-
Analytical Methods : Advancing Methods... Jun 2023Sulfur mustard (SM) is an important chemical warfare agent (CWA) and has been used frequently in various conflicts. It is important to develop a facile, rapid, sensitive...
Sulfur mustard (SM) is an important chemical warfare agent (CWA) and has been used frequently in various conflicts. It is important to develop a facile, rapid, sensitive and selective detection method for SM. In this work, we constructed a novel fluorescent probe PCS capable of generating active sensing species for rapid and selective detection of SM and its simulant CEES (2-chloroethyl ethyl sulfide). PCS exhibits excellent chemical and photostability and can generate reactive species for rapid (within 90 s, at 60 °C) and selective detection of SM and CEES in solution with high sensitivity (∼nM level). Moreover, PCS could enable the detection of mustards . A test strip with PCS and KOH was prepared and realized the sensitive and selective detection of CEES in the gas phase. In addition, the PCS probe can realize facile and rapid detection of CEES-contaminated surfaces by spraying its sensing system (ethanol solution containing PCS and KOH). The sensing mechanism was well demonstrated through the separation and characterization of the sensing product.
Topics: Mustard Gas; Fluorescent Dyes; Chemical Warfare Agents
PubMed: 37264865
DOI: 10.1039/d3ay00350g -
Journal of the European Academy of... Sep 2023Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from... (Review)
Review
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from early-stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health-related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem-cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment-related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin-directed therapies (SDTs) as first-line treatment for early-stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.
Topics: Humans; Mechlorethamine; Quality of Life; Mustard Gas; Mycosis Fungoides; Skin Neoplasms; Tumor Microenvironment
PubMed: 37262305
DOI: 10.1111/jdv.19237 -
Stem Cell Research & Therapy May 2023Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or...
BACKGROUND
Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clinical data show that acute lung injury (ALI) is responsible for most mortality and morbidity after SM exposure. Extracellular vesicles are natural materials that participate in intercellular communication by delivering various substances and can be modified. In this study, we aim to show that extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (hucMSC-EVs) could exert therapeutic effects on SM-induced ALI, and to explain the underlying mechanism of effects.
METHODS
MiR-146a-5p contained in hucMSC-EVs may be involved in the process of hucMSC-EVs modulating the inflammatory response to SM-induced ALI. We utilized miR-146a-5p delivered by extracellular vesicles and further modified hucMSCs with a miR-146a-5p mimic or inhibitor to collect miR-146a-5p-overexpressing extracellular vesicles (miR-146a-5p-EVs) or miR-146a-5p-underexpressing extracellular vesicles (miR-146a-5p-EVs), respectively. Through in vivo and in vitro experiments, we investigated the mechanism.
RESULTS
The effect of miR-146a-5p-EVs on improving the inflammatory reaction tied to SM injury was better than that of hucMSC-EVs. We demonstrated that miR-146a-5p delivered by hucMSC-EVs targeted TRAF6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo.
CONCLUSION
In summary, miR-146a-5p delivered by hucMSC-EVs targeted TRAF6, causing hucMSC-EVs to exert anti-inflammatory effects in SM-induced ALI; thus, hucMSC-EVs treatment may be a promising clinical therapeutic after SM exposure.
Topics: Humans; MicroRNAs; Mustard Gas; TNF Receptor-Associated Factor 6; Extracellular Vesicles; Inflammation
PubMed: 37254188
DOI: 10.1186/s13287-023-03375-8 -
ACS Omega May 2023Developing an accurate chemical warfare agent (CWA) vapor generator is critical for homeland security because it enables real-time monitoring of target agent...
Development of a Rapid and Accurate Vapor Generation System for Real-Time Monitoring of a Chemical Warfare Agent (CWA) by Coupling Fourier Transform Infrared (FT-IR) Spectroscopy.
Developing an accurate chemical warfare agent (CWA) vapor generator is critical for homeland security because it enables real-time monitoring of target agent concentration for testing and evaluation. We designed and built an elaborate CWA vapor generator that offers reliable long-term stability and real-time monitoring capabilities by coupling it with Fourier transform infrared (FT-IR) spectroscopy. We evaluated the reliability and stability of the vapor generator using a gas chromatography-flame ion detector (GC-FID) and conducted a comparison between the experimental and theoretical results of sulfur mustard (HD, bis-2-chloroethylsulfide), a real CWA, at concentrations ranging from 1 to 5 ppm. Our FT-IR-coupled vapor generation system showed real-time monitoring ability, which enables rapid and accurate evaluation of chemical detectors. The vapor generation system was able to generate CWA vapor continuously for over 8 h, demonstrating its long-term vapor generation capability. In addition, we vaporized another representative CWA, viz., GB (Sarin, propan-2-yl ethylphosphonofluoridate), and conducted real-time monitoring of GB vapor concentration with high accuracy. This versatile vapor generator approach can enable the rapid and accurate evaluation of CWAs for homeland security against chemical threats and can be used in constructing a versatile real-time monitoring vapor generation system for CWAs.
PubMed: 37251177
DOI: 10.1021/acsomega.3c01301 -
Cellular and Molecular Biology... Jan 2023The city of Halabja situated in Kurdistan-Iraq faced a deadly attack using chemical warfare including the use of sulfur mustard (SM) in 1988. The survivors of this...
The city of Halabja situated in Kurdistan-Iraq faced a deadly attack using chemical warfare including the use of sulfur mustard (SM) in 1988. The survivors of this attack also faced the consequences of exposure to the toxic chemical SM in the form of multiple health complaints. The aim of this study is focused to gather data about the biochemical and hematological findings of Halabja victims who suffered from Sulfur Mustard (SM) exposure after completing 34 years of the attacks. A total of Twenty-five non-smoker patients (f: m19:6, mean age 59.2 years (range 35-85) and ten non-smokers control, healthy people (f: m 3:7, mean age 25.3 years (range 20-37) were interviewed and subjected to be tested. A purposive sampling strategy was adopted to recruit the study participants in August 2022. There were no significant differences between patients and controls regarding thyroid function markers. The levels of total protein and total albumin were significantly lower in the victims than in the controls (total protein: 7.67 ± 0.55 g/dL, P < 0.05, albumin: 4.30 ± 0.26 g/dL, P < 0.01). In addition, the serum high-density lipoprotein (HDL) was decreased significantly in patients compared to control groups (43.02 ± 8.15 mg/dL, P < 0.01). Moreover, triglyceride, low-density lipoprotein (LDL) and total cholesterol were not considerably increased in the patients. On the other hand, hematological parameters did not show a significant difference except for the mean corpuscular hemoglobin concentration (MCHC) level significantly lower in the victims than in the controls (33.48 ± 0.56 g/dL, P < 0.01). Finally, there were significant differences in total iron and ferritin levels in the groups. From this study, it was concluded that some of the victim's biochemical factors can be influenced owing to the long-term consequences of SM. From the similarity of functional test results of thyroid and hematology between groups, it is also stated that biochemical changes detected may be due to a patient's delayed respiratory complications.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Mustard Gas; Chemical Warfare Agents; Iraq
PubMed: 37213154
DOI: 10.14715/cmb/2022.69.1.11 -
Small (Weinheim An Der Bergstrasse,... Aug 2023The development of efficient metal-free photocatalysts for the generation of reactive oxygen species (ROS) for sulfur mustard (HD) decontamination can play a vital role...
The development of efficient metal-free photocatalysts for the generation of reactive oxygen species (ROS) for sulfur mustard (HD) decontamination can play a vital role against the stockpiling of chemical warfare agents (CWAs). Herein, one novel concept is conceived by smartly choosing a specific ionic monomer and a donor tritopic aldehyde, which can trigger linker-independent regioselective protonation/deprotonation in the polymeric backbone. In this context, the newly developed vinylene-linked ionic polymers (TPA/TPD-Ionic) are further explored for visible-light-assisted detoxification of HD simulants. Time-resolved-photoluminescence (TRPL) study reveals the protonation effect in the polymeric backbone by significantly enhancing the life span of photoexcited electrons. In terms of catalytic performance, TPA-Ionic outperformed TPD-Ionic because of its enhanced excitons formation and charge carrier abilities caused by the donor-acceptor (D-A) backbone and protonation effects. Moreover, the formation of singlet oxygen ( O ) species is confirmed via in-situ Electron Spin Resonance (ESR) spectroscopy and density functional theory (DFT) analysis, which explained the crucial role of solvents in the reaction medium to regulate the ( O ) formation. This study creates a new avenue for developing novel porous photocatalysts and highlights the crucial roles of sacrificial electron donors and solvents in the reaction medium to establish the structure-activity relationship.
PubMed: 37165579
DOI: 10.1002/smll.202302045 -
Small (Weinheim An Der Bergstrasse,... Sep 2023Developing effective catalysts to degrade chemical warfare agents is of great significance. Herein, a mesoporous MIL-101(Cr) composite material dangled with porphyrin...
Developing effective catalysts to degrade chemical warfare agents is of great significance. Herein, a mesoporous MIL-101(Cr) composite material dangled with porphyrin molecules (denote as TCPP@MIL-101(Cr), TCPP = tetra(4-carboxyphenyl)porphyrin) is reported, which can be used as a heterogeneous photocatalyst for detoxification of mustard gas simulants 2-chloroethyl ethyl sulfide (CEES) to 2-chloroethyl ethyl sulfoxide (CEESO) with a half-life of 1 min. The catalytic performance of TCPP@MIL-101(Cr) is comparable to that of homogeneous molecular porphyrin. Mechanistic studies reveal that both O and O are efficiently generated and play vital roles in the oxidation reaction. Gold nanoparticles (AuNPs) are attached to the TCPP@MIL-101(Cr) to further enhance the catalytic activity with a benchmark half-life of 45 s, which is the fastest record so far. A medical mask loaded TCPP@MIL-101(Cr) is fabricated for practical applications, which can selectively photoxidize CEES to CEESO under sunlight and air atmosphere, exhibiting the best degradation performance among the reported fabric-like composite materials.
PubMed: 37162490
DOI: 10.1002/smll.202301050 -
Experimental Eye Research May 2023Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various...
Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1 and 3, and weekly for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation and immunostaining were used to examine corneal cross-sections collected at the completion of follow-up. A biphasic ocular injury was observed in mice exposed to NM, most prominent in the corneal epithelium and anterior stroma. Following exposure, mice experienced central corneal epithelial erosions and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma. The epithelium was recovered by day 3, followed by exacerbated punctuate erosions alongside persistent stromal edema that arose and continued onward to four weeks post-exposure. The endothelial cell density was reduced on the first day after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at this time included dysmorphic basal epithelial cells, and in the limbal cornea included decreased cellular layers and p63 area, along with increased DNA oxidization. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas. Our research suggests DNA oxidation contributes to the long-term effects of nitrogen mustard on limbal stem cells.
PubMed: 37142048
DOI: 10.1016/j.exer.2023.109495 -
Small (Weinheim An Der Bergstrasse,... Sep 2023The tetratopic linker, 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H TBAPy) along with rare-earth (RE) ions is used for the synthesis of 9 isostructures of a metal-organic...
The tetratopic linker, 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H TBAPy) along with rare-earth (RE) ions is used for the synthesis of 9 isostructures of a metal-organic framework (MOF) with shp topology, named RE-CU-10 (RE = Y(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Tm(III), Yb(III), and Lu(III)). The synthesis of each RE-CU-10 analogue requires different reaction conditions to achieve phase pure products. Single crystal X-ray diffraction indicates the presence of a RE -cluster in Y- to Tm-CU-10, while a RE -cluster is observed for Yb- and Lu-CU-10. The photooxidation performance of RE-CU-10 analogues is evaluated, observing competition between linker-to-metal energy transfer versus the generation of singlet oxygen. The singlet oxygen produced is used to detoxify a mustard gas simulant 2-chloroethylethyl sulfide, with half-lives ranging from 4.0 to 5.8 min, some of the fastest reported to date using UV-irradiation and < 1 mol% catalyst, in methanol under O saturation.
PubMed: 37116124
DOI: 10.1002/smll.202302173 -
Experimental Eye Research Jun 2023The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite...
The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite clinical evidence of SM-exposure causing unexplained retinal deficits, there have been no animal studies conducted to examine the retinal toxicity of this vesciant. The cardinal hallmark of retinal response to stressors or injury is the activation of reactive gliosis, a cellular process largely governed by Müller glia. Previously we showed that corneal exposure to sodium hydroxide elicits rapid induction of reactive gliosis and results in retinal degeneration in a dose-related manner. Based on this evidence, we hypothesized that the vesicant nitrogen mustard (NM), an analog of SM, may also elicit reactive gliosis. To test this idea, we developed a mouse model of NM ocular injury and investigated corneal and retinal effects focusing on citrullination, a posttranslational modification (PTM) of proteins. This PTM was recently linked to alkali injury and has also been shown to occur in retinal degenerative conditions. Here, we demonstrate that corneal exposure to 1% NM causes a synchronous activation of citrullination in both the cornea and retina with hypercitrullination becoming apparent temporally and manifesting with altered cellular expression characteristics. A key finding is that ocular citrullination occurs acutely as early as 1-h post-injury in both the cornea and retina, which underscores a need for expeditious interception of this acute corneal and retinal response. Moreover, exploiting dose response and temporal studies, we uncoupled NM-induced retinal citrullination from its induction of retinal gliosis. Our findings demonstrate that hypercitrullination is a common corneo-retinal mechanism that sensitizes the eye to NM injury and suggests that counteracting hypercitrullination may provide a suitable countermeasure to vesicant injury.
Topics: Animals; Mice; Mechlorethamine; Irritants; Gliosis; Cornea; Eye Injuries; Retina; Mustard Gas; Retinal Diseases
PubMed: 37080381
DOI: 10.1016/j.exer.2023.109485