CURRENT CANCER DRUG TARGETS
·
2024
·Vol. 25
·期 3
·294-305
·
IF 2.3
Yiping Zheng,Jianfeng Cai,Qiuhong Ji,Luanmei Liu,Kaijun Liao,Lie Dong,Jie Gao,Yinghui Huang
BackgroundLung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression.MethodsEmploying in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1.ResultsLung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation.ConclusionThis study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.
研究领域:
肿瘤学
·
免疫学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Dan Lin,Yanjun Chai,Yifan Ma,Bing Duan,Yuan Yuan,Changsheng Liu
Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification , is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo . Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological “prep-state” of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular “prep-state” with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a “chondrogenic/osteogenic balance” at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity , together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency.
研究领域:
组织工程
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再生医学
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生物材料科学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 17
·期 1
·519-524
·
IF 1.41
Li Wang,Wei Gu,Ying Shi,Yubao Chen,Yan Tan
The diaphragmatic fatigue that results from airflow obstruction is associated with the severe morbidity of patients with chronic obstructive pulmonary disease. Astragaloside IV (AS‑IV) has antioxidant, anti‑apoptotic and anti‑inflammatory activities in various cell types. The present study aimed to evaluate the protective effects of AS‑IV in diaphragmatic muscle cells. Diaphragmatic muscle cells extracted from neonatal rats were treated with a series of AS‑IV concentrations (5, 10 or 20 mg/l) and the AKT inhibitor GSK690693 in the presence of interleukin‑8 (IL‑8). Cell proliferation and AKT phosphorylation were measured using Cell Counting Kit‑8 and western blot assays, respectively. Cell apoptosis and reactive oxygen species (ROS) production were evaluated using flow cytometric analysis. Caspase activity and concentrations of proinflammatory factors (tumor necrosis factor‑α, IL‑6 and IL‑8) were assessed using a caspase colorimetric assay and ELISA, respectively. IL‑8 treatment resulted in decreased rates of cell proliferation and increased rates of AKT phosphorylation, cell apoptosis, caspase 3/9 activity, ROS production and proinflammatory factor production. AS‑IV and GSK690693 treatment reversed the effects of IL‑8. The effects of AS‑IV were dose‑dependent. The present results suggested that AS‑IV is a candidate for the treatment of diaphragmatic fatigue due to its antioxidant, anti‑apoptotic and anti‑inflammatory activity.
研究领域:
药理学
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肺科学
·
细胞生物学
·
免疫学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Zihao Zhao,Mengjie Xu,Zhou Zhang,Xing Yin,Ximing Pu,Juan Wang,Xiaoming Liao,Zhongbing Huang,Shunze Cao,Guangfu Yin
The in vitro expanded seed cells and the supraphysiological doses of exogenous growth factors both pose huge safety risks in bone regeneration. In this study, a novel IL-8/tDM/PLGA composite scaffold was developed, where chemokine interleukin-8 (IL-8) and transferable decellularized matrix (tDM) were uniformly overlaid on exterior and interior surfaces of poly(lactic-co-glycolic acid) (PLGA) porous substrates. The in vitro experiments confirmed that the synergy of tDM and IL-8 achieved the obvious promotion of osteogenesis and angiogenesis via enhancing chemotaxis, adhesion, spreading, osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). IL-8 mediated the in situ recruitment of BMSCs and macrophages via binding with C–X–C motif chemokine receptor 2 (CXCR2), while maintaining cellular viability without inducing macrophage polarization. Moreover, tDM improved BMSC adhesion and spreading via the recognition and binding of the affinitive ligand existing in tDM by the cell adhesion molecules (CAMs) on the BMSC cytomembrane. Furthermore, tDM promoted the osteogenic differentiation and mineralization of BMSCs, benefiting from the retained growth factors. In a rat femoral defect model, the IL-8/tDM/PLGA scaffold significantly accelerated new bone mineralization and maturation through synergistic regulations of cell recruitment, matrix adhesion, and osteogenic signaling pathways. After 8 weeks post-implantation of the IL-8/tDM/PLGA scaffolds, the bone volume fraction of the newly formed bone, trabecular number, and trabecular separation at the defect site were 47%, 1.21 mm−2, and 0.50 mm, respectively, which presented significantly better bone repair effects than those in other groups. These results demonstrated that the innovative bone regeneration strategy combining chemokine-driven recruitment and endogenous tDM regulation offered a potential solution for clinical repair of large-sized bone defects.
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产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2022
·Vol. 9
·期 8
·2653-2664
·
IF 9.473
Guofang Zhang,Guoli Cao,Rong-Hua Luo,Qingle Song,Yanqiao Zeng,Ke Liu,Jing Qu,Xian Lin,Feng-Liang Liu,Guocheng Wang,Hongchang Li,Liang Li,Yong-Tang Zheng,Diana Boraschi,Lidong Wu,Yan-Zhong Chang,Yang Li
Microplastics (MP) pollution is a global issue that raises concerns about potential toxicity for environmental and human health. The notion that SARS-CoV-2 is more stable when adsorbed on plastic surfaces urged us to examine whether the virus can attach to MP, which may facilitate infection upon inhalation or ingestion. Here, we describe that MP can bind SARS-CoV-2 pseudovirus on their surface and enhance infection of human cells in vitro. This enhanced in vitro infectivity was confirmed with authentic SARS-CoV-2, in parallel with increased expression of inflammation-related caspase-3, IL-8 and TNF-α genes. These results suggest that the presence of MP in the environment or in our respiratory or gastrointestinal tracts has the potential to interact with SARS-CoV-2, and potentially increase viral infectivity and spreading.
研究领域:
环境科学
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病毒学
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毒理学
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细胞生物学
✓ 已验证
DOI
高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2020
·
IF 2.681
Min Chen,Cuifen Chen,Yun Gao,Dongming Li,Dan Huang,Ziyu Chen,Xuanna Zhao,Qiu Huang,Dong Wu,Tianwen Lai,Guomei Su,Bin Wu,Beixian Zhou
Background Bergenin , a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive , and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor α (TNF-α)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-α-stimulated human bronchial epithelial (16-HBE) cells. Methods Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot , and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. Results Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-κB-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. Conclusions These findings demonstrate that bergenin could suppress TNF-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway , which may provide beneficial effects for the treatment of airway inflammation associated with asthma.
研究领域:
药理学
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免疫学
·
细胞生物学
·
呼吸医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
·
2025
·
IF 3.4
Huang Saiping,Wu Guoyuan,Xu Tianfu,Lin Dong,Zhan Zhijian
This study investigates the diagnostic potential of matrix metalloproteinase-9 (MMP-9), IL-8, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) as combined biomarkers for post-infectious bronchiolitis obliterans (PIBO) in children. BALF samples from children with PIBO were analyzed using ELISA to quantify MMP-9, IL-8, and MPO levels. Receiver operating characteristic (ROC) curves were used to assess their diagnostic values, while Pearson correlation analysis examined their associations with lung function and inflammation markers. A PIBO mouse model was established via nebulized nitric acid inhalation, and targeted inhibition of MMP-9, IL-8, and MPO using small interfering RNAs (siRNAs) was performed given via intratracheal administration. The effects on airway inflammation and pathological lung changes were evaluated. Bioinformatics analysis identified upstream microRNAs (miRNAs) regulating MMP-9, IL-8, and MPO, which were validated using dual-luciferase assay and Western blotting. Results revealed significant upregulation of MMP-9, IL-8, and MPO in the BALF of children with PIBO. Combined detection of these biomarkers demonstrated high diagnostic accuracy. MMP-9, IL-8, and MPO levels in BALF were negatively correlated with lung function indicators but positively correlated with inflammatory factors. Targeted inhibition of these molecules reduced airway hyperresponsiveness and inflammation in PIBO mice. miR-766-3p was downregulated in the lung tissues of PIBO mice and in the BALF of affected children, showing a negative correlation with MMP-9, IL-8, and MPO. Functional assays confirmed that miR-766-3p directly targeted MMP-9, IL-8, and MPO. In conclusion, MMP-9, IL-8, and MPO serve as reliable combined biomarkers for PIBO diagnosis and may aid in early clinical identification. miR-766-3p is an upstream miRNA for MMP-9, IL-8, and MPO.
研究领域:
呼吸病学
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分子生物学
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儿科医学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 10
·1-10
·
IF 5.3
Yang Haixia,Xue Yijiong,Wang Tingting,Lu Yan,Yang Minghui,Li Xiaoqing,Li Ting
Ratio-based fluorescence assays can reduce environmental interference, allowing for the identification of biomarkers with higher specificity. However, the complicated preparation procedures involved in developing multi-fluorescent emission probes and the challenges associated with isolating and enriching specific biomarkers from complex samples present formidable obstacles. Magnetic nanoparticles enable the quick separation and enrichment of biomarkers, hence, the present study developed a ratio-fluorescence assay for the detection of interleukin-8 (IL-8) using carbon dots (CDs) with both magnetic and fluorescent properties. In this approach, magnetic and fluorescent Fe 3 O 4 -CDs-1 (FCs) hybrid nanoparticles were initially synthesized, followed by the growth of SiO 2 nanorods on their surface. FCs@SiO 2 -Ab 1 was then prepared by immobilizing capture IL-8 antibody (Ab 1 ) through amino modification onto FCs@SiO 2 to selectively capture and enrich target IL-8 from samples. Subsequently, CDs-2 modified with detection IL-8 antibody (Ab 2 ) served as IL-8 detection probe, which formed sandwich structure with FCs@SiO 2 -Ab 1 in the presence of IL-8. As the concentration of IL-8 increased, the fluorescence intensity of CDs-2 enhanced accordingly while the fluorescence intensity of FCs remained relatively unchanged. This ratio-fluorescence sensing platform exhibits a wide linear range (20-1000 pg·mL −1 ) and an impressive low detection limit (6.9 pg·mL −1 ). Furthermore, this method enables the reliable detection of IL-8 in human serum, thereby offering promising prospects for the development of enrichment and detection systems for other biomarkers. Graphical
研究领域:
免疫学
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分子诊断
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纳米生物技术
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生物分析化学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virulence
·
2024
·
IF 5.5
Xiaofei Ji,Qianwen Wu,Xinying Cao,Shuzhen Liu,Jianhui Zhang,Si Chen,Jiangfan Shan,Ying Zhang,Boqing Li,Huilin Zhao
CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.
研究领域:
微生物学
·
分子生物学
·
肿瘤学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Shuang Luo,Xiangliang Deng,Qi Liu,Zengfeng Pan,Zhongxiang Zhao,Lian Zhou,Xia Luo
Emodin is an anthraquinone compound derived from Rheum officinale Baill . Several reports showed that emodin had efficacy on acute pancreatitis , keratitis , myocarditis , and rheumatoid arthritis . However, the potency of emodin on ulcerative colitis(UC) remains unclear. In this study, we investigated the effect of emodin on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Our results showed that emodin significantly alleviated the symptoms of DSS-induced UC in mice, involving prevented the loss of body weight and colon shortening, decreased the disease activity index (DAI), intestinal damages and the count of white blood cells (WBC) in peripheral blood. In addition, emodin treatment decreased the level of anti-flagellin antibody in serum and significantly down-regulated the expression of TLR5 and NF-κB p65 in colon of the UC mice. Further study in vitro showed that emodin down-regulated the expression of TLR5 and MyD88 , up-regulated the expression of IκB, inhibited the nuclear translocation of NF-κB p65 and decreased the release of IL-8 in flagellin-stimulated HT-29 cells. These results, for the first time, demonstrated that emodin had the therapeutic potential to ameliorate UC symptoms possibly via regulating the flagellin-TLR5 signaling pathway . Emodin may be a potential candidate ingredient for ulcerative colitis.
研究领域:
药理学
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免疫学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 7
·2114
·
IF 4.927
Yi Li,Xia-Jin Liu,Shu-Lan Su,Hui Yan,Sheng Guo,Da-Wei Qian,Jin-Ao Duan
Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9.Keywords:Flos Chrysanthemi;chrysanthemum stem and leaf;inflammatory bowel disease (IBD);zebrafish;UPLC-TQ/MS
研究领域:
药理学
·
炎症研究
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水生毒理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Xinkun Shen,Yonglin Yu,Pingping Ma,Zhong Luo,Yan Hu,Menghuan Li,Ye He,Yangyang Zhang,Zhihong Peng,Guanbin Song,Kaiyong Cai
Before mesenchymal stem cells (MSCs) adhere to the surface of an implant and differentiate into osteoblasts, monocytes (especially macrophages) arrive at the bone injury site and interact with the implant and subsequent MSCs. In our previous study, large titania nanotubes (TNT 110 ) had been verified to endow superior oxidation resistance to osteoblasts. The early regulation between macrophages and MSCs by surface nanotubes under oxidative stress (OS) was evaluated further in this study. Cellular and molecular results show that TNT 110 greatly increased early inflammation of macrophages by activating integrin/FAK-mediated MAPK and NFκB signals and simultaneously promoted their gene expression of SDF1, IL-8, and CCL2 (chemokines) compared with 30 nm nanotubes and titanium substrates. Co-culture results show that more MSCs were recruited by those chemokines and may promote osteogenic self-differentiation, reducing early inflammation of macrophages by accelerating their M1-to-M2 transition in the TNT 110 group. All findings reveal that the early cellular behavior of macrophages and MSCs was effectively regulated by TNT 110 , indicating large nanotubes would be more suitable to prevent oxidative damages.
研究领域:
生物材料
·
细胞生物学
·
组织工程
✓ 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）