Wenhui Song

Evaluation of the antiepileptic activity of hesperidin via near-infrared fluorescence imaging based on viscosity.

Parkinson's disease (PD) is one of the major neurodegenerative diseases caused by complex pathological processes. As a signal molecule, formaldehyde is closely linked to nervous systems, but the relationship between PD and formaldehyde levels remains largely unclear. We speculated that formaldehyde might be a potential biomarker for PD. To prove it, we constructed the first near-infrared (NIR) lysosome-targeted formaldehyde fluorescent probe (named NIR-Lyso-FA) to explore the relationship between formaldehyde and PD. The novel fluorescent probe achieves formaldehyde detection in vitro and in vivo, thanks to its excellent properties such as NIR emission, large Stokes shift, and fast response to formaldehyde. Crucially, utilizing the novel probe NIR-Lyso-FA, formaldehyde overexpression was discovered for the first time in cellular, zebrafish, and mouse PD models, supporting our guess that formaldehyde can function as a possible biomarker for PD. We anticipate that this finding will offer insightful information for PD pathophysiology, diagnosis, medication development, and treatment.

Endoplasmic reticulum (ER) is sensitive to changes in the intracellular environment such as pH and viscosity, and slight changes may trigger stress response. Besides, different from apoptosis and necrosis, ferroptosis is the result of lipid peroxidation accumulation. There is evidence that ferroptosis is closely related to endoplasmic reticulum stress (ERS). However, the possible changes in the pH and viscosity of the ER during the ferroptosis process have not yet been studied. Therefore, we used a new type of ER-targeted dual-excitation fluorescent probe (DSPI-3) to investigate the possible changes of pH and viscosity of ER during the ferroptosis. The novel probe DSPI-3 exhibited a highly sensitive and selective response to pH and viscosity. During the bioimaging process, it was found that the ER acidified and viscosity increased during the ferroptosis process induced by erastin, while the cells treated with ferrostatin-1 did not alter significantly. In addition, when dithiothreitol (DTT) and erastin stimulated the cells at the same time, we discovered that ER was acidified considerably at short notice, but the pH was slightly increased in the later stage. Besides, the change of the viscosity enhanced slowly with the passage of time, and there was a noteworthy decline in the later stage, demonstrating that the DTT-induced ERS accelerated the process of ferroptosis. We hope that this unique fluorescent probe can provide an effective method for studying the relationship between ERS and ferroptosis.

Diabetes is closely related to the presence of excess HClO induced by endoplasmic reticulum stress.

1,4-Dithiothreitol (DTT) is a robust reducing agent that contributes significantly to the folding process of proteins and maintaining endoplasmic reticulum (ER) homeostasis. Abnormally high levels of DTT can lead to severe endoplasmic reticulum stress (ERS), which induces cell death. In addition, DTT can also hinder cell growth and enhance reactive oxygen species (ROS) production in the ER. Herein, an effective turn-on ER-targeting fluorescent probe, ER-DTT, was designed to image DTT for the first time. The probe ER-DTT was based upon naphthalimide as a fluorophore, p-toluenesulfonamide as an exceptional unit for ER-targeting, and sulfoxide as a response site for imaging DTT based on an intramolecular charge transfer (ICT) mechanism. Optical-response experiments showed that the probe ER-DTT had good selectivity and sensitivity for DTT. Furthermore, confocal microscopy indicated that ER-DTT was suitable for selectively targeting ER in living cells and could be implemented to recognize cellular DTT.

A novel NIF fluorescent probe, ZM-V, was designed, in which interior imidazole and benzopyrene moieties serve as rotators, which can spin around multiple C–C bonds in the conjugated skeleton.