Zhi-Chuan-Ling alleviates OVA-induced allergic asthma by suppressing M2 macrophage polarization via the PI3K/AKT/mTOR/STAT6 pathway.

Dual-drug nanoplatform HPA@NPs reprograms the fibrotic microenvironment by suppressing EMT and M2 macrophage polarization in pulmonary fibrosis.

ITAM-Syk signaling mediates the rebound phenomenon after anti-RANKL antibody discontinuation.

LncRNA KCNQ1OT1 modulates M2 macrophage polarization and angiogenic signaling via the miR-142-3p/TRIM24 axis in retinal neovascularization.

USP18 improves mitochondrial homeostasis by stabilizing PKM2 and promoting M2 polarization in macrophages to relieve acute lung injury.

Abnormal upregulation of SPP1 promotes fibrotic scar after peripheral nerve repair (FS-PNR) by driving M2 macrophage polarization.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disorder characterized by unexplained fibrosis and limited therapeutic options, highlighting the urgent need for innovative treatments. Hyaluronic acid (HA), which is upregulated in IPF and correlates with disease severity, plays an undefined role in its pathogenesis. Hyaluronic acid synthase 2 (HAS2), a key enzyme in HA production, has an unclear function in IPF progression, particularly regarding its involvement in macrophage polarization. Understanding this mechanism is essential for identifying novel therapeutic targets and developing effective drugs for IPF. The present study investigated the roles of HAS2 and HA in IPF and identified potential therapeutic agents. Transcriptomic analysis revealed HAS2 as a critical IPF‑associated gene in patient samples, bleomycin (BLM)‑induced mouse models, and transforming growth factor β1 (TGF‑β1)‑induced myofibroblasts. Single‑cell RNA sequencing further confirmed the fibroblast‑specific upregulation of HAS2 in fibrotic lungs. Experimental validation showed elevated HAS2 expression and HA accumulation in fibrosis models. HA facilitated macrophage M2 polarization and TGF‑β1 secretion through CD44‑dependent STAT6 activation, with CD44 inhibition blocking this effect. Knockdown of HAS2 in fibroblasts decreased HA release and impaired their ability to promote M2 polarization, suggesting that fibroblast‑derived HA drives this process. High‑throughput virtual screening, coupled with absorption, distribution, metabolism and excretion (ADME) profiling, identified orcinol glucoside (OG) as a potential HAS2 inhibitor, which was validated through surface plasmon resonance, cellular thermal shift assays, and molecular dynamics simulations. OG suppressed HA synthesis in TGF‑β1‑induced and HAS2‑overexpressing myofibroblasts in a dose‑dependent manner, inhibiting M2 polarization induction. In vivo, OG reduced collagen deposition, HA, and TGF‑β1 levels in BLM‑induced fibrotic mice. These findings established HAS2 as a central pathogenic factor in IPF and suggested OG as a promising therapeutic candidate, providing a novel approach for IPF treatment by targeting HA synthesis and macrophage polarization.

Yeast β-glucan accelerates diabetic wound healing via macrophage polarization and anti-inflammatory modulation.

Fighting periodontitis with a pH-triggered nanocoating: A sustained-release strategy for simvastatin delivery.

Identification of mitochondrial dysfunction-related biomarkers and immune infiltration in liver ischemia-reperfusion injury via integrated bioinformatics and machine learning.

Safety and toxicity assessment of Lactobacillus salivarius AP-32 with Probiotic potential in vivo and in vitro.

Pancreatic ductal adenocarcinoma (PDAC), the main pancreatic cancer type, was highly aggressive and lethal. Studies showed that the epidermal growth factor receptor pathway substrate 8-Like protein 3 (EPS8L3) was significantly upregulated in PDAC. This study aimed to explore how EPS8L3 promoted PDAC progression. First, bioinformatics analysis, qRT-PCR, and western blot (WB) techniques were utilized to ascertain the expression profile of EPS8L3 in clinical samples and cells of PDAC. Subsequently, EdU proliferation assays, cell apoptosis detection, glycolysis assay kits, in vivo xenograft tumor experiments, and immunohistochemical (IHC) staining were conducted to explore the impact of EPS8L3 silencing on PDAC cell proliferation, apoptosis, glycolytic pathway, and tumor growth in vivo. Meanwhile, flow cytometry was employed to analyze the expression of CD163, a marker of macrophage M2 polarization. Furthermore, with the aid of JASPAR and GEPIA websites, combined with chromatin immunoprecipitation (Ch-IP) experiments and dual luciferase reporter gene experiments, the interaction between transcription factor AP-2α (TFAP2A) and EPS8L3 was further confirmed. Finally, a rescue experiment was performed with EPS8L3 overexpression in TFAP2A-knockdown cells to validate the potential impact of EPS8L3 on TFAP2A function. EPS8L3 was highly expressed in PDAC tumors and PDAC cells, and its silencing effectively inhibited the proliferation of PDAC cells and promoted their apoptosis. Furthermore, the glycolytic pathway in PDAC cells, tumor growth in vivo, and M2 polarization of macrophages were also blocked by EPS8L3 knockdown. TFAP2A interacted with EPS8L3 and positively regulated its expression. Overexpression of EPS8L3 restored the effects of TFAP2A knockdown on PDAC cell progression. TFAP2A positively regulated EPS8L3 to facilitate M2 polarization of macrophages and the malignant progression of PDAC cells.

Neutrophil-mimetic M2 macrophage extracellular vesicle for targeted spinal cord injury therapy.

Effects of the Dental Implant Surface Topography and Macrophage Polarisation on Osteogenesis and Angiogenesis.

Diabetic foot ulcers, affecting millions worldwide, face impaired healing due to dysregulated macrophage polarization. However, the epigenetic mechanisms underlying aberrant macrophage polarization remain to be elucidated. This study introduces a multifunctional, exosome-based delivery platform that combines miR-493-5p-engineered M2 macrophage exosomes with piezoelectric GelMA microneedles to reprogram macrophage metabolism and epigenetics for diabetic wound healing. Engineered EXO@miR-493-5p are embedded in GelMA microneedles (MN) and delivered via a ZnO piezoelectric substrate with a nanosilver/GOx coating to provide antibacterial and antioxidant benefits. Ultrasound-induced electrostimulation enhances exosome deposition and endocytic uptake, enabling sustained, localized cargo release. Mechanistically, miR-493-5p targets HDAC1 to amplify histone H3K18 lactylation, activating the STAT6 axis and driving metabolic reprogramming toward M2 polarization with upregulation of Arg1. In vitro, EXO@miR-493-5p promote M2 markers and angiogenesis. In vivo, they accelerate wound closure, promote re-epithelialization, collagen deposition, and neovascularization, while reducing ROS and inflammation. The integrated platform offers a translatable, epigenetic-metabolic strategy for chronic diabetic wounds.

Temporal-spatial hierarchical immunomodulating dressing promotes high-quality wound healing through M2 macrophage balancing.

Core regulatory mechanisms of macrophage dynamic polarization and multicellular interaction networks in driving venous thromboembolism.

Single-cell transcriptomics combined with spatial proteomics defines phagocytes type-specific immune regulation in diabetic cataract.

"Restauro" strategy: Siderophore-like antibiofilm coating combats prosthetic joint infection and preserves implants via bacterial ferroptosis-like death.

Bacterial infection and severe inflammatory responses are major barriers to successful wound healing. Drug delivery systems have shown promise in precision medicine by enhancing the targeting and protection of therapeutic agents. However, their use is limited by challenges such as biocompatibility issues, structurally complex, high manufacturing costs, suboptimal drug loading, unstable release, and premature immune clearance. Although targeted delivery aims to improve efficacy, it may increase the risk of toxicity. Consequently, conventional non-carrier drugs often remain more practical and effective. Emerging vehicle-free systems with multifunctional capabilities show promise for precise targeting, controlled release, reduced toxicity, and simplified manufacturing. Here, we rationally designed and established a vehicle-free perfluoroalkyl material (PFAS)-gallium composites (PFASs@Ga) through introducing gallium (Ga) in PFASs, taking advantage of the collective merits of Ga's antibacterial and pro-healing properties and PFAS's well-recognized oxygen absorption, carrying of oxygen, chemical inertness, and tunable physicochemical properties. Extensive characterization showed well-defined morphology, elemental configuration, and distinct profiles of gallium ion release. The PFUnA@Ga composite improves gallium integration, Ga release, and O2 delivery. This allowed it to demonstrate potent broad-spectrum antibacterial activity against bacteria, including MRSA and E. coli, which are known to be resistant. In a MRSA-infected wound model, PFUnA@Ga enhances wound closure and reduces bacterial load, thereby promoting regeneration and angiogenesis. The downregulation of pro-inflammatory M1 macrophages and the upregulation of anti-inflammatory M2 macrophages and CD31+ endothelial cells, representing immunomodulatory effects that facilitate inflammation resolution and vascularization. Results confirmed the composites' antibacterial activity and accelerated wound-healing efficacy. This multifunctional composite offers a novel approach for advanced wound management. More specifically, the synergistic approach combines metal-ion mediated bacterial inactivation with sustained oxygenation to support infection control and tissue repair.