Biology subjects

jiang, x.

Publications and source records attributed to jiang, x..

3 recordsLinked to original sources

bioRxiv2026

Metformin promotes broad neuroprotection and proteostatic resilience via rngo/DDI2 stabilisation

Alzheimers disease (AD) is one of the most common age-related causes of death, with limited effective disease-modifying treatments. Although metformin shows promise as a disease-modifying agent for AD, its molecular mechanism--specifically how it confers neuroprotection despite potentially increasing amyloid-beta (A{beta}) load--remains obscure. Here, we demonstrate that metformin functions as a pharmacological activator of the ubiquitin-binding protease rngo/DDI2. Through a genetic screen in Drosophila, we identified rngo/DDI2 as a potent suppressor of A{beta} toxicity. We provide in silico and genetic evidence that metformin interacts with the conserved D257 residue of the rngo/DDI2 RVP domain, inducing homodimerisation and subsequent protein stabilisation. This activation boosts proteasome activity in the presence of A{beta} preferentially clearing highly abundant proteins to preserve proteostasis. Crucially, this intervention is broadly effective; rngo/DDI2 upregulation robustly suppresses toxicity in models of TDP-43 and C9orf72-repeat expansion pathology, indicating a generalised mechanism of neuroprotection. Supported by human iPSC data and evidence of DDI2 depletion in AD patient brains, our results identify rngo/DDI2 as a conserved regulator of neuronal resilience. We propose that directly targeting DDI2 stabilisation represents a novel, broadly applicable therapeutic strategy to counteract proteotoxic stress across a broad spectrum of neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Integrating Network Pharmacology And Experimental Verification To Explore The Mechanism Of Qionggui Power Against Atherosclerosis

Qionggui Power (QP), a classic prescription in Traditional Chinese Medicine (TCM), has shown potential in the treatment of atherosclerosis during the past decades. However, the mechanism that mediates these cardiovascular benefits remains to be fully elucidated. Here, we investigated the effects and mechanisms of QP against atherosclerosis with network pharmacology approaches and in vitro model. The active ingredients and related targets of QP were collected from public databases. The hub targets and signaling pathways of QP against AS were defined by extensive application of bioinformatics approaches, including the protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). The predicted major targets were validated in LPS-stimulated murine macrophages RAW264.7. The anti-inflammatory properties of QP were also evaluated in this model. In silico investigation of QP resulted in the identification of 18 active ingredients and 49 chemical targets intersecting with AS-related genes. And KEGG pathway analysis revealed a high enrichment in the Lipid and Atherosclerosis pathway of these chemical targets. Biochemical analysis showed marked effects of QP on the expression of predicted chemical targets (PPARr, CAT, PTGS2) and LPS-induced inflammatory genes (IL1, IL6, and TNF). And these inhibitory effects were linked to the suppression of the NF-{kappa}B signaling pathway, which was activated by the LPS stimulus. Our findings revealed the therapeutic potential of QP in the prevention and treatment of atherosclerosis. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

pharmacology and toxicology↗

bioRxiv2019

Dynamic response of RNA editing to temperature in Grape by RNA deep-sequencing

RNA editing is a post-transcriptional process of modifying genetic information on RNA molecules, which provides cells an additional level of gene expression regulation. Unlike mammals, in land plants, RNA editing converts C to U residues in organelles. However, its potential role in response to different stressors (heat, salt and so on) remains unclear. Grape is one of the most popular and economically important fruits in the world, and its production, like other crops, must deal with abiotic and biotic stresses, which cause reductions in yield and fruit quality. In our study, we tested the influence of the environmental factor temperature on RNA processing in the whole mRNA from grape organelle. In total, we identified 123 and 628 RNA editing in chloroplast and mitochondria respectively with the average editing extent nearly ~60%. The analyses revealed that number of non-synonymous editing sites were higher than that of synonymous editing sites, and the amino acid substitution type tend to be hydrophobic. Additionally, the overall editing level decreased with the temperature rises, especially several gene transcripts in chloroplast and mitochondria (matK, ndhB etc.). 245 sites were furthermore determined as stress-responsive sites candidates. We also found that the expression level of PPR genes decreased with the temperature rises, which may contribute to the loss of RNA editing at high temperature. Our findings suggest that the RNA editing events are very sensitive to high temperature, the changes of amino acid in these genes may contribute to the stress adaption for grape.

plant biology↗