Friend or foe: The role of stress granule in neurodegenerative disease.

Stress granules (SGs) are dynamic membraneless organelles that form in response to cellular stress. SGs are predominantly composed of RNA and RNA-binding proteins that assemble through liquid-liquid phase separation. Although the formation of SGs is considered a transient and protective response to cellular stress, their dysregulation or persistence may contribute to various neurodegenerative diseases. This review aims to provide a comprehensive overview of SG physiology and pathology. It covers the formation, composition, regulation, and functions of SGs, along with their crosstalk with other membrane-bound and membraneless organelles. Furthermore, this review discusses the dual roles of SGs as both friends and foes in neurodegenerative diseases and explores potential therapeutic approaches targeting SGs. The challenges and future perspectives in this field are also highlighted. A more profound comprehension of the intricate relationship between SGs and neurodegenerative diseases could inspire the development of innovative therapeutic interventions against these devastating diseases.

Hyaluronic acid modified extracellular vesicles targeting hepatic stellate cells to attenuate hepatic fibrosis.

RATIONALE: Transforming growth factor-beta1 (TGF-ß1) plays a pivotal role in promoting hepatic fibrosis, pirfenidone (PFD) could inhibit TGF-ß1 signaling pathway to alleviate hepatic stellate cells (HSC) activation mediated hepatic fibrosis. The targeting delivery strategy of PFD to hepatic stellate cells is a challenge. Extracellular vesicles (EVs), cell-derived membranous particles are intraluminal nano-vesicles that play a vital role in intercellular communication, they also be considered as an ideal nano-carrier. METHODS: In this study, we developed a target strategy to deliver PFD to HSC with CD44 over-expression by EVs, hyaluronic acid (HA) modified DSPE-PEG2000 endows the active targeting ability of activated HSCs to PFD-loaded EVs. RESULTS: In both rat hepatic stellate cell line HSC-T6 and rat hepatocyte cell line BRL, HA@EVs-PFD demonstrated the capacity to down-regulate the expression of collagen-synthesis-related proteins and showed superior inhibition efficacy of HSC-T6 activation compared to free PFD. In hepatic fibrosis model, 4 weeks of HA@EVs-PFD treatment resulted in a reduction in liver collagen fibers, significant improvement in hepatic cell morphology, and amelioration of hepatic fibrosis. CONCLUSIONS: HA@EVs-PFD, as a drug delivery system that effectively targets and inhibits activated HSCs to treat hepatic fibrosis, holds promise as a potential therapeutic agent against hepatic fibrosis.