NEUROSCIENCE LETTERS
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2021
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IF 3.046
Hui Tian,Yahong Cheng,Yiyuan Zhang,Xinying Bai,Yuan Jiang,Jinjin Li,Shiqi Fan,Hong Ding
This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
研究领域:
神经科学
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药理学
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免疫学
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DOI
高影响因子
MOLECULAR CARCINOGENESIS
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2019
·Vol. 58
·期 8
·1481-1491
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IF 3.411
Yuan-yuan Guo,Chen Xu,Yan Fang,Cai-e Wang,Na Gao,Qiang Wen,Hai-ling Qiao
Cytochrome P450 2E1 (CYP2E1) is an important drug-metabolizing enzyme that has been recognized as one of the risk factors for hepatofibrosis. Macrophages play key roles in regulating hepatofibrosis progression and resolution. However, whether CYP2E1 is involved in the regulation of macrophage polarization during hepatofibrosis is still unclear. Herein, we measured CYP2E1 activity and the expression of CD163 (an M2 marker) and CD68 (a pan-macrophage marker) in hepatofibrotic tissue from HCC patients (n = 26) with comparison to normal liver tissue (n = 26). The relationship of CYP2E1 activity in vivo and the CD163/CD68 ratio (an indicator of M2 polarization), as well as the extent of hepatofibrosis, were evaluated in diethylnitrosamine (DEN)-treated Sprague-Dawley rats. Strikingly, CYP2E1 activity and expression of CD68 increased and the CD163/CD68 ratio decreased, especially in hepatofibrotic tissue with higher CYP2E1 activity. Expression of α-SMA, Ki67, and PCNA were positively correlated with CYP2E1 activity and inversely correlated with the CD163/CD68 ratio. Furthermore, CYP2E1 activity showed an inverse correlation with the CD163/CD68 ratio. Overall, high CYP2E1 activity aggravates hepatofibrosis by restraining M2 macrophage polarization, providing a novel insight for understanding the profibrotic activity of CYP2E1 and a promising avenue for hepatofibrosis therapy.
研究领域:
肝病学
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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
International Journal of Nanomedicine
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2024
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IF 6.6
Kai Dong,Ying Zhang,Hong Rui Ji,Ze Lin Guan,Dan Yang Wang,Zi Yang Guo,Shu Jing Deng,Bin Yang He,Jian Feng Xing,Cui Yu You
Background The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms.Purpose A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects.Methods Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model.Results The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy.Conclusion The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.
研究领域:
药学
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免疫学
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消化病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Stroke & Cerebrovascular Diseases
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
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2023
·
IF 10.9
Ruoyu Li,Hongyu Zhang,Xiaohong Yao,Bin Tang,Paul K Chu,Xiangyu Zhang
The surface topography of implants plays a major role in osteogenesis and immunomodulation. In this study, three types of TiO 2 nanoarrays including nanorod arrays with a diameter of 45 nm (TiO 2 -N), nanorod arrays with a diameter of 60 nm (TiO 2 -N N), and nanocone arrays (TiO 2 -NW) are prepared on titanium and the behavior of bone marrow stromal cells (BMSCs) and polarization of macrophages are studied. Compared to the planar titanium control, TiO 2 nanoarrays facilitate osteogenesis of BMSCs and stimulate the pro-healing M2 phenotype. However, adhesion, spreading, proliferation, and osteogenic differentiation of BMSCs are more pronounced on TiO 2 -N N than both TiO 2 -N and TiO 2 -NW. TiO 2 -NN also produces the best immune microenvironment, while TiO 2 -NW is more favorable than TiO 2 -NN from the viewpoint of cell adhesion and spreading of osteoblasts.
研究领域:
生物材料
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组织工程
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生物医学工程
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOTHERAPY RESEARCH
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2022
·Vol. 36
·期 4
·1678-1691
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IF 6.388
Shiquan Chang,Xin Li,Yachun Zheng,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Guoqiang Qian,Guoping Zhao
Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti-inflammatory properties. This study is aimed to investigate the analgesic and anti-inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS-induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF-ĸB signaling pathway plays a major role in kaempferol-mediated alleviation of neuroinflammation. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF-κB pathways in LPS-activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype.
研究领域:
神经科学
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药理学
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炎症
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疼痛管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER IMMUNOLOGY IMMUNOTHERAPY
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2024
·Vol. 73
·期 7
·1-24
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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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
Advanced Science
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2024
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IF 14.3
Jin Liu,Yilin Shi,Yajun Zhao,Yue Liu,Xiaoru Yang,Kai Li,Weiwei Zhao,Jianmin Han,Jianhua Li,Shaohua Ge
Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal–phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr 2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2023
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IF 0
Ruiqiang Hang,Zhenlong Wang,Hui Wang,Yi Zhang,Yuyu Zhao,Long Bai,Xiaohong Yao
Although various bone defect repair materials have been used clinically, the influence of the material properties on bone repair and regeneration as well as the underlying mechanisms are not fully understood. We hypothesize that the material stiffness affects initial platelet activation during hemostasis phase, which in turn mediates subsequent osteoimmunomodulation of macrophages, finally determining clinical outcomes. To verify the hypothesis, the present work used polyacrylamide hydrogels with different stiffness (10, 70, and 260 kPa) as model materials to investigate matrix stiffness induced platelet activation behavior and its mediation on osteoimmunomodulation of macrophages. The results showed that the matrix stiffness was positively related with activation degree of platelets. However, the extracts of platelets incubated on middle-stiff matrix polarized macrophages to pro-healing M2 phenotype when compared with that on soft and stiff matrixes. ELISA results showed when compared with that on soft and stiff matrixes, the platelets incubated on middle-stiff matrix released more TGF-β and PGE 2 , both of which could polarize macrophages to M2 phenotype. The M2 macrophages could promote angiogenesis of endothelial cells and osteogenesis of bone marrow mesenchymal stem cells, two important and coupled processes involved in bone repair and regeneration. These findings suggest bone repair materials with 70 kPa stiffness can mediate proper platelet activation, which can polarize macrophages to pro-healing M2 phenotype, potentially contributing to bone repair and regeneration.
研究领域:
生物材料
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免疫学
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组织工程
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骨科
✓ 已验证
DOI
PubMed
JOURNAL OF APPLIED POLYMER SCIENCE
·
2022
·Vol. 139
·期 25
·e52265
·
IF 3.057
Suyuan Huang,Lin Cao,Wei Li,Zhidan Lin,Peng Zhang
It is well-known that a lower wear rate, favorable mechanical properties, and limited inflammatory response are critical factors in determining the long-term service of orthopedic implants. In this study, we prepare TaB 2 /PEEK coatings by electrophoretic deposition (EPD) of borated tantalum (TaB 2 ) and polyether-ether-ketone (PEEK) particles on a pure titanium plate (TA2). Nanoindenter, reciprocating ball-on-disc tester, and in vitro biological experiments were used to investigate the effects of TaB 2 particles on the mechanical properties, tribological properties, and biological properties of composite coatings. The results demonstrate that a small amount of TaB 2 particles were equally dispersed in the PEEK matrix, and the mechanical properties are improved, resulting in better tribological properties of the coating. In particular, the wear rate of P-TB-3 coating in the simulated body fluid (SBF) was 72% lower than that of the PEEK coating, with a friction coefficient (COF) of 0.164 and a wear rate of 1.45 × 10 −6 mm 3 ·N −1 m −1 , respectively. Furthermore, the P-TB-3 surface boosted Raw264.7 macrophage adherence and proliferation, with a potential to promote Raw264.7 macrophage transition to the M2 phenotype. These results suggest that the P-TB-3 coating prepared by EPD is considered as a promising implant replacement material.
研究领域:
材料科学
·
生物医学工程
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表面工程
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Yinying Sheng,Junjie Yang,Xueyang Zhao,Hui Liu,Shaogang Cui,Lianxi Chen,Rong Zeng,Xiaojian Wang,Chi-Hsien Huang,Wei Li
Zinc (Zn) alloys are promising alternatives to magnesium (Mg)- and iron (Fe)-based alloys because of their moderate corrosion rate and superior biocompatibility. To reduce the mass release of Zn2+ and improve the biocompatibility of Zn implants, the biomimetic zwitterionic polymer layer (phosphorylcholine chitosan—PCCs) was immobilized on the plasma-treated Zn1Mg surface. It is the chemical bonds between the −NH2 groups of the PCCs chain and O–C═O (C═O) groups on the plasma-treated Zn1Mg (Zn1Mg-PP) that contributes to the strong bonding strength between the film and the substrate, by which the PCCs (approx. 200 nm thick) layer can bear a 5.93 N normal load. The electrochemical impedance spectroscopy (EIS) results showed that the PCCs layer remarkably increased the resistance against corrosion attack, protecting substrates from over-quick degradation, and the protective effect of the layer with a thickness of 200 nm lasts for about 24 h. The corrosion products of Zn1Mg-PP-PCC in NaCl solution were determined as Zn5(OH)8Cl2·H2O and Zn3(PO4)2. Besides, the bulk Zn1Mg can trigger more aggressive macrophage activity, while the surface of Zn1Mg-PP and Zn1Mg-PP-PCC and their corrosion products (Zn3(PO4)2) tend to promote the differentiation of macrophages into the M2 phenotype, which is beneficial for implant applications.
研究领域:
材料科学
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生物医学工程
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表面工程
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腐蚀科学
·
生物材料
✓ 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）