Frontiers in Pharmacology
·
2025
·
IF 4.8
Qian Feng,Cai-Zhi Li,Yi-Hua Zou,Xue-Yu Wang,Xia Yang,Rong Zhang*,Zhong-Qiu Liu*,Rong-Rong Zhang
Introduction: Brain metastasis (BM) is the most common and serious complication of breast cancer (BC). There is significant interest in investigating the crosstalk between BC cells and immune cells. β-elemene is the main pharmacodynamic component of Curcumae Rhizoma, a traditional Chinese medicine that is commonly used for the clinical treatment and prevention of various tumors. However, the specific underlying mechanism of β-elemene in BC-BM is still unclear.Methods: An intracardiac (ICT) injection model was used to establish specific BC-BM cells, then an intracarotid (ICD) injection model was used to verify the inhibitory effect of β-elemene in BC-BM. Tumor-cell-conditioned media, a primary microglia co-culture model, and an in vitro recruitment experiment were used to explore crosstalk between BC cells and immune cells. TMT-based quantitative proteomic, ELISA, IF, and other molecular biotechnologies were used to investigate the mechanisms.Results: The BC-BM cells established in our study not only increased BM rates but also exhibit mesenchymal phenotype and activated the JAK–STAT signaling pathway. Microglia, particularly M2 microglia, were enriched in BM lesions and secreted high levels of both IL6 and CCL2. Hypersecretory IL6 reversed the MET process of BC cells by regulating the JAK2/STAT3 signaling pathway to promote colonization in the brain. Increased levels of CCL2 significantly recruited monocytic myeloid-derived suppressor cells (M-MDSCs) to induce an immunosuppressive brain microenvironment. β-elemene could significantly inhibit BC-BM in mice by regulating the IL6/STAT3 signaling pathway and suppressing the M-MDSC recruitment.Conclusion: Our work first demonstrated that β-elemene regulated the IL6/STAT3 axis and M-MDSC recruitment to reconstruct immunosuppressive brain microenvironment to suppress BC-BM.
研究领域:
肿瘤学
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免疫学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shun Yu,Ying Luo,Xiaoli Jia,Pan Du,Zili Sun,Yuying Wang,Guozhong Lyu,Chenyang Liu
Our previous research established that treatment with IFN-γ and TNF-α (IT) significantly enhanced the paracrine activity of MSCs, resulting in a more effective wound healing response when applied to the wound surface with supernatant from IT-stimulated MSCs (S-IT MSCs). While S-IT MSCs hold promise for advancing wound healing therapy, challenges remain in developing an approach that enhances therapeutic efficacy and simplifies administration. This study proposed a scaffold composed of sericin, known for its skin regeneration properties, to load S-IT MSCs, designated as Se + S-IT MSCs, for the protection of bioactive factors. Additionally, whether Se + S-IT MSCs exhibit a superior effect on wound healing was investigated using a rat total skin excision model. Results indicated that Se + S-IT MSCs outperformed silk sericin loaded with MSC supernatant (Se + S-MSCs) in promoting migration, proliferation, and activation of HUVECs, HaCaTs, macrophages, and HDFs. Furthermore, Se + S-IT MSCs significantly promoted macrophage polarization toward the M2 phenotype, potentiated vascularization and re-epithelialization, and enhanced collagen deposition. These effects collectively accelerated wound healing in vivo in rats. This study highlights the potential of Se + S-IT MSCs to facilitate rapid and effective wound healing, with silk sericin scaffolds serving as efficient carriers to expedite the process.
研究领域:
再生医学
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组织工程
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免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
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.
研究领域:
生物医学工程
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糖尿病研究
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组织修复与再生
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DOI
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2019
·Vol. 9
·期 8
·1108-1113
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IF 0.824
Fan Gaofu,Xu Zhenguo,Tang Jie,Liu Longyun,Dai Ruomeng
Objection: To study the effect of modified formulae for ellagic acid (EA) on wound healing and macrophage phenotype transformation in diabetic mice. Materials and Methods: 10 db/m mice regarded as normal group, Dividing 20 db/db mice as the model group and EA group, 10
in every group. Surgical operation on the back was made to prepare experimental wound models. External medicines were applied and changed dressings every other day and measurement. Wound tissues were gained when animals were sacrificed by anesthesia 7 days later. Pathological changes were
observed by HE and Masson staining methods, while using RT-PCR and IHC to measure mRNA and protein levels of MI/M2 type cytokines of the wound tissues. Results: Compared with the normal group, the wound area of db/db was greater (P < 0.001), while EA group less (P <
0.001). IL-12 and TNF-α mRNA and proteins levels in model group were higher (P < 0.001, respectively), while VEGF and TGF-βmRNA and proteins were lower. mRNA and protein levels of inflammato cytokines of EA group was all lower (P < 0.001), while
the growth factor were significantly higher (P < 0.001). Conclusion: Wound healing of db/db mice was delayed and modified formulae for EA had effects on wound healing. The way by decreasing the Ml type inf1ammatory factors and improving the M2 type growth factors might be
one of the mechanisms for wound healing.
研究领域:
医学
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药理学
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分子生物学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Chunyou Lai,Yunchao Yang,Pengfei Wei,Guangming Xiang,Guan Wang,Shasha Liu,Li Zeng,Guanghong Du,Ke Yang,Maozhu Yang,Xueying Zhang,Yunhuan Li,Xueqiao Yu,Bo Zhao,Yutong Yao
Pancreaticojejunostomy presents significant challenges due to the high risk of complications such as pancreatic leakage and poor tissue regeneration. However, current approaches to enhance surgical outcomes are often limited by issues related to biocompatibility, tissue repair efficacy, and inflammation modulation. Here, we report the potential of an adhesive polyethylene glycol (PEG) hydrogel incorporating M2 macrophage-derived exosomes (PEG/Exo M2 ) for improving tissue repair in pancreaticojejunostomy. M2 macrophage-derived exosomes exhibit potent anti-inflammatory properties and pro-angiogenic effects, making them ideal candidates for tissue regeneration. The PEG/Exo M2 hydrogel demonstrates excellent mechanical strength and strong antibacterial activity. In vitro assays reveal that the PEG/Exo M2 hydrogel promotes angiogenesis and cell migration while modulating inflammatory responses. In animal models, the PEG/Exo M2 hydrogel effectively reduces fibrosis and inflammation in a subcutaneous implantation model, and significantly improves tissue regeneration. In a pancreaticojejunostomy model, the PEG/Exo M2 hydrogel facilitates wound sealing, lowers the risk of pancreatic leakage, and enhances anastomotic repair, outperforming conventional sutures. These results highlight the PEG/Exo M2 hydrogel as a promising biomaterial for tissue repair and regeneration, with strong potential for clinical applications in surgical wound healing.
研究领域:
生物材料学
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再生医学
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外科手术
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DOI
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-11
·
IF 3.9
Yi Zhirong,Jia Qingling,Wang Yujiao,Zhang Yuqin,Xie Tianyi,Ling Jianghong
Background Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.Methods The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.Results Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.Conclusion sThe results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.
研究领域:
药理学
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肿瘤学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jianfa Wu,Lingli Jiang,Sihong Wang,Lei Peng,Rong Zhang,Zhou Liu
The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-β1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-β1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-β1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-β1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-β1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-β1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2025
·Vol. 39
·期 1
·27
·
IF 3.1
Xu Jianfeng,Lei Deng,Xu Peng,Wang Yuqi,Li Zhupeng,Wu Jiacheng,Feng Weizhong,Zhou Junqing
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic success, partly due to heterogeneous responses to neoadjuvant chemotherapy (NAC). Tumor-derived exosomes and tumor-associated macrophages play critical roles in shaping the immunosuppressive tumor microenvironment, but their crosstalk in EC chemoresistance remains unclear. In this study, we identified tumor-derived exosomal miR-145-5p as a potential predictor of poor NAC response. Elevated exosomal miR-145-5p levels were associated with increased M2 macrophage infiltration and enhanced expression of M2 markers in EC tissues. Mechanistically, miR-145-5p promoted M2 macrophage polarization through the suppression of transferrin receptor (TFRC) and subsequent disruption of iron uptake. Consequently, these tumor-promoting M2-polarized macrophages enhanced EC cell proliferation, migration, invasion, and cisplatin resistance. In vivo, macrophages overexpressing miR-145-5p facilitated tumor growth and markedly weakened the therapeutic effects of cisplatin. Overall, our findings reveal that EC cells utilize exosomal miR-145-5p to remodel macrophages into a pro-tumorigenic phenotype through TFRC-dependent iron metabolic reprogramming, contributing to malignant progression and chemoresistance. Exosomal miR-145-5p may represent a promising biomarker for NAC response and a therapeutic target to improve treatment outcomes in EC.
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Shukun Zhao,Qiong Jiang,Ling Yu,Quan Liu,Zi Chen,Danting Zhan,Shuyu Chen,Yuqiong Yang,Jiacheng Zhong,Bingxin Guo,Fei Shi,Rongchang Chen,Lingwei Wang,Lang Rao,Junxia Zheng,Qian-Fang Meng,Shanze Chen
Eosinophilic asthma is a chronic inflammatory disease driven by Type 2 immune cells and cytokines. While cytokine-based immunotherapies have shown promising efficacy in asthma treatment, current approaches often fail to simultaneously target multiple cytokines. In this study, we present nanodecoys derived from the cellular membranes of M2 macrophages, which exhibit a high density of cytokine receptors, enabling efficient sequestration of multiple Type 2 cytokines. This mechanism significantly alleviates OVA-induced eosinophilic asthma inflammation in mice. To enhance therapeutic efficacy, D-mannose glycans, a potential immunoregulatory molecule for asthma, were modified onto the surface of the nanovesicles. This modification facilitates the phagocytic clearance of absorbed cytokines by targeting the mannose receptor (CD206). Consequently, the mannose-modified nanovesicles exhibit synergistic immunosuppressive effects on asthmatic inflammation by inhibiting M2 macrophage polarization, CD4+ T cell Th2 polarization, and eosinophil activation, as revealed by single-cell RNA sequencing and in vitro analyses. In summary, this study presents a safe and effective nanotechnology-based immunotherapy for asthma and potentially other Type 2 inflammatory diseases.
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yumeng Guo,Fei Chen,Qian Wang,Siqi Huang,Ziyu Chen,Quan Zhou,Congju Li,Ying Zheng
Continuous decompression and drainage are a vital surgical strategy for managing severe tissue infections. In vital pulp therapy (VPT) for irreversible pulpitis, there is a clinical demand for advanced biomaterials capable of effectively sealing the pulp cavity, alleviating pulpal hypertension, preventing bacterial infiltration, and resolving acute pulp inflammation in bacteria-rich environments. In this study, we developed a polydopamine@zinc oxide nanoparticle (ZnO-NP)-coated polytetrafluoroethylene (PTFE) membrane with tunable Zn content ranging from 2.51 to 7.45 wt%. The polydopamine enhanced ZnO-NP adhesion to the PTFE membrane, enabling superior fluid permeability and robust antibacterial efficacy against E. faecalis and S. mutans , while maintaining excellent biocompatibility. In a minipig pulpitis model, the ZnO-coated membrane significantly outperformed iRootBP PLUS by promoting faster dentine bridge formation (934.0 ± 91.3 μm vs. 116.3 ± 45.4 μm), preserving the integrity of the underlying pulp tissue and inducing M2 macrophage polarization.These findings deomstrate that ZnO-functionalized fibrous membrane can address key challenges in VPT by alleviating pulp hypertension, preventing microbial invasion, and simultaneously promoting pulp tissue regeneration. This approach offers a promising strategy to enhance tharepeutic outcomes of vital pulp therapy.
研究领域:
生物材料
·
牙科医学
·
组织工程
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 20
·5666-5676
·
IF 6.183
Qi Wei,Na Shen,Haiyang Yu,Yue Wang,Zhaohui Tang,Xuesi Chen
Combretastatin A4 nanoparticles (CA4-NPs), which notably inhibit tumor growth, were found to cause tumor regrowth due to the intratumoral enrichment of M2-type macrophages after treatment. Since BLZ945, an inhibitor of CSF-1 receptor (CSF-1R), depletes and inhibits the proliferation of M2-type macrophages, it has the potential to relieve the immunosuppressive microenvironment and improve anti-tumor therapy of CA4-NPs. However, CSF-1R exists widely, not only in macrophages, and BLZ945 could cause potential hepatotoxicity. It is necessary to establish a tumor-targeting drug delivery system to reduce the off-target and side effects of BLZ945. In this study, FXIIIa substrate peptide A15 decorated BLZ945 nanoparticles (A15-BLZ-NPs) were developed, in which, BLZ945-poly(D,L-lactide) (BLZ945-PLA), produced by ring-opening polymerization, was encapsulated in poly(ethylene glycol)-poly(D,L-lactide) (PEG5k-PLA5k), and A15 was decorated on the surface PEG segment. A15-BLZ-NPs could crosslink with fibrin through elevated FXIIIa and specifically target intratumoral coagulation spots induced by CA4-NPs. In vivo studies showed that CA4-NPs induced enhanced distribution of BLZ945 in tumors, as the BLZ945 content was 3.75-fold in the CA4-NP + A15-BLZ-NP group compared to that of A15-BLZ-NP single treatment. Meanwhile, compared to the CA4-NP group, the combination treatment significantly reduced the proportion of M2-type macrophages (from 64.4% to 24.5%) and enriched cytotoxic T lymphocytes (from 1.5% to 18.9%) in tumors, suggesting that A15-BLZ-NPs remodeled and activated tumor immunity after CA4-NP treatment. Furthermore, the combined treatment effectively improved the tumor inhibition rate to 73.4%, which was significantly higher than that of CA4-NP (15.5%) or A15-BLZ-NP (23.9%) single treatment. This work established a novel combination strategy for anti-tumor therapy.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 30
·2202201
·
IF 15.153
Hongqin Zhu,Feng Ren,Tingting Wang,Zhilin Jiang,Qiao Sun,Zhen Li
Developing dynamic and highly sensitive methods for imaging M2-type tumor-associated macrophages (TAMs) is vital for monitoring the tumor progression and assessing the therapeutic efficacy. Here, the fabrication and application of rationally designed Er-based rare-earth nanoprobes for the targeted imaging of M2-type TAMs in glioblastoma (GBM) through the second near-infrared (NIR-II) fluorescence beyond 1500 nm is reported. The NIR-IIb fluorescence of Er-based rare-earth nanoparticles can be remarkably enhanced by optimizing their core-shell structures and the shell thickness, which allows for in vivo imaging under excitation by a 980 nm laser with the lowest power density (40 mW cm -2 ). These bright Er-based nanoparticles functionalized with M2pep polypeptide show notable targeting ability to M2-type macrophages, which has been well tested in both in vitro and in vivo experiments by their up-conversion (UC) fluorescence (540 nm) and down-shifting (DS) fluorescence (1525 nm), respectively. The targeting capability of these nanoprobes in vivo is also demonstrated by the overlap of immunofluorescence of M2-type TAMs and Arsenazo III staining of rare-earth ions in tumor tissue. It is envisioned that these nanoprobes can serve as a companion diagnostic tool to dynamically assess the progression and prognosis of GBM.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
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