Author

Yu Wang

View on Semantic Scholar

2 papers indexed here

We haven’t gathered this author’s papers yet. Follow them and we’ll fetch their work.

Not the right person? Other researchers publish under this name.

Open access Jul 2026

Electroacupuncture-mediated lncRNA TUG1 regulates the miR-127-3p/NF-κB p65 axis to inhibit IBS-D low-grade intestinal inflammation

Background Electroacupuncture (EA) demonstrates efficacy in alleviating diarrhea-predominant irritable bowel syndrome (IBS-D), yet its mechanisms concerning low-grade intestinal inflammation remain insufficiently elucidated. This study investigated whether EA ameliorates IBS-D symptoms by modulating the long non-coding RNA Taurine Upregulated Gene 1 (lncRNA TUG1)/microRNA-127 -3p (miR-127-3p)/nuclear factor-kappa B p65 (NF-κB p65) axis. Methods An IBS-D rat model was established using maternal separation, acetic acid enema, and chronic restraint stress. Rats were randomly allocated into control, model, EA (at ST-25 and ST-37), drug (rifaximin), and PDTC (NF-κB p65 inhibitor) groups. Behavioral assessments (body weight, loose stool rate, abdominal withdrawal reflex) were conducted. Molecular analyses included dual-luciferase reporter assays, RT-qPCR, western blot, ELISA, and immunofluorescence to evaluate the TUG1/miR-127-3p/NF-κB p65 axis, inflammatory factors (TNF-α, NLRP3, IL-6), and tight junction proteins (occludin, claudin-1, ZO-1). Intestinal ultrastructure was examined by electron microscopy. Results EA significantly improved general status, reduced diarrhea and visceral hypersensitivity in IBS-D rats, comparable to rifaximin and PDTC. Mechanistically, EA upregulated colonic lncRNA TUG1 expression, which sequesters miR-127-3p and partially derepresses NF-κB negative regulators (IκBα, A20), consistent with attenuated NF-κB pathway activation. This was associated with downregulated downstream pro-inflammatory mediators (NF-κB p65, TNF-α, NLRP3, IL-6) in serum and colon tissues. Furthermore, EA restored intestinal barrier integrity, as evidenced by improved mucosal ultrastructure and increased expression of tight junction proteins. Conclusion EA alleviates low-grade intestinal inflammation and visceral hypersensitivity in IBS-D rats. The therapeutic effect is mediated, at least in part through upregulation of lncRNA TUG1, which sponges miR-127-3p to inhibit the NF-κB p65 signaling pathway, thereby reducing inflammatory cytokine release and repairing the intestinal epithelial barrier. These findings suggest the TUG1/miR-127/NF-κB axis as a candidate therapeutic target for EA in IBS-D.

Kuiwu Li, Jiaojiao Wang, Ling Zou et al. · Frontiers in Immunology · 0 citations

Jul 2026

Discovery of highly potent and selective VAV1 molecular glue degraders for the treatment of inflammatory disorders 2332299

VAV1 is a highly specific target for immune-mediated diseases. VAV1 functions as a guanine nucleotide exchange factor (GEF) in T- and B-cell receptor signaling and is essential for immune cell activation, proliferation, and inflammatory responses. Despite its therapeutic potential, VAV1 has historically been difficult to target with small molecules due to its multidomain architecture and dual roles as both a GEF and a scaffolding protein involved in GEF-independent signaling pathways. Here, we describe a novel protein degradation strategy using molecular glue degraders (MGDs) to overcome these challenges. Endogenous Vav1 protein levels were detected in Jurkat cells by HiBiT assay. In human and mouse whole blood assays, cells were profiled for VAV1 levels in CD3+ T cells with flow cytometry. Label-free mass spectrometry with data-independent acquisition (DIA) proteomics were used to detect protein abundance levels in human PBMC treated with compounds. In vivo pharmacokinetics and efficacies of the compounds upon oral treatment were evaluated in ICR mice and inflammatory disease models including collagen-induced arthritis (CIA), experimental autoimmune encephalomyelitis (EAE) and naïve CD4+ T cell transfer model of inflammatory bowel disease (IBD). The compounds demonstrated robust VAV1 degradation in both cellular and whole blood assays. The half-maximal degradation concentration (DC50) ranged from sub-nanomolar to low nanomolar, with Dmax values exceeding 95%. Proteomics analysis of human PBMCs confirmed consistent and selective VAV1 degradation. Oral administration of the compounds in animal models resulted in dose-dependent VAV1 degradation and corresponding improvements in disease scores. We have discovered potent and selective VAV1 molecular glue degraders with favorable in vivo pharmacokinetic and pharmacodynamic properties. Further investigations are needed to explore their potential in treating a range of inflammatory conditions, including neuroinflammation. n/a Therapeutic Approaches to Autoimmunity (THER)

Li Xing, Jingbing Wang, Wei Zhu et al. · Journal of Immunology · 0 citations