FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Hongli Zhang,Ziyu Lan,Hui Wang,Haojie Yao,Ruiyan Zheng,Zijing Chen,Xiang Luo,Peng Wu,Yuanyuan Cheng,Zhongqiu Liu
Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, characterized by a complex clinical syndrome. Pubescenoside A (PBA), a phenylpropanoid derived from Ilex pubescens , exhibits significant anti-inflammatory effects; however, the impact and underlying mechanism of PBA on UC remain unclear. Therefore, the aim of this study is to investigate the potential mechanism of PBA against UC using in vivo and in vitro experiments. Pubescenoside A effectively enhances weight loss in UC mice, decreases the disease activity index (DAI). Regarding colonic morphology, PBA ameliorates colorectal stenosis and shortening, reduces intestinal mucosal ulceration, diminishes inflammatory cell infiltration, and tends to normalize glandular arrangement. Furthermore, PBA effectively suppresses pro-inflammatory factors. Mechanism studies have shown that PBA can directly target Kelch Like ECH Associated Protein 1 (Keap1), subsequently promoting the interaction between Keap1 and DEAD-box RNA helicase 5 (DDX5) to enhance ubiquitination and degradation of DDX5, leading to a down-regulation of C-C motif chemokine ligand 3 (CCL3) expression. Additionally, PBA disrupts the Keap1/Nrf2 complex, facilitating Nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear entry to inhibit the Nuclear factor-κB (NF-κB) pathway. Importantly, in Gpt-lgr5-creERT2 Keap1 flox/flox mice, the anti-UC effect of PBA was attenuated. Our results indicated that PBA mitigated UC by targeting Keap1, thereby promoting the ubiquitination degradation of DDX5 and facilitating the nuclear entry of Nrf2.
研究领域:
药理学
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分子生物学
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免疫学
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胃肠病学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Cell Stem Cell
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2017
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IF 23.394
Huanhuan Li,Ping Lai,Jinping Jia,Yawei Song,Qing Xia,Kaimeng Huang,Na He,Wangfang Ping,Jiayu Chen,Zhongzhou Yang,Jiao Li,Mingze Yao,Xiaotao Dong,Jicheng Zhao,Chunhui Hou,Miguel A. Esteban,Shaorong Gao,Duanqing Pei,Andrew P. Hutchins,Hongjie Yao
Summary RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Ryb p upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b , a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.
研究领域:
分子生物学
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干细胞研究
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表观遗传学
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DOI
PubMed
高影响因子
BMEMat
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2026
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IF 17.2
Kairui Liu,Bo Zhang,Yue Wan,Zhiru Yang,Abdusami Abdurahman,Mengxin He,Shengtao Hu,Yi Zhang,Xiaoke Li,Jin Chang,Jun Kang,Liren Liu,Wanghua Liu,Shao Li
Hepatocellular carcinoma (HCC), ranking as the third leading cause of cancer-related mortality globally, continues to pose significant therapeutic challenges. Here, we developed an innovative nanosystem, Phl@PT, based on Pt-TiO 2 nanoparticles for the co-delivery of Phlorezin, presenting a novel approach for HCC treatment through sonodynamic therapy (SDT). Phl@PT demonstrated remarkable efficacy in inducing mitochondrial membrane potential collapse and cristae damage in vitro. Transcriptomic sequencing analysis revealed that Phl@PT treatment led to the downregulation of key genes: CLDN6 , involved in the cell adhesion molecules pathway, and BCKDHB and SUCLG2 , associated with propanoate metabolism. Through a comprehensive target fishing strategy combined with Bio-Layer Interferometry analysis, we identified DDX5, a DEAD-box RNA helicase, as a novel target protein of Phlorezin, which plays a crucial role in tumor progression and prognosis. In vivo studies demonstrated that US-activated Phl@PT not only effectively inhibited HCC growth in murine models but also activated CD8 + /CD4 + T cells, promoted dendritic cell maturation, and enhanced the expression of key immune cytokines including TNF-α, IL-12, and IFN-γ, thereby establishing a robust immunotherapeutic response. Collectively, our findings demonstrate that the Pt-TiO 2 mesoporous nanoagent co-delivering phlorezin represents a promising therapeutic platform for HCC treatment through synergistic sonodynamic-chemo-immunotherapy.
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产品关联
DOI
高影响因子
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