查找使用阿拉丁产品的科研文献

Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites

Kai Dong,Ying Zhang,Hong Rui Ji,Ze Lin Guan,Dan Yang Wang,Zi Yang Guo,Shu Jing Deng,Bin Yang He,Jian Feng Xing,Cui Yu You

Background The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms.Purpose A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects.Methods Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model.Results The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy.Conclusion The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

Follicle-stimulating hormone peptide-conjugated liposomes in the treatment of epithelial ovarian cancer through the induction of M2-to-M1 macrophage repolarization

Shengxia Hu,Dan Sun,Ling Tang,Liang Kong,Yang Liu,Fang Liu,Dongmei Tang,Xuhong Lu,Yuanyuan Wang

Introduction The silent killer epithelial ovarian cancer (EOC) is a lethal malignancy with high mortality rate and often diagnosed at an advanced stage. Traditional chemotherapy for EOC remains unsatisfactory as the tumor microenvironment (TME) is complicated and contains multiple factors such as tumor associated macrophages (TAMs). Therefore, a drug delivery system which codelivery chemotherapy drug and immune modulator for EOC treatment is urgently needed. Methods Follicle-stimulating hormone peptide-conjugated paclitaxel and ginsenoside Rh2 codelivery liposomes (FSH@PTX-Rh2-Lips) were prepared in this study. FSH was decorated on the liposomal surface to enhance cellar uptake, PTX was used to kill cancer cells, and Rh2 was added to induce macrophages repolarization as well as a member material. The targeting, anti-tumor effect and impact on macrophage repolarization of FSH@PTX-Rh2-Lips were evaluated in vitro and in vivo. Results With the ideal physicochemical properties, FSH@PTX-Rh2-Lips displayed increased cellular uptake, strong cytotoxicity to ID8 cells, inhibitory effect of tumor cell metastasis, and ability to induce macrophage repolarization from M2 to M1 in vitro. The tumor-bearing mice model suggested FSH@PTX-Rh2-Lips showed significant effect on antitumor and tumor recurrence, and the mechanism of FSH@PTX-Rh2-Lips in treatment of EOC was related to inhibiting tumor growth and inducing macrophage repolarization. Conclusion FSH@PTX-Rh2-Lips with function of affecting TAMs repolarization and altering the TME were successfully prepared and might offer an effective therapeutic strategy against EOC.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism

Li Gao,Ai-ping Zhang,Lei Fu,Qian-wen Li,Xue-mei Qin,Jing Zhao

Background The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. Purpose The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. Methods The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. Results Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 μM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. Conclusion In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Co-Delivery of Ferrostatin-1 and M2 Macrophage-Derived Exosomal Signals via Engineered Hybrid Nanovesicles Enables Synergistic Neuroprotection in Traumatic Brain Injury

Wenyan Hao,Nan Sun,Ruifen Xue,Junkai Chang,Xiaocong Pang,Ying Zhou,Chunsheng Gao

Secondary brain injury after traumatic brain injury (TBI) is driven largely by ferroptosis-induced neuronal death and maladaptive neuroinflammation. Current therapies are limited by poor drug delivery and the narrow scope of single-pathway interventions. Here, we report a biomimetic hybrid nanovesicle (hMLV) engineered to codeliver the ferroptosis inhibitor ferrostatin-1 (Fer-1) and M2 macrophage–derived exosomes, enabling simultaneous suppression of neuronal ferroptosis and reprogramming of the immune microenvironment. The liposomal core encapsulates hydrophobic Fer-1 to enhance solubility and stability, while the exosomal membrane promotes blood–brain barrier penetration, lesion targeting via chemokine receptors, and immune evasion through CD47 expression. Within injured brain tissue, released Fer-1 restores glutathione peroxidase 4 (GPX4) activity, reduces lipid peroxidation, and prevents ferroptotic neuronal death. Concurrently, exosomal cytokines such as interleukin-10 and transforming growth factor-β drive macrophage polarization toward a reparative M2 phenotype, mitigating neuroinflammation. This dual mechanism establishes a positive therapeutic cycle: ferroptosis inhibition dampens inflammatory triggers, while M2 polarization reduces oxidative stress. In a murine TBI model, hMLV treatment conferred superior neuroprotection and functional recovery compared with monotherapies. These findings highlight hMLV as a clinically translatable nanoplatform for synergistic, mechanism-guided intervention in secondary brain injury.

β-hydroxybutyrate regulates microglia M1/M2 polarization and phagocytosis through the JAK1/STAT1 pathway to reduce neuroinflammation and exert anti-epileptic effects

Yang Hui,Wang Huifen

New breakthrough in dye removal: Ultrafast removal of high concentration MB with biochar-based organic photocatalysts under indoor light (30W/m2) drive

Songlin Cai,Ciyuan Huang,Caiyun Wang,Libin Zhang,Kai Huang,Haili Dong,Houjin Luo,Kai Chen,Shangfei Yao,Hongxiang Zhu,Ke Sun,Gang Li,Tao Yang,Bo Tang,Bingsuo Zou,Tao Liu

At the present stage, the light sources used in the photocatalytic degradation of organic pollutants are generally UV and simulated sunlight, which invariably increase the extra energy loss. Therefore, it is important to find an effective strategy for the rapid removal of high concentrations of organic pollutants in a cleaner and low-light environment with lower energy consumption. Here we prepare three biochar-based organic photocatalytic materials PM6:TPIC/BC, PM6:TPIC-2Cl/BC, PM6:TPIC-4Cl/BC by impregnation method. Among the three photocatalysts, PM6:TPIC-4Cl/BC exhibits the highest apparent rate constant (0.105 min −1 ), which is 3 times and 1.5 times higher than PM6:TPIC/BC (0.034 min −1 ) and PM6:TPIC-2Cl/BC (0.071 min −1 ) respectively. Due to a wider range of light absorption, the best material is able to completely degrade high concentrations of MB in 3 min. Moreover, photoluminescence (PL), time-resolved photoluminescence (TRPL), electrochemical impedance (EIS), and photocurrent (PCR) measurements confirm its exceptional photogenerated electron-hole separation. Free radical trapping identifies h + , ·OH, and ·O 2 − as key reaction species. DFT analysis reveal atoms with higher Fukui index ( f 0 ) as prime free radical targets. LC-MS detects intermediates, suggesting possible degradation pathways. The reduced toxicity of the degradation products after photocatalysis indicates an environmentally friendly approach. This work demonstrates the valuable of PM6:TPIC-4Cl/BC organic photocatalysts for treating organic wastewater.

Lactate transmission from hypoxic tumor cells promotes macrophage senescence and M2 polarization via the DNMT1-NHE7 axis to accelerate endometrial cancer progression

Yang Shizhou,Ma Yuejiang,Wu Tingting,Huang Xiufeng

Although hypoxia is a well-known key driver of metabolic reprogramming in endometrial cancer (EC), its role in lactate-mediated macrophage activation remains unclear. This study investigates whether hypoxia-mediated lactate metabolism reprogramming facilitated EC progression via macrophages. Our data demonstrated that hypoxia-inducible factor 1 subunit alpha (HIF1A) drives a lactate-regulated metabolic cascade, elevating glycolytic genes and monocarboxylate transporter 3 (MCT3) in EC cells to produce and export more lactate. This lactate is transported to macrophages by MCT1 to drive M2 macrophage polarization. Mechanistically, lactate induces lactylation of Histone 3 in the promoter of DNA methyltransferase 1 (DNMT1) gene and activates transcription in macrophages, leading to the silencing of NHE7 gene expression, a key regulator of intracellular pH. Critically, NHE7 downregulation drives M2 polarization and senescence through the mitogen-activated protein kinase (MAPK) pathway activation in macrophages, ultimately facilitating EC progression. In vivo, we successfully established a xenograft tumor model using Ishikawa cells, and the data further confirmed that NHE7-overexpressing macrophages effectively abrogate exogenous lactate-accelerated xenograft tumor growth, as well as its M2 polarization and senescence. These findings uncover that hypoxia-mediated lactate production and transmission promote tumor-macrophage crosstalk via the DNMT1-NHE7 axis and EC progression, which offers novel therapeutic targets for EC.

CCL25/CCR9-induced M2 macrophage polarization promotes lung cancer progression via TGF-β1-mediated activation of the JAK/STAT-PIM2 signaling pathway

Wen Qiang,Yuan Yi,Liu Zhihua,Wang Lei,Pan Chunguo

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. While the chemokine CCL25 is implicated in the tumor microenvironment, its specific role in LC is not fully understood. Here, we identify CCL25 as a key promoter of tumor progression through a novel macrophage-mediated signaling axis. Bioinformatics and clinical analyses revealed that CCL25 is highly expressed in LC and correlates with M2 macrophage infiltration and poorer patient survival. In vitro, tumor-derived CCL25 drove M2 polarization of macrophages by upregulating its receptor CCR9. Functionally, these CCL25-CCR9-induced M2 macrophages secreted TGF-β1 and significantly enhanced the proliferation, migration, and invasion of LC cells. Mechanistically, this effect was mediated through the activation of the JAK/STAT signaling pathway and the subsequent upregulation of the downstream oncogene PIM2 in tumor cells. Both pharmacological inhibition of JAK/STAT and genetic knockdown of PIM2 reversed the tumor-promoting crosstalk. Single-cell transcriptomics confirmed the presence of a TGF-β1-expressing CCR9 + M2 macrophage subset in human tumors and revealed co-expression of CCR9 and PIM2 in tumor cells. In vivo, CCL25 overexpression accelerated tumor growth and M2 macrophage infiltration. Collectively, our findings define a complete CCL25-CCR9-TGF-β1-JAK/STAT-PIM2 signaling circuit wherein tumor cells educate macrophages to, in turn, fuel their own malignant progression, highlighting this axis as a potential therapeutic target in lung cancer.

Callicarpa nudiflora-derived extracellular vesicle-like particles loaded with budesonide enhance the treatment of ulcerative colitis by regulating M1/M2 macrophage polarization

Yuxin Xi,Jiayi Zou,Liang Chen,Xinyao Ma,Yishan Yan,Desheng Liang,Fan Liao,Haijun Zhong,Feng Guo

Conventional drug therapy effectively controls early-stage ulcerative colitis (UC) symptoms, but long-term use and high doses may compromise safety and patient tolerance. Here, Callicarpa nudiflora -derived extracellular vesicle-like particle (CN-EVLP) was extracted from the fresh leaves of Callicarpa nudiflora . An oral delivery system of budesonide using CN-EVLP (CN-EVLP-Bud) was designed, and the loading conditions were explored and optimized to improve the encapsulation efficiency and drug loading. We found that encapsulating budesonide in CN-EVLP enhanced its biocompatibility and promoted cellular uptake in both Caco-2 and Raw264.7 cells. In lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium (DSS)-induced murine colitis models, CN-EVLP-Bud showed significantly stronger anti-inflammatory and antioxidant effects than free budesonide, including suppressing pro-inflammatory cytokines (IL-6, TNF-α) and reducing oxidative stress. Moreover, CN-EVLP could modulate macrophage M1/M2 polarization, further enhancing its anti-inflammatory efficacy. Thus, CN-EVLP shows promising potential as a novel nanomedicine delivery vehicle for UC therapy.

In situ forming ROS-scavenging hydrogel with STING inhibitor delivery promotes bone mesenchymal stem cells osteogenic differentiation via regulating macrophage M2 polarization

Zeyue Sun,Xiaojun Li,Xueheng Sun,Liuting Chen,Zihang Wang,Xin Feng,Luying Wang,Wenjie Jin,Xin Sun,Jiaju Lu

Bone regeneration is frequently impaired by excessive reactive oxygen species (ROS) and prolonged inflammation, which disrupt the immune microenvironment and hinder osteogenesis. The stimulator of interferon gene (STING) pathway is an innate immune pathway and a critical mediator of the inflammatory response, has been increasingly implicated in inflammatory bone loss and impaired repair. While STING inhibition represents a promising therapeutic strategy, its effective implementation within the bone microenvironment requires spatiotemporally controlled delivery. Here, we developed an injectable and photocrosslinkable hydrogel system (GMPP+H151) that integrates ROS-responsive scavenging with targeted STING inhibition to synergistically guide immune microenvironment remodeling and bone regeneration. The GMPP hydrogel was fabricated through dual crosslinking of phenylboronic acid (PBA)-modified gelatin (GelMA) and polyvinyl alcohol (PVA), endowing it with self-healing properties and ROS-scavenging capacity. H151, a small molecule inhibitor of STING, was caged by PBA chemistry for on-demand release under oxidative stress. The GMPP+H151 can significantly reduce ROS levels in macrophages and promote their phenotypic differentiation from M1 to M2 by suppressing the STING pathway, downregulating pro-inflammatory cytokines, and upregulating anti-inflammatory factors. Furthermore, it efficiently enhanced survival, spreading, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), leading to increased expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). This study presents a smart, multifunctional hydrogel drug delivery system that integrates immunomodulation and osteoinduction, offering a promising strategy for promoting osteogenic differentiation and in situ bone defect repair.

ROS-Responsive Hydrogel with M2 Macrophage Nanovesicles for Diabetic Wound Healing: Targeted CO Delivery to Regulate Mitochondrial Metabolism and Reprogram Wound Microbiota

Chenyu Ma,Wen Ding,Peiting Li,Qiyue Wang,Xueming Li,Zhengjie Meng,Hao Ren

Macrophage dysregulation and microbial dysbiosis at diabetic chronic wound sites are two of the main drivers that hinder the healing process. To address this, a reactive oxygen species (ROS)-responsive hydrogel wound dressing (NVs@CO-TP) is fabricated through boronic ester bonds between poly(vinyl alcohol) hydroxyl groups and phenylboronic acid moieties, which incorporates M2 macrophage-derived nanovesicles (NVs) loaded with manganese carbonyl (NVs@CO). Upon exposure to a high level of ROS in the wound, the hydrogel responds, scavenges ROS, and subsequently releases NVs@CO, exhibiting the synergistic efficacy of CO gas and NVs. Due to its intrinsic inflammation-tendency ability, NVs@CO specifically targets activated M1 macrophages and releases CO to regulate mitochondrial metabolism, promoting M1 apoptosis and increasing the M2 phenotype. This process decreases the release of inflammatory cytokines and enhances anti-inflammatory processes, promoting chronic diabetic wound healing. More interestingly, the dressing also beneficially modulates the wound microbiota by enhancing the beneficial microbial richness and overall microbiome composition, which further improves the healing microenvironment. Therefore, NVs@CO-TP acts through two primary mechanisms: the targeted delivery of CO to M1 macrophages regulates the mitochondrial metabolism to repolarize macrophages while simultaneously modulating the wound microbiome. This combined anti-inflammatory strategy facilitates chronic wound healing and demonstrates significant potential for clinical translation in treating various difficult-to-heal wounds.

An M2 macrophage-polarized anti-inflammatory hydrogel combined with mild heat stimulation for regulating chronic inflammation and impaired angiogenesis of diabetic wounds

Yang Yuan,Daidi Fan,Shihong Shen,Xiaoxuan Ma

At present, approximately 19–34% of diabetic patients (nearly 450 million) may have complications involving diabetic foot ulcers (DFUs). Wound healing of DFUs still faces huge problems, such as long-term chronic inflammation and impaired angiogenesis . Therefore, an M2 macrophage-polarized anti-inflammatory hydrogel (HTHE-M@D) combined with mild heat stimulation is designed for DFUs treatment. The HTHE-M@D hydrogel is prepared by enzymatic cross-linking of epigallocatechin gallate dimer-grafted hyaluronic acid (HA-EGCG) and tyramine-grafted human-like collagen (HLC-TA) and integrating deferoxamine-loaded mesoporous polydopamine nanoparticles (M@D). The hydrogel exhibits prominent enhancement of angiogenesis, which is attributed to the combination of mild heat stimulation via photothermal effects and the angiogenic drugs (deferoxamine) released from the hydrogel. The hydrogel also promotes the transformation of macrophages from the M1 to M2 phenotype and exhibits good anti-inflammatory, antibacterial, antioxidant, hemostatic properties and biocompatibility. Additionally, the hydrogel has desirable mechanical strength, enhanced tissue adhesion and injectability, thus making it more adaptive to DFUs. The results demonstrate that the combination of the hydrogel and mild thermal stimulation promotes skin regeneration of diabetic wounds and shortens the healing time to 13 days. The combined treatment might offer a promising therapeutic strategy for DFUs.