Journal of Stroke & Cerebrovascular Diseases
·
2021
·
IF 2.136
Zhiyu Xi,Canxin Xu,Xiao Chen,Baofeng Wang,Zhihong Zhong,Qingfang Sun,Yuhao Sun,Liuguan Bian
Objectives Microglia activation, a key process in secondary injury following intracerebral hemorrhage (ICH), is divided to M1 and M2 phenotype. Protocatechuic acid (PCA) is a phenolic acid been proved neuroprotection in ICH without understanding of details. Thus, this study aimed to observe the influence of PCA on microglia activation and explore underlying mechanisms. Materials and methods To assess PCA affected microglia activation in vivo, an experimental ICH mice model was established and then treated with PCA intraperitoneal injection . Immunofluorescence staining was performed in brain slices at day 3 post ICH. BV2 cells were stimulated with hemin for activation, then M1 and M2 biomarkers were analyzed using Western Blot and qPCR. At last, we detected the expression of mTOR and its downstream molecules to discuss possible mechanisms. Results At day 3 post ICH, less activated microglia gathering around hematoma after PCA treatment . Furtherly, in hemin treated BV2 cells, PCA downregulated M1 and promoted M2 biomarkers expression in both mRNA and protein level. PCA inhibited the phosphorylation of mTOR, S6K1 and 4E-BP1, while the inhibition was disappeared after supplemented with mTOR activator. Conclusions PCA impacted microglia activation by suppressing the mTOR signaling pathway , thereby improving M1/M2 switch and attenuated neuroinflammation .
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CANCER IMMUNOLOGY IMMUNOTHERAPY
·
2024
·Vol. 73
·期 7
·1-24
·
IF 4.6
Liu Hongxu,Yao Maojin,Ren Jiaoyan
The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.
研究领域:
免疫学
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肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhihuang Zhang,Yan Peng,Liyan Qiu
The enrichment of M2-phenotype tumor-associated macrophages (TAMs) is the main factor to create an immunosuppressive microenvironment, which seriously attenuates antitumor treatment. Herein, we explored the capability of rigid nanoparticles to reprogram TAMs to the M1-like phenotype via mechanical force. We designed and synthesized amphiphilic copolymer PLA- b -PItEG initiated by the HO-Pd(II) complex. In contrast to polyethylene glycol, the hydrophilic PItEG segments have a helical conformation, which endows the self-assembled PLA- b -PItEG nanoparticles with stiff surface characteristics of higher Young’s modulus and hydrophobicity. The rigid nanoparticles displayed strong interaction with TAMs to produce greater deformation of cell membrane and activated mechanosensitive potassium ion channel. Consequently, rigid nanoparticles exerted a positive effect on the proinflammatory polarization of TAMs. The expression level of CD86, a typical M1 macrophage marker, was increased by 60% compared with that in the soft PEG-NP group while CD206, a typical M2 macrophage marker, was decreased. Furthermore, several M1-related cytokines such as TNF-α, IL12p40, IL-6 and IL-1β were upregulated. In vitro and in vivo immune responses triggered by rigid nanoparticles could significantly inhibit B16F10 tumor growth with 71.44% tumor inhibitory rate. This study offers new insight into the use of mechanical forces for tumor immunotherapy.
研究领域:
纳米技术
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免疫治疗
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
·
IF 6.953
Huayan Yang,Sijia Lu,Shengkun Wang,Lihong Liu,Bo Zhu,Shaoning Yu,Shouning Yang,Junbiao Chang
When nanoparticles (NPs) come into contact with bioenvironments, a protein corona forms on the NP surface. Previous reports showed that the constituents of the corona change with time. However, how different protein corona compositions influence cells, especially immune cells, has received less attention. Macrophages are important immune cells that can be polarized into a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype. In this study, AuNPs were incubated with human plasma for different periods to obtain time-related AuNP-coronas, and the influences of time-related AuNP-coronas on macrophage polarization were investigated. The macrophage morphology, biomarkers, cytokine secretion studies show that the pristine AuNPs and 4 h-AuNP-corona induced macrophage cells into M2 phenotype, while the co-incubation of 12 h-AuNP-corona and macrophage cells result in M1 phenotype. Further proteomic analysis showed that the compositions of protein corona were changing constantly after AuNPs contacted with plasma. When the incubation time increased to 12 h, the immune proteins in protein corona were increased significantly, which play a key role in modulation of the different macrophages polarization. Our findings demonstrated that plasma incubation time is an important parameter that needs to be taken into account in the study of nano-immune interactions and safe use of NPs in biological systems. Moreover, our finding can be a new efficient strategy for activating inflammatory or anti-inflammatory in medical treatment.
研究领域:
纳米技术
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免疫学
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生物医学工程
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蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2023
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IF 5.8
Xingming Wang,Xiupeng Zhu,Danni Wang,Xiaoxu Li,Juan Wang,Guangfu Yin,Zhongbing Huang,Ximing Pu
Inefficient use and loss of exogenously implanted mesenchymal stem cells (MSCs) are major concerns in MSCs-based bone tissue engineering. It is a promising approach to overcome the above issues by recruiting and regulation of endogenous MSCs. However, there are few substances that can recruit MSCs effectively and specifically to the site of bone injury. In this study, we identified a phage clone (termed P11) with specific affinity for MSCs through phage display biopanning, and further investigated the effects of P11 on the cytological behavior of MSCs and macrophages. The results showed that P11 could bind MSCs specifically and promote the proliferation and migration of MSCs. Meanwhile, P11 could polarize macrophages to the M1 phenotype and significantly changed their morphology, which further enhanced the chemotaxis of MSCs. Additionally, RNA-seq results revealed that P11 could promote the secretion of osteogenesis-related markers in MSCs through the TPL2-MEK-ERK signaling pathway. Altogether, P11 has great potential to be used as growth factor alternatives in bone tissue engineering, with the advantages of cheaper and stable activity. Our study also advances the understanding of the effects of phages on macrophages and MSCs, and provides a new idea for the development in the field of phage-based tissue engineering.
研究领域:
组织工程
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干细胞生物学
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骨再生
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噬菌体疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2021
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IF 6.684
Zang Jiankun,Wu Yousheng,Su Xuanlin,Zhang Tianyuan,Tang Xionglin,Ma Dan,Li Yufeng,Liu Yanfang,Weng Ze’an,Liu Xuanzhuo,Tsang Chi Kwan,Xu Anding,Lu Dan
Exosomes contribute to cell–cell communications. Emerging evidence has shown that microglial exosomes may play crucial role in regulation of neuronal functions under ischemic conditions. However, the underlying mechanisms of microglia-derived exosome biosynthesis are largely unknown. Herein, we reported that the microglial PDE1-B expression was progressively elevated in the peri-infarct region after focal middle cerebral artery occlusion. By an oxygen-glucose-deprivation (OGD) ischemic model in cells, we found that inhibition of PDE1-B by vinpocetine in the microglial cells promoted M2 and inhibited M1 phenotype. In addition, knockdown or inhibition of PDE1-B significantly enhanced the autophagic flux in BV2 cells, and vinpocetine-mediated suppression of M1 phenotype was dependent on autophagy in ischemic conditions. Co-culture of BV2 cells and neurons revealed that vinpocetine-treated BV2 cells alleviated OGD-induced neuronal damage, and treatment of BV2 cells with 3-MA abolished the observed effects of vinpocetine. We further demonstrated that ischemia and vinpocetine treatment significantly altered microglial exosome biogenesis and release, which could be taken up by recipient neurons and regulated neuronal damage. Finally, we showed that the isolated exosome per se from conditioned BV2 cells is sufficient to regulate cortical neuronal survival in vivo. Taken together, these results revealed a novel microglia-neuron interaction mediated by microglia-derived exosomes under ischemic conditions. Our findings further suggest that PDE1-B regulates autophagic flux and exosome biogenesis in microglia which plays a crucial role in neuronal survival under cerebral ischemic conditions.
研究领域:
神经科学
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药理学
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细胞生物学
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神经保护
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产品关联
DOI
PubMed
高影响因子
NPG Asia Materials
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2018
·Vol. 10
·期 10
·1002-1015
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IF 7.208
Huang Yanyu,Mei Chaoming,Tian Yiqiao,Nie Tianqi,Liu Zhuang,Chen Tianfeng
Rational design of smart nanosystems with high biological safety is a critical milestone for realizing precise imaging-guided cancer theranostics. Herein, a bioinspired nanosystem was designed by camouflaging SPIO@DOX-ICG nanoparticles with cancer cell membrane (CCM) to realize precise cancer treatment through simultaneous chemotherapy, hyperthermia-therapy, and radiotherapy. CCM surface decoration preserves the cancer adhesion molecules and surface antigens in the nanosystem, endowing the nanosystem with tumor-homing ability and high biocompatibility. Guided by dual-modal imaging, the nanosystem specifically accumulated in the tumor region and achieved synergistic anticancer effects after combined treatment, without causing toxic side effects in major organs. Interestingly, the combined treatment also antagonized tumor hypoxia and reprogrammed the polarization of tumor associated macrophages to the antitumor M1 phenotype. Taken together, this study offers a smart strategy for designing a bioinspired tumor-homing nanosystem for precise cancer therapy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Liqiang Wang,Xiaoyu Yuan,Qianyu Cai,Yutong Chen,Zhi Jia,Qiongmei Mai,Jie Liu,Yanan Liu
ABSTRACT Mitochondrial dysfunction in microglia has been implicated as a key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). Abnormal production of reactive oxygen species (ROS) and neuroinflammation caused by mitochondrial oxidative stress are important factors leading to neuronal death in AD. Herein, a "dual brake" strategy to synergistically halt mitochondrial dysfunction and neuroinflammation targeting mitochondria in microglia is proposed. To achieve this goal, (3-carboxypropyl) triphenyl-phosphonium bromide (TPP)-modified Cu 2-x Se nanozymes (Cu 2-x Se-TPP NPs) with dual enzyme-like activities was designed. Cu 2-x Se-TPP NPs with superoxide dismutase-mimetic (SOD) and catalase-mimetic (CAT) activities can effectively scavenge ROS in the mitochondria of microglia and relieve mitochondrial oxidative stress. In vivo studies demonstrated that Cu 2-x Se-TPP NPs can alleviate oxidative stress and promote neuroprotection in the hippocampus of AD model mice. In addition, Cu 2-x Se-TPP NPs can regulate the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, promote A β phagocytosis and reshape the AD inflammatory microenvironment, thus effectively attenuating AD neuropathology and rescuing cognitive deficits in AD model mice. Taken together, this strategy preventing mitochondrial damage and remodeling the inflammatory microenvironment will provide a new perspective for AD therapy.
研究领域:
神经科学
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药理学
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纳米技术
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生物医学工程
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jia-Xian Li,Na Shu,Yao-Jun Zhang,Qi-Song Tong,Ling Wang,Jing-Yang Zhang,Jin-Zhi Du
Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.
研究领域:
药理学
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免疫学
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纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2023
·
IF 14.5
Huiwen Liu,Honglan Wang,Qiyu Li,Yiwei Wang,Ying He,Xuejing Li,Chunyan Sun,Onder Ergonul,Füsun Can,Zhiqing Pang,Bo Zhang,Yu Hu
Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro , the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo , the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
研究领域:
药理学
·
心血管疾病
·
炎症
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纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Yuqing Wang,Danyu Yao,Linhao Li,Zhiyong Qian,Wei He,Rui Ding,Haifeng Liu,Yubo Fan
Biomaterial implantation is followed by an inflammatory cascade dominated by the macrophages, which polarized to the proinflammation M1 phenotype or prohealing M2 phenotype. Generally, silk sericin (SS) is considered to be of high immunogenicity associated with native silk fibers. The blends of silk fibroin (SF) and SS in different mass ratios might elicit different host immune responses and induce macrophage phenotype switch. The objective of this study was to assess the effects of electrospun SF–SS fibrous films with different mass ratios (10:0, 9:1, 8:2, and 7:3) on the macrophage phenotypes and explore the optimal ratio of SF and SS for angiogenesis. Our results indicated that the macrophages were activated by the addition of SS. When the mass ratio of SF and SS reached 7:3, the film displayed the highest degree of vascularization. The macrophages were induced to secrete more M1 and M2 cytokines accompanying with high M2/M1 ratio. Taken together, this study provided a perspective to promote neovascularization by modulating appropriate host response and macrophage phenotypes in tissue engineering field.
研究领域:
生物材料
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免疫学
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Mei Xie,Jiao-Jiao Hao,Jun-Zhuo Shi,Yun-Feng Zhou,Peng-Fei Liu,Feng Wang,Xiao-Ming Zheng,Xiu-Ying Yu,Chen-Chen Wang,Yi Yan,Guan-Hua Du,Jun-Ke Song,Yang-Yang He,Xiao-Bin Pang
Alzheimer’s disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1β and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.
研究领域:
神经科学
·
药理学
·
神经退行性疾病
·
炎症
✓ 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）