Qingdao Municipal Hospital

JOURNAL/nrgr/04.03/01300535-202506000-00028/figure1/v/2024-08-08T040853Z/r/image-tiff The pathophysiology of Huntington’s disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington’s disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington’s disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS (a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2 inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington’s disease by activating nuclear factor erythroid 2-related factor 2, suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington’s disease.

Targeting oxidative phosphorylation of bacteria is a novel antibiotic strategy leading to rapid cell death as a result of respiration suppress. Herein, a conductive polymer termed polypyrrole (PPy) is used to short-circuit the electron transfer chain (ETC) of bacteria cells owing to its higher electron affinity to electrons than all of the electron carriers on ETC. A hydrogel is fabricated using PPy which is anticipated to seize electrons from ETC and inhibit respiration of bacteria cells. The results show that the prepared PPy hydrogel can mediate an effective direct current (DC) antibacterial therapy which greatly enhances intracellular reactive oxygen species (ROS) level of Escherichia coli (E. coli), suppresses respiration, induces apoptosis-like cell death of E. coli accompanied by chromosomal condensation and loss of structural integrity, and rapidly cleared E. coli infection in vivo. Taken into the photothermal property of PPy, a combined direct current-photothermal therapy is developed which can enhance bacteria-killing effects with the assistance of an 808 nm laser. Our findings provide a new antibiotic strategy with metabolic pathway as a target.