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Archives of Toxicology Nov 2022Chronic wounds, skin blisters, and ulcers are the result of skin exposure to the alkylating agent sulfur mustard (SM). One potential pathomechanism is senescence, which...
Chronic wounds, skin blisters, and ulcers are the result of skin exposure to the alkylating agent sulfur mustard (SM). One potential pathomechanism is senescence, which causes permanent growth arrest with a pro-inflammatory environment and may be associated with a chronic wound healing disorder. SM is known to induce chronic senescence in human mesenchymal stem cells which are subsequently unable to fulfill their regenerative function in the wound healing process. As dermal fibroblasts are crucial for cutaneous wound healing by being responsible for granulation tissue formation and synthesis of the extracellular matrix, SM exposure might also impair their function in a similar way. This study, therefore, investigated the SM sensitivity of primary human dermal fibroblasts (HDF) by determining the dose-response curve. Non-lethal concentrations LC (3 µM) to LC (65 µM) were used to examine the induction of senescence. HDF were exposed once to 3 µM, 13 µM, 24 µM, 40 µM or 65 μM SM, and were then cultured for 31 days. Changes in morphology as well as at the genetic and protein level were investigated. For the first time, HDF were shown to undergo senescence in a time- and concentration-dependent manner after SM exposure. They developed a characteristic senescence phenotype and expressed various senescence markers. Proinflammatory cytokines and chemokines were significantly altered in SM-exposed HDF as part of a senescence-associated secretory phenotype. The senescent fibroblasts can thus be considered a contributor to the SM-induced chronic wound healing disorder and might serve as a new therapeutic target in the future.
Topics: Alkylating Agents; Cellular Senescence; Cytokines; Fibroblasts; Humans; Mustard Gas; Skin
PubMed: 35906424
DOI: 10.1007/s00204-022-03346-7 -
Iranian Journal of Public Health Feb 2022There is no comprehensive study addressing all the epidemiological aspects of Lung cancer (LC) in Iran, therefore this systematic review investigated the epidemiological... (Review)
Review
BACKGROUND
There is no comprehensive study addressing all the epidemiological aspects of Lung cancer (LC) in Iran, therefore this systematic review investigated the epidemiological aspects of lung cancer in Iran.
METHODS
The search was performed until the Aug. 2020 on the in international databases based on PRISMA protocol by Pulmonary Neoplasms, Lung Neoplasm, Neoplasm, Lung, Lung Cancer, Cancer, Pulmonary Cancer, Cancer, Pulmonary, Cancers, Cancer of the Lung, Iran, incidence, death, risk factors keywords and different combinations of them. Articles that evaluated epidemiological aspects of lung cancer were included in the analysis.
RESULTS
Of 1420 articles, 82 cases were entered the analysis. Based on studies, in Iran, lung cancer has been the most common cancer and its prevalence is increasing. Squamous cell carcinoma and adenocarcinoma is the most common type of lung cancer in men and women, respectively. Cigarette smoking, human papilloma virus (HPV) infection, mustard gas, occupational risk factors and genetic factors considered as the major reported risk factors for lung cancer and vegetarian diet as a protective factor.
CONCLUSION
In according to the increasing trend of incidence and mortality of lung cancer in Iran, elimination of the major risk factors can decrease this issue and national comprehensive planning should be considered in health promotion plans.
PubMed: 35866136
DOI: 10.18502/ijph.v51i2.8683 -
ACS Omega Jul 2022Protection and decontamination of surfaces after exposure to chemical warfare agents (CWAs) are of considerable interest to the homeland defense and battlespace...
Protection and decontamination of surfaces after exposure to chemical warfare agents (CWAs) are of considerable interest to the homeland defense and battlespace operation communities. In this work, polyurethane was spin-coated onto aluminum oxide quartz crystal microbalance (QCM) sensors. Polyurethane film thickness was varied by altering the concentration of the polymer/chloroform solution used for spin-coating. Atomic force microscopy confirmed the formation of smooth, homogeneous films on the QCM sensor surface. Aluminum oxide QCM sensors coated with polyurethane were exposed to saturated vapors of dichloropentane (DCP), a mustard gas (HD) simulant, and dimethyl methylphosphonate (DMMP), a sarin gas (GB) simulant, and the mass uptake, diffusion coefficient, volume fraction, and partition coefficient of the simulant in the film were determined from QCM data. Results showed that both DCP and DMMP readily sorbed into the films although the mass uptake of DCP was greater than that of DMMP owing to DCP's higher vapor pressure. Additionally, the CWA simulant uptake increased with polyurethane film thickness. Sorption diffusion coefficients were 1 × 10 cm/s and 1 × 10 cm/s for DCP and DMMP vapor, respectively. Simulant desorption was also measured and showed that some DMMP remained in the film/substrate system, while DCP sorption was fully reversible. Reversible desorption for both CWA simulants was relatively quick and independent over the range of film thicknesses studied, with average desorption diffusion coefficients of 2 × 10 cm/s and 1 × 10 cm/s for DCP and DMMP, respectively. Collectively, this study is expected to inform protection and decontamination strategies of equipment and structures upon exposure to CWAs.
PubMed: 35811928
DOI: 10.1021/acsomega.2c02257 -
Experimental and Molecular Pathology Oct 2022Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional alkylating agent synthesized for chemical warfare. The eyes are particularly sensitive...
Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional alkylating agent synthesized for chemical warfare. The eyes are particularly sensitive to SM where it causes irritation, pain, photophobia, and blepharitis, depending on the dose and duration of exposure. In these studies, we examined the effects of SM vapor on the corneas of New Zealand white male rabbits. Edema and hazing of the cornea, signs of acute injury, were observed within one day of exposure to SM, followed by neovascularization, a sign of chronic or late phase pathology, which persisted for at least 28 days. Significant epithelial-stromal separation ranging from ~8-17% of the epithelial surface was observed. In the stroma, there was a marked increase in CD45 leukocytes and a decrease of keratocytes, along with areas of disorganization of collagen fibers. SM also disrupted the corneal basement membrane and altered the expression of perlecan, a heparan sulfate proteoglycan, and cellular fibronectin, an extracellular matrix glycoprotein. This was associated with an increase in basement membrane matrix metalloproteinases including ADAM17, which is important in remodeling of the basement membrane during wound healing. Tenascin-C, an extracellular matrix glycoprotein, was also upregulated in the stroma 14-28 d post SM, a finding consistent with its role in organizing structural components of the stroma necessary for corneal transparency. These data demonstrate that SM vapor causes persistent alterations in structural components of the cornea. Further characterization of SM-induced injury in rabbit cornea will be useful for the identification of targets for the development of ocular countermeasures.
Topics: Male; Rabbits; Animals; Mustard Gas; Heparan Sulfate Proteoglycans; Tenascin; Fibronectins; Corneal Injuries; Basement Membrane; Extracellular Matrix; Alkylating Agents; Sulfides; Collagen
PubMed: 35798063
DOI: 10.1016/j.yexmp.2022.104807 -
Supporting discovery and development of medical countermeasures for chemical injury to eye and skin.Experimental Eye Research Aug 2022Vesicants, from vesica (Latin for blister), can cause local and systemic toxicity. They include the chemotherapy drug nitrogen mustard and chemical warfare agents sulfur...
Vesicants, from vesica (Latin for blister), can cause local and systemic toxicity. They include the chemotherapy drug nitrogen mustard and chemical warfare agents sulfur mustard, Lewisite, and phosgene oxime. These agents are commonly released in vapor form and consequently, eyes and skin are the most vulnerable. The ocular and cutaneous injuries can be acute, subacute, or chronic, and can predispose casualties to secondary deleterious effects. Underlying these broad organ responses are shared and tissue-specific cellular and molecular biological cascades that attempt to counteract such chemical injuries. Depending on the severity of the chemical insult, biological responses often lead to inadequate wound healing and result in long-term pathology instead. Exposure to other toxic industrial chemicals such as acrolein, chloropicrin, and hydrogen fluoride, can also cause prominent eye and skin damage. There are currently no FDA-approved drugs to counteract these injuries. Hence, the possibility of a mass casualty emergency involving these chemicals is a major public health concern. Recognizing this critical challenge, the United States Department of Health and Human Services (HHS) is committed to the development of medical countermeasures to advance national health and medical preparedness against these highly toxic chemicals. Here, we provide an overview of various HHS funding and scientific opportunities available in this space, emphasizing parallels between eye and skin response to chemical injury. We also discuss a main limitation of existing data and suggest ways to overcome it.
Topics: Burns, Chemical; Chemical Warfare Agents; Humans; Mechlorethamine; Medical Countermeasures; Mustard Gas; Skin; United States
PubMed: 35716762
DOI: 10.1016/j.exer.2022.109156 -
Molecules (Basel, Switzerland) May 2022The pyrolysis of biomass material results in pyroligneous acid (PA) and biochar, among other by-products. In agriculture, PA is recognized as an antimicrobial agent,...
The pyrolysis of biomass material results in pyroligneous acid (PA) and biochar, among other by-products. In agriculture, PA is recognized as an antimicrobial agent, bio-insecticide, and bio-herbicide due to antioxidant activity provided by a variety of constituent materials. Application of PA to crop plants and soil can result in growth promotion, improved soil health, and reduced reliance on polluting chemical crop inputs. More detailed information regarding chemical compound content within PA and identification of optimal chemical profiles for growth promotion in different crop species is essential for application to yield effective results. Additionally, biochar and PA are often applied in tandem for increased agricultural benefits, but little is known regarding the optimal proportion of each crop input. This work reports on the effect of combined applications of different proportions of PA (200- and 800-fold dilutions) and chemical fertilizer rates (100%, 75%, 50%, and 0%) in the presence or absence of biochar on Komatsuna ( var. , Japanese mustard spinach) plant growth. To elucidate the chemical composition of the applied PA, four different spectroscopic measurements of fluorescence excitation were utilized for analysis-excitation-emission matrix, ion chromatography, high-performance liquid chromatography, and gas chromatography-mass spectrometry. It was determined that PA originating from pyrolysis of Japanese pine wood contained different classes of biostimulants (e.g., tryptophan, humic acid, and fulvic acid), and application to Komatsuna plants resulted in increased growth when applied alone, and in different combinations with the other two inputs. Additionally, application of biochar and PA at the higher dilution rate increased leaf accumulation of nutrients, calcium, and phosphorus. These effects reveal that PA and biochar are promising materials for sustainable crop production.
Topics: Agriculture; Charcoal; Fertilizers; Soil; Terpenes
PubMed: 35684334
DOI: 10.3390/molecules27113397 -
BMC Public Health Jun 2022Mustard gas (MG) is one of the most widely used chemical weapons in the past century. However, little information exists concerning long-term mortality from MG...
BACKGROUND
Mustard gas (MG) is one of the most widely used chemical weapons in the past century. However, little information exists concerning long-term mortality from MG exposure. In this study, we investigated mortality rate among civilian people exposed to MG during Iran-Iraq war in Sardasht in Iran after 32 years. METHODS: In this retrospective cohort study, data of people exposed to MG in Sardasht in 1987 were extracted from the Veterans and Martyr Affair Foundation of Iran up to March 20, 2019. Mortality rate, cumulative mortality and standardized mortality ratio with 95% confidence interval were calculated to explain mortality in the cohort, and then compared with general Iranian population. Cox regression analysis was used to indicate factor affecting the risk of death in the cohort. RESULTS: Out of 1,203 exposed people at the beginning of the period, 148 people died by the end of the study, with an average age of 66.42 at the time of death. Total person-years of the people up to end of the study were 38,198.63 and mortality rate was equal to 387 per 100,000 persons-years. Total number of observed deaths was less than expected death and the all-cause standardized mortality ratio (SMR) was determined as 0.680 (95% CI: 0.574 - 0.798). Cause-specific SMR showed that observed death due to respiratory diseases was higher than expected (SMR: 1.75) (95% CI: 1.145 - 2.569). The results of univariate and multivariate cox regression analysis showed that increasing age and having severe late complications in lung were associated with increased risk of death among people in the cohort.
CONCLUSION
In general, this result indicated that acute exposure to MG, even without wearing protective clothing and masks, could not increase all-cause mortality after 32 years if accompanied by special and ongoing care for those exposed.
Topics: Aged; Chemical Warfare Agents; Cohort Studies; Humans; Iran; Iraq; Mustard Gas; Retrospective Studies
PubMed: 35681169
DOI: 10.1186/s12889-022-13520-2 -
Food Chemistry: X Jun 2022The potential of ZJ316 (ZJ316) as a starter culture for quality improvement and microbial community regulation in pickled mustard fermentation was elucidated in this...
The potential of ZJ316 (ZJ316) as a starter culture for quality improvement and microbial community regulation in pickled mustard fermentation was elucidated in this study. Our results show that ZJ316 can deter the occurrence of nitrite peaks and maintain the nitrite content of pickled mustard at a low level (0.34 mg/kg). The headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry results indicate that ZJ316 gives a good flavor to pickled mustard. According to the 16S rDNA results, Firmicutes were the predominant microbiota after inoculation with ZJ316, and the abundances of , , and decreased simultaneously. In addition, antibacterial activity analysis showed that the supernatant of pickled mustard inoculated with ZJ316 had a significant inhibitory effect on D48, DH5α, and LM1. In conclusion, ZJ316 has potential for use as an ideal starter in the process of vegetable fermentation.
PubMed: 35669456
DOI: 10.1016/j.fochx.2022.100344 -
Archives of Toxicology Aug 2022In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in...
In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in armed conflicts in the Middle East. The vaporized or aerolized agent might be inhaled and have direct contact to skin and hair. Reaction products of SM with plasma proteins (adducts) represent well-established systemic targets for the bioanalytical verification of exposure. The SM-derived hydroxyethylthioethyl (HETE)-moiety is attached to nucleophilic amino acid side chains and allows unambiguous adduct detection. For shipping of common blood and plasma samples, extensive packaging rules are to be followed as these matrices are considered as potentially infectious material. In contrast, hair is considered as non-infectious thus making its handling and transportation much less complicated. Therefore, we addressed this matrix to develop a procedure for bioanalytical verification. Following optimized lysis of SM-treated human scalp hair and pepsin-catalyzed proteolysis of adducts of keratin type I and II, microbore liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HR MS) was used to detect three alkylated keratin-derived biomarker peptides: AE(-HETE)IRSDL, FKTIE(-HETE)EL, and LE(-HETE)TKLQF simultaneously. All bear the HETE-moiety bound to a glutamic acid residue. Protein adducts were stable for at least 14 weeks at ambient temperature and contact to air, and were not affected by washing the hair with shampoo. The biomarker peptides were also obtained from beard, armpit, abdominal, and pubic hair. This is the first report introducing stable local peptide adduct biomarkers from hair, that is easily accessible by a non-invasive sampling process.
Topics: Biomarkers; Chemical Warfare Agents; Hair; Humans; Hydroxyeicosatetraenoic Acids; Keratins; Mustard Gas; Peptides; Serum Albumin, Human; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 35570235
DOI: 10.1007/s00204-022-03307-0 -
Pharmaceuticals (Basel, Switzerland) Jan 2022The present work reveals a comprehensive decontamination study on real and simulated biological and chemical warfare agents (BCWA). The emphasis was on evaluating the...
Antimicrobial Activity and Degradation Ability Study on Nanoparticle-Enriched Formulations Specially Designed for the Neutralization of Real and Simulated Biological and Chemical Warfare Agents.
The present work reveals a comprehensive decontamination study on real and simulated biological and chemical warfare agents (BCWA). The emphasis was on evaluating the antimicrobial activity against real biological warfare agents, such as , and also the capacity of neutralizing real chemical warfare agents, such as mustard gas or soman, by employing three different types of organic solutions enriched with ZnO, TiO, and zeolite nanoparticles, specially designed for decontamination applications. The capacity of decontaminating BCWA was evaluated through specific investigation tools, including surface monitoring with the swabs method, minimum inhibitory (MIC) and minimum bactericidal concentration (MBC) evaluations, time-kill tests for microorganisms, and GC-MS for monitoring chemical agents on different types of surfaces (glass, painted metal, rubber, and cotton butyl rubber). These tests revealed high decontamination factors for BCWA even after only 10 min, accomplishing the requirements imposed by NATO standards. At the completion of the decontamination process, the formulations reached 100% efficacy for after 10-15 min, for soman after 20-30 min, and for mustard gas in an interval comprised between 5 and 24 h depending on the type of surface analyzed.
PubMed: 35056158
DOI: 10.3390/ph15010097