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1.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 8-14, 2022.
Artículo en Chino | WPRIM | ID: wpr-1015732

RESUMEN

Autophagy is a lysosomal-dependent catabolic pathway that is widely present in eukaryote andinvolved in multiple biological functions, such as cytodifferentiation, starvation tolerance and immunedefense. Specially, the autophagy process that recognizes and eliminates intracellular pathogens is definedas xenophagy, which is a vital way for immune cells to execute host defense. However, pathogens haveevolved several strategies to cope with xenophagy via distinct types of virulence factors (effectors, surfaceproteins, etc.). Studies have shown that the autophagy regulatory signals are sophisticated, which areprecisely directed by a variety of autophagy related proteins (ATG proteins). It has been proved that thekey steps of autophagy undergo extensive protein post-translational modifications (PTMs), such asphosphorylation/ dephosphorylation, and ubiquitination/ deubiquitination, etc. These modifications endowthe autophagy regulation with a high degree of dynamics and reversibility via affecting the structure, stability, activity and location of the proteins. Recently, some virulence factors were found to hijackPTMs of the ATG proteins and then affect host autophagy related pathways, thereby resisting xenophagyand promoting pathogens’ survival in the host cell. This review summarizes the current knowledge ofPTMs in xenophagy, especially the mechanisms that pathogens manipulate host xenophagy through PTMs, providing a guidance for exploring xenophagy intervention strategies and controlling infectious diseases.

2.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 432-441, 2021.
Artículo en Inglés | WPRIM | ID: wpr-881084

RESUMEN

Esculetin, a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini, has a variety of pharmacological effects, especially in anti-inflammation. However, it is not clear whether esculetin has a therapeutic effect on sepsis. This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis. The results showed that the lung injury was significantly relieved with the treatment of esculetin, accompanied with the restrained production of inflammatory factors including IL-1β, IL-6, TNF-α, CCL2 and iNOS during the early phase of E.coli-induced sepsis. Of note, activation of NF-κB and STAT1/STAT3 signals, the main upstream signals of many inflammatory factors, were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage. These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect, which was at least partly due to its inhibition on NF-κB and STAT1/STAT3 signaling pathway in macrophage. Thus, esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.

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