Astragaloside IV (AS-IV) is a chemical found in traditional Chinese medicine called Astragalus membranaceus (Fisch.) Bunge that has antitumor properties. However, the roles and mechanisms of AS-IV in uterine leiomyomas (ULMs) are unclear. The immunosuppressive enzyme indoleamine-2,3-dioxygenase-1 (IDO1) is involved in tumor formation. IDO1 is a new and reliable prognostic indicator for several cancers. In this work, AS-IV was applied to ULM cells in various concentrations. CCK-8, immunofluorescence, and flow cytometry were used to examine the proliferation and apoptosis of ULM cells caused by AS-IV. After lentiviral vector transduction with IDO1 short hairpin RNA (shRNA), the knockdown and overexpression of IDO1 were stable in ULM cells. To verify the antitumor effect of AS-IV in vivo, we established a rat model of uterine leiomyoma. HE staining, Masson staining, and transmission electron microscopy were used to observe pathological changes in the uterus, and the levels of serum sex hormones were measured by radio immune assay (RIA). The levels of CD3+T, CD4+T, and CD25+ Foxp3+Treg in rat peripheral blood were detected by flow cytometry. Western blotting and immunohistochemistry were used to examine protein expression. We found that AS-IV dramatically increased the apoptotic rate of ULM cells and reduced viability in a time- and dosage-dependent manner. After sh-IDO1 lentiviral transfection, we discovered that knocking down IDO1 reversed the effects of AS-IV on ULM cell proliferation and autophagy. We also found that AS-IV can effectively inhibit the growth of ULMs in vivo. AS-IV may promote apoptosis and autophagy in ULMs by activating PTEN/PI3K/AKT signaling through inhibition of IDO1. These findings imply that AS-IV exerts antifibroid effects, and the underlying mechanism may be IDO1, which is involved in proliferation, apoptosis, and autophagy.

Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes.

Uterine leiomyoma (UL) is characterized by excessive proliferation, extracellular matrix accumulation, and inflammatory activation, yet its upstream regulatory mechanisms remain incompletely defined. Here, we investigated the role of METTL3-associated signaling in mediating the anti-leiomyoma effects of quercetin. Quercetin significantly inhibited proliferation and induced apoptosis in UL cells, accompanied by suppression of inflammatory cytokine production. Transcriptomic profiling revealed that METTL3 silencing was associated with enrichment of MAPK and inflammation-related pathways. Mechanistically, quercetin downregulated METTL3 expression and suppressed phosphorylation of MEK, ERK, JNK, and p38, whereas METTL3 overexpression partially reversed these effects, supporting a functional role of METTL3 in mediating MAPK pathway activation. Consistently, METTL3 knockdown recapitulated the anti-proliferative, pro-apoptotic, and anti-inflammatory effects of quercetin. In a hormone-induced UL rat model, quercetin attenuated uterine enlargement, fibrosis, and proliferative activity, accompanied by decreased METTL3 expression and MAPK activation. Collectively, these findings demonstrate that quercetin suppresses UL progression, at least in part, through modulation of METTL3-mediated MAPK signaling, highlighting METTL3 as a critical regulatory node and a potential therapeutic target in UL.