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Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients.International Immunopharmacology Dec 2019The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems.
BACKGROUND
The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems.
MATERIALS AND METHODS
In this study, 128 SM-exposed patients and 31 healthy control participants participated. Tear and serum levels of chemokines were assessed by ELISA method.
RESULTS
There was no significant difference in the serum level of IL-8/CXCL8, CX3CL1/fractalkine, CCL2/MCP-1, and CCL5/RANTES between all SM-exposed subjects and control groups. The tear level of IL-8 in the SM-exposed group was lower than the control group, but the difference was not significant. In the SM-exposed group with the abnormalities in tear breakup time (TBUT) test, fundus and pannus formation were significantly higher than SM-exposed patients without these problems. CX3CL1 levels have significantly increased in SM-exposed group with blepharitis, pterygium, and conjunctival pigmentation as compared with the control group. Besides, significantly higher levels of CX3CL1 were observed in SM-exposed group with or without bulbar conjunctival hyperemia and abnormal vessels a well as with fundus abnormality compared to the control group. Only, SM-exposed group with subconjunctival fibrosis had significantly lower levels of CCL5 than SM-exposed group without this problem.
CONCLUSION
The higher level of CX3CL1 and consistent levels of IL-8/CXCL8, MCP-1/CCL2, and RANTES/CCL5 in SM-exposed individuals may indicate an anti-inflammatory response against the destructive effects of SM gas. High tear level of IL-8/CXCL8 reflects the severity of ocular surface abnormalities, yet significantly low tear level found in mild SM-exposed subgroup compared with the control group. The lower levels of CX3CL1 and RANTES/CCL5 may represent the different pathophysiology which requires further studies.
Topics: Adult; Chemical Warfare Agents; Cytokines; Eye Injuries; Humans; Male; Middle Aged; Mustard Gas; Severity of Illness Index; Tears
PubMed: 31669888
DOI: 10.1016/j.intimp.2019.105844 -
International Immunopharmacology Mar 2020Autophagy is an intracellular hemostasis mechanism, responding to extracellular or intracellular stresses. Sulfur mustard (SM) induces cellular stress. Iranian soldiers...
BACKGROUND
Autophagy is an intracellular hemostasis mechanism, responding to extracellular or intracellular stresses. Sulfur mustard (SM) induces cellular stress. Iranian soldiers exposed to SM gas, during the Iraq-Iran war, suffer from delayed complications even 30 years after exposure. In this study, for exploring the SM effect on autophagy pathway, gene and protein expression of autophagy markers are evaluated in the lung of SM-exposed people.
METHODS
52 FFPE lung tissues of SM-exposed people and 33 lung paraffin blocks of non-exposed patients to SM were selected. LC3 and Beclin-1 mRNA expressions were evaluated by QRT-PCR. LC3-B protein and LC3II/LC3I proteins ratio were detected by Immunohistochemistry and immunoblotting method. The collected data were analyzed in SPSS, and P value ≤ 0.05 was considered significant.
RESULTS
LC3 gene expression in SM-exposed subjects (median CT value = 4.97) increased about 4 fold compared with the control group (median CT value = 0.46, P = 0.025). Beclin-1 mRNA expression had not significant difference between two groups. After adjusting the confounding variables such as drug usage, LC3-B protein (P = 0.041) and LC3II/LC3I ratio (P = 0.044) were found significantly lower in the lung cells of SM-exposed group.
CONCLUSION
Upon exposure to SM gas, the lung cells are affected by acute cellular stress such as oxidative stress. The study results show that LC3 mRNA level increases in these patients, but, surprisingly, LC3-B protein via unknown mechanism has been down-regulated. N-acetyl cysteine and salbutamol drugs could induce the autophagy, and help to reduce the SM effects and improve the clinical condition of SM-injured patients.
Topics: Acetylcysteine; Adult; Albuterol; Armed Conflicts; Autophagy; Beclin-1; Case-Control Studies; Chemical Warfare Agents; Down-Regulation; Female; Humans; Iran; Lung; Lung Injury; Male; Microtubule-Associated Proteins; Middle Aged; Military Personnel; Mustard Gas; Oxidative Stress; Time Factors
PubMed: 31952904
DOI: 10.1016/j.intimp.2019.105896 -
Environmental Science and Pollution... Sep 2021Oxidative stability of prototypical groundnut oil (GO) and mustard oil (MO) blended with a significant characteristic addition of antioxidants, α-tocopherol (α-T) and...
Oxidative stability of prototypical groundnut oil (GO) and mustard oil (MO) blended with a significant characteristic addition of antioxidants, α-tocopherol (α-T) and TBHQ (tert-butyl hydroquinone), at different concentrations was analysed. α-T (natural) and TBHQ (synthetic) antioxidants at a different concentrations from 0 to 20 mg/L were blended with GO and MO to prepare 18 samples. Compositional analysis of groundnut oil and mustard oil was carried out using gas chromatography and mass spectra (GCMS). Electrical properties like dielectric constant, tanδ, specific resistance etc. were investigated at frequencies from 1 Hz to 10 MHz for the modified samples. Thermal properties like breakdown voltage, flash and fire points and viscosity of all samples were also premeditated. It was observed that dielectric constant (ε') of GO reduces from 3.58 to 2.82 with the addition of α-T but increases to 3.29 with the addition of TBHQ, whereas in MO, dielectric constant increases from 2.93 to 3.38 with the addition of α-T and rises to 3.27 with the addition of TBHQ at 15 mg/L. The synergistic effect of antioxidants in regulating the insulation nature of the oil is found to be more effective with α-tocopherol compared to TBHQ in GO. Higher breakdown voltage and more stability were observed in oil with the addition of antioxidant (TBHQ) in low concentration. The study would be useful in the selection of eco-friendly coolants in engineering and industry.
Topics: Antioxidants; Gas Chromatography-Mass Spectrometry; Hydroquinones; Oxidation-Reduction; Plant Oils; alpha-Tocopherol
PubMed: 33954923
DOI: 10.1007/s11356-021-14081-4 -
Analytical Chemistry Mar 2021Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared...
Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared via 11 different synthetic routes were analyzed using gas chromatography/high-resolution mass spectrometry. A large number of compounds were detected, and multivariate data analysis of the mass spectrometric results enabled the discovery of route-specific signature profiles. The performance of two supervised machine learning algorithms for retrospective synthetic route attribution, orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), were compared using external test sets. Complete classification accuracy was achieved for test set samples (2/2 and 9/9) by using classification models to resolve the one-step routes starting from ethylene and the thiodiglycol chlorination methods used in the two-step routes. Retrospective determination of initial thiodiglycol synthesis methods in sulfur mustard samples, following chlorination, was more difficult. Nevertheless, the large number of markers detected using the nontargeted methodology enabled correct assignment of 5/9 test set samples using OPLS-DA and 8/9 using RF. RF was also used to construct an 11-class model with a total classification accuracy of 10/11. The developed methods were further evaluated by classifying sulfur mustard spiked into soil and textile matrix samples. Due to matrix effects and the low spiking level (0.05% w/w), route determination was more challenging in these cases. Nevertheless, acceptable classification performance was achieved during external test set validation: chlorination methods were correctly classified for 12/18 and 11/15 in spiked soil and textile samples, respectively.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Mustard Gas; Retrospective Studies; Soil
PubMed: 33709707
DOI: 10.1021/acs.analchem.0c04555 -
PloS One 2021Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop...
Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop inflammation, ulceration, neovascularization (NV), impaired vision, and partial/complete blindness depending upon the concentration of SM, exposure duration, and bio-physiological conditions of the eyes. Comprehensive in vivo studies have established ocular structural alterations, opacity, NV, and inflammation upon short durations (<4 min) of SM exposure. In this study, detailed analyses of histopathological alterations in corneal structure, keratocytes, inflammatory cells, blood vessels, and expressions of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and cytokines were performed in New Zealand white rabbits, in a time-dependent manner till 28 days, post longer durations (5 and 7 min) of ocular SM exposure to establish quantifiable endpoints of injury and healing. Results indicated that SM exposure led to duration-dependent increases in corneal thickness, opacity, ulceration, epithelial-stromal separation, and epithelial degradation. Significant increases in NV, keratocyte death, blood vessels, and inflammatory markers (COX-2, MMP-9, VEGF, and interleukin-8) were also observed for both exposure durations compared to the controls. Collectively, these findings would benefit in temporal delineation of mechanisms underlying SM-induced corneal toxicity and provide models for testing therapeutic interventions.
Topics: Animals; Biomarkers; Blood Vessels; Cell Survival; Chemical Warfare Agents; Cornea; Corneal Injuries; Corneal Keratocytes; Cyclooxygenase 2; Interleukin-8; Matrix Metalloproteinase 9; Mustard Gas; Rabbits
PubMed: 34637469
DOI: 10.1371/journal.pone.0258503 -
RSC Advances Jul 2022By combining the anionic salt meso-tetra(4-carboxyphenyl)porphyrin (TCPP) and the Keggin polyoxometalate cation cluster [AlO(OH)(HO)] a simple ion-exchange method, a...
Enhancing the quantum yield of singlet oxygen: photocatalytic degradation of mustard gas simulant 2-chloroethyl ethyl sulfide catalyzed by a hybrid of polyhydroxyl aluminum cations and porphyrin anions.
By combining the anionic salt meso-tetra(4-carboxyphenyl)porphyrin (TCPP) and the Keggin polyoxometalate cation cluster [AlO(OH)(HO)] a simple ion-exchange method, a hybrid (CHNO)[AlO(OH)(HO)](OH)·18HO (Al-TCPP) was prepared and thoroughly characterized as a prototype of polyoxometalate-porphyrin hybrids for the photocatalytic degradation of the mustard gas simulant 2-chloroethyl ethyl sulfide (CEES). The experimental results showed that the catalytic degradation rate of CEES in the presence of Al-TCPP reached 96.16 and 99.01% in 180 and 90 min in methanol and methanol-water solvent mixture (v/v = 1 : 1), respectively. The reaction followed first-order reaction kinetics, and the half-life and kinetic constant in methanol and solvent mixture were 39.8 min, -0.017 min and 14.7 min, -0.047 min. Mechanism analysis indicated that under visible light irradiation in air, CEES was degraded through a combination of oxidation and alcoholysis/hydrolysis in methanol and the methanol-water solvent mixture. The superoxide radical (O˙) and singlet molecular oxygen (O) generated by Al-TCPP selectively oxidized CEES into a non-toxic sulfoxide. The singlet oxygen capture experiments showed that Al-TCPP ( = 0.236) had a higher quantum yield of singlet oxygen generation than HTCPP ( = 0.135) under visible light irradiation in air. The material Al-TCPP has good reusability, and the degradation rate of CEES can still reach 98.37% after being recycled five times.
PubMed: 35919596
DOI: 10.1039/d2ra01821g -
BMC Pulmonary Medicine Nov 2022During Iraq-Iran conflict, chemical weapons, particularly SM gas, were used numerous times, whose aftereffects are still present. This study aimed to compare serum...
During Iraq-Iran conflict, chemical weapons, particularly SM gas, were used numerous times, whose aftereffects are still present. This study aimed to compare serum proteome in the chronic ML (n = 10) and HC (n = 10). TMT label-based quantitative proteomics was used to examine serums from two groups. Among total significant proteins, 14 proteins were upregulated (log ≥ FC 0.5, p 0.05), and 6 proteins were downregulated (log ≤ FC - 0.5, p 0.05). By helping PPI network, and EA, 11 main pathways connected to significantly different protein expression levels were discovered, including inflammatory and cell adhesion signaling pathways. It may be deduced that the wounded organs of exposed individuals experience poor repair cycles of cell degeneration and regeneration because certain repair signals were elevated while other structural and adhesion molecules were downregulated. The systems biology approach can help enhance our basic knowledge of biological processes, and contribute to a deeper understanding of pathophysiological mechanisms, as well as the identification of potential biomarkers of disease.
Topics: Humans; Systems Biology; Proteomics; Mustard Plant; Disease Progression; Lung
PubMed: 36419000
DOI: 10.1186/s12890-022-02240-3 -
Inhalation Toxicology 2022Over 40% of veterans from the Persian Gulf War (GW) (1990-1991) suffer from Gulf War Illness (GWI). Thirty years since the GW, the exposure and mechanism contributing to... (Review)
Review
Over 40% of veterans from the Persian Gulf War (GW) (1990-1991) suffer from Gulf War Illness (GWI). Thirty years since the GW, the exposure and mechanism contributing to GWI remain unclear. One possible exposure that has been attributed to GWI are chemical warfare agents (CWAs). While there are treatments for isolated symptoms of GWI, the number of respiratory and cognitive/neurological issues continues to rise with minimum treatment options. This issue does not only affect veterans of the GW, importantly these chronic multisymptom illnesses (CMIs) are also growing amongst veterans who have served in the Afghanistan-Iraq war. What both wars have in common are their regions and inhaled exposures. In this review, we will describe the CWA exposures, such as sarin, cyclosarin, and mustard gas in both wars and discuss the various respiratory and neurocognitive issues experienced by veterans. We will bridge the respiratory and neurological symptoms experienced to the various potential mechanisms described for each CWA provided with the most up-to-date models and hypotheses.
Topics: Humans; Chemical Warfare Agents; Persian Gulf Syndrome; Gulf War; Veterans; Sarin
PubMed: 36394251
DOI: 10.1080/08958378.2022.2147257 -
IScience Jun 2024Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is...
Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.
PubMed: 38883811
DOI: 10.1016/j.isci.2024.110042 -
BMC Health Services Research Dec 2023Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the...
BACKGROUND
Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the eight-year Iran-Iraq conflict and permanently injured while the socioeconomic imbalance in their healthcare utilization (HCU) and health expenditures remains. This study aims to describe the HCU of SM-exposed survivors in Iran from 2018 to 2021; identify high-risk areas; and apply an inequality analysis of utilization regarding the socioeconomic groups to reduce the gap by controlling crucial determinants.
METHODS
From Oct 2018 to June 2021, the Veterans and Martyrs Affairs Foundation (VMAF) recorded 58,888 living war survivors with eye, lung, and skin ailments. After cleaning the dataset and removing junk codes, we defined 11 HCU-related variables and predicted the HCU for the upcoming years using Bayesian spatio-temporal models. We explored the association of individual-level HCU and determinants using a Zero-inflated Poisson (ZIP) model and also investigated the provincial hotspots using Local Moran's I.
RESULTS
With ≥ 90% confidence, we discovered eleven HCU clusters in Iran. We discovered that the expected number of HCU 1) rises with increasing age, severity of complications in survivors' eyes and lungs, wealth index (WI), life expectancy (LE), and hospital beds ratio; and 2) decreases with growing skin complications, years of schooling (YOS), urbanization, number of hospital beds, length of stay (LOS) in bed, and bed occupancy rate (BOR). The concentration index (CInd) of HCU and associated costs in age and wealth groups were all positive, however, the signs of CInd values for HCU and total cost in YOS, urbanization, LOS, and Hospital beds ratio groups were not identical.
CONCLUSIONS
We observed a tendency of pro-rich inequity and also higher HCU and expenditures for the elderly population. Finally, health policies should tackle potential socioeconomic inequities to reduce HCU gaps in the SM-exposed population. Also, policymakers should allocate the resources according to the hotspots of HCU.
Topics: Humans; Bayes Theorem; Health Expenditures; Health Services Accessibility; Iran; Mustard Gas; Spatio-Temporal Analysis; Healthcare Disparities; Socioeconomic Factors
PubMed: 38093322
DOI: 10.1186/s12913-023-10352-7