As the most abundant nonprotein biothiol in living cells, glutathione (GSH) prevents cellular components from oxidative damage and maintains the intracellular redox homeostasis. For further exploring whether GSH can be employed as a bioindicator to discriminate tumor lesion at a cellular level, the highly selective detection and accurate quantification of GSH under pathological conditions are critical. Herein, we design a coumarin derivative-based two-photon fluorescent probe Cou-Br for the detection of GSH in living cells, mice models, and clinical specimens. The prepared probe is capable of sensitively and selectively detecting GSH in complex biological systems. Cou-Br displays a good linear relationship in response to GSH and a low limit of detection. With the fluorescence signal positively associated with intracellular GSH levels, the probe enables real-time imaging of GSH in various cell lines. Under the condition of CS 2 stimulation, Cou-Br can rapidly respond to the fluctuation of intracellular GSH induced by oxidative damage. Furthermore, the in situ and in vivo bioimaging performances of Cou-Br are demonstrated. Typically, relying on the different cellular concentrations of GSH, the probe is successfully employed to identify the human laryngeal cancer lesion with outstanding capabilities of deep tissue imaging and tumor margin recognition. We assume that the abnormal expression level of GSH may be utilized as a potential bioindicator to discriminate tumor tissues from the surrounding disease-free tissues. To conclude, the proposed probe Cou-Br may potentially serve as a powerful chemical tool for the surgical navigation of cancer in clinic.
Chronic rhinosinusitis (CRS) is a complex condition brought on for many reasons, and its prevalence is rising gradually around the world. Xanthii Fructus (XF) has been used in the treatment of CRS for decades and is effective. The chemical and pharmacological profiles of XF, on the other hand, are still unknown and need to be clarified. The potential mechanisms of XF in CRS treatment were investigated using a network pharmacology approach in this study. OB and DL were in charge of screening the bioactive components in XF and drug-likeness. TCMSP and PubChem databases were used to identify prospective XF proteins, whereas GeneCards and the DisGeNET database were used to identify potential CRS genes. An interactive network of XF and CRS is built using the STRING database based on common goals identified by the online tool Venny. Cytoscape was used to visualize the topological characteristics of nodes, while the biological function pathways were identified by GO Knowledge Base, KEGG. There were 26 bioactive components and 115 potential targets in XF that bind to CRS or are considered therapeutically relevant. Five significant signaling pathways have been found for CRS by the pathway analysis including the HIF-1 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and PI3K-Akt signaling pathway. We simultaneously confirmed that the PI3K-Akt pathway promotes the development of CRS. Finally, this study took a holistic approach to the pharmacological actions and molecular mechanisms of XF in the treatment of CRS. TNF, INS, CCL2, CXCL8, IL-10, VEGFA, and IL-6 have all been identified as potential targets for anti-inflammatory and immune-boosting effects. This network pharmacology prediction could be useful in manifesting the molecular mechanisms of the Chinese herbal compound XF for CRS.
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