资源类型

期刊论文 9

年份

2023 4

2022 1

2021 1

2018 1

关键词

多模态鉴定 1

宣肺败毒方 1

巨噬细胞 1

巨噬细胞活化 1

巨噬细胞迁移 1

排斥反应 1

炎症 1

移植 1

耐受 1

调节性巨噬细胞 1

展开 ︾

检索范围：

排序： 展示方式：

Activation of phagocytosis by immune checkpoint blockade

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 473-480 doi: 10.1007/s11684-018-0657-5

摘要：

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.

关键词： CD47     PD-1     PD-L1     immunotherapy     TAM     phagocytosis     macrophage    

HTML PDF 收藏

Applications of atomic force microscopy in immunology

Jiping Li, Yuying Liu, Yidong Yuan, Bo Huang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 43-52 doi: 10.1007/s11684-020-0769-6

摘要： Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.

关键词： cellular mechanics     atomic force microscopy     neutrophil extracellular trap     macrophage phagocytosis     pore formation    

HTML PDF 收藏

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial

《医学前沿（英文）》 2023年 第17卷 第4期   页码 781-795 doi: 10.1007/s11684-023-0986-x

摘要： Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs’ metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

关键词： dry eye disease     glycolytic reprogramming     pyroptosis     inflammation     2-DG    

HTML PDF 收藏

Biomimetic Macrophage–Fe3O4@PLGA Particle-Triggered Intelligent Catalysis for Killing Multidrug-Resistant

Jieni Fu,Xiangmei Liu,Zhaoyang Li,Yufeng Zheng,Yu Zhang,Hui Jiang,Yanqin Liang,Shengli Zhu,Zhenduo Cui,Shuilin Wu,

《工程（英文）》 doi: 10.1016/j.eng.2023.05.022

摘要： Infections with multidrug-resistant (MRD) Gram-negative bacteria, such as MRD Escherichia coli (E. coli), remain a challenge due to the lack of safe antibiotics and high fatality rates under anti-infection therapies. This work presents a form of biomimetic intelligent catalysis inspired by the selective biocatalytic property of macrophages, consisting of an intelligent controlling center (a living macrophage, MΦ) and a Fenton reaction catalyst (Fe3O4@poly(lactic-co-glycolic acid) (PLGA) nanoparticles) for killing MDR E. coli without harming normal cells. The MΦ–Fe3O4@PLGA particles (i.e., the intelligent catalysis particles) exhibit selective biocatalysis activity toward MDR E. coli by producing H2O2 and lipid droplets (LDs). This process activates the lipid metabolism and glycan biosynthesis and metabolism pathways based on the result of RNA sequencing data analysis. The H2O2 further reacts with Fe3O4@PLGA to form highly toxic hydroxyl radicals (•OH), while the LDs contain antimicrobial peptides and can target MDR E. coli. The highly toxic •OH and antimicrobial peptides are shown to combat with MDR E. coli, such that the antibacterial efficiency of the MΦ–Fe3O4@PLGA particles against MDR E. coli is 99.29% ± 0.31% in vitro. More importantly, after several passages, the intelligent catalysis function of the MΦ–Fe3O4@PLGA particles is well maintained. Hence, the concept of biomimetic intelligent catalysts displays potential for treating diseases other than infections.

关键词： Multidrug-resistant Escherichia coli     Macrophage–Fe3O4@PLGA particles     Biomimetic intelligent catalysis    

HTML PDF 收藏

基于转录组学及多尺度生物测定多模态鉴定宣肺败毒方抑制巨噬细胞免疫反应的活性成分 Article

赵璐, 刘豪, 王迎超, 王书芳, 荀得金, 王毅, 程翼宇, 张伯礼

《工程（英文）》 2023年 第20卷 第1期   页码 63-76 doi: 10.1016/j.eng.2021.09.007

摘要：

宣肺败毒方（XFBD）是一种临床用于治疗新型冠状病毒肺炎（COVID-19）病患的中药方剂，在临床实践中表现出了显著的疗效，但对其潜在的药理学机制尚不清楚。本研究结合网络药理学、转录组学和多模型系统生物测定等综合研究方法，研究了XFBD生物活性物质及其药理作用机制。通过高分辨质谱与分子网络相结合，对XFBD中的主要活性物质进行了分析，共鉴定或初步鉴定了104种化合物，包括黄酮类、萜类、羧酸类和其他类型的成分。基于所鉴定的XFBD化学组分，开展了网络药理学分析并将炎症相关通路确定为主要靶点。在脂多糖诱导的急性炎症小鼠模型中，XFBD明显减轻了肺部炎症，降低了血清促炎细胞因子水平。转录组学分析表明，经XFBD治疗后，与巨噬细胞功能相关的基因表达水平发生改变。在巨噬细胞细胞系和斑马鱼创伤模型中，XFBD对巨噬细胞的激活和迁移均有很强的抑制作用。最终，通过多模型系统筛选，发现XFBD中虎杖、芦根、化橘红显著下调巨噬细胞活化，虎杖苷、异甘草苷、毛蕊花糖苷为活性化合物；青蒿和麻黄显著抑制内源性巨噬细胞迁移，麻黄碱、白术内酯和山奈酚为活性化合物。综上所述，本研究通过多模态方法研究了XFBD调节炎症的活性成分以及相关药理学机制，从而为XFBD的临床疗效提供了生物学例证。

关键词： 炎症     巨噬细胞活化     巨噬细胞迁移     多模态鉴定     宣肺败毒方    

HTML PDF 收藏

Application of StrucGP in medical immunology: site-specific -glycoproteomic analysis of macrophages

《医学前沿（英文）》 2023年 第17卷 第2期   页码 304-316 doi: 10.1007/s11684-022-0964-8

摘要： The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc4Hex5Fuc1Neu5Ac1, N4H5F1S1) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.

关键词： macrophage     glycoproteome     glycopeptides     N-glycan structures     PD-L1    

HTML PDF 收藏

巨噬细胞在器官移植急性排斥反应中的双重作用 Review

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

《工程（英文）》 2022年 第10卷 第3期   页码 21-29 doi: 10.1016/j.eng.2021.10.015

摘要：

天然免疫细胞在移植免疫反应中发挥着重要作用。巨噬细胞是重要的天然免疫细胞；在发生排斥反应的同种异基因移植器官中，巨噬细胞也是浸润的众多免疫细胞之一。巨噬细胞的浸润与器官移植的短期和长期效果呈负相关。在功能方面，巨噬细胞具有异质性和可塑性。在器官移植排斥反应中，巨噬细胞可以为适应性免疫提呈同种异基因抗原以及提供共刺激信号和细胞因子，也可以直接损伤移植器官。此外，一些具有免疫调节功能的巨噬细胞亚群，可以通过抑制排斥反应和促进免疫耐受来保护移植器官。尽管目前研究人员已认识到巨噬细胞在移植器官损伤过程中的潜在作用，但他们对巨噬细胞在移植排斥反应中的不同作用关注不够。为此，本文就巨噬细胞在急性移植免疫反应中的独特作用以及免疫抑制剂对巨噬细胞的影响进行了综述和讨论。通过分析发现，对于巨噬细胞在移植免疫中的作用的相关研究中，应更多地关注其复杂性和关键功能，并应更多地致力于开发针对巨噬细胞的免疫抑制药物，并使之有利于提高移植器官的长期存活率和移植免疫耐受的建立。

关键词： 巨噬细胞     移植     耐受     排斥反应     调节性巨噬细胞    

HTML PDF 收藏

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy

《医学前沿（英文）》 2023年 第17卷 第4期   页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment     tumor-associated macrophage     metabolism    

HTML PDF 收藏

SWIR Fluorescence Imaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration Article

Mo Chen, Yuzhou Chen, Sijia Feng, Shixian Dong, Luyi Sun, Huizhu Li, Fuchun Chen, Nguyen Thi Kim Thanh, Yunxia Li, Shiyi Chen, You Wang, Jun Chen

《工程（英文）》 doi: 10.1016/j.eng.2023.05.010

摘要：

Skeletal muscle has a robust regeneration ability that is impaired by severe injury, disease, and aging, resulting in a decline in skeletal muscle function. Therefore, improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders. Owing to their significant role in tissue regeneration, implantation of M2 macrophages (M2Mø) has great potential for improving skeletal muscle regeneration. Here, we present a short-wave infrared (SWIR) fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2Mø transplantation. SWIR fluorescence imaging was employed to track implanted M2Mø in the injured skeletal muscle of mouse models. It is found that the implanted M2Mø accumulated at the injury site for two weeks. Then, SWIR fluorescence imaging of blood vessels showed that M2Mø implantation could improve the relative perfusion ratio on day 5 (1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01) and day 9 (1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01) post-injury, as well as augment the degree of skeletal muscle regeneration on day 13 post-injury. Finally, multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration. These results provide more in vivo details about M2Mø in skeletal muscle regeneration and confirm that M2Mø could promote angiogenesis and improve the degree of skeletal muscle repair, which will guide the research and development of M2Mø implantation to improve skeletal muscle regeneration.

关键词： In vivo     Short-wave infrared     Skeletal muscle     Macrophage     Regeneration    

HTML PDF 收藏

标题 作者 时间 类型 操作

Activation of phagocytosis by immune checkpoint blockade

null

期刊论文

Applications of atomic force microscopy in immunology

Jiping Li, Yuying Liu, Yidong Yuan, Bo Huang

期刊论文

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial

期刊论文

Biomimetic Macrophage–Fe3O4@PLGA Particle-Triggered Intelligent Catalysis for Killing Multidrug-Resistant

Jieni Fu,Xiangmei Liu,Zhaoyang Li,Yufeng Zheng,Yu Zhang,Hui Jiang,Yanqin Liang,Shengli Zhu,Zhenduo Cui,Shuilin Wu,

期刊论文

基于转录组学及多尺度生物测定多模态鉴定宣肺败毒方抑制巨噬细胞免疫反应的活性成分

赵璐, 刘豪, 王迎超, 王书芳, 荀得金, 王毅, 程翼宇, 张伯礼

期刊论文

Application of StrucGP in medical immunology: site-specific -glycoproteomic analysis of macrophages

期刊论文

巨噬细胞在器官移植急性排斥反应中的双重作用

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

期刊论文

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy

期刊论文

SWIR Fluorescence Imaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Mo Chen, Yuzhou Chen, Sijia Feng, Shixian Dong, Luyi Sun, Huizhu Li, Fuchun Chen, Nguyen Thi Kim Thanh, Yunxia Li, Shiyi Chen, You Wang, Jun Chen

期刊论文