INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Yao Guo,Jing Cui,Xueyi Liang,Taoyu Chen,Chong Lu,Tao Peng
Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.
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高影响因子
ACS Applied Polymer Materials
·
2023
·
IF 5
Yiwen Pan,Shaoqing Chen,Yanyan Meng,Mu He,Chun Liu,Cheli Wang,Xinye Ni
The treatment of bone defects caused by diseases, trauma, or tumor has always been a great clinical challenge. Implantation of bone biomaterials into bone defect areas is an effective method for bone injury repair. In this study, we used three-dimensional (3D) printing technology to prepare nano-hydroxyapatite (nHA)/sodium alginate (SA)/gelatin (Gel) hydrogel scaffolds loaded with different ratios (0, 0.13, 0.26, 0.39, 0.53, and 0.79‰) of emodin (EM) (EM/nHA/SA/Gel). Scanning electron microscopy showed that the scaffolds had a smooth surface without fracture and nHA was evenly distributed on the surface. The cell proliferation and migration results showed that the 0.39‰ EM group, in particular, could significantly promote the proliferation and migration of mouse embryonic osteoblast precursor (MC3T3-E1) cells and significantly increase the mRNA expression of osteogenic differentiation-related genes (bone morphogenetic protein/BMP-2, BMP-9, osteocalcin). In addition, the 0.39‰ EM group exhibited the best effect on osteogenic differentiation-related proteins (alkaline phosphatase, Runx 2, OSX). The expression of M2 polarization-related genes (arginase-1, CD206) also significantly increased after the treatment with the 0.39‰ EM group. Micro-CT showed that in the rat skull defect model, the EM/nHA/SA/Gel scaffold group significantly promoted bone regeneration after being implanted into the skull for 30 days. Our results indicate that the EM/nHA/SA/Gel hydrogel scaffolds can not only directly promote the proliferation and differentiation of osteoblasts but also indirectly promote osteogenic differentiation by supporting M2 polarization of macrophages. EM/nHA/SA/Gel hydrogel scaffolds are potential bone tissue engineering materials for bone regeneration.
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高影响因子
PHARMACEUTICAL BIOLOGY
·
2025
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IF 4.8
Yong-xiang Huang,Jin-ru Zhang,Shi-hua Fu,Zhe Liu,Hui-jun Zhong,Qing-yang Zhong,Yin-di Luo,Ying-jie Hu,Hai-peng Zhu,Bin Wen,Song Chen
Context Macrophages play a critical role in the pathogenesis of ulcerative colitis (UC). Indirubin (IDR), a natural ligand of the aryl hydrocarbon receptor (AhR), has been shown to ameliorate DSS-induced colitis in our previous study (Liu Z et al.).Objective To investigate whether IDR exerts its protective effects by regulating M1/M2 polarization and inhibiting ferroptosis in macrophages.Materials and Methods Immunohistochemistry staining targeting CD206 and F4/80 was performed to evaluate the effect of IDR on the polarization of M1/M2 macrophages in colitis. Subsequently, the effects of IDR on the M1- or M2-polarization of THP-1-derived macrophages were investigated. Furthermore, the effects of IDR on ferroptosis in the colon tissue of mice and on RSL3-induced ferroptosis in THP-1-derived macrophages were assessed. The results were verified in mouse peritoneal macrophages.Results In addition to reducing the infiltrated macrophages, IDR treatment preserved CD206+ macrophages in DSS-induced colitis. Using cultured THP-1 cells, we demonstrated that IDR inhibited M1 polarization and prompted M2 polarization. Furthermore, we showed that IDR treatment decreased levels of 4-HNE while increasing GPX4 and NRF2 in DSS-induced colitis and THP-1 cells. IDR treatments also reduced cellular reactive oxygen species (ROS) and iron content, and mitigated RSL3-induced ferroptosis in THP-1-derived macrophages. Similarly, IDR augmented M2-polarization and alleviated ferroptosis in peritoneal macrophages.Discussion and Conclusion IDR skews the polarization of macrophages from M1 to M2. Furthermore, it inhibits ferroptosis in both mice and THP-1-derived macrophages. These mechanisms may contribute to the therapeutic effects of IDR in the treatment of UC.
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高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Yaozhong Hu,Jiaxin Gu,Jing Lin,Yi Wang,Feier Yang,Jia Yin,Zhenting Yu,Sihao Wu,Huan Lv,Xuemeng Ji,Shuo Wang
The intervention of EGCG on M1/M2 macrophage polarization was still unclear and should be studied comprehensively. In this context, the intervention of EGCG on macrophage polarization has been investigated to reveal that EGCG promoted M2 polarization of RAW264.7 upon treating with EGCG. A significant inhibitory effect of EGCG on M1 polarization was observed upon stimulating with LPS and IFN-γ. The expression of macrophage phenotype related marker genes (iNOS, COX-2, IL-1β for M1; Arg-1, Ym-1, IL-10 for M2) demonstrated the suppression of M1 polarization and the promotion of M2 polarization in liver, colon, spleen, and brain. Further analysis against peritoneal macrophages verified the increased M2 phenotypes and decreased M1 macrophages, and the similar variation in liver were confirmed by immunohistochemistry (IHC). No significant variation of spleen macrophages was observed with the general macrophages in declined tendency. Bio-distribution of EGCG and its metabolites (EGC, GA) in different organs has been further determined.
研究领域:
免疫学
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药理学
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细胞生物学
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高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2025
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IF 2.5
Zhihua Wang,Denghui Li,Yanghao Wang,Ping Yuan,Wan Zhang,Yihe Zhang,Fei He,Jianyi Yang,Hangchuan Bi,Hao Duan
(1)Background: Inflammation plays a key role in spinal cord injury (SCI), where excessive inflammatory responses exacerbate neural damage and hinder regeneration. Modulating macrophage polarization, particularly through the sustained release of IL-10 to promote the anti-inflammatory M2 phenotype, represents a promising strategy to mitigate inflammation. In this study we developed a Hyaluronic Acid Methacryloyl (HAMA) hydrogel capable of sustained IL-10 release to regulate macrophage polarization and explore its therapeutic potential. (2)Methods: A photo-curable HAMA hydrogel was synthesized via methacrylation and designed for the sustained release of IL-10. The structural and functional properties were characterized using NMR and FT-IR. In vitro assays, including immunofluorescence, flow cytometry, and Western blotting, were performed to evaluate IL-10’s effect on macrophage polarization. The anti-inflammatory and reparative effects of the hydrogel were further validated in a rat SCI. (3)Results: The HAMA hydrogel with sustained IL-10 release demonstrated excellent biocompatibility. It significantly promoted macrophage polarization to the anti-inflammatory M2 phenotype by increasing the expression of CD206. In vivo studies demonstrated that the group treated by HAMA with IL-10 exhibited recovery of sensory and motor functions, along with improvement of the inflammatory microenvironment at the site of injury. (4)Conclusion: The HAMA hydrogel with sustained IL-10 release effectively alleviates inflammation, enhances motor function after SCI, and serves as a promising immunomodulatory platform. This novel approach presents considerable potential for improving neural regeneration.
研究领域:
生物材料学
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神经科学
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免疫学
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PubMed
高影响因子
MATERIALS TECHNOLOGY
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2026
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IF 4
Jingjing Zhang,Xuehai Dong,Zhaoyang Zeng
Diabetic ulcer treatment is complicated by bacterial infections and immune microenvironment dysregulation. This study developed a multifunctional composite hydrogel by non-covalently functionalizing molybdenum disulfide with tannic acid and integrating it with silk fibroin. The resulting hydrogel demonstrates superior dispersion and photothermal properties, reaching 65.1 °C under near-infrared irradiation while minimizing mechanical damage to host cells. In vitro results confirm significant synergistic photothermal bactericidal effects against E. coli and S. aureus. Furthermore, the hydrogel remodels the immune microenvironment by downregulating inflammatory factors (TNF-α, IL-6) and upregulating M2 macrophage markers (CD206, IL-10). The incorporation of SF further improves biocompatibility and promotes fibroblast migration and proliferation. This TA-MoS2-SF hydrogel provides a promising ‘antibacterial-immunomodulatory-repair’ strategy for clinical DU management.
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高影响因子
MATERIALS & DESIGN
·
2026
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IF 8.2
Jiali Deng,Xiaoqiong Huang,Yang Yang,Linjuan Li,Jiaqi Shen,Wenyi Zeng,Xiaolin Yu,Feilong Deng,Ruogu Xu,Zhengchuan Zhang
Ti‑preconditioned exosomes suppress macrophage inflammation via autophagy activation. • Lyophilized exosome–loaded biomimetic periosteum was successfully constructed. • The delivery system promotes M2 macrophage polarization to facilitate angiogenic osteogenesis. Critical-sized bone defects remain a clinical challenge due to dysregulated inflammation that impairs angiogenesis. Here, we developed a cell-free biomaterial system consisting of a decellularized biomimetic periosteum (DBP) loaded with engineered exosomes derived from nanoporous titanium–preconditioned mesenchymal stem cells (Ti–Exos). We further demonstrated that Ti-Exos significantly attenuated LPS-induced macrophage inflammation by enhancing autophagy through the inhibition of the PI3K/AKT/mTOR pathway, thereby promoting M1-to-M2 macrophage polarization and anti‑inflammatory cytokine secretion. The bilayer DBP scaffold enabled sustained release of Ti-Exos and mimicked key functions of natural periosteum. In a rat critical-sized calvarial defect model, DBP/Ti-Exos facilitated the early macrophage transition from the M1 to M2 phenotype, reduced inflammatory infiltration, stimulated angiogenesis, and ultimately enhanced the formation of mature and mineralized bone. Collectively, this study demonstrates that the engineered exosomes integrated within a biomimetic periosteum can synergistically orchestrate immunomodulation and angiogenesis, offering a promising cell–free therapeutic strategy for vascularized bone regeneration of critical-sized bone defects. This study introduces an engineered exosome–based cell–free strategy that orchestrates the local immune microenvironment to accelerate vascularized bone repair. Specifically, nanoporous Ti-preconditioned exosomes (Ti-Exos) were fabricated and proven to attenuate LPS-induced macrophage inflammation by inhibiting PI3K/AKT/mTOR to activate autophagy. Lyophilized Ti-Exos-loaded decellularized biomimetic periosteum (DBP/Ti-Exos) was constructed and exhibited uniform distribution of Ti-Exos. DBP/Ti-Exos was demonstrated to drive M1-to-M2 macrophage polarization, and promote angiogenic osteogenesis in rat calvarial defects. Download: Download high-res image (182KB) Download: Download full-size image
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高影响因子
MOLECULAR NEUROBIOLOGY
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2026
·Vol. 63
·期 1
·518
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IF 5.5
Ma Ya-nan,Wang Zijie,Liang Yuchang,Tan Guoao,Hu Xiqi,Xia Ying
This study aims to investigate the effect of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exo) on microglial polarization and its potential therapeutic role in Alzheimer’s disease (AD). OM-MSCs-Exo were isolated and purified from the mice olfactory mucosa, followed by phenotypic characterization. Proteins transferred by OM-MSCs-Exo were screened using proteomic analysis. The AD model was established in microglial cells and mice with Aβ 1–42 . Immunofluorescence and biochemical assays were employed to assess the impact of OM-MSCs-Exo and its secreted protein FGFR1 on microglial polarization. Protein–protein interactions and immunoprecipitation were used to identify the target proteins of FGFR1 in microglial cells. Additionally, the effects of OM-MSCs-Exo-induced microglial polarization on neuronal inflammation and cognitive function in mice were evaluated. OM-MSCs-Exo were successfully isolated and purified. FGFR1 was significantly upregulated in OM-MSCs-Exo compared to OM-MSCs. Aβ 1–42 induced M1 polarization and suppressed M2 polarization of microglia, which was reversed by OM-MSCs-Exo. FGFR1 overexpression in OM-MSCs-Exo further enhanced M2 polarization in microglial cells. Phospholipase C gamma 1 (PLCγ1) was identified as the target of FGFR1, and knocking down PLCγ1 reversed the effects of FGFR1-overexpressing OM-MSCs-Exo. OM-MSCs-Exo alleviated cognitive decline and neuroinflammation in AD mice, with FGFR1 overexpression further enhancing these effects. OM-MSCs-Exo promote M2 polarization of microglia in AD mice through the FGFR1/PLCγ1 pathway, alleviating neuronal inflammation and cognitive dysfunction.
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高影响因子
CERAMICS INTERNATIONAL
·
2018
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IF 3.057
Mingxu Sui,Tianqi Fu,Xiaodong Sun,Guangzhen Cui,Xuliang Lv,Guangxin Gu
Unary and binary M 2+ (M=Mn, Co, Ni, Zn) substituted hollow Fe 3 O 4 were prepared by one-step solvothermal method. The crystallographic structure, morphology, element components and microwave absorbing properties of as-prepared products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM), Energy-dispersive X-ray (EDX) and vector network analyzer (VNA). The unary and binary Co 2+ substitution of hollow Fe 3 O 4 could result in a significant improvement of microwave absorption performance, including the expanding of effective absorption bandwidth, the thinner thickness and the increment of absorbing intensity. The sample of CoFe 2 O 4 could reach an optimal reflection loss of − 28.78 dB at 15.52 GHz under the thickness of 1.5 mm, moreover, the efficient absorption bandwidth (less than −10 dB) is expanded to 5.56 GHz which is most outstanding among these samples. The minimum reflection loss of Co 0.75 Zn 0.25 Fe 2 O 4 could reach − 49.60 dB at 9.88 GHz under the thickness of 2 mm. The as-prepared products could be used as microwave absorber with the advantages of strong absorption, broad bandwidth and thin thickness. The favorable performance could be attributed to the strong magnetic loss, dielectric loss and good impedance matching properties.
研究领域:
材料科学
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电磁学
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高影响因子
Cancer & Metabolism
·
2026
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IF 5.9
Gan Chao,Wu Dan,Yuan Yue,Li Lingling,Bai Jia,Xu Yanmei,Lv Haihong
Objective Hepatocellular carcinoma (HCC) poses a substantial health burden globally. We explored the mechanism of PFKFB4 affecting M2 polarization of tumor-associated macrophages (TAMs) in HCC. Methods The correlation between PFKFB4 expression and macrophage infiltration was analyzed by TIMER database. HCC and adjacent tissues from 30 HCC patients were collected to analyze the PFKFB4 positive expression rate, and the infiltration percentages of the M1- and M2-phenotype TAMs via immunohistochemistry and flow cytometry. PFKFB4 was knocked down or overexpressed in HCC cells, with cell glycolytic, proliferation, and migration assessed. M0 macrophages were co-cultured with HCC cells, with lactate level and TAM M2 polarization detected. H3K18 lactylation (H3K18la) level in TAMs, and its enrichment on the M2 polarization-related gene promoters (arginase 1 [Arg-1], CD206) were assessed by western blot and ChIP. Arg-1 and CD206 levels were tested by RT-qPCR and western blot. In vivo validations were performed in nude mice. Results PFKFB4 expression was increased in HCC, and was correlated with poor prognosis. The positive expression rate of PFKFB4 was positively correlated with M2-polarized TAM infiltration. PFKFB4 was up-regulated in HCC cells, which promoted the proliferation and migration of HCC cells via the glycolytic pathway and stimulated lactate production. Co-culture of TAMs with PFKFB4-overexpressing HCC cells promoted TAM M2 polarization. PFKFB4 stimulated tumor growth by promoting TAM M2 polarization via the glycolysis/lactate/H3K18la pathway in vivo. Conclusion PFKFB4 promoted lactate accumulation in the tumor microenvironment via glycolysis, stimulated the H3K18la/M2 polarization regulatory axis in TAMs, thus regulating the immune microenvironment and promoting HCC growth. Graphical The alternative text for this image may have been generated using AI.
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高影响因子
Materials
·
2026
·Vol. 19
·期 11
·2317
·
IF 3.7
Jiahui Xu,Xueying Zhang,Xiaohui Ma,Jiachen Liu
High-emissivity coatings on flexible fibrous fabrics are promising thermal-insulation materials for thermal protection systems in hypersonic vehicles. However, the interfacial bonding strength between the high-emissivity coating and the flexible fibrous substrate remains a critical challenge. A high-emissivity double-layer TiO2interlayer modified by metal ions (Mg2+, Co2+, Ni2+, and Zn2+) with high-entropy (M2+@TiO2-HE) coating was developed on an aluminosilicate fiber fabric. The interlayer of the M2+@TiO2-HE coating not only enhances bonding strength through mechanical interlocking but also improves thermal insulation performance by acting as an infrared reflective layer. The bonding strength between the M2+@TiO2-HE coating and the ASFF substrate showed an 183% enhancement compared to that of the single-layer high-emissivity high-entropy coating. Under one-sided heating at 1400 °C, the backside temperature of the coated ASFF stabilizes at 330 °C, which is approximately 50 °C lower than that of the sample with the single-layer high-emissivity high-entropy coating. In the wavelength range of 0.3–2.0 μm, the average reflectivity of the M2+@TiO2coating was 0.70, and in the wavelength range of 1–14 μm, the average emissivity of the M2+@TiO2-HE coating was 0.89. The M2+@TiO2-HE coating with high emissivity and reflectivity enhances both the bonding strength and thermal insulation performance of ASFF, showing its potential for applications in aerospace thermal protection systems.
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高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Siming Huang,Wangshu Zhu,Fang Zhang,Guosheng Chen,Xiaoxue Kou,Xieqing Yang,Gangfeng Ouyang,Jun Shen
Triple-negative breast cancer (TNBC) is typically associated with poor prognosis due to its only partial response to chemotherapy and lack of clinically established targeted therapies coupled with an aggressive disease course. Aerobic glycolysis is a hallmark of reprogrammed metabolic activity in cancer cells, which can be repressed by small-interfering RNA (siRNA). However, the lack of effective carriers to deliver vulnerable siRNA restricts the clinical potentials of glycolysis-based gene therapy for TNBC. Herein, we develop a tumor-targeted, biomimetic manganese dioxide (MnO2)-shrouded metal–organic framework (MOF) based nanomedicine to deliver siRNA against pyruvate kinase muscle isozyme M2 (siPKM2), wherein PKM2 is a rate-limiting enzyme in glycolysis, to inhibit the reprogrammed glycolysis of TNBC. This MOF-based genetic nanomedicine shows excellent monodispersity and stability and protects siPKM2 against degradation by nucleases. The nanomedicine not only substantially blocks the glycolytic pathway but also improves intracellular hypoxia in TNBC cells, with a resultant O2-enhanced anticancer effect. In the mice orthotopic TNBC model, the nanomedicine shows a remarkable therapeutic effect. Meanwhile, the Mn2+ ions released from acid microenvironment-responsive MnO2 enable in vivo monitoring of the therapeutic process with magnetic resonance imaging (MRI). Our study shows great promise with this MRI-visible MOF-based nanomedicine for treating TNBC by inhibition of glycolysis via the RNA interference.
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高影响因子
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