时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
We tested the ability of OPR to release GP at different times under SGF or simulated intestinal fluid (SIF) (pH = 6.5, SIF) using high‐performance liquid chromatography‐mass spectrometry (LC‐MS), respectively.；To further validate the mechanism of OPR targeting against IBD lesion sites, we investigated the in vitro adhesion ability of OPR to TF protein and MUC2 protein.；PCoA, principal co‐ordinates analysis; qPCR, quantitative polymerase chain reaction; DAPI, 4',6‐diamidino‐2‐phenylindole; L‐LA, L‐lactic acid.To investigate the mechanism of OPR regulation on Clostridium difficile, we treated H2O2‐induced HT29 cells with TcdB toxin from Clostridium difficile, and evaluated whether OPR or GP could protect the IECs from the toxins by CCK‐8 assay.
方法
INTRODUCTIONThe prevalence of inflammatory bowel disease (IBD) continues to rise worldwide, currently affecting about 7 million patients, and has become a major challenge in the field of global public health [1].；IBD patients with CDI have a worse prognosis [4].；This bidirectional pathological interference mechanism puts patients at risk of alternating worsening of symptoms, highlighting the critical need for therapeutic strategies capable of breaking this “IBD‐CDI” cycle without exacerbating the underlying disease or infection.Significant upregulation of uncoupling protein 2 (UCP2) expression is observed in human IBD intestinal tissue and IBD mouse models, and is positively correlated with disease severity [8].
核心结论
Genipin has been widely studied and recognized as a specific UCP2 inhibitor, and we found that UCP2 may play an important role in IBD pathology, so we selected Genipin as the main effector component of OPR for specific inhibition of UCP2 [18].；In a mouse IBD model, OPR can alleviate pyroptosis of IECs, subsequently inhibit activation of the macrophage cGAS‐STING pathway, and demonstrate a therapeutic effect far superior to that of first‐line clinical therapeutic drugs, including 5‐Aminosalicylic Acid (5‐ASA), Dexamethasone (DEX), JAK1 inhibitor Upadacitinib (UPA), and TNF‐α monoclonal antibody Infliximab (INF).；In summary, this study provides a new paradigm for the treatment of IBD‐CDI syndrome from the perspective of inhibiting IEC pyroptosis and increasing toxin tolerance of IECs.RESULTSUCP2 in IBD and synthesis of OPR targeting IBD lesionTo confirm the role of UCP2 in IBD, we performed a comprehensive analysis of the human source dataset [GEO]GSE179285 from the GEO database.
局限
However, simple inhibition of UCP2 can lead to increased ROS [9], whereas excessive ROS aggravates IBD [15].；However, Genipin itself does not have the ability to target the intestine, so it needs to be structurally modified, and we chose glycine as another component for the following reasons: ① The nanoparticles synthesized by Genipin and glycine have a negative charge on the surface and can target IBD intestinal lesions through charge attraction. ② Glycine is a natural amino acid with the smallest molecular weight and simplest structure.；However, GP (73.2 ± 2.6%) had no significant weight recovery effect due to its lack of intestinal targeting ability.
对本项目的价值
中高价值：属「干细胞 / 部分重编程与再生」方向；干细胞 / 再生 / 重编程栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 121,163 字符，题名指纹 0.93，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：口服质子重编程纳米药物打破炎症性肠病-艰难梭菌感染恶性循环
- 英文标题：Oral proton-reprogrammed nanomedicine to break the inflammatory bowel disease-Clostridium difficile infection vicious cycle.
- 期刊与标识：iMeta · PMID 42974105 · DOI 10.1002/imt2.70112 · PMC PMC13726583