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The Journal of the Royal College of... Jun 2023The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and...
The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and in foundational insights into the molecular basis of development. From the 1930s until today, researchers at the University of Edinburgh have used to tackle questions in basic and biomedical science. Here the history of the initial decades of this research is explored, beginning with the introduction of research to Edinburgh by Francis Albert Eley Crew, in the newly established Institute of Animal Genetics. This period of research includes the discovery that chemicals can cause genetic mutation. This was demonstrated by research of the effects of mustard gas on flies by Charlotte Auerbach and colleagues, guided by the future Nobel laureate Hermann Muller. research was also formative in Conrad Hal Waddington's conceptual thinking about developmental biology, including in his vision of the epigenetic landscape. This holistic, systems-level view of the control of development was far before its time and has continued to be influential to this day in our conceptualisation of developmental biology and in the increasingly important field of systems biology. Waddington's experiments with in Edinburgh also gave rise to the evolutionary concept of genetic assimilation, in which an environmentally induced phenotype subsequently becomes genetically encoded.
Topics: Animals; Drosophila; Drosophila melanogaster; Phenotype; Biological Evolution; Mutation
PubMed: 36927337
DOI: 10.1177/14782715231162675 -
International Journal of Preventive... 2016Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main... (Review)
Review
BACKGROUND
Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings.
METHODS
The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed.
RESULTS
Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma.
CONCLUSIONS
SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure.
PubMed: 27280012
DOI: 10.4103/2008-7802.182733 -
Iranian Journal of Allergy, Asthma, and... Sep 2023Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA...
Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.
PubMed: 37767679
DOI: 10.18502/ijaai.v22i4.13609 -
The British Journal of Ophthalmology Jul 1940
PubMed: 18169706
DOI: 10.1136/bjo.24.7.370 -
Iranian Journal of Pathology 2022Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of...
BACKGROUND & OBJECTIVE
Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of mustard-exposed cornea after more than 30 years.
METHODS
Fourteen corneas after Lamellar keratoplasty were evaluated in this study. Corneal tissues were prepared by histologic methods and stained by H&E.
RESULTS
The main histopathological findings in these cases were the presence of severe stromal edema and corneal scar. In the sections with visible superficial epithelium, subepithelial bullae formation was observed. Focal or diffuse disruption of Bowman's membrane and replacement with fibrosis were also seen. There was no evidence of stromal vascularization and inflammation in all specimens.
CONCLUSION
After more than 30 years, an extensive corneal scar is seen in sulfur mustard exposed patients. Scar tissue without vascularization and fibroblastic proliferation is the main finding in the sulfur mustard exposed cornea. This pathology result is different from other scars. No evidence of inflammation or immune cell infiltration should be considered in managing DMGK.
PubMed: 36247510
DOI: 10.30699/IJP.2022.538950.2722 -
Tanaffos 2017Today, a host of veterans who were exposed to mustard gas suffer from substantially poor quality of life (QoL). However, factors that influence these patients' QoL have...
BACKGROUND
Today, a host of veterans who were exposed to mustard gas suffer from substantially poor quality of life (QoL). However, factors that influence these patients' QoL have not been yet scrutinized. QoL is deemed as a crucial construct that demands careful attention during evaluation as well as intervention. The present study aimed to delve into the physical, mental, and social factors that affect the QoL of mustard gas victims.
MATERIALS AND METHODS
All the physical, mental, and social parameters that influence the QoL of mustard gas victims were scrutinized through a systematic review. We searched for Persian and English scientific databases, i.e., PubMed, Scopus, and Google Scholar, and national databanks, namely SID, IranMedex, and Magiran to identify studies related to chemical victims conducted up to the end of 2015. Next, the quality of 21 articles and studies were assessed using the checklist of the National Institute of Health (NIH), and subsequently, 13 articles were selected for the stages of data extraction and analysis.
RESULTS
Findings revealed that, among the physical factors, coexistence of several medical conditions caused by chemical injury and the severity of the chemical injury had the greatest impact on the QoL of chemically injured veterans. Besides, suffering from psychological and neurological disorders, along with educational level and employment status, were the most influential psychosocial parameters that influenced veterans' QoL.
CONCLUSION
The review conducted herein identified the physical and psychosocial factors affecting the QoL of mustard gas victims. In fact, it is the first to present a large collection of descriptive information on QoL contributors in a systematic and orderly fashion.
PubMed: 29308076
DOI: No ID Found -
Sensors (Basel, Switzerland) Jul 2022On-site detection and initial identification of chemical warfare agents (CWAs) remain difficult despite the many available devices designed for this type of analysis.... (Review)
Review
On-site detection and initial identification of chemical warfare agents (CWAs) remain difficult despite the many available devices designed for this type of analysis. Devices using well-established analytical techniques such as ion mobility spectrometry, gas chromatography coupled with mass spectrometry, or flame photometry, in addition to unquestionable advantages, also have some limitations (complexity, high unit cost, lack of selectivity). One of the emerging techniques of CWA detection is based on acoustic wave sensors, among which surface acoustic wave (SAW) devices and quartz crystal microbalances (QCM) are of particular importance. These devices allow for the construction of undemanding and affordable gas sensors whose selectivity, sensitivity, and other metrological parameters can be tailored by application of particular coating material. This review article presents the current state of knowledge and achievements in the field of SAW and QCM-based gas sensors used for the detection of blister agents as well as simulants of these substances. The scope of the review covers the detection of blister agents and their simulants only, as in the available literature no similar paper was found, in contrast to the detection of nerve agents. The article includes description of the principles of operation of acoustic wave sensors, a critical review of individual studies and solutions, and discusses development prospects of this analytical technique in the field of blister agent detection.
Topics: Blister; Chemical Warfare Agents; Humans; Nerve Agents; Quartz Crystal Microbalance Techniques; Sound
PubMed: 35957163
DOI: 10.3390/s22155607 -
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 -
Disaster Medicine and Public Health... Oct 2023To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and...
Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin.
PURPOSE
To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and lung: Consideration of models, mechanisms, organ systems, and medical countermeasures."
METHODS
Summary on topics includes: (1) an overview of the radiation and chemical countermeasure development programs and missions; (2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses.
RESULTS
There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, US Government program officials, and regulators to discuss lung-, and skin- specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries.
CONCLUSIONS
Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall US Government emergency preparedness.
Topics: Animals; Humans; Mustard Gas; Lung; Skin; Burns, Chemical; Biomarkers
PubMed: 37852927
DOI: 10.1017/dmp.2023.176 -
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