Reprogramming Macrophage Function via Cholesterol Modulation and Redox Signaling Using a Multifunctional Nanoplatform for Postoperative Breast Cancer Management.

Postoperative recurrence and infection remain major obstacles to effective breast cancer recovery, often driven by cholesterol-mediated macrophage dysfunction. Here, we report the development of CuMPmC, a multifunctional nanoplatform constructed through copper-dopamine chelation and self-polymerization, functionalized with mannose for selective targeting of M2-like macrophages, and loaded with cholesterol oxidase (ChOx). CuMPmC depletes macrophage membrane cholesterol via ChOx-mediated oxidation, enhancing plasma membrane fluidity and thereby promoting macrophage chemotaxis.

Novel Swelling-Lytic Cell Death Triggered by Cargo-Free Ionizable Lipid Nanoparticles.

Lipid nanoparticles (LNPs) are recognized as robust and versatile drug delivery platforms holding significant promise for personalized and precision medicine applications. However, their intrinsic biological effects, including dose-limiting toxicity and acute inflammation, limit their widespread application. Elucidating the underlying mechanisms paradoxically enables dual-path optimization: targeted mitigation strategies for adverse effects and deliberate amplification of adverse effects for repurposing ("waste-to-resource").

Role and mechanism of cardiac insulin resistance in occurrence of heart failure caused by myocardial hypertrophy.

Cardiac insulin resistance plays an important role in the development of heart failure, but the underlying mechanisms remain unclear. Here, we found that hypertrophic hearts exhibit normal cardiac glucose oxidation rates, but reduced fatty acid oxidation rates, compared to Sham controls under basal (no insulin) conditions. Furthermore, insulin stimulation attenuated insulin's effects on cardiac substrate utilization, suggesting the development of cardiac insulin resistance.

MiR-26a-5p regulates cardiac fibroblasts collagen expression by targeting ULK1.

MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway.