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The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment. The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC). The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-ΰB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold). CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway. [ABSTRACT FROM AUTHOR]

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1β, IL-18, and IL-1βR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients. [ABSTRACT FROM AUTHOR]

Sulfur Mustard (SM), a cytotoxic vesicant chemical warfare agent, has powerful irritant and blistering effects on the skin, eyes and respiratory tract. Since during the Iraq-Iran war, many Iranian soldiers and civilians were exposed to SM, there are several victims still suffering from long-term cutaneous, ocular and pulmonary complications. Currently, there is no definite treatment for long-term complications of SM, and only supportive medical care is being taken to minimize the symptoms. In this study, we compared the cost-effectiveness of common drugs that are used against long-term SM-induced complications in Iranian patients. In this review article, electronic databases were checked using the following key words: sulfur mustard, lung, skin, eye, cost-effectiveness, pharmacoeconomics and treatment. Abstracts of non-English papers and proceedings of congresses on SM were also assessed. Among the studied drugs, high-dose oral N-acetyl cysteine and long-acting inhaled corticosteroids against respiratory complications, topical corticosteroids and oral antihistamines against cutaneous complications and non-steroidal anti-inflammatory drugs and corticosteroids ophthalmic drops against ocular complications were found to be cost-effective. Usage of different drugs in the treatment of SM injuries in Iran, have imposed a significant economic burden to patients and their families because many drugs that are effective against chemical injuries are not covered by insurance. In addition, the development of more effective drugs in this field is considered as an urgent demand that should be noticed by the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. −0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. −0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: −5.26 ± 4.46 vs. −2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms. [ABSTRACT FROM AUTHOR]

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using ¹H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteins - as well as elastase activity - were significantly increased in PMN from 'diseased' hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects' PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione- S-transferase isoforms were differentially expressed in the cells from the SM-exposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients. [ABSTRACT FROM AUTHOR]

Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients ( n = 15) were administered IFNγ (100 μg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-β] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ ( p < 0.001) and CAT ( p < 0.001) scores, decreased severity of cough ( p = 0.001), dyspnea ( p < 0.001), and morning dyspnea ( p < 0.001), reduced frequency of sputum production ( p < 0.001) and hemoptysis ( p < 0.001), and elevated FEV1 ( p = 0.065). Serum levels of IL-4 ( p < 0.001), IL-6 ( p < 0.001), IL-10 ( p < 0.001), CGRP ( p < 0.001), MMP-9 ( p = 0.001), TNFα ( p < 0.001), TGFβ ( p < 0.001) and MDA ( p = 0.001) were decreased while those of IL-2 ( p < 0.001), IFNγ ( p < 0.001), and both total ( p = 0.005) and reduced glutathione ( p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNγ. [ABSTRACT FROM AUTHOR]

Background: Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15-20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients. Methods: Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA. Results: Total protein concentration was significantly lower in tears of the SM compared to control group ( p < 0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group ( p < 0.01). Tear CGRP concentration was found to be lower in the SM vs. control group ( p < 0.05) but no significant difference in CGRP/total protein was observed ( p > 0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups ( p > 0.05). Conclusion: The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications. [ABSTRACT FROM AUTHOR]

To discriminate between different alcoholic, aldehyde, and ester species of urine samples, a colorimetric sensor array consisting of dopamine-capped copper-silver bimetallic nanoparticles (Ag@Cu BMNPs) combined with 12 organic dyes is introduced. Based on the sensing mechanism, the nanozyme catalyzed the reactions of oxidation, dehydrogenation, and hydrolysis of volatile organic compounds. The products could alter the amount of hydronium ions in the detection media, making a variation in the color intensity of pH-sensitive indicators. Also, they could be connected to other organic dyes through nucleophilic/electrophilic or H-bonding interactions in order to form new complexes. The colorimetric responses of the sensor were visible to the naked eye and evaluated by image analysis software, thereby obtaining a unique detection pattern for each sample. The statistical data indicated that the sensor can completely distinguish between compounds with different functional groups. As a practical study, the efficiency of the sensor was investigated for the identification of the war veterans who injured by sulfur mustard in Iran-Iraq war and their differentiation from control people. Based on the output of the assay, the sensor was found to create a special color pattern for each studied group, achieving a total accuracy of 78.0% for this discrimination. The color change of the proposed sensor has a good correlation with the severity of the injury, being independent of the metabolic changes caused by the age of the participants. Accordingly, the fabricated sensor array can be a suitable tool to detect oxygen-containing compounds in environmental or biological samples., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using (1)H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Sulfur mustard (SM) is a chemical warfare agent that has been repeatedly used since World War I. SM has chronic and deleterious effects on different body organs such as lungs, skin and eyes., Objectives: To determine dental and oral health status of chemical victims of SM who were exposed to SM during the Iraqi-Iran war., Material and Methods: In this case-control study, 100 male subjects exposed to SM were chosen as cases, and 100 non-exposed volunteers were chosen as controls. These groups were selected randomly according to their referral number, and were matched regarding age. Collection of information was performed using Oral Health Assessment Form designed by the World Health Organization. Quantitative and qualitative data were compared between the groups using independent samples t-test and Chi-square test, respectively., Results: There was a significant difference between the case and control groups with respect to the frequencies of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease, being higher in the former group. There was also a positive association between the frequency of candidiasis and the percentage of disability; pharyngeal erythema and/or hyperplasia and use of salmeterol spray; and between hairy tongue and antibiotic use in the case group., Conclusions: Exposure to SM and the use of drugs for controlling long-term complications does not increase the risk of tooth decay, tooth loss, and intra and/or extra oral lesions in patients, but may be associated with increased incidence of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease.samples of oral precancerous and cancerous lesions to test sensitivity and specificity and thus validate the clinical applicability of fluorescence imaging in (pre)cancerous diagnostics. Key words:Sulfur mustard, oral health, candidiasis.