Dual-channel discrimination of two lethal chemical warfare agents using an ESIPT-ICT-based fluorescent probe.

Among all kinds of chemical warfare agents, only cyanide and nerve agents can cause massive mortality at low concentrations. In this work, a dual-channel fluorescent probe CWAs-Thia capable of detecting cyanide and nerve agents is presented. The two reactive recognition units, pyridine and the thiazole-2-carbonyl group, of the probe for cyanide and nerve agents, respectively, produced red and blue fluorescent responses, respectively, which were attributed to excited-state intramolecular proton transfer and intramolecular charge transfer. CWAs-Thia is the first probe that can selectively recognize cyanide and nerve agent. And it has proven to be effective in visualizing cyanide and nerve agents in living cells.

Visual detection and discrimination of nerve and blood agents using a dual-site fluorescent probe in living cells and mice.

Of all chemical warfare agents (CWAs), only nerve and blood agents cause massive mortality at low concentrations. To better detect and discriminate nerve and blood agents, a reliable detection method is desirable. We report a series of fluorescent probes for nerve and blood agent detection. Among the tested probes, SR-Pip detected nerve and blood agents quickly (within 10 s for nerve agents and 1 min for blood agents). SR-Pip coupled with nerve agent produced a weak orange fluorescence with good sensitivity [limit of detection (LOD)= 5.5 µM]. Upon reaction with blood agent, the fluorescence of SR-Pip changed from orange fluorescence to blue fluorescence with detection limits as low as 9.6 nM. This probe effectively visualised different concentrations of nerve agents in living cells and mice. A portable test kit using SR-Pip instantly detected nerve and blood agents. To the best of our knowledge, SR-Pip is the first fluorescent probe for nerve and blood agent detection.

Endothelium-Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury.

Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium-derived engineered extracellular vesicles (eEVs) that deliver microRNA-125b-5p (miRNA-125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell-targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA-125b is loaded into EVs. Finally, LET-EVs-miRNA-125b is constructed. The results show that compared to the EVs, miRNA-125b, and EVs-miRNA-125b, LET-EVs-miRNA-125b exhibit the most significant treatment efficacy in ALI. Moreover, LET-EVs-miRNA-125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET-EVs-miRNA-125b downregulates early growth response-1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET-EVs-miRNA-125b can treat ALI by protecting the endothelial barrier integrity.

In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design.

Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.

HMSCs exosome-derived miR-199a-5p attenuates sulfur mustard-associated oxidative stress via the CAV1/NRF2 signalling pathway.

Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell-derived exosomes (HMSCs-Ex). We noted that HMSCs-Ex-derived miR-199a-5p played a vital role in reducing pneumonocyte oxidative stress and apoptosis by reducing reactive oxygen species, lipid peroxidation products and increasing the activities of antioxidant enzymes in BEAS-2B cells and mouse models after exposure to SM for 24 h. Furthermore, we demonstrated that the overexpression of miR-199a-5p in HMSCs-Ex treatment induced a further decrease of Caveolin1 and the activation of the mRNA and protein level of NRF2, HO1 and NQO1, compared with HMSCs-Ex administration. In summary, miR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signalling pathway.

MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury.

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.

Fluorescent probes for the detection of chemical warfare agents.

Chemical warfare agents (CWAs) are toxic chemicals that have been intentionally developed for targeted and deadly use on humans. Although intended for military targets, the use of CWAs more often than not results in mass civilian casualties. To prevent further atrocities from occurring during conflicts, a global ban was implemented through the chemical weapons convention, with the aim of eliminating the development, stockpiling, and use of CWAs. Unfortunately, because of their relatively low cost, ease of manufacture and effectiveness on mass populations, CWAs still exist in today's world. CWAs have been used in several recent terrorist-related incidents and conflicts (e.g., Syria). Therefore, they continue to remain serious threats to public health and safety and to global peace and stability. Analytical methods that can accurately detect CWAs are essential to global security measures and for forensic analysis. Small molecule fluorescent probes have emerged as attractive chemical tools for CWA detection, due to their simplicity, ease of use, excellent selectivity and high sensitivity, as well as their ability to be translated into handheld devices. This includes the ability to non-invasively image CWA distribution within living systems (in vitro and in vivo) to permit in-depth evaluation of their biological interactions and allow potential identification of therapeutic countermeasures. In this review, we provide an overview of the various reported fluorescent probes that have been designed for the detection of CWAs. The mechanism for CWA detection, change in optical output and application for each fluorescent probe are described in detail. The limitations and challenges of currently developed fluorescent probes are discussed providing insight into the future development of this research area. We hope the information provided in this review will give readers a clear understanding of how to design a fluorescent probe for the detection of a specific CWA. We anticipate that this will advance our security systems and provide new tools for environmental and toxicology monitoring.

Evaluation and countermeasures of contracted services of Chinese family doctors from demanders' point of view - a case study of a city.

BACKGROUND: The "gatekeepers" for residents' health are their family doctors. The implementation of contracted services provided by family doctors is conducive to promoting hierarchical diagnosis and treatment and achieving the objective of providing residents comprehensive and full-cycle health services. Since its implementation in 2016, the contract service system for Chinese family doctors has yielded a number of results while also highlighting a number of issues that require further investigation. Consequently, the purpose of this study is to assess the impact of family doctors' contracted services in a Chinese city from the perspective of demanders (i.e., contracted residents), identify the weak links, and then propose optimization strategies. METHODS: In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. Take the PCAT-AS(Adult Short) scale revised in Chinese as the research tool to understand the medical experience of contracted residents in primary medical institutions, and interview some family doctors and residents to obtain more in-depth information. RESULTS: Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The types of contracting institutions, residents' age, marital status, occupation, and whether chronic diseases are confirmed are the influencing factors of PCAT scores. CONCLUSION: The family doctors' contracted services in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during non-working hours, incomplete service items, an imperfect referral system, and inadequate utilization of traditional Chinese medicine services, it is recommended that the government continue to enhance and increase its investment in relevant policies and funds. Primary medical institutions should improve the compensation mechanism for family doctors and increase their work enthusiasm, improve and effectively implement the two-way referral system, gradually form an orderly hierarchical pattern of medical treatment, provide diversified health services in accordance with their own service capacity and the actual needs of residents, and improve the utilization rate of traditional Chinese medicine services in primary medical institutions.

Rapid detection of nerve agents in environmental and biological samples using a fluorescent probe.

Nerve agents are highly toxic chemical warfare agents that are easy to synthesize and have recently been applied many times in local wars and terrorist attacks. Fluorescent probes have been widely used in life science and medical research due to their features of short reaction time, high sensitivity and good selectivity. Herein, two fluorescent compounds, NMU-1 and NMU-2, were synthesized for the selective detection of nerve agents. NMU-1 exhibited good detection performance for nerve agents. With increasing nerve agent concentration, the fluorescence signal of NMU-1 at 498 nm gradually decreased with an excellent linear relationship. NMU-1 exhibited a low LOD (4.6 µM for DCP and 8.41 µM for soman), a rapid response (less than 3 min) and a large Stokes shift (98 nm) along with obvious color changes. Due to its high sensitivity and good selectivity, NMU-1 was successfully applied to image nerve agents in living PC12 cells. Furthermore, NMU-1 was used as a key element to develop chemical warfare agent test paper, which exhibited significant fluorescent changes under hand-held 365-nm UV light upon contact with nerve agents.

BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis.

Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 µg/kg in 200 µL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 µg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelial barrier repair and may be an alternative approach to stem cell-based therapy.

Two birds with one stone: The detection of nerve agents and AChE activity with an ICT-ESIPT-based fluorescence sensor.

Nerve agents are among the world's deadliest poisons, and the target enzyme is acetylcholinesterase (AChE). To better diagnosis nerve agent poisonings, a reliable diagnostic method for both nerve agents and AChE is desirable. Herein, we synthesized a series of fluorescent sensors for both real nerve agents and acetylcholinesterase activity detection. Among these sensors, HBQ-AE exhibited a fast response rate (within 10 s for nerve agent and 8 min for AChE), good sensitivity (the limit of detection is 6 nM and 0.2 U/mL) and a high off/on contrast. To the best of our knowledge, HBQ-AE is the first fluorescence sensor for nerve agents and AChE activity detection. The fluorescent change of HBQ-AE from nonfluorescence to blue fluorescence (nerve agent) or orange fluorescence (AChE) by excitation at 365 nm can be easily observed with the naked eye. HBQ-AE was successfully applied to image nerve agents and AChE activity in living cells. Moreover, HBQ-AE is the vital member to construct a test paper that can be employed to detect and diagnose chemical warfare agents.

Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy.

Aflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

Development of a Series of Fluorescent Probes for the Early Diagnostic Imaging of Sulfur Mustard Poisoning.

Sulfur mustard is one of the most harmful chemical warfare agents and can induce skin, eye, and lung injuries. However, it is hard for medical stuff to diagnose sulfur mustard poisoning early because of the incubation period after sulfur mustard exposure. Detecting intact sulfur mustard in vivo might be an effective approach for the early diagnosis of sulfur mustard poisoning. A series of fluorescent probes for intact sulfur mustard detection were developed in this study. All of the developed probes could react with sulfur mustard selectivity. Among these probes, SiNIR-SM exhibited an extremely good response rate and a high off/on contrast. To the best of our knowledge, SiNIR-SM is the first near-infrared fluorescent probe for the sulfur mustard detection. Both SiNIR-SM and OxSM-1 were successfully applied to image sulfur mustard in living cells. Using SiNIR-SM, we found that sulfur mustard accumulates in the mitochondria of living cells. This result could provide a new insight for the treatment of sulfur mustard injuries. We also found that SiNIR-SM is suitable for the early diagnostic imaging of sulfur mustard poisoning in SKH-1 mice via the detection of intact sulfur mustard.

Indole alkaloids from Gelsemium elegans.

Five previously undescribed monoterpenoid indole alkaloids were isolated from the roots of Gelsemium elegans. Their structures with absolute configurations were elucidated by HRESIMS, X-ray diffraction, ECD spectra, and molecular modeling. 19,20-Epoxyhumantenine is a humantenine-type alkaloid with an epoxypropyl group at the C-20 position, (4R)-19-oxo-gelsevirine N4-oxide is a gelsemine-related alkaloid, and gelsedethenine is a gelsedine-type alkaloid with a butenyl group at the C-20 position. Moreover, 10,11-dimethoxy-N1-demethoxy-gelsemamide is an open-loop indole alkaloid and 11-demethoxy-gelsemazonamide is an aromatic azo-linked dimeric indole alkaloid. Among the five alkaloids, (4R)-19-oxo-gelsevirine N4-oxide and 10,11-dimethoxy-N1-demethoxy-gelsemamide exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophage cells, with IC50 values of 6.18 ±â€¯1.07 and 12.2 ±â€¯1.02 µM, respectively.

The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard.

BACKGROUND: Sulfur mustard (SM) is a notorious chemical warfare agent that can cause severe acute lung injury (ALI), in addition to other lesions. Currently, effective medical countermeasures for SM are lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs) possess self-renewal and multipotent differentiation capacity. BMSCs can also migrate to inflammation and injury sites and exert anti-inflammatory and tissue repair functions. Here, we report the curative effect of BMSCs on SM-induced ALI in a mouse model. METHODS: Mice BMSCs were injected into mice via the tail vein 24 h after SM exposure. The distribution of BMSCs in mice was detected by fluorescence imaging. The therapeutic potential of BMSCs was evaluated by the calculating survival rate. The effects of BMSCs on lung tissue injury and repair assessment were examined by staining with H&E and measuring the lung wet/dry weight ratio, BALF protein level, and respiratory function. The effects of BMSCs on the infiltration and phenotypic alteration of inflammatory cells were analyzed by immunohistochemistry and flow cytometry. The levels of chemokines and inflammatory cytokines were examined using the Luminex Performance Assay and ELISA. RNA interference, western blotting, and ELISA were applied to explore the role of the TLR4 signaling pathway in the anti-inflammatory effects of BMSCs. The extent of tissue repair was analyzed by ELISA, western blotting, and immunohistochemistry. RESULTS: Fluorescence imaging indicated that the lung is the major target organ of BMSCs after injection. The injection of BMSCs significantly improved the survival rate (p < 0.05), respiratory function, and related lung damage indexes (wet/dry weight ratio, total proteins in BALF, etc.) in mice. BMSC administration also reduced the level of pro-inflammatory cytokines, chemokines, and inflammatory cell infiltration, as well as affected the balances of M1/M2 and Th17/Treg. Furthermore, solid evidence regarding the effects of BMSCs on the increased secretion of various growth factors, the differentiation of alveolar epithelial cells, and the enhancement of cell barrier functions was also observed. CONCLUSION: BMSCs displayed protective effects against SM-induced ALI by alleviating inflammation and promoting tissue repair. The present study provides a strong experimental basis in a mouse model and suggests possible application for future cell therapy.

Protective effects of polydatin against sulfur mustard-induced hepatic injury.

Sulfur mustard (SM) is a chemical warfare agent that was applied in a series of military conflicts and still poses a severe threat to civilians and military personnel. Although the cellular and molecular mechanisms of SM toxicity are still not fully understood, oxidative stress has been considered as the initial vital process for damage. Polydatin, the product of resveratrol and glucose, is a promising candidate for the treatment of oxidative stress-related diseases. However, its effects on SM-induced hepatic injury remain unknown. Thus, we investigated the protective effects of polydatin against SM-induced hepatic injury and its possible mechanism. We found that treatment with polydatin remarkably improved the survival rate of mice bear subcutaneously injected with SM. Polydatin decreased the SM-induced increase of serum aminotransferase levels and ameliorated hepatic pathological damage. We also found that indexes of oxidative stress were improved in mouse liver samples and L02 cells. Meanwhile, changes in the Sirtuin family after treatment with SM were explored in mice and cells since polydatin is a potent activator of Sirt1 and Sirt3. Polydatin significantly increased the expression of Sirt1, HO-1, and NQO1; and the nuclear translocation of Nrf2 in mouse liver and L02 cells. Furthermore, we also observed that either Sirt1 or Nrf2 knockdown abolished the protective effect of polydatin. Our data indicated that polydatin could provide protection against SM-induced hepatic injury through the Sirt1/Nrf2 pathway, suggesting that polydatin is a novel potential antidote for sulfur mustard.

An off-on fluorescent probe for the detection of mitochondria-specific protein persulfidation.

Protein persulfidation is a newly defined oxidative posttranslational modification and plays important roles in many biological processes. Detection of protein persulfidation in living systems is urgently needed to advance the study of H2S/H2Sn-based signalling and cellular redox regulation. Here, we developed a novel off-on fluorescent probe for the detection of persulfidation using a chemical sensor, HQO-SSH, in biological systems. HQO-SSH features fast reaction, good selectivity and high sensitivity. Due to the distinctive features of HQO-SSH, this probe was successfully applied to image protein persulfidation changes in pulmonary cells. We also demonstrated that the probe is suitable for imaging protein persulfidation in lung tissues. In addition, confocal imaging with this method revealed that sulfur mustard, a commonly used chemical warfare agent, decreased mitochondrial protein persulfidation in living lung cells and tissues. Due to these results, this probe holds great promise for exploring the role of protein persulfidation in a variety of pathophysiological conditions.

Advanced biotherapy for the treatment of sulfur mustard poisoning.

CONTEXT: Sulfur mustard (SM), a bifunctional alkylating agent, can react with a variety of biochemical molecules (DNA, RNA, proteins and other cell components) to cause a series of serious health issues or even death. Although a plethora of research has been done, the pathogenesis of SM poisoning has yet to be fully understood due to its high complexity. As a consequence, a specific antidote has not yet been developed and the treatment of SM poisoning remains a medical challenge. In recent years, various biological products and cell transplantation in the treatment of SM poisoning offered a significant clinical treatment progress. By highlighting these and other research studies, we hereby summarize the progress in this field in an effort to provide useful information on the clinical treatment of SM poisoning. OBJECTIVE: This review summarizes the major advances of SM poisoning therapy by means of biological products (peptide and protein drugs, polysaccharides drugs, nucleic acid drugs, etc.), and cell transplantation (e.g., bone marrow, limbal stem cells, mesenchymal stem cells), as well as other relevant biotherapeutic approaches. METHOD: We searched the database PubMed for published domestic and international articles using web based resources for information on histological, immunochemical, ultrastructural, and treatment features of SM-induced manifestations in both animal models and human tissues. To this end, we applied keywords containing mustard gas, chemical warfare, SM, eye, lung and skin. RESULTS AND CONCLUSION: Our review provides a comprehensive understanding of the advances of available biotherapies in SM poisoning, and its potential for the treatment of SM-induced injuries. Potentially, our review will provide new insights for future research studies in this field.

Neglected role of hydrogen sulfide in sulfur mustard poisoning: Keap1 S-sulfhydration and subsequent Nrf2 pathway activation.

Sulfur mustard (SM) is a chemical warfare agent and a terrorism choice that targets various organs and tissues, especially lung tissues. Its toxic effects are tightly associated with oxidative stress. The signaling molecule hydrogen sulfide (H2S) protects the lungs against oxidative stress and activates the NF-E2 p45-related factor 2 (Nrf2) pathway. Here, we sought to establish whether endogenous H2S plays a role in SM induced lesion in mouse lungs and lung cells and whether endogenous H2S plays the role through Nrf2 pathway to protect against SM-induced oxidative damage. Furthermore, we also explored whether activation of Nrf2 by H2S involves sulfhydration of Kelch-like ECH-associated protein-1 (Keap1). Using a mouse model of SM-induced lung injury, we demonstrated that SM-induced attenuation of the sulfide concentration was prevented by NaHS. Concomitantly, NaHS attenuates SM-induced oxidative stress. We also found that H2S enhanced Nrf2 nuclear translocation, and stimulated expression of Nrf2-targeted downstream protein and mRNA levels. Incubation of the lung cells with NaHS decreased SM-induced ROS production. Furthermore, we also found that H2S S-sulfhydrated Keap1, which induced Nrf2 dissociation from Keap1, and enhanced Nrf2 nuclear translocation. Our data indicate that H2S is a critical, however, being long neglected signal molecule in SM-induced lung injury.

A highly selective and sensitive near-infrared fluorescent probe for imaging of hydrogen sulphide in living cells and mice.

Hydrogen sulphide (H2S), the third endogenous gaseous signalling molecule, has attracted attention in biochemical research. The selective detection of H2S in living systems is essential for studying its functions. Fluorescence detection methods have become useful tools to explore the physiological roles of H2S because of their real-time and non-destructive characteristics. Herein we report a near-infrared fluorescent probe, NIR-HS, capable of tracking H2S in living organisms. With high sensitivity, good selectivity and low cytotoxicity, NIR-HS was able to recognize both the exogenous and endogenous H2S in living cells. More importantly, it realized the visualization of endogenous H2S generated in cells overexpressing cystathionine ß-synthase (CBS), one of the enzymes responsible for producing endogenous H2S. The probe was also successfully applied to detect both the exogenous and endogenous H2S in living mice. The superior sensing properties of the probe render it a valuable research tool in the H2S-related medical research.