CELLULAR SIGNALLING
·
2025
·
IF 3.7
Caiqi Xu,Yaoyao Wu,Sui Yang,Xuechun Zhao,Hao Zhang,Yunwen Yan,Jiemin Zhao,Wei Wei,Qian Meng,Yujuan Wang,Rui Zhang
DJ-1, also known as PARK7 (Parkinson's disease protein 7), which is involved in cell viability, apoptosis, transcriptional regulation, and oxidative stress adaptation, is also involved in the pathogenesis of various human diseases including carcinogenesis. Here, we aimed to determine the novel mechanism by which DJ-1 inhibition suppresses tumor growth. Our results showed that DJ-1 knockdown in cancer cells promoted the secretion of a significantly larger amount of mitochondrial transcription factor A (TFAM) into the cell culture medium. DJ-1 knockdown promotes p53 translocation to the mitochondria and stimulates the intrinsic mitochondrial apoptosis pathway, resulting in TFAM release. Moreover, DJ-1 knockdown induced the downregulation of sirtuin 3 (SIRT3), which increased the acetylation of TFAM and triggered its release. Furthermore, we found that extracellular TFAM played a critical role in antitumor activity by upregulating the expression of chemokine (C C motif) ligand 4 (CCL4) and chemokine (C-X-C motif) ligand 5 (CXCL5) in cancer cells, contributing to the promotion of M1 macrophage polarization in the tumor microenvironment (TME). Finally, we confirmed that the DJ-1 inhibitor suppressed tumor growth by increasing TFAM release from cancer cells and M1 macrophage polarization in vivo. These findings indicate that the depletion of DJ-1 stimulates apoptosis-dependent TFAM secretion that triggers M1 macrophage polarization, indicating a new therapeutic strategy by interfering with the DJ-1 function in cancer therapy.
研究领域:
肿瘤学
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免疫学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Donglin Cai,Zhelun Li,Wendong Gao,Yuqing Mu,Jiaying Liu,Yufeng Zhang,Xiaohan Mei,Jingjing Quan,Lan Xiao,Yin Xiao
The temporary transition of macrophages from a pro-inflammatory macrophages (M1) to an anti-inflammatory macrophages (M2) is crucial for tissue repair and regeneration processes. Selectively targeting M1 macrophages is preferred to modulate inflammatory responses. However, macrophage populations are inherently heterogeneous, and the competitive phagocytosis of nanoparticles (NPs) by these two subtypes has not been thoroughly investigated. This study establishes a 3D cell co-culture system to evaluate the competitive phagocytosis of M1-targeting NPs under dynamic fluidic flow conditions. Bacterial outer membrane vesicles (OMVs) are utilized as a “trojan horse” to decorate gold nanocage (AuNC), creating hybrid NPs (AuNC-OM) capable of selectively targeting M1 macrophages. It is noted that the selective uptake of AuNC-OM by M1 macrophages is mediated through phagocytosis-related receptors CD64 and CD14, which are highly expressed on the M1 macrophage surfaces. Furthermore, the study demonstrates that AuNC-OM selectively targets M1 macrophages without affecting the phagocytosis of M2 macrophages. Once internalized, the nanoparticles release anti-inflammatory drugs, effectively reversing the inflammation. The release of dexmedetomidine from AuNC-OM protects against lipopolysaccharide (LPS)-induced bone resorption in a mouse model. This study presents a novel system for accurately assessing the M1 macrophage-targeting capabilities and introduces an innovative strategy for M1 macrophage-targeted therapy.
研究领域:
免疫学
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Tianying Bian,Hu li,Haohao Liu,Mudi Guo,Yiding Zhang,Pinli Hu,Meihua Chen
Objectives To explore the effects and biological mechanism of apabetalone on periodontal inflammation by regulating glycolysis and metabolites. Methods A ligature-induced periodontitis model was established in mice and apabetalone was administered on the ligation silk for two weeks. Inflammation levels and alveolar bone absorption were explored using micro-computed tomography and histopathological analysis. To observe the role of apabetalone in macrophage polarization and the macrophage-mediated immune microenvironment, a Luminex assay, quantitative real-time polymerase chain reaction, a conditioned medium experiment, a Seahorse extracellular flux assay and quantitative metabolomics were used for molecular biological analysis. Results Apabetalone-treated mice exhibited ameliorated alveolar bone loss and inflammatory infiltration in the periodontium. Furthermore, apabetalone significantly inhibited the production of proinflammatory cytokines and suppressed the levels of M1-specific biomarkers both in vivo and in vitro . Apabetalone also promoted the osteogenic potential of mouse periodontal ligament cells in a macrophage-mediated microenvironment. Apabetalone restrained LPS-induced glucose uptake and lactic acid production. Apabetalone inhibited glycolysis by suppressing the transcription and protein expression of hexokinase 2, glucose transporter 1 and phosphofructokinase-2/fructose-2,6- bisphosphatase 3 (PFKFB3) in a dose-dependent manner. Quantitative analysis of certain carbohydrates involved in energy metabolism revealed that apabetalone reserved the disruption of the tricarboxylic acid (TCA) cycle and inhibited glycolysis and the pentose phosphate pathway. In addition, apabetalone increased the oxygen consumption rate. Conclusion Collectively, these findings indicate that apabetalone improves the periodontal immune microenvironment by regulating metabolites in macrophages. Apabetalone exerts anti-inflammatory and osteo-protective effects by replenishing the broken TCA cycle and suppressing glycolysis. Apabetalone is a potential candidate for the treatment of periodontitis.
研究领域:
口腔医学
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免疫学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Biology
·
2025
·
IF 2.6
Xi-Ting Lv,Wen-Xiu Yang,Xiao Zhang,Bao-Ling Li,Wen-Ying Wang,Guo-En Wang
Guilongwan (GLW), a representative of traditional Chinese Medicine (TCM) has been utilized to treating diabetic foot ulcer (DFU)-related syndrome including an intolerance of cold with cold limbs, blood circulation disorder, and immune dysfunction for decades. However, the chemical and biological mechanisms of GLW remain unclear. This study aims to discover the biological mechanisms of GLW on DFU by using streptozotocin- and skin-puncher-induced DFU rat models, in vitro macrophage models, and in silico analysis. The alterations in pathology, Notch1 signaling, and macrophage polarization are detected. The results indicated that GLW promoted wound healing, cutaneous cell proliferation, and angiogenesis in DFU rats by inhibiting delta-like (DLL) 4/Notch1 signaling. In addition, GLW inhibited M1 polarization and promoted M2 polarization in diabetic wounds. Seventeen chemical compounds in GLW-medicated serum are identified. In silico analysis and in vitro experiments demonstrated that GLW-medicated serum and its main compounds inhibited the expression of DLL4 in matrix metalloproteinase-9-induced M1 macrophages. In conclusion, GLW ameliorated experimental DFU rats via the inhibition of DLL4/Notch1 signaling in M1 macrophages. This study provided a new biologic mechanism for GLW in the treatment of DFU.
研究领域:
药理学
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分子生物学
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中医药学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 9
·2243
·
IF 5.4
Jiayi Zhang,Bing Gu,Shimiao Wu,Lin Liu,Ying Gao,Yucen Yao,Degong Yang,Juan Du,Chunrong Yang
Tumor hypoxia is considered one of the key causes of the ineffectiveness of various strategies for cancer treatment, and the non-specific effects of chemotherapy drugs on tumor treatment often lead to systemic toxicity. Thus, we designed M1 macrophage-biomimetic-targeted nanoparticles (DOX/CAT@PLGA-M1) which contain oxygen self-supplied enzyme (catalase, CAT) and chemo-therapeutic drug (doxorubicin, DOX). The particle size of DOX/CAT@PLGA-M1 was 202.32 ± 2.27 nm (PDI< 0.3). DOX/CAT@PLGA-M1 exhibited a characteristic core-shell bilayer membrane structure. The CAT activity of DOX/CAT@PLGA-M1 was 1000 (U/mL), which indicated that the formation of NPs did not significantly affect its enzymatic activity. And in vitro drug release showed that the cumulative release rate of DOX/CAT@PLGA-M1 was enhanced from 26.93% to 50.10% in the release medium of hydrogen peroxide, which was attributed to the reaction of CAT in the NPs. DOX/CAT@PLGA-M1 displayed a significantly higher uptake in 4T1 cells, because VCAM-1 in tumor cells interacted with specific integrin (α4 and β1), and thereby achieved tumor sites. And the tumor volume of the DOX/CAT@PLGA-M1 group was significantly reduced (0.22 cm3), which further proved the active targeting effect of the M1 macrophage membrane. Above all, a novel multifunctional nano-therapy was developed which improved tumor hypoxia and obtained tumor targeting activity.Keywords:tumor microenvironment;M1 macrophage;tumor hypoxia;catalase;cancer treatment
研究领域:
癌症生物学
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药学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Qianqian Zheng,Gui Mei,Ping Cheng,Yahong Li,Qingfeng Zhang,Mingwei Ye
Given the demonstrated mitigating effect of omega-9 monounsaturated fatty acids (ω-9MUFAs) on lipopolysaccharide (LPS)-induced acute lung injury (ALI), we deeply explored corresponding mechanisms. Sprague-Dawley rats experienced ALI modeling, and received ω-9 MUFAs (3 mg/kg) injection via the tail vein. Post incubation in 100 ng/mL phorbol-12-myristate-13-acetate and 100 ng/mL LPS for 24 h each, THP-1 macrophages were transfected with shHSPH1 and c-MYC overexpression plasmid. Lung injury detection depended on H&E staining. Levels of inflammation-related factors were detected by ELISA. Levels of inflammation-related factors, heat shock protein family H (Hsp110) member 1 (HSPH1), c-MYC, stimulator of interferon response CGAMP interactor 1 (STING) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were measured by qRT-PCR. Levels of pyroptosis-related factors, HSPH1, c-MYC, STING, NLRP3, and M1 macrophage biomarkers were assayed by Western blot. Proportion of M1 macrophages and pyroptosis were detected by flow cytometry. Localization of HSPH1 and CD68 was measured by immunofluorescence assay. ω-9MUFAs reduced the inflammation, the proportion of M1 and pyroptotic macrophages and levels of HSPH1, c-MYC, STING and NLRP3 in ALI rats. The expression positions of HSPH1 and CD68 were overlapped in ALI rat lung tissue. HSPH1 silencing reversed the changes in inflammation, the proportion of M1 and pyroptotic macrophages and levels of c-MYC, STING and NLRP3 in LPS-induced THP-1 macrophages, and c-MYC overexpression offset these effects of HSPH1 silencing. Collectively, ω-9MUFAs ameliorated LPS-induced ALI by regulating HSPH1/c-MYC expression, down-regulating M1 macrophage polarization and pyroptosis.
研究领域:
免疫学
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Wanyu Li,Qingbang Ye,Zhonghao Jiang,Dong Xia,Zhuo Yan,Dan Wang,Yanan Chen,Tianshou Cao,Jilong Wang,Chihao Lin,Huiling Yang,Junjie Deng,Jiantao Lin
Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy.
研究领域:
生物材料学
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Emergency Medicine International
·
2021
·
IF 1.112
Chen Zongyun,Lin Bixia,Ding Fadian,Hong Xiaoping,Chen Hongbin,Deng Yu,Liu Qicai,Ye Xiaoyi,Zeng Kai
Introduction. The advances in cerebral ischemia treatment have resulted in a larger proportion of patients get the benefits of rebuilding blood flow to the brain. Then, ischemia-reperfusion injury has emerged as a new essential problem. Dectin-1 plays an important role in cerebral ischemia-reperfusion injury by regulating the function of immune cells. Methods. C57BL/6 was blindly divided into four groups including the sham-operated group and the three different kinds of middle cerebral artery occlusion (MCAO) groups (after 6 hours, 12 hours, and 24 hours after plug removal). The protein expression levels of dectin-1, proapoptosis molecule, and antiapoptosis molecule were measured by using western blot analysis. The brain tissue was analyzed by flow cytometry to detect the M1 macrophage levels. Results. The correlation analysis of dectin-1 and infarct areas showed that there was an obviously positive correlation in between them (R = 0.9603). Dectin-1, cleaved caspase-3, and Bax increased, while antiapoptosis molecule, Bcl-2, decreased at three appropriate time points (after 6 hours, 12 hours, and 24 hours). The level of M1 macrophages in the experimental group increased after ischemia-reperfusion injury compared to the control group. Conclusions. The high expression level of dectin-1 may affect M1 macrophage polarization and brain cell apoptosis in cerebral ischemia-reperfusion injury.
研究领域:
神经科学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
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IF 3.095
Liang Pang,Ying Zhu,Jing Qin,Wenjie Zhao,Jianxin Wang
Glioma remains difficult to treat because of the infiltrative growth of tumor cells and their resistance to standard therapy. Despite rapid development of targeted drug delivery system, the current therapeutic efficacy is still challenging. Based on our previous studies, macrophages have been proved to be promising drug carrier for active glioma delivery. To make full use of macrophage carrier, primary M1 macrophages were proposed to replace regular macrophage to deliver nanodrugs into glioma, because M1 macrophages not only have the natural ability to home into tumor tissues, but they also have stronger phagocytic capability than other types of macrophage, which can enable them to uptake enough drug-loaded nanoparticles for therapy. In addition, M1 macrophages are not easily affected by harsh tumor microenvironment and inhibit tumor growth themselves. In this study, M1 macrophage-loaded nanoparticles (M1-NPs) were prepared by incubating poly(lactide-co-glycolide) (PLGA) nanoparticles with primary M1 macrophages. In vitro cell assays demonstrated M1 macrophage still maintained good tumor tropism capability after particle loading, and could efficiently carry particles across endothelial barrier into tumor tissues. In vivo imaging verified that M1-NPs exhibited higher brain tumor distribution than free nanoparticles. DOX@M1-NPs (doxorubicin-loaded M1-NPs) presented significantly enhanced anti-glioma effect with prolonged survival median and increased cell apoptosis. In conclusion, the results provided a new strategy exploiting M1 macrophage as carrier for drug delivery, which improved targeting efficiency and therapeutic efficacy of chemodrugs for glioma therapy.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Huahui Zeng,Man Li,Zhirong Wang,Tianqi Wang,Zhenqiang Zhang,Xiangxiang Wu
M1 macrophages play a crucial role in the development of rheumatoid arthritis (RA), which can produce various inflammation cytokines, and reactive oxygen species (ROS). Disulfide bonds as reduction-responsive linkages have been extensively employed in the drug delivery systems. However, disulfide bonds are rarely reported in the development of the oxidation-responsive drug carriers. Herein, we designed and synthetized novel oxidation-responsive drug carriers based on disulfide bonds, and further developed nanoparticles (FA-TP@NPs) by self-assembly for the RA treatment. FA-TP@NPs was decorated with folic acid and loaded with triptolide (TP), a potent anti-inflammation Chinese medicine, to target and enter M1 macrophages through the folate receptor on the cytomembrane for simultaneous repolarization of the M2 macrophage and elimination of the M1 macrophage. As expected, FA-TP@NPs exhibited an oxidation-responsive TP release via disulfide-bond oxidation and ester-bond hydrolysis in the presence of intracellular ROS, which accumulated preferentially in inflamed joints. FA-TP@NPs exerted a potent anti-arthritic effect with high biosafety in CIA mice, as evidenced by repolarizing M2 macrophages, inducing M1 macrophage apoptosis, and reducing TNF-α, IL-6, and IL-1β expression. This work shows that FA-TP@NPs give a deep insight into disulfide bond-based oxidation-responsive drug delivery systems, and provide a potential platform for RA treatment.
研究领域:
药学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-13
·
IF 3.8
Zhu Dongsheng,Chen Feng,Qiang Hongjia,Qi Han
To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4’s inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.
研究领域:
免疫学
·
分子生物学
·
细胞生物学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Xiaoling Zeng,Baohui Chen,Luping Wang,Yingxiao Sun,Zhao Jin,Xuanyong Liu,Liping Ouyang,Yun Liao
Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1β and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.
研究领域:
生物医学工程
·
药学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）