JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2025
·Vol. 113
·期 12
·e70006
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IF 3.9
Jing Dai,Xuechun Wang,Siyu Li,Shaoqing Chen,Xinye Ni,Min Lin
Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disease with no effective treatment to control inflammation currently. Macrophages, particularly peritoneal macrophages (PMOs), play a pivotal role in SAP inflammation by polarizing into M1 or M2 phenotypes, which exhibit distinct functional properties and cytokine expression profiles. Galectin-9 (Gal-9) modulates macrophage polarization, but its specific effect on PMOs in SAP remains unclear. In this study, hyaluronic acid-chitosan nanoparticles encapsulating Gal-9 (HA-CS-Gal-9 NPs) were developed for delivery. In vitro, HA-CS-Gal-9 NPs enhanced M2 marker expression and suppressed M1 markers in both naive (M0) and LPS-induced M1 macrophages. In vivo, HA-CS-Gal-9 NPs effectively delivered Gal-9, showing effective uptake by PMOs without notable toxicity, resulting in reduced IL-6, and increased IL-10 expression in PMOs. Treatment with these nanoparticles (NPs) decreased systemic pro-inflammatory cytokines, thereby alleviating pancreatitis severity. These findings demonstrate that Gal-9-loaded NPs robustly promoted M2 macrophage polarization, highlighting a promising therapeutic strategy for SAP.
研究领域:
纳米医学
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免疫学
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胃肠病学
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炎症性疾病
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药物递送系统
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 10.2
Xiaowen Zheng,Wenqi Wang,Xiaolong Wei,Jianguo Niu,Wei Zhang,Zhenxun Lin,Wei Wei,Shipeng Ning,Min Wang,Xianwen Wang,Qingjun Wei
Precise spatiotemporal control of inflammation serves as an effective means to regulate the inflammatory microenvironment and promote wound healing. This study constructed strontium‒luteolin (Sr‒Lut) nanoparticles with a spherical morphology, which demonstrated outstanding radical scavenging capacity through synergistic metal‒ligand effects. Specifically, Sr-Lut efficiently scavenges reactive oxygen species, inhibits the TNF-α/NF-κB and JAK-STAT signaling pathways, promotes M2 polarization, and simultaneously reduces the proinflammatory factor IL-1β and increases the anti-inflammatory factor IL-10. Transcriptomic analysis revealed that Sr-Lut reprogrammed macrophages to downregulate Ccl4 and Retnlg while upregulating extracellular matrix remodeling-associated genes. In vivo experiments demonstrated that Sr-Lut accelerated wound closure in a dose-dependent manner, achieving a healing rate of 94.33% by day 11, which was significantly greater than the 58.54% reported in the control group, while also enhancing re-epithelialization and collagen deposition. Wound tissue RNA sequencing revealed that Sr-Lut inhibits the IL-17, Toll-like receptor and NF-κB signaling pathways while promoting the expression of genes associated with epidermal structural components. In summary, a dual-function nanocomposite with both anti-inflammatory and tissue-repair capabilities has been developed, offering a promising immunomodulatory strategy for wound treatment.
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DOI
PubMed
高影响因子
Small
·
2026
·
IF 11.8
Shundong Cai,Mengdie Li,Jingbin Zhuang,Jinfa Ye,Songyi Wang,Jinglei Zhang,Mingyou Zhang,Qixuan Dai,Yun Han,Min Su,Wei Li,Gang Liu,Chengchao Chu
Uveitis poses a severe threat to vision and represents a critical clinical challenge. Conventional therapeutic approaches often exhibit limited efficacy in controlling disease progression and lack efficient mechanisms for managing localized oxidative stress. Given that molecular hydrogen (H 2 ) holds substantial promise for treating oxidative and inflammatory diseases via its selective antioxidant properties, we report a metal–organic framework (MOF) nanozyme-based hydrogen nanogenerator. This system integrates photocatalytic visible-light-triggered H 2 generation with multi-enzyme-like antioxidant functions for targeted uveitis management. The engineered Pt-embedded MOF nanozymes (Pt@MOF) concurrently catalyze hydrogen evolution under visible light and display superoxide dismutase- and catalase-like activities, achieving comprehensive scavenging of overproduced reactive oxygen species (ROS). Furthermore, camouflaging the nanozyme with M2 macrophage-derived cell membrane vesicles (CMVs) endows the nanoplatform with active inflammation-targeting ability, thereby enhancing the accumulation in inflamed ocular tissues. Following topical administration, this biomimetic nanomedicine successfully mitigates oxidative stress and suppresses pro-inflammatory cytokines both in vitro and in a rat model of acute uveitis. Overall, this study underscores the immense potential of integrating light-driven hydrogen therapy with nanozyme therapy, offering a highly effective strategy that could revolutionize future therapeutic interventions for inflammatory eye diseases.
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DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
·
2025
·
IF 2.9
Yiqi Wang,Xiuhua Zhang,Jiannan Zhang,Mingbo Zhao,Yang Chong,Quankuan Gu,Xianglin Meng,Mingyan Zhao
Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties. This study aims to investigate the effects of ANAPC5 on ALI and its underlying molecular mechanism. In the lung tissue of an ALI mouse model induced by lipopolysaccharide (LPS) administration, we observed downregulation of ANAPC5. Through both in vivo and in vitro experiments, we assessed the effect of ANAPC5 on lung injury by conducting pathological analysis and molecular biological detection. ANAPC5 overexpression alleviated inflammatory cell infiltration, reduced alveolar wall thickening, suppressed pulmonary inflammation, and decreased the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue of the ALI model. Moreover, ANAPC5 inhibited M1 polarization and promoted M2 polarization of macrophages both in vitro and in vivo . We also found that ANAPC5 significantly suppressed the activation and expression of the epidermal growth factor receptor (EGFR) through inducing its ubiquitination in macrophages. In LPS-induced M1 macrophages, the presence of EGFR significantly decreased CD24 expression, followed by reversing the inhibitory effects of ANAPC5 on inflammatory responses and macrophage polarization. Collectively, our findings suggest that ANAPC5 serves as a therapeutic molecular target that mitigates ALI through regulating macrophage M1/M2 polarization via the EGFR/CD24 axis.
研究领域:
免疫学
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呼吸病学
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分子生物学
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炎症反应调控
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转化医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Pei Liu,Yuan Xiong,Lang Chen,Chuanchuan Lin,Yayan Yang,Ze Lin,Yongsheng Yu,Bobin Mi,Guohui Liu,Xiufeng Xiao,Qian Feng
With the increase of diabetics, the incidence of diabetic wound, a common complication of diabetes, rapidly grows in clinical. Meanwhile, the high recurrence rate and mortality of diabetic wound make its treatment still a great challenge. Here, we design a M2 macrophage exosome loaded multifunctional hydrogel as the diabetic wound dressing. The combined injectable, self-healing, and tissue-adhesive properties of this hydrogel make it form a protective barrier covering the wound timely to stop bleeding quickly and provide a good healing condition for the wound. Then, the continuous releasing of M2 macrophage exosome is able to promote the angiogenesis in wound, therefore accelerating the diabetic wound healing.
研究领域:
生物医学工程
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组织工程
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药学
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DOI
高影响因子
Journal for ImmunoTherapy of Cancer
·
2026
·Vol. 14
·期 5
·e014533
·
IF 11.7
Qindan Du,Zhen Han,Yumeng Zhang,Ying Li,Ao Sun,Bin Wang,Yongquan Chen,Xiaoying Wang
Background The N-terminal domain of gasdermin D (GSDMD) is a known suppressor of prostate cancer (PCa), primarily recognized for its tumoricidal pyroptotic function. However, research on the full-length GSDMD protein and its relationship with PCa remains unexplored. Therefore, the aim of this study was to investigate the potential non-pyroptotic mechanism of action of GSDMD in preventing PCa immune evasion. Methods The study used GSDMD deletion models to assess its impact on tumor progression and immune cell profiles. Molecular techniques, including protein interaction analysis, were employed to identify the binding partner of GSDMD and the subsequent signaling pathways. Correlative analysis was performed between GSDMD expression and immune markers in human PCa samples. Results GSDMD deletion increased tumor progression and reduced survival, cytotoxic T lymphocyte (CTL) activation/infiltration and tumor cell susceptibility to T-cell death, promoting an immunosuppressive tumor microenvironment (TME). GSDMD-bound laminin subunit gamma-2 (LAMC2), thus inducing its ubiquitin-mediated degradation. Consequently, GSDMD deficiency stabilized LAMC2, driving M2 macrophage polarization and CXC motif chemokine ligand 5 (CXCL5) secretion. CXCL5 interacted with CXCR2 to activate the AKT/NF-κB axis, increasing vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and suppressing CTL activity. GSDMD expression in human PCa positively correlated with CD8 + T-cell infiltration and negatively with M2-phenotype tumor-associated macrophages. Conclusion This study reveals a novel non-pyroptotic pathway through which GSDMD inhibits PCa immune evasion by targeting LAMC2 for degradation, thereby preventing the establishment of an immunosuppressive TME. The findings suggest that activating GSDMD represents a promising therapeutic strategy to reprogram the TME from immunosuppressive (“cold”) to immunoreactive (“hot”), potentially enhancing the efficacy of immunotherapy in advanced PCa.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Ziwei Kang,Ruoyan Xie,Yiming Cui,Zhiwei Chen,Jincheng Li,Jinyu Lv,Weijia Ye,Peixin Zhao,Keke Zhang,Jian Hong,Hengdong Qu
Introduction:: Pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis, plays a critical role in macrophage activation and a broad spectrum of chronic liver diseases. However, whether PKM2 contributes to the pathogenesis of acute liver injury (ALI) remains largely unexplored.Methods: PKM2 expression was assessed in human and mouse ALI livers. Macrophage-specific PKM2 knockout mice were challenged by two independent ALI models, induced by acetaminophen (APAP) and lipopolysaccharide/D-galactosamine (LPS/D-GalN), to explore the role and regulatory mechanism of macrophage PKM2 in ALI progression.Results: By bioinformatic screening and analysis of ALI liver, we found that PKM2 was significantly upregulated in the liver tissues of ALI patients and mice. Immunofluorescence staining further demonstrated that PKM2 was markedly upregulated in macrophages during ALI progression. Notably, macrophage PKM2 depletion effectively alleviated APAP- and LPS/D-GalN-induced ALI, as demonstrated by ameliorated immune cells infiltration, pro-inflammatory mediators, and hepatocellular cell death. PKM2-deficient macrophages showed M2 anti-inflammatory polarization in vivo and in vitro. Furthermore, PKM2 deletion limited HIF-1α signaling and aerobic glycolysis of macrophages, which thereby attenuated macrophage pro-inflammatory activation and hepatocyte injury. Pharmacological PKM2 antagonist efficiently ameliorated liver injury and prolonged the survival of mice in APAP-induced ALI model.Discussion:: Our study highlights the pivotal role of macrophage PKM2 in advancing ALI, and therapeutic targeting of PKM2 may serve as a novel strategy to combat ALI.
研究领域:
医学
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免疫学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2025
·
IF 10.9
Zhiwen Wang,Yue Xie,Mingcun Hu,Min Yang,Xingjian Zou,Chun Zhang
Effective countermeasures for acute kidney injury (AKI) remain unsatisfactory. During AKI progression, the timely and appropriate transition of macrophages from pro-inflammatory to anti-inflammatory states is critical for resolving acute inflammation and promoting tissue repair. Timely clearing of excess reactive oxygen species (ROS) and promotion of M2 polarization of macrophages are key determinants of AKI progression. Accordingly, we report an engineered renal-targeting nanozyme constructed from a novel two-dimensional nanomaterial, MXene nanosheets, via surface conjugation of the anticomplement component 5a aptamer (ac5a-Apt) and magnesium ions (Mg 2 + ). After AKI, the engineered nanozyme can not only target the kidneys but also navigates to inflammatory areas under the guidance of the ac5a-Apt, clear excessive ROS, inhibits the C5a-C5aR complement system activation and promote M2 polarization of macrophages. Importantly, after MXene reacts with ROS and degrades, the surface-loaded Mg 2+ is released, further suppressing the MAPK/ NF-κB signaling pathway to achieve sequential therapy. The engineered renal-targeting nanozyme offers a novel strategy based on ROS clearance and immune modulation for sequential AKI treatment.
研究领域:
医学
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生物材料学
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免疫学
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产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2022
·
IF 6.1
Nan Yang,Xiang Li
Epigallocatechin gallate (EGCG) is an active catechin in green tea and has multiple biological functions, such as anti-inflammation, anti-cancer, and immune regulation. This work aimed to study the protective function of EGCG against asthma and the mechanism. Asthma in mice was induced by house dust mite (HDM) challenge. EGCG treatment alleviated tissue injury, inflammation, mucus production and collagen deposition, and it reduced M2 macrophage infiltration in mouse lung tissues induced by HDM. The bioinformatics analyses in this study suggested that target genes of EGCG were enriched in the hypoxia inducible factor-1 (HIF-1) pathway, EGCG treatment targeted HIF-1α and thereby suppressed vascular endothelial growth factor A (VEGFA) activation. Adenovirus (AAV) overexpression vectors of HIF-1α and VEGFA were administrated into mice after EGCG treatment. Either restoration of HIF-1α or VEGFA significantly blocked the protective functions of EGCG treatment against HDM-induced allergic asthma . In conclusion, this study demonstrates that EGCG treatment relieves asthmatic symptoms in mice by suppressing HIF-1α/VEGFA-mediated M2 skewing of macrophages.
研究领域:
免疫学
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药理学
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呼吸医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Hepatology Communications
·
2026
·Vol. 10
·期 5
·e0916
·
IF 6
Xiao-Wen Wang,Wen-Jie Zheng,Hao-Qi Chen,Tao Huang,Yuan Zhang,Xi-Jing Yan,Wen-Chao Li,Long Zou,Jie-Zhong Wu,Wen-Feng Zhu,Qi-Wei Yang,Gen-Shu Wang,Kun-Peng Hu
Background: Hepatic ischemia–reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation patients. The role of Arrb2 in liver injury is unclear. Our study aimed to determine the role of Arrb2 in hepatic IRI and to identify its underlying mechanisms. Methods: An analysis of clinical samples was conducted to assess the association between Arrb2 expression and the prognosis of liver transplantation. A 70% hepatic ischemia/reperfusion model in mice was established to verify the mechanism of Arrb2 in hepatocytes promoting M2 macrophage polarization in attenuating hepatic IRI by regulating 6-ketoLCA. A model of hypoxia/reoxygenation in vitro was established to investigate the molecular mechanism of 6-ketoLCA in promoting M2 macrophage polarization and pharmacological screening. Results: Arrb2 in hepatocytes has been shown to provide significant liver protection against hepatic IRI, primarily through promoting the polarization of liver macrophages to M2. Arrb2 remodels bile acids and upregulates 6-ketoLCA through Cyp7a1 in hepatocytes, promoting M2 polarization of macrophages, thereby alleviating hepatic IRI. Mechanistically, TGR5 plays a crucial role in promoting the induction of M2 polarization in macrophages by 6-ketoLCA. Pharmacological screening indicates that dutasteride enhances the activity of the Arrb2 promoter and upregulates Arrb2 expression in hepatocytes, thereby mitigating hepatic IRI. Conclusions: Arrb2 in hepatocytes attenuates hepatic IRI by promoting macrophages toward the M2 phenotype through bile acid. Moreover, dutasteride, a selective agonist of Arrb2, emerges as a promising targeted therapeutic agent for the clinical management of liver injury.
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PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2025
·
IF 4
Ling Zhu,Congyan Liu,Yang Wang,Xuanang Zhu,Lei Wu,Lvan Chen,Jing Zhou,Fan Wang
Background Microglia-mediated neuroinflammation is closely related to the development of Alzheimer's disease (AD). This study further elucidated the regulatory mechanism of microglia polarization in AD. Method Microglia polarization was assessed using RT-qPCR, ELISA, and immunofluorescence (IF). Western blot (WB) analyzed inflammation-related, p-tau, and apoptosis-related proteins. Neuronal damage was evaluated by immunofluorescence, and neuronal apoptosis by flow cytometry and TUNEL assay. METTL3 and IκBα expression were detected using RT-qPCR and WB. N 6 -methyladenosine (m 6 A) levels were quantified with a colorimetric assay. RNA pull-down assay examined METTL3, IGF2BP2, and IκBα mRNA binding. IGF2BP expression was assessed by RT-qPCR. Learning and memory abilities were evaluated using morris water maze (MWM) test and novel object recognition (NOR) test. Inflammation-related proteins were detected using IF. Results Stimulation with Aβ 1-42 led to microglia M1 polarization, upregulation of inflammation-related proteins, and exacerbation of neuronal injury and apoptosis, along with increased p-tau expression in neurons. METTL3/IGF2BP2 modulated IκBα m 6 A modification through binding to IκBα mRNA, enhancing its expression. Enhanced METTL3 or IGF2BP2 expression suppressed M1 polarization, inflammation, and neuronal apoptosis in microglia, reversed by knockdown of IκBα. AD model mice exhibited cognitive impairments, neuroinflammation, and elevated M1 polarization. METTL3 or IGF2BP2 overexpression improved cognitive function, reduced neuroinflammation, and inhibited M1 polarization, and this effect was similarly reversed by knockdown of IκBα. Conclusion Our study demonstrates that the METTL3/IGF2BP2/IκBα axis is involved in neuroinflammation in AD by modulating microglia M1/M2 polarization, which sheds light on the treatment of AD.
研究领域:
神经生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 19
·期 5
·3707-3713
·
IF 1.851
Shuyu Liang,Jinzhen Cai,Yani Li,Rui Yang
Macrophage polarization serves an important role in immune regulation that is regulated by T‑cell immunoglobulin‑mucin‑3 (Tim‑3). The objective of the present study was to explore the role of 1,25‑dihydroxy‑vitamin D3 [1,25(OH)2D3] in macrophage polarization. Plasmid transfection techniques were applied to prepare RAW264.7 cells with silenced or overexpressed Tim‑3 gene. ELISAs were used to examine the level of inflammatory factors secreted by macrophages. Proteins levels were determined by western blot analysis. mRNAs expression levels were assessed using reverse transcription quantitative polymerase chain reaction. It was identified that 1,25(OH)2D3 upregulated Tim‑3 levels and promoted the secretion of interleukin (IL)‑10. 1,25(OH)2D3 was also observed to increase the level of transforming growth factor‑β and to inhibit tumor necrosis factor‑α and IL‑6. The results also suggested that Tim‑3 gene silencing induced macrophages polarization to classically activated macrophages (M1), and that overexpression of the Tim‑3 gene induced macrophage polarization to alternatively activated macrophages (M2). 1,25(OH)2D3 treatment upregulated the expression level of Tim‑3 in macrophages, which promoted cell polarization to M2 and inhibited polarization to M1. The data from the present study indicated that Tim‑3 may induce macrophage polarization to M2, and that 1,25(OH)2D3 produced immunosuppressive effects by upregulating Tim‑3.
研究领域:
免疫学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
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