Integrative transcriptome-proteome approach reveals key hypoxia-related features involved in the neuroprotective effects of Yang Xue oral liquid on Alzheimer's and Parkinson's disease.

Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action.

Cynaroside protects the blue light-induced retinal degeneration through alleviating apoptosis and inducing autophagy in vitro and in vivo.

BACKGROUND: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear. PURPOSE: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo. STUDY DESIGN/METHODS: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn. RESULTS: Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 µg/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-κB and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo. CONCLUSION: Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.