A cysteine-triggered fluorogenic donor base on native chemical ligation for tracking H2S delivery in vivo.

A hydrogen sulfide (H2S) donor is a fundamental molecular tool used as an exogenous source in biological studies and therapies. However, finding a controllable and visual fluorescent H2S donor is difficult. We report a new H2S donor, HSD560, the H2S release of which is triggered by cysteine. Importantly, the H2S generation is accompanied with enhanced green fluorescence, which could be utilized to track H2S release in cells using microscopy. H2S release from HSD560 undergoes a non-enzymatic native chemical ligation (NCL) process, which provides an accurate match with activated fluorescence and localization of H2S in zebrafish.

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy.

BACKGROUND: Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer's disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. RESULTS: PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. CONCLUSION: PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

Photo-controlled and photo-calibrated nanoparticle enabled nitric oxide release for anti-bacterial and anti-biofilm applications.

After numerous efforts to elucidate the biological role of nitric oxide (NO), NO treatments have become a hotspot at the forefront of medicine. NO-releasing substances are constantly needed, while the direct use of NO gas is unattainable in bio-systems. An ideal NO donor should possess controllable and visible NO-release capability. The reported NO donating nanoparticles, prepared via encapsulating a hydrophobic NO-releasing compound into DSPE-PEG2000, meet the criteria mentioned previously. The localization and flux of NO released from these nanoparticles could be manipulated by UV or blue light. Meanwhile, NOD-NPs emit a dose-dependent fluorescence intensity to calibrate the generation of NO. While the good biocompatibility of NOD-NPs has been validated, the NO from our nanoparticles demonstrates efficient anti-bacterial and anti-biofilm effects toward Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Therefore, the NOD-NPs developed in this work have potential application in evaluating the regulation of microbes by NO.