 2.5 to 150 mg m sulfur mustard, 2.5 to 250 mg m sarin, and 0.5 to 25 g m chlorine gas. The vapors of the selected chemicals were generated under controlled conditions in a dedicated set-up. After sample preparation and digestion, the samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and liquid chromatography high resolution tandem mass spectrometry (LC-HRMS/MS), respectively. In the case of chlorine exposure, it was found that 3-chloro- and 3,5-dichlorotyrosine adducts were formed. As a result of sarin exposure, the -isopropyl methylphosphonic acid adduct to tyrosine could be analyzed, and after sulfur mustard exposure the N1- and N3-HETE-histidine adducts were identified. The lowest vapor exposure levels for which these plant adducts could be detected, were 2.5 mg m for sarin, 50 mg m for chlorine and 12.5 mg m for sulfur mustard. Additionally, protein adducts following a liquid exposure of only 2 nmol Novichock A-234, 0.4 nmol sarin and 0.2 nmol sulfur mustard could still be observed. For both vapor and liquid exposure, the amount of adduct formed increased with the level of exposure. In all cases synthetic reference standards were used for unambiguous identification. The window of opportunity for investigation of agent exposure through the analysis of plant material was found to be remarkably long. Even three months after the actual exposure, the biomarkers could still be detected in the living plants, as well as in dried leaves. An important benefit of the current method is that a relatively simple and generic sample work-up procedure can be applied for all agents studied. In conclusion, the presented work clearly demonstrates the possibility of analyzing chemical warfare agent biomarkers in plants, which is useful for forensic reconstructions, including the investigation into alleged use in conflict areas.
Topics: Chemical Warfare Agents; Mustard Gas; Chromatography, Liquid; Sarin; Chlorine; Tandem Mass Spectrometry; Biomarkers
PubMed: 36524843
DOI: 10.1039/d2ay01650h -
ACS Sensors Jul 2022Herein, a novel blue aggregation-induced enhanced emission (AIEE) material 4--(naphthalen-l-yl)-3,5-bis(4--phenyl-1-naphthylamine)phenyl-4-1,2,4-triazole () is developed...
Herein, a novel blue aggregation-induced enhanced emission (AIEE) material 4--(naphthalen-l-yl)-3,5-bis(4--phenyl-1-naphthylamine)phenyl-4-1,2,4-triazole () is developed and used as a fluorescent chemosensor for sulfur mustard (SM) simulant 2-chloroethyl ethyl sulfide (2-CEES) vapor. The chemosensor is designed by introducing an electron-donating -phenyl-1-naphthylamine group at 3 and 5 position of 4-1,2,4-triazole (TAZ) to enhance the nucleophilicity of the TAZ group, and a naphthalene ring is connected to 4 position of the TAZ group to construct an AIEE molecule. The films show extraordinary stability and then are further used as reliable and portable fluorescent chemosensors. Upon exposure to 2-CEES vapor, the chemosensor exhibits an instantaneous fluorescence response (not more than 1 s). What should be noted is that this fluorescent chemosensor realizes the visualized detection of fluorescent color change from blue to green at "room temperature", which is rarely reported. The limit of detection is estimated to be 0.55 ppm, which is below the AEGL-1 (0.6 ppm for 1 min) safety ceiling level to SM exposure. Moreover, the chemosensor shows high selectivity toward 2-CEES vapor over closely related substances, including alkylating agents, aryl halide compounds, sulphur-containing compounds, and nerve agent mimics. More impressively, the chemosensor demonstrates good recyclability by water treatment. Also, the sensing mechanism is adequately proved by using multiple experimental methods and theoretical calculation. In addition, the -based facile filter paper-constructed test strips are fabricated for real-time and on-spot detection of leaked 2-CEES gas specifically. Therefore, this fluorescent chemosensor with excellent sensing performance greatly advances the practical detection of SM species at room temperature.
Topics: Alkylating Agents; Chemical Warfare Agents; Coloring Agents; Mustard Gas; Temperature; Triazoles
PubMed: 35819023
DOI: 10.1021/acssensors.2c00708 -
Toxicology Letters Oct 2020Despite many studies investigating the mechanism of Sulfur Mustard (SM) induced lung injury, the underlying mechanism is still unclear. Inflammatory and subsequent... (Review)
Review
Despite many studies investigating the mechanism of Sulfur Mustard (SM) induced lung injury, the underlying mechanism is still unclear. Inflammatory and subsequent fibroproliferative stages of SM-toxicity are based upon several highly-related series of events controlled by the immune system. The inhalation of SM gas variably affects different cell populations within the lungs. Various studies have shown the critical role of macrophages in triggering a pulmonary inflammatory response as well as its maintenance, resolution, and repair. Importantly, macrophages can serve as either pro-inflammatory or anti-inflammatory populations depending on the present conditions at any pathological stage. Different characteristics of macrophages, including their differentiation, phenotypic, and functional properties, as well as interactions with other cell populations determine the outcomes of lung diseases and the extent of long- or short-term pulmonary damage induced by SM. In this paper, we summarize the current state of knowledge regarding the role of alveolar macrophages and their mediators in the pathogenesis of SM in pulmonary injury. Investigating the specific cells and mechanisms involved in SM-lung injury may be useful in finding new target opportunities for treatment of this injury.
Topics: Adaptive Immunity; Animals; Chemical Warfare Agents; Humans; Immunity, Innate; Immunity, Mucosal; Lung; Macrophages, Alveolar; Mustard Gas
PubMed: 32758513
DOI: 10.1016/j.toxlet.2020.07.035 -
BMC Medical Genomics Aug 2022Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran-Iraq wars. One of the target organs of SM is the skin....
Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran-Iraq wars. One of the target organs of SM is the skin. Understanding the mechanisms involved in the pathogenesis of SM may help better identify complications and find appropriate treatments. The current study collected ten SM-exposed patients with long-term skin complications and ten healthy individuals. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the skin protein profile, and statistical bioinformatics methods were used to identify the differentially expressed proteins. One hundred twenty-nine proteins had different expressions between the two groups. Of these 129 proteins, 94 proteins had increased expression in veterans' skins, while the remaining 35 had decreased expression. The hub genes included RPS15, ACTN1, FLNA, HP, SDHC, and RPL29, and three modules were extracted from the PPI network analysis. Skin SM exposure can lead to oxidative stress, inflammation, apoptosis, and cell proliferation.
Topics: Chemical Warfare Agents; Graft vs Host Disease; Humans; Mustard Gas; Proteomics; Skin; Veterans
PubMed: 35933451
DOI: 10.1186/s12920-022-01328-3 -
The Journal of the Royal College of... Jun 2023The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and...
The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and in foundational insights into the molecular basis of development. From the 1930s until today, researchers at the University of Edinburgh have used to tackle questions in basic and biomedical science. Here the history of the initial decades of this research is explored, beginning with the introduction of research to Edinburgh by Francis Albert Eley Crew, in the newly established Institute of Animal Genetics. This period of research includes the discovery that chemicals can cause genetic mutation. This was demonstrated by research of the effects of mustard gas on flies by Charlotte Auerbach and colleagues, guided by the future Nobel laureate Hermann Muller. research was also formative in Conrad Hal Waddington's conceptual thinking about developmental biology, including in his vision of the epigenetic landscape. This holistic, systems-level view of the control of development was far before its time and has continued to be influential to this day in our conceptualisation of developmental biology and in the increasingly important field of systems biology. Waddington's experiments with in Edinburgh also gave rise to the evolutionary concept of genetic assimilation, in which an environmentally induced phenotype subsequently becomes genetically encoded.
Topics: Animals; Drosophila; Drosophila melanogaster; Phenotype; Biological Evolution; Mutation
PubMed: 36927337
DOI: 10.1177/14782715231162675 -
Environmental Toxicology and... May 2020Our previous study showed that percutaneous sulfur mustard (SM) exposure induced pulmonary toxicity, which was attenuated by DRDE-07 (S-2[2-aminoethylamino] ethyl phenyl...
Our previous study showed that percutaneous sulfur mustard (SM) exposure induced pulmonary toxicity, which was attenuated by DRDE-07 (S-2[2-aminoethylamino] ethyl phenyl sulphide) pretreatment. The present study aimed to evaluate the protective efficacy of DRDE-07 and its analogues viz., DRDE-30 (S-2(2-aminoethyl amino)ethyl propyl sulphide) and DRDE-35 (S-2(2-aminoethyl amino)ethyl butyl sulphide) against SM. Thirty minutes before percutaneous SM (0.8 LD) exposure, female Swiss mice were orally gavaged with DRDE-07 and its analogues(0.2 LD). Animals were sacrificed on day 3 and 7, BAL fluid (BALF) and lung tissue were collected for biochemical, histopathological studies. As results, DRDE-07 and its analogues were beneficial in reducing the number of BALF inflammatory cells, protein level, lactate dehydrogenase (LDH) activity, myeloperoxidase (MPO) and β-glucuronidase activity, while content of BALF and lung reduced glutathione level (GSH) were significantly protected. The pretreatment of DRDE-07 and its analogues inhibited the recruitment of inflammatory cells into the lung. The beneficial effects of DRDE-07 and its analogues were attributed to their antioxidant and anti-inflammatory activity. Among the analogues, DRDE-30 exhibited significant beneficial effects as compared to the other two compounds. These analogues may be considered as prototype candidate molecules as there is no effective antidote for SM toxicity.
Topics: Amifostine; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Chemical Warfare Agents; Female; Gene Expression Regulation, Enzymologic; Inflammation; Lung; Lung Diseases; Macrophages; Malondialdehyde; Matrix Metalloproteinase 9; Mice; Mustard Gas; Oxidative Stress
PubMed: 32062414
DOI: 10.1016/j.etap.2020.103333 -
European Journal of Nutrition Oct 2023The leaky gut barrier is an important factor leading to various inflammatory gastrointestinal disorders. The nutritional value of honey and variety of its health...
PURPOSE
The leaky gut barrier is an important factor leading to various inflammatory gastrointestinal disorders. The nutritional value of honey and variety of its health benefits have long been recognized. This study was undertaken to assess the role of Indian mustard honey in preventing lipopolysaccharide (LPS)-induced intestinal barrier dysfunction using a combination of in vitro and in vivo experimental model systems.
METHODS
LPS was used to induce intestinal barrier damage in a trans-well model of Caco-2 cells (1 µg/ml) and in Swiss albino mice (5 mg/kg body weight). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to analyse sugar and phenolic components in honey samples. The Caco-2 cell monolayer integrity was evaluated by transepithelial electrical resistance (TEER) and paracellular permeability assays. The histopathology of intestinal tissue was analysed by haematoxylin and eosin dual staining. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the transcription of genes. The protein expression was analysed by immunofluorescence, western blot and ELISA-based techniques.
RESULTS
The in vitro data showed that honey prevented LPS-induced intestinal barrier dysfunction dose dependently as was measured by TEER and paracellular flux of FITC-dextran dye. Further, the in vivo data showed a prophylactic effect of orally administered honey as it prevented the loss of intestinal barrier integrity and villus structure. The cellular localization and expression of tight junction (TJ) proteins were upregulated along with downregulation of pro-inflammatory cytokines in response to the administration of honey with LPS.
CONCLUSIONS
The findings of this study suggest a propitious role of honey in the maintenance of TJ protein integrity, thereby preventing LPS-induced intestinal barrier disintegration.
Topics: Humans; Mice; Animals; Caco-2 Cells; Tight Junction Proteins; Up-Regulation; Lipopolysaccharides; Honey; Tight Junctions; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Mucosa; Permeability
PubMed: 37493680
DOI: 10.1007/s00394-023-03203-y -
Iranian Journal of Allergy, Asthma, and... Sep 2023Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA...
Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.
PubMed: 37767679
DOI: 10.18502/ijaai.v22i4.13609 -
Experimental Eye Research Oct 2023Sulfur mustard (SM) ocular exposure severely damages the cornea and causes vision impairment. At present, no specific therapy exists to mitigate SM-induced corneal...
Sulfur mustard (SM) ocular exposure severely damages the cornea and causes vision impairment. At present, no specific therapy exists to mitigate SM-induced corneal injury and vision loss. This study performed transcriptome profiling of naïve, SM-damaged, and SM-undamaged rabbit corneas using RNA-seq analysis and bioinformatic tools to gain a better mechanistic understanding and develop SM-specific medical countermeasures. The mRNA profiles of rabbit corneas 4 weeks post SM vapor exposure were generated using Illumina-NextSeq deep sequencing (Gene Expression Omnibus accession # GSE127708). The RNA sequences of naïve (n = 4), SM-damaged (n = 5), and SM-undamaged (n = 5) corneas were subjected to differential expression (DE) analysis after quality control profiling with FastQC. DE analysis was performed using HISAT2, StringTie, and DESeq2. The log2(FC)±2 and adjusted p˂0.05 were chosen to identify the most relevant genes. A total of 5930 differentially expressed genes (DEGs) (upregulated: 3196, downregulated: 2734) were found in SM-damaged corneas compared to naïve corneas, whereas SM-undamaged corneas showed 1884 DEGs (upregulated: 1029, downregulated: 855) compared to naïve corneas. DE profiling of SM-damaged corneas to SM-undamaged corneas revealed 985 genes (upregulated: 308, downregulated: 677). The DE profiles were subsequently subjected to signaling pathway enrichment, and protein‒protein interactions (PPIs) were analyzed. Pathway enrichment was performed for the genes associated with cellular apoptosis, death, adhesion, migration, differentiation, proliferation, extracellular matrix, and tumor necrosis factor production. To identify novel targets, we narrowed the pathway analysis to upregulated and downregulated genes associated with cell proliferation and differentiation, and PPI networks were developed. Furthermore, protein targets associated with cell differentiation and proliferation that may play vital roles in corneal fibrosis and wound healing post SM injury were identified.
Topics: Animals; Rabbits; Mustard Gas; Protein Interaction Maps; RNA-Seq; Cornea; Gene Expression Profiling; Gene Expression; Computational Biology
PubMed: 37683796
DOI: 10.1016/j.exer.2023.109644 -
Iranian Journal of Pathology 2022Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of...
BACKGROUND & OBJECTIVE
Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of mustard-exposed cornea after more than 30 years.
METHODS
Fourteen corneas after Lamellar keratoplasty were evaluated in this study. Corneal tissues were prepared by histologic methods and stained by H&E.
RESULTS
The main histopathological findings in these cases were the presence of severe stromal edema and corneal scar. In the sections with visible superficial epithelium, subepithelial bullae formation was observed. Focal or diffuse disruption of Bowman's membrane and replacement with fibrosis were also seen. There was no evidence of stromal vascularization and inflammation in all specimens.
CONCLUSION
After more than 30 years, an extensive corneal scar is seen in sulfur mustard exposed patients. Scar tissue without vascularization and fibroblastic proliferation is the main finding in the sulfur mustard exposed cornea. This pathology result is different from other scars. No evidence of inflammation or immune cell infiltration should be considered in managing DMGK.
PubMed: 36247510
DOI: 10.30699/IJP.2022.538950.2722