Frontiers in Pharmacology
·
2023
·
IF 5.6
Han Sun,Xue-Kai Wang,Jian-Rui Li,Mei Tang,Hu Li,Lei Lei,Hong-Ying Li,Jing Jiang,Jia-Yu Li,Biao Dong,Jian-Dong Jiang,Zong-Gen Peng
The cell adhesion between leukocytes and endothelial cells plays an important balanced role in the pathophysiological function, while excessive adhesion caused by etiological agents is associated with the occurrence and development of many acute and chronic diseases. Cell adhesion inhibitors have been shown to have a potential therapeutic effect on these diseases, therefore, efficient and specific inhibitors against cell adhesion are highly desirable. Here, using lipopolysaccharide-induced human umbilical vein endothelial cells (HUVECs) and calcein-AM-labeled human monocytic cell THP-1, we established a high-throughput screening model for cell adhesion inhibitors with excellent model evaluation parameters. Using the drug repurposing strategy, we screened out lifitegrast, a potent cell adhesion inhibitor, which inhibited cell adhesion between HUVEC and THP-1 cells by directly interrupting the adhesion interaction between HUVEC and THP-1 cells and showed a strong therapeutic effect on the mouse acute liver injury induced by poly (I:C)/D-GalN. Therefore, the screening model is suitable for screening and validating cell adhesion inhibitors, which will promote the research and development of inhibitors for the treatment of diseases caused by excessive cell adhesion.
研究领域:
药理学
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细胞生物学
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免疫学
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治疗学
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DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 10
·1-12
·
IF 2.6
Bi Jinli,Huang Xin,Meng Liqin,Li Jinghan,He Yu,Jin Jing,Li Taijie
Hypervirulent Klebsiella pneumoniae (hvKP) possesses multiple virulence factors and causes severe infections with elevated mortality rates. It induces a strong inflammatory response in the host, with macrophages playing a key role in defense and inflammation. However, the signaling pathways of macrophages involved in response to hvKP infection remain unclear. In this study, we developed a stable hvKP infection model in differentiated THP-1 macrophages, confirmed by CFU assay and LDH cytotoxicity assay, and subsequently performed transcriptomic profiling analysis of hvKP-infected cells to characterize infection-induced gene expression changes. Pathway and differential gene correlation network analyses identified 14 potential regulatory genes primarily involved in inflammation. These changes in gene expression were further validated by Reverse transcription quantitative PCR (RT-qPCR). KEGG and GO analyses revealed several key signaling pathways involved in inflammation and immune response, particularly the TNF, IL-17, NF-κB, and JAK-STAT pathways. Further analysis indicated that the NF-κB signaling pathway plays a central role in the inflammatory response to hvKP infection, whereas the TNF and IL-17 pathways act synergistically to upregulate pro-inflammatory cytokines and chemokines. Western blot analysis confirmed the expression of TRAF6 and NF-κB p65 protein during hvKP infection. This study provides valuable insights into the molecular mechanisms of macrophage responses to hvKP, offering potential targets for therapeutic intervention.
研究领域:
微生物学
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免疫学
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分子生物学
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传染病学
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基因组学
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细胞生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Ying Wang,Kunzhan Dong,Yan Zhang,Qi Li,Chang Liu,Shijie Cai,Zhiye Xu,Jingyang Shan,Sen Wang
Excessive inflammation can cause severe damage to biological tissues and organs, and current anti-inflammatory drugs still have certain limitations. This study aims to explore anti-inflammatory strategies. Nanozymes, a class of nanomaterials with enzyme-like catalytic properties, have gained significant attention in recent years. In this study, iron ion integrated coordination polymer nanodots (FNDs) were synthesized. The anti-inflammatory effects of FNDs were investigated from multiple aspects, including material characterization, antioxidant performance testing, in vitro cell experiments, and mouse model experiments. The results demonstrated that FNDs have the characteristics of small size, high stability, and excellent antioxidant capacity. In vitro cell experiments showed that FNDs significantly inhibited the production of LPS-induced TNF-α, IL-1β, and IL-6 in THP-1 macrophages. Further analysis of signaling pathways revealed that FNDs markedly suppressed the NF-κB and MAPK pathways and downregulated the expression of TLR4 and CD14 on the surface of macrophages. Experiments in mouse models indicated that FNDs significantly suppressed inflammation and cellular damage in organs such as the lungs and liver, and reduced the number of inflammatory cells and the concentrations of TNF-α, IL-1β, and IL-6 in peripheral blood. This study demonstrates that FNDs possess excellent antioxidant and anti-inflammatory properties, providing a strategy for the treatment of inflammatory diseases.
研究领域:
纳米技术
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免疫学
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药理学
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生物医学工程
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产品关联
DOI
高影响因子
Nanoscale
·
2018
·Vol. 11
·期 3
·1286-1294
·
IF 7.233
Yulian Li,Lingyun Feng,Wei Yan,Irshad Hussain,Li Su,Bien Tan
Copper nanoclusters (CuNCs) exhibit susceptibility to oxidation in the subnanometer size range. In this work, a facile and green protocol is reported for the successful synthesis of water soluble CuNCs, with poly(vinylpyrrolidone) as a template and ascorbic acid as a mild reducing agent. The as-prepared CuNCs exhibit a green fluorescence and high quantum yield (QY = 44.67%) in water, which is the highest among the reported water soluble CuNCs. The origin of their highly luminescent nature was also investigated. In addition, the obtained CuNCs show good tolerability to high ionic strength, superior antioxidation properties, good photostability, time-stability, a large Stokes shift and ultralow cytotoxicity, laying the foundation for living cell imaging in THP-1 macrophages. A bright green fluorescence can be observed from the cells, indicating the potential practicality of CuNCs as a fluorescence marker in bioapplications. Interestingly, the as-prepared CuNCs exhibit a good selective fluorescence quenching response towards trinitrophenol over other nitro compounds. Furthermore, CuNCs were employed for sensing trinitrophenol based on the inner filter effect. A good linear relationship was obtained in the low concentration range of trinitrophenol, with a limit of detection of 3.91 × 10−7 M in aqueous medium. This result suggests the potential application of CuNCs as a probe in sensing and monitoring toxic trinitrophenol in the field of environmental security.
研究领域:
纳米技术
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材料科学
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分析化学
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生物医学工程
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环境科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2018
·
IF 3.52
Li Xiaotian,Yu Chunbo,Hu Yi,Xia Xinyi,Liao Yue,Zhang Jing,Chen Huiwen,Lu Weili,Zhou Wei,Song Zhongchen
Psoralen and angelicin are two effective compounds isolated from psoraleae, a traditional Chinese medicine. They have a wide range of applications for bone disease treatment and immune modulation. In this study, we explored their new applications for the treatment of periodontal diseases. This study aimed to investigate the effects of psoralen and angelicin on Porphyromonas gingivalis growth and P. gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation, and further to evaluate their effects on osteogenesis. Finally, the effects of angelicin on a mouse model of periodontitis were also investigated. The results showed that psoralen and angelicin had beneficial dose-dependent effects regarding the inhibition of planktonic P. gingivalis and biofilms of P. gingivalis. There were no significant differences in the viability of monocyte-like THP-1 cells and human periodontal ligament cells (hPDLCs) treated with either psoralen or angelicin compared to the untreated control cells. Psoralen and angelicin also markedly decreased the mRNA expression and release of inflammatory cytokines (interleukin [IL]-1β and IL-8) by THP-1 cells in a dose-dependent manner. They significantly enhanced the alkaline phosphatase (ALP) activity of hPDLCs and up-regulated the expression of osteogenic proteins (runt-related transcription factor 2 [RUNX2], distal-less homeobox 5 [DLX5], and osteopontin [OPN]). Angelicin significantly attenuated alveolar bone loss and inflammation response in the mice with periodontitis. In conclusion, our data demonstrated that psoralen and angelicin could inhibit the growth of planktonic P. gingivalis and P. gingivalis biofilm. It is also the first report on the anti-inflammatory effect of psoralen and angelicin against Pg-LPS. They also had an osteogenesis-potentiating effect on hPDLCs. The in vivo study also indicated the effect of angelicin regarding protection against periodontitis. Our study highlighted the potential ability of psoralen and angelicin to act as novel natural agents to prevent and treat periodontitis.
研究领域:
牙科
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Jia-Yi Dou,Mei-Jie Zhou,Mei-Yan Xuan,Jia Guo,Sai-Hu Liu,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background Astilbin (ATB), a natural dihydroflavonol compound, exists in many plants, processed and functional foods. ATB has multiple pharmacological effects, such as antioxidant, lipid-lowering, and hepatoprotective. However, its anti-hepatic fibrosis and mechanisms remain unclearly elucidated. Purpose This study explored the effect of ATB against the hepatic fibrosis and its regulation of hepatic microenvironment by regulating hepatic stellate cells-macrophage crosstalk. Method Thioacetamide (TAA) was intraperitoneal injected to establish hepatic fibrosis mice, and treated with ATB or curcumin by gavage, respectively. Hepatic stellate cells (HSCs) were stimulated with TGF-β or conditioned medium (CM) from LPS-induced THP-1, then cultured with ATB, PXR agonist or antagonist. Results In TAA-induced mice, ATB improved histopathological changes, serum transaminases increase; alleviated extracellular matrix (ECM) deposition, epithelial-mesenchymal transformation (EMT), inflammatory infiltration, PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy and activated pregnane X receptor (PXR) expression. In vitro , ATB significantly reduced ECM, inflammatory cytokines release, mitophagy, EMT, and activated PXR expression. ATB could increase PXR and decrease PINK1/Parkin, functioning as a PXR agonist. PXR deficiency in LX-2 could degrade the regulation of ATB on ECM, inflammation, EMT, and mitophagy. CM from LPS-induced THP-1 activated LX-2 and resulted in PXR decreasing, while ATB could regulate the crosstalk between HSCs and macrophages. Deficiency of PXR, whether in LX-2 or in macrophages, all weakened the inhibitory effect of ATB on α-SMA, EMT, inflammatory cytokines, and PINK1/Parkin signaling. Conclusion ATB ameliorated hepatic fibrosis by inhibiting HSCs activation, inflammation and EMT through PXR-mediated PINK1/Parkin signaling. Especially, ATB targeted the hepatic microenvironment between hepatic stellate cells and macrophages, which might be a promising strategy for the treatment of hepatic fibrosis.
研究领域:
药理学
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肝病学
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2024
·
IF 2.2
Xinpeng WANG,Linguo XIE,Chunyu LIU
CCR2 (C-C chemokine receptor type 2) is a monocyte chemokine associated with oxidative stress and inflammation. Kidney stones (KS) are composed of calcium oxalate (CaOx), which trigger renal oxidative stress and inflammatory. This study aims to evaluate the effects of CCR2 on KS in vivo and in vitro. Eight-week-old male C57BL/6J mice were intraperitoneally injected with glyoxylate (GOX) daily to establish a KS model, and along with CCR2 antagonist (INCB3344) treatment on days 2, 4, and 6. The results showed that CCR2 antagonist reduced renal injury markers (blood urea nitrogen and serum creatinine), alleviated renal tubular injury and CaOx crystal deposition. CCR2 antagonist also decreased CCR2 expression induced by GOX treatment and increased Nrf2 expression. GOX treatment promoted malondialdehyde (MDA) production, decreased glutathione (GSH) content, and inhibited catalase (CAT) and superoxide dismutase (SOD) activity, however, CCR2 antagonist attenuated the above effects of GOX. CCR2 antagonist had inhibitory effects on GOX-induced inflammatory cytokine expression (IL1B, IL6 and MCP1), and inhibited apoptosis by increasing Bcl-2 expression and decreasing Bax and cleaved-caspase 3 expression. In vitro experiments were performed by co-culture model of CaOx-induced damaged HK-2 cells and macrophage-like THP-1 cells. CCR2 antagonist inhibited CaOx-induced THP-1 cell M1 polarization by decreasing the TNF-α, IL6 and iNOS levels, and further alleviated CaOx-induced oxidative stress damage, inflammatory response and apoptosis of HK-2 cells. The study suggests that CCR2 antagonist may be resistant to CaOx crystals-induced oxidative stress and inflammation by inhibiting macrophage M1 polarization.
研究领域:
药理学
·
肾病学
·
炎症
·
氧化应激
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Zhuojun Yu,Yi Li,Liping Bai,Yanbo Zheng,Xiujun Liu,Yongsu Zhen
Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.
研究领域:
免疫学
·
药理学
·
炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2023
·
IF 7
Hui Zou,Tingting Ben,Ping Wu,Geoffrey I.N. Waterhouse,Yilun Chen
This novel study identifies the effective anti-inflammatory phenolic compounds in dandelion and provides mechanistic insights into their interactions with receptor proteins (toll‐like receptor 4, TLR4; co‐receptor myeloid differentiation protein-2, MD-2) using UHPLC-ESI-MS/MS, lipopolysaccharide (LPS)-stimulated THP-1 cell line, fluorescence quenching and anisotropy, molecular docking (single ligand and multi-ligand docking) and molecular dynamics simulation. A 50 % aqueous methanol extract had a greater anti-inflammatory effect and higher chicoric acid content, compared with the 100 % water and 100 % methanol extracts. Chicoric acid, chlorogenic acid, methylophiopogonone A, caffeic acid, gallic acid monohydrate and 4'- O -demethylbroussonin A had relatively high binding energies and contents in all extracts. Chicoric acid competed with chlorogenic acid, 4'- O -demethylbroussonin A and quercetin for MD-2. Among dandelion’s phenolics, chicoric acid most effectively hindered TLR4-MD-2 complex formation, with a quenching constant of 0.62 × 10 6 L/mol for MD-2 or TLR4 at 320 K, and binding energies of –6.87 and –5.97 kcal/mol, respectively, for MD-2 and TLR4.
研究领域:
药理学
·
生物化学
·
分子生物学
·
分析化学
·
免疫学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Ke Deng,Ping Du,Kun Liu,Xuelian Tao,Javad Harati,Jhe-Wei Jhang,Jua Kim,Peng-Yuan Wang
Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1β) and M2 genes (i.e., TGF-β and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.
研究领域:
材料科学
·
生物医学工程
·
细胞生物学
·
组织工程
·
再生医学
✓ 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）