Injectable curdlan-derived hydrogel with differential release of copper and zinc ions for synergistic therapy of infected wounds.

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

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

Adenovirus induces pediatric pneumonia via triggering macrophage polarization and IL-6 production via NF-κB activation.

Calycosin ameliorates high-altitude pulmonary edema by regulating macrophage polarization through the PPAR-γ/NF-κB pathway: a comprehensive analysis of network pharmacology, molecular docking, and experimental validation.

Pulpitis represents a prevalent clinical condition in dentistry. Macrophages play pivotal roles in pulpitis immunopathology, while dental pulp stem cells (DPSCs) serve as key effectors in pulp tissue repair and immune regulation. Although mesenchymal stem cells are known to regulate immunity through mitochondrial transfer, this mechanism remains unexplored in pulpitis. This study investigated how mitochondrial transfer influences pulpitis progression and resolution. To investigate DPSC-macrophage mitochondrial transfer and its role in polarisation of macrophages, Lipopolysaccharide-stimulated cocultures were established. Transfer dynamics were analysed by fluorescence microscopy and flow cytometry. Macrophage polarisation (assessed via quantitative real-time polymerase chain reaction (qRT-PCR)/flow cytometry) in the cocultures was detected after mitochondrial transfer agonist/inhibitor treatment. Macrophage polarisation (assessed via qRT-PCR/flow cytometry) and mitochondrial function (reactive oxygen species production, membrane potential) were compared between mitochondria-receiving (Mito+) and non-receiving (Mito-) macrophages. Immunometabolic profiles (itaconate/succinate) were evaluated by qRT-PCR/immunofluorescence. Human dental pulp explants and experimental rat pulpitis models demonstrated the anti-inflammatory and reparative effects of mitochondrial transfer agonists. Data were analysed by one-way ANOVA and unpaired t-tests (α = 0.05). Mitochondrial transfer from DPSCs to macrophages reduced during inflammation. Pharmacological inhibition of mitochondrial transfer exacerbated M1 macrophage polarisation, whereas its enhancement promoted M2 polarisation. Mito+ macrophages exhibited stronger M2 polarisation, improved mitochondrial function, and reduced itaconate/succinate metabolism compared to Mito- cells. Notably, using the inflamed dental pulp explant and the experimental rat pulpitis model, we demonstrated that augmenting mitochondrial transfer can effectively alleviate pulpitis and promote repair. Mitochondrial transfer from dental pulp stem cells to macrophages via tunnelling nanotubes improved macrophage metabolic profiles. Enhanced mitochondrial transfer promoted M2 macrophage polarisation, thereby alleviating pulpal inflammation and promoting repair.

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.

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

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

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

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.

Carcinoma‑associated fibroblasts (CAFs) exhibit notably heterogeneity and are closely implicated in immune checkpoint blockade (ICB) resistance in head and neck squamous cell carcinoma (HNSCC). However, the specific subtypes and mechanisms involved remain to be elucidated. By analyzing two single‑cell RNA sequencing datasets (GSE103322 and GSE139324) and The Cancer Genome Atlas (TCGA)‑HNSCC dataset, two distinct fibroblasts subtypes were identified: Perostin (POSTN)‑ and POSTN+ fibroblasts. A comparison with reported markers revealed that extracellular matrix‑related markers were highly expressed in POSTN+ fibroblasts. In addition, fibroblast activation protein and POSTN expression were positively associated with macrophage infiltration and predicted ICB resistance in TCGA‑HNSCC dataset. Immunogold labeling confirmed the enrichment of POSTN on the membrane surface of CAF‑derived small extracellular vesicles (sEVs) and it was indicated that these POSTN+ sEVs may promote THP‑1‑derived macrophages polarization toward the M2 phenotype. Additionally, sEVs derived from CAFs with POSTN knockdown reduced bone morphogenetic protein (BMP) 4 expression in macrophages, thereby inhibiting M2 polarization through the BMP receptor 2/Smad pathway. Collectively, these findings revealed that a POSTN+ fibroblasts fosters an immunosuppressive microenvironment via sEV‑mediated macrophage polarization, nominating POSTN as a potential therapeutic target to overcome ICB resistance in HNSCC.

Coupling regulation the pyroptosis and polarization of macrophage: Novel insights into the pathogenesis and immunotherapy of osteoarthritis.

Cedrol from Platycladus orientalis (L.) Franco regulates M1/M2 polarization of macrophages and promotes hair regeneration.

Clostridium butyricum ameliorates atherosclerotic inflammation through regulation of gut microbiota.

Nitric oxide (NO) plays a central role in wound healing, by regulating vascular homeostasis, inflammation, and antimicrobial effects. However, chronic diabetic wounds are difficult to heal due to the hyperglycemic microenvironment, which reduces endogenous NO production. Therefore, developing intelligent dressings capable of spatiotemporally programmed NO delivery holds great promise in promoting diabetic wound healing. Herein, we engineered an environmentally activatable hydrogel that enabled on-demand NO release for diabetic wound healing. The CS-SNAP hydrogel was achieved by covalent grafting of NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto the matrix of carboxymethyl chitosan methacryloyl (CMCSMA), and by subsequent fast photopolymerization during only 10 s. The CS-SNAP hydrogel enabled sustained release of NO over 300 min by simply modulating ambient light and temperature. When applied to diabetic wounds, not only did the CS-SNAP hydrogel exhibit effective antibacterial activity, but it also showed good angiogenic ability and promoted M1-to-M2 polarization of macrophages. Together, this environmentally activatable platform demonstrates great potential to shorten the inflammatory phase of diabetic wounds, prevent bacterial colonization, and accelerates diabetic wound healing.

Natural polysaccharide-nucleic acid nanocomplex alleviates myocardial infarction by driving chronologically programmed macrophage polarization.

Click-chemistry hydrogel for blood vessel organoids self-sustaining delivery to enhance flap survival.

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

ITLN1 suppresses colorectal cancer progression by inhibiting Wnt/β-catenin-mediated EMT and reprogramming macrophage polarization.