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Experimental and Molecular Pathology Oct 2019Sulfur mustard (SM), a potent vesicating chemical warfare agent, and its analog nitrogen mustard (NM), are both strong bi-functional alkylating agents. Eyes, skin, and...
Sulfur mustard (SM), a potent vesicating chemical warfare agent, and its analog nitrogen mustard (NM), are both strong bi-functional alkylating agents. Eyes, skin, and the respiratory system are the main targets of SM and NM exposure; however, ocular tissue is most sensitive, resulting in severe ocular injury. The mechanism of ocular injury from vesicating agents' exposure is not completely understood. To understand the injury mechanism from exposure to vesicating agents, NM has been previously employed in our toxicity studies on primary human corneal epithelial cells and ex vivo rabbit cornea organ culture model. In the current study, corneal toxicity from NM ocular exposure (1%) was analyzed for up to 28 days post-exposure in New Zealand White male rabbits to develop an acute corneal injury model. NM exposure led to conjunctival and eyelid swelling within a few hours after exposure, in addition to significant corneal opacity and ulceration. An increase in total corneal thickness and epithelial degradation was observed starting at day 3 post-NM exposure, which was maximal at day 14 post-exposure and did not resolve until 28 days post-exposure. There was an NM-induced increase in the number of blood vessels and inflammatory cells, and a decrease in keratocytes in the corneal stroma. NM exposure resulted in increased expression levels of cyclooxygenase-2, Interleukin-8, vascular endothelial growth factor and Matrix Metalloproteinase 9 indicating their involvement in NM-induced corneal injury. These clinical, biological, and molecular markers could be useful for the evaluation of acute corneal injury and to screen for therapies against NM- and SM-induced ocular injury.
Topics: Acute Disease; Animals; Chemical Warfare Agents; Cornea; Corneal Injuries; Cyclooxygenase 2; Humans; Immunohistochemistry; Interleukin-8; Male; Matrix Metalloproteinase 9; Mechlorethamine; Mustard Gas; Rabbits; Vascular Endothelial Growth Factor A
PubMed: 31233733
DOI: 10.1016/j.yexmp.2019.104275 -
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 -
Antioxidants (Basel, Switzerland) May 2021The study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure...
The study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure homogenization, without using organic solvents, were optimized using the Taguchi design followed by the central composite design. The optimized CSLNs exhibited a high assay/drug content (0.6% /), solubility (6 × 10 times), and EE (75%) with a particle size < 200 nm (PDI-0.143). The CSLNs were safe (in vitro and in vivo), photostable, autoclavable, stable up to one year at 30 °C and under refrigeration and exhibited a controlled release (zero-order; 5 days). XRD, FTIR, and DSC confirmed solubilization and entrapment of the curcumin within the SLNs. TEM and FESEM revealed a smooth and spherical shape. The CSLNs showed a significant antimicrobial effect (MIC of 64 µg/mL for planktonic cells; 512 µg/mL for biofilm formation; and 2 mg/mL for mature biofilm) against 9144, while free curcumin dispersion did not exhibit any effect. This is the first report on the disruption of mature biofilms by curcumin solid lipid nanoparticles (CSLNs). The cell proliferation potential of CSLNs was also evaluated in vitro while the wound healing potential of CSLNs (incorporated in a hydrogel) was assessed in vivo. In (i) nitrogen mustard gas and (ii) a full-thickness excision wound model, CSLNs exhibited (a) significantly faster wound closure, (b) histologically and immunohistochemically better healing, (c) lower oxidative stress (LPO) and (d) inflammation (TNFα), and (e) increased angiogenesis (VEGF) and antioxidant enzymes, i.e., catalase and GSH levels. CSLNs thus offer a promising modern wound therapy especially for infected wounds, considering their effects in mature biofilm disruption.
PubMed: 34063003
DOI: 10.3390/antiox10050725 -
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 -
BMC Pulmonary Medicine Apr 2021This study was performed to evaluate the anti-inflammatory effect of atorvastatin in patients with chronic bronchitis, exposed to sulfur mustard gas. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study was performed to evaluate the anti-inflammatory effect of atorvastatin in patients with chronic bronchitis, exposed to sulfur mustard gas.
METHODS
In this randomized double-blinded clinical trial we recruited patients with chronic bronchitis after exposure to sulfur mustard gas. Ninety men 45-75 years old diagnosed with chronic bronchitis after exposure to mustard gas during the Iran-Iraq war, were randomly assigned to receive either atorvastatin (40 mg) or placebo once a day for 3 months. The interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), procalcitonin, highly sensitive CRP and COPD assessment test (CAT) score was compared at baseline and after 12 weeks.
RESULTS
After consuming atorvastatin for 12 weeks, IL-6 level (mean difference [95%CI]; 0.2 [- 0.05, 0.5]), TNF-α (mean difference [95%CI]; - 0.07 [- 0.2, 0.07]), high sensitive CRP (mean difference [95%CI] - 0.1 [- 1.2, 0.9]), and procalcitonin (mean difference [95%CI]; 0.003 [- 0.02, 0.03]) did not change significantly. However, in the placebo group, only IL-6 (mean difference [95%CI]; 0.6 [0.2, 1.05]) decreased significantly after 12 weeks, but levels of high sensitive CRP (mean difference [95%CI]; - 0.3 [- 1.4, 0.8]) TNF-α (mean difference [95%CI]; - 0.2 [- 0.34, - 0.06]) and procalcitonin (mean difference [95%CI]; 0.02 [- 0.001, 0.04]) did not change significantly. After 12 weeks, the mean differences in TNF- α, IL-6 level, high sensitive CRP, procalcitonin, and CAT score did not significantly differ between the two groups.
CONCLUSIONS
The administration of 40 mg atorvastatin for 3 months did not significantly change the inflammatory markers or the quality of life of patients exposed to mustard gas with chronic bronchitis.
TRIAL REGISTRATION
IRCT, IRCT138904144312N1. Registered 16 August 2014, https://en.irct.ir/trial/4577 .
Topics: Aged; Armed Conflicts; Atorvastatin; Bronchitis, Chronic; C-Reactive Protein; Double-Blind Method; Humans; Inflammation Mediators; Interleukin-6; Iran; Male; Middle Aged; Mustard Gas; Procalcitonin; Quality of Life; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 33794865
DOI: 10.1186/s12890-021-01481-y -
Communications Chemistry Mar 2021Bis(2-chloroethyl) sulfide or sulfur mustard (HD) is one of the highest-tonnage chemical warfare agents and one that is highly persistent in the environment. For...
Bis(2-chloroethyl) sulfide or sulfur mustard (HD) is one of the highest-tonnage chemical warfare agents and one that is highly persistent in the environment. For decontamination, selective oxidation of HD to the substantially less toxic sulfoxide is crucial. We report here a solvent-free, solid, robust catalyst comprising hydrophobic salts of tribromide and nitrate, copper(II) nitrate hydrate, and a solid acid (Nafion) for selective sulfoxidation using only ambient air at room temperature. This system rapidly removes HD as a neat liquid or a vapor. The mechanisms of these aerobic decontamination reactions are complex, and studies confirm reversible formation of a key intermediate, the bromosulfonium ion, and the role of Cu(II). The latter increases the rate four-fold by increasing the equilibrium concentration of bromosulfonium during turnover. Cu(II) also provides a colorimetric detection capability. Without HD, the solid is green, and with HD, it is brown. Bromine K-edge XANES and EXAFS studies confirm regeneration of tribromide under catalytic conditions. Diffuse reflectance infrared Fourier transform spectroscopy shows absorption of HD vapor and selective conversion to the desired sulfoxide, HDO, at the gas-solid interface.
PubMed: 36697596
DOI: 10.1038/s42004-021-00465-7 -
Journal, Physical Therapy Education Sep 2023Full-time clinical education experiences (CEEs) constitute a significant component of entry-level physical therapy education. COVID-19 challenged clinical education...
INTRODUCTION
Full-time clinical education experiences (CEEs) constitute a significant component of entry-level physical therapy education. COVID-19 challenged clinical education throughout the country by affecting the availability of CEEs.
REVIEW OF LITERATURE
Research suggested that the number of clinical education spots available would stay the same. By contrast, the number of students enrolling in physical therapist (PT) and physical therapist assistant (PTA) education programs continues to rise. In response to the COVID-19 pandemic, students and faculty expressed concerns about the lack of student readiness and the availability of CEEs. The purpose of this study was to examine prepandemic factors that influenced the number of CEE slots available in Florida and the impact that the COVID-19 pandemic had on slot availability. Furthermore, researchers sought to identify factors that prevented a return to prepandemic levels of CEE spot offerings and recognize solutions to overcome those barriers. Finally, the researchers aimed to pinpoint suggestions to enhance collaborations between the clinical sites and physical therapy education programs.
SUBJECTS
Forty-eight site coordinators of clinical education (SCCEs) from various settings and regions in Florida completed the survey.
METHODS
An online survey was distributed to Florida SCCEs to ascertain their perceptions on how COVID-19 influenced clinical education. The researchers used descriptive and inferential statistics to analyze the data.
RESULTS
Clinical instructor (CI) volunteerism was the primary determinant of CEE spots available before the COVID-19 pandemic. The number of CEE spots was reduced for both PT and PTA education programs during the COVID-19 pandemic. Although the PTA slots returned to their baseline from 2019, the PT placements remained significantly lower in 2021. Social distancing and CI availability had the most considerable impact on CEE offerings. Site coordinators of clinical education also suggested that the greatest supports needed from the academic institutions were educating students on COVID-19 prevention and providing personal protective equipment (PPE) to students for their CEEs. This article also offers suggested incentives that academic sites can provide their clinical partners, such as in-services earning continuing education units, to enhance their participation in clinical education.
DISCUSSION AND CONCLUSION
All clinical education stakeholders must collaborate to provide students with the required clinical educational opportunities. Academic sites should continue to provide support, training, and incentives to CIs to enhance participation from clinical education sites. Educational programs must add content about COVID-19 to their curriculum and consider providing students with PPE during their rotations to restore the number of CEEs post-COVID-19 pandemic.
Topics: Humans; Florida; Pandemics; COVID-19; Physical Therapy Modalities; Mustard Gas
PubMed: 38478814
DOI: 10.1097/JTE.0000000000000286 -
Experimental and Molecular Pathology Aug 2020Sulfur mustard (SM), a dermal vesicant that has been used in chemical warfare, causes inflammation, edema and epidermal erosions depending on the dose and time following...
Sulfur mustard (SM), a dermal vesicant that has been used in chemical warfare, causes inflammation, edema and epidermal erosions depending on the dose and time following exposure. Herein, a minipig model was used to characterize wound healing following dermal exposure to SM. Saturated SM vapor caps were placed on the dorsal flanks of 3-month-old male Gottingen minipigs for 30 min. After 48 h the control and SM wounded sites were debrided daily for 7 days with wet to wet saline gauze soaks. Animals were then euthanized, and full thickness skin biopsies prepared for histology and immunohistochemistry. Control skin contained a well differentiated epidermis with a prominent stratum corneum. A well-developed eschar covered the skin of SM treated animals, however, the epidermis beneath the eschar displayed significant wound healing with a hyperplastic epidermis. Stratum corneum shedding and a multilayered basal epithelium consisting of cuboidal and columnar cells were also evident in the neoepidermis. Nuclear expression of proliferating cell nuclear antigen (PCNA) was contiguous in cells along the basal epidermal layer of control and SM exposed skin; SM caused a significant increase in PCNA expression in basal and suprabasal cells. SM exposure was also associated with marked changes in expression of markers of wound healing including increases in keratin 10, keratin 17 and loricrin and decreases in E-cadherin. Trichrome staining of control skin showed a well-developed collagen network with no delineation between the papillary and reticular dermis. Conversely, a major delineation was observed in SM-exposed skin including a web-like papillary dermis composed of filamentous extracellular matrix, and compact collagen fibrils in the lower reticular dermis. Although the dermis below the wound site was disrupted, there was substantive epidermal regeneration following SM-induced injury. Further studies analyzing the wound healing process in minipig skin will be important to provide a model to evaluate potential vesicant countermeasures.
Topics: Animals; Cadherins; Cell Differentiation; Epidermis; Membrane Proteins; Mustard Gas; Proliferating Cell Nuclear Antigen; Skin; Swine; Swine, Miniature; Wound Healing
PubMed: 32445752
DOI: 10.1016/j.yexmp.2020.104470 -
Toxicological Sciences : An Official... Dec 2020Sulfur mustard (SM) inhalation causes debilitating pulmonary injury in humans which progresses to fibrosis. Herein, we developed a rat model of SM toxicity which...
Sulfur mustard (SM) inhalation causes debilitating pulmonary injury in humans which progresses to fibrosis. Herein, we developed a rat model of SM toxicity which parallels pathological changes in the respiratory tract observed in humans. SM vapor inhalation caused dose (0.2-0.6 mg/kg)-related damage to the respiratory tract within 3 days of exposure. At 0.4-0.6 mg/kg, ulceration of the proximal bronchioles, edema and inflammation were observed, along with a proteinaceous exudate containing inflammatory cells in alveolar regions. Time course studies revealed that the pathologic response was biphasic. Thus, changes observed at 3 days post-SM were reduced at 7-16 days; this was followed by more robust aberrations at 28 days, including epithelial necrosis and hyperplasia in the distal bronchioles, thickened alveolar walls, enlarged vacuolated macrophages, and interstitial fibrosis. Histopathologic changes were correlated with biphasic increases in bronchoalveolar lavage (BAL) cell and protein content and proliferating cell nuclear antigen expression. Proinflammatory proteins receptor for advanced glycation end product (RAGE), high-mobility group box protein (HMGB)-1, and matrix metalloproteinase (MMP)-9 also increased in a biphasic manner following SM inhalation, along with surfactant protein-D (SP-D). Tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), inflammatory proteins implicated in mustard lung toxicity, and the proinflammatory/profibrotic protein, galectin (Gal)-3, were upregulated in alveolar macrophages and in bronchiolar regions at 3 and 28 days post-SM. Inflammatory changes in the lung were associated with oxidative stress, as reflected by increased expression of heme oxygenase (HO)-1. These data demonstrate a similar pathologic response to inhaled SM in rats and humans suggesting that this rodent model can be used for mechanistic studies and for the identification of efficacious therapeutics for mitigating toxicity.
Topics: Animals; Chemical Warfare Agents; Fibrosis; Inflammation; Lung; Lung Injury; Mustard Gas; Oxidative Stress; Rats
PubMed: 33002157
DOI: 10.1093/toxsci/kfaa150 -
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