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Background: 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. Results: We noted that HMSCs-Ex showed better antioxidant abilities to attenuate SM-induced apoptosis. Furthermore, it was identified that HMSCs-Ex-derived miR-199a-5p played the vital role in reducing pneumonocyte oxidative stress. We observed that the overexpression of miR-199a-5p in HMSCs-Ex exerted protective effects against SM-induced oxidative injury by activating the NRF2 signaling pathway. Moreover, it was confirmed that Caveolin1 (CAV1) was the target gene regulated by miR-199a-5p. MiR-199a-HMSCs-Ex reduced CAV1 expression, leading to the upregulation of NRF2 and the activation of the NRF2 antioxidant signal pathway.Conclusions: MiR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signaling pathway.

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.

OBJECTIVE: To explore the pharmacologically active ingredients in Toujie Quwen granules (TJQW) for treatment of coronavirus disease 2019 (COVID-19) in light of systemic pharmacology. METHODS: We performed database search, literature mining and drug-like index screening to identify the bioactive components in TJQW, the positive drugs for disease treatment and their therapeutic targets. The core disease target was investigated based on the cross-linking interaction of the bioactive components, positive drug and potential disease target, and the target proteins at the key nodes were analyzed by GO and KEGG analyses. Based on the therapeutic targets for COVID-19, virtual screening was conducted to screen the compounds in TJQW and construct the network cross-linking the key bioactive molecules in TJQW, key node targets of the disease, and the related biological pathways. RESULTS: We identified 159 compounds in TJQW and obtained 18 core proteins based on the cross-linking of the bioactive components, positive drugs and disease targets. The key node targets consisted of 22 targets including the latest 4 COVID-19 proteins. Virtual screening results showed that at least 14 compounds could bind with the core disease target proteins. The material basis of TJQW for COVID-19 treatment was explained in multi-pathway, multi-component and multi-target perspectives. In terms of the structural characteristics of the compounds, we screened the top 30 molecules with strong binding with the target proteins, among which flavonoids were the predominant components. CONCLUSION: This investigation reveals the therapeutic mechanism of TJQW for COVID-19 involving multiple components, targets and pathways from the perspective of key bioactive molecules, disease key node targets and related biological pathways. We screened 30 active precursors from TJQW, which provides reference for the clinical application and further development of TJQW.