INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Lei Zhu,Guan Zhang,Jiasai Kang,Xinru Xu,Haoshu Zhang,Yingying Pu,Yong Huang,Dewen Tong,Qian Du
Background Folium Isatidis (Da Qing Ye), a traditional Chinese medicine, exhibits broad-spectrum antiviral and immunomodulatory properties and has been widely used in treating respiratory diseases. Porcine circovirus type 2 (PCV2), a widespread swine virus, causes respiratory disease complex in piglets and leads to substantial economic losses in the global swine industry. This study aimed to evaluate the anti-PCV2 activity of Folium Isatidis . Materials and methods The anti-PCV2 activity of Folium Isatidis was first validated through both in vivo and in vitro experiments. Potential targets of Folium Isatidis were identified using TCMSP, BATMAN-TCM, and SwissTargetPrediction databases, and intersected with PCV2-related targets. Mechanism exploration involved PPI network analysis, GO annotation, and KEGG enrichment. Molecular docking analyzed component-target interactions, followed by experimental validation of the core component. Finally, the anti-PCV2 effect of the core component was verified through in vitro and in vivo experiments. Results A total of 135 overlapping targets between Folium Isatidis components and PCV2-related disease targets were identified. Key targets, including AKT1 and TNF-α, were implicated in the therapeutic effects of Folium Isatidis against PCV2. Isovitexin was identified to be the core component that directly binds to AKT1 and TNF-α, thereby inhibiting the PI3K/AKT signaling pathway and regulating TNF-α expression and activity to suppress PCV2 replication and alleviate PCV2-induced lung injury. Conclusions Our study reveals that Isovitexin, the core anti-PCV2 component of Folium Isatidis , exerts its effect by inhibiting the PI3K/AKT pathway and modulating TNF-α, thereby outlining a novel therapeutic strategy for combating PCV2 infection and associated respiratory injuries.
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高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Shuifang Mao,Bin Wang,Lin Yue,Wenshui Xia
In order to improve the anti-inflammatory activity of chitosan oligosaccharide (COS), chitosan oligosaccharide graft citronellol derivatives (COS-g-Cit1-3) were successfully synthesized via grafting citronellol (Cit) onto COS backbone. The degrees of substitution (DS) of COS-g-Cit1-3 were 0.165, 0.199 and 0.182, respectively. The structure of COS-g-Cit1-3 was confirmed by UV–vis, FT-IR, 1 H NMR and elemental analysis. The in vivo anti-inflammatory activity evaluation results displayed that COS-g-Cit1-3 drastically reduced the paw swelling, and the oedema inhibitions were 22.58 %, 29.03 % and 25.81 %, respectively. The results indicated that the anti-inflammatory effects of COS-g-Cit1-3 were significantly higher than COS and COS-g-Cit2 exhibited the highest anti-inflammatory ability. The results also presented that COS-g-Cit1-3 reduced the expression levels of TNF-α by promoting the secretion of IL-4 and IL-10. Moreover, western blot analysis data proved that COS-g-Cit1-3 inactivated the NF-κB signaling pathway via inhibiting the phosphorylation of p65, IKBα and IKKβ.
研究领域:
药学
·
生物技术
·
生物化学
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PubMed
高影响因子
BIOMEDICAL MICRODEVICES
·
2017
·Vol. 19
·期 3
·1-8
·
IF 2.062
Li Yuan,Lu Yao,Chen Qiong,Kang Yuejun,Yu Ling
Retinopathy is a complication of diabetes that affects the eyes; it stems from damage to the microvasculature of the retina and eventually compromises vision. The diagnosis of retinopathy is difficult to make because there are no early symptoms or warning signs. Dysfunction of the retina’s microvascular networks is believed to be associated with inflammatory cytokines and tumor necrosis factor alpha (TNF-α). To investigate the effect of these cytokines, such as TNF-α, a polydimethylsiloxane (PDMS)/glass hydride microfluidic device reflecting the physiological structure of the retina’s microvasculature was developed. In this model, the bifurcations and tortuosity of branch vessels were based on photographs of the fundus and an endothelial cell layer (EA.hy926 cells) were reconstructed within the microfluidic network. The adhesion, spreading, and growth of cells was ensured by optimizing the conditions for cell seeding and perfusion. Fluorescent staining was used to visualize the cytoskeleton and measurement of the nitric oxide (NO) level proved that the endothelial EA.hy926 cells had spread in the direction of flow perfusion system, forming artificial vascular networks. The endothelial layer was further challenged by TNF-α perfusion. Cytokine treatment increased the anchoring of peripheral blood mononuclear cells (PBMCs) on the endothelial layer. The microfluidic device developed in this study provides a low-cost platform reflecting the physiological structures of the retina’s microvasculature. It is anticipated that this device will be useful in evaluating the diseased retina as well as in drug screening.
研究领域:
医学
·
生物工程
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高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 11
·1-15
·
IF 2.6
Shen Wei,Wang Meng,Han Ting,Yao Yan,Ying Xinyi,Cui Yuyue,Du Peng
Previous research has indicated that the exopolysaccharide galactosaminogalactan (GAG) from Aspergillus fumigatus plays a pivotal role in the pathogenesis of experimental invasive aspergillosis by promoting virulence. However, it remains unclear whether the exopolysaccharide is directly virulent to host cells. In this study, we established a co-incubation system using human THP-1-derived macrophages and GAG extracted from A. fumigatus ATCC 1022 to assess the capacity of GAG to induce necroptosis in THP-1 cells, as well as to elucidate the underlying mechanisms of this process. Our findings indicate that the proportion of N-acetylgalactosamine in the GAG fraction derived from strain ATCC 1022 was lower, while GAG demonstrated a significantly greater ability to induce the production of the pro-inflammatory cytokines TNF-α and IL-1β, which was accompanied by the induction of necroptosis. Western blotting analysis revealed a significant increase in the phosphorylation of RIP1, RIP3, and MLKL proteins in GAG-treated THP-1 cells, and RIP1-RIP3-MLKL signaling activation and GAG-induced caspase activity-independent cell death were effectively inhibited by the TNF-α receptor-1 (TNFR1) inhibitor R-7050, the neutralizing antibody against TNF-α or necroptosis inhibitor Necrostatin-1. It's worth noting that the expression of CLEC4E, the gene encoding the Mincle receptor in macrophages, was elevated in the co-incubation system, potentially enhancing TNF-α-mediated necroptotic cell death. In addition to the RIP1-RIP3-MLKL axis, BAX, cleaved PARP, and JNK were also activated following GAG treatment, warranting further investigation into their roles in the regulation of necroptosis. Our findings demonstrate that GAG produced by A. fumigatus conidia during germination triggers necroptotic cell death in human THP-1 cells via TNF-α-mediated RIP1-RIP3-MLKL signaling.
研究领域:
微生物学
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免疫学
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分子生物学
·
感染性疾病
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真菌病理学
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细胞死亡机制
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高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Jie Liu,Mei-qi He,Gao-peng Guan,Xin-xing Wan,Ping Jin
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms. Despite a significant increase in ISG15 levels following viral infection, the specific role of ISG15 in the impairment of insulin-producing β-cells is unclear. To address this issue at the clinical level, we conducted this experimental work, and found elevated levels of ISG15 in the peripheral blood of T1D patients, suggesting a potential link between ISG15 and T1D. In the T1D animal model, we discovered that both ISG15 levels and cellular apoptosis were increased in pancreatic islet tissue. To investigate at the cellular level, we cultured MIN6 cells in the presence of supernatants derived from iBMDM cells transfected with poly(I:C) (PIC), a viral mimic. This exposure led to an upregulation of ISG15 expression in MIN6 cells, which was accompanied by the suppression of their functional capabilities and viability. Intriguingly, the direct transfection of MIN6 cells with PIC increased the expression of ISG15. We further found that elevated levels of ISG15 had a direct inhibitory effect on insulin secretion and it also contributed to β-cell apoptosis in a TNF-α-dependent manner. In conclusion, our study revealed a potential underlying mechanism through which ISG15 increases the apoptosis of β-cells, providing valuable insights that could facilitate the development of T1D treatment strategies.
研究领域:
免疫学
·
内分泌学
·
糖尿病学
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高影响因子
Journal of Essential Oil Bearing Plants
·
2020
·
IF 0.824
Yu Chen,Lejing Chi,Xiaoxin Liang,Yaohui Shi,Tongyun Wu,Mao Ye,Ping Han,Li Lin,Lanyue Zhang,Peng Xu,Zhiyun Du
Cedrus deodara is a cedar plant from the Pinaceae family. Because Cedrus is widely used in health care products, cosmetics, medicine, and insecticides, the essential oils of Cedrus deodara (CDEOs) are gaining increasing levels of attention. However, there have only been a few studies on the anti-inflammatory effects of CDEOs. This study aimed to systematically study the composition and biological effects of CDEOs, in line with this, the study assessed the chemical composition of CDEOs and evaluated their anti-inflammatory mechanisms in mice. Gas chromatography-mass spectrometry (GC-MS) was used to determine and analyze a total of 41 compounds from CDEOs. It was found that the major components of CDEOs are thujopsene (28.23%), α-cedrene (17.01%), and cedrol (15.55%); moreover, our results showed that the active ingredients in CDEOs have anti-inflammatory and antioxidant effects and that the active ingredients in CDEOs can be used as an antioxidant, as an important biological resource in functional food, and as ingredients in cosmetics and pharmaceuticals. Taken together, these CDEOs serve as ideal additives for anti-inflammatory drugs.
研究领域:
药理学
·
植物化学
·
炎症研究
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高影响因子
CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 5
·e71355
·
IF 2.9
Zeyu Yi,Siyu Liu,Lincheng Bai,Fan Yang,Zhenkun Wang,Xiubo Zhu,Zunpeng Shu,Hua Han,Xiaojin Yu
Rosa davurica Pall. (RDP), a rosa fruit rich in bioactive compounds, has shown potential in alleviating cardiovascular diseases, yet its chemical composition and mechanisms against acute myocardial ischemia (AMI) remain unclear. This study comprehensively characterized 99 compounds in RDP extracts using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), including flavonoids, terpenoids, and phenolic acids. By integrating transcriptomics and network pharmacology, we identified the tumor necrosis factor-alpha (TNF-α) signaling pathway as a key target in AMI progression. In vivo experiments demonstrated that RDP significantly ameliorated isoproterenol (ISO)-induced myocardial injury by reducing oxidative stress and suppressing the release of inflammatory cytokines (IL-6, IL-2, IL-17). Molecular docking and dynamics simulations further revealed that bioactive components in RDP, such as rutin and hyperoside, effectively bind to TNF-α and its receptor TNF receptor 1 (TNFR1), thereby modulating inflammatory responses. These findings provide valuable insights into the multi-target cardioprotective effects of RDP, supporting its application as a promising functional food. Graphical Rosa davurica Pall. (RDP) effectively ameliorates acute myocardial ischemia by neutralizing oxidative stress and disrupting the pro-inflammatory TNF-α/TNFR1 signaling axis. By integrating multi-omics profiling, molecular dynamics, and in vivo models, this study uncovers the multi-target cardioprotective mechanisms of RDP, establishing a robust scientific foundation for its application as a novel cardiovascular functional food.
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Biomaterials Science
·
2021
·Vol. 9
·期 16
·5519-5532
·
IF 6.843
Qiyuan Dai,Qingtao Li,Huichang Gao,Longtao Yao,Zefeng Lin,Dingguo Li,Shuangli Zhu,Cong Liu,Zhen Yang,Gang Wang,Dafu Chen,Xiaofeng Chen,Xiaodong Cao
The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol–gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.
研究领域:
生物医学工程
·
组织工程
·
骨科
·
材料科学
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高影响因子
Materials Today Bio
·
2026
·
IF 11
Longqing Hu,Zhongyuan Yin,Songwei Tan,Yu Deng,Xincai Qu,Ting Hu,Qiong Wang
Triple-negative breast cancer (TNBC) derives only limited clinical benefit from radiotherapy (RT), partly due to abnormalities in the tumor microenvironment and dysregulated signaling pathways. By integrating TNBC cases from the METABRIC and TCGA cohorts, we implemented an analysis framework centered on RT-by-gene interaction terms, implicating TNF-α–NF-κB signaling and inflammatory response as potential effect modifiers of RT benefit. Based on a pathway-guided polyphenol–gene interaction screen, curcumin (Cur) was prioritized as a modulator of TNF-α–NF-κB/inflammation-related programs. We then engineered a multifunctional nanoplatform (TCC) that couples catalytic modulation of the tumor microenvironment with suppression of adaptive pro-survival programs. TCC was built on pH-responsive nanoceria (CeO 2 nanozymes) to modulate redox homeostasis and alleviate hypoxia, loaded with Cur, and coated with D-α-tocopherol polyethylene glycol succinate (TPGS) to improve stability and cellular uptake; cRGD was further introduced to generate cRGD-TCC for enhanced tumor targeting. In vitro and in vivo, TCC promoted G 2 /M-phase arrest, amplified RT-induced reactive oxygen species generation and DNA damage, and attenuated TNF-α–NF-κB/inflammatory programs and markers of inflammation, survival, and invasion. Collectively, TCC provides an integrated radiosensitization strategy that addresses microenvironmental barriers and adaptive tumor signaling, thereby potentially enhancing RT response in TNBC.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2014
·
IF 5.71
Simin Yan,Xu Zhang,Haili Zheng,Danhong Hu,Yongtian Zhang,Qinghua Guan,Lifang Liu,Qilong Ding,Yunman Li
Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis . Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck , was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes–endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα , suppressed IκB kinase-β (IKK-β) activity, lowered O 2 ∙− and H 2 O 2 levels, tackled p47 phox translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-β that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-β activity was also inhibited by (polyethylene glycol) PEG–catalase, N -acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte–HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis.
研究领域:
药理学
·
免疫学
·
心血管研究
·
分子生物学
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高影响因子
Letters in Drug Design & Discovery
·
2020
·Vol. 17
·期 4
·502-511
·
IF 1.169
Song Mingxia,Liu Bing,Yu Shengwang,He Shihui,Liang Yuqiu,Li Sifan,Chen Qiuyan,Deng Xianqing
Background: Several series of hydrazone derivatives of pyrazole-4-carboxaldehydes (4- 11) were designed and synthesized to screen their inflammatory activity. Methods: The products were characterized by 1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo
xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Results and Conclusion: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF-α at the concentration of 10 μg/mL. Compounds 7b and 11c, two of the most potent
compounds, exhibited TNF-α inhibitory ability in a dose-dependent manner with IC50 values of 5.56 and 3.69 μM, respectively. In vivo, intraperitoneal administration with 7b and 11c markedly inhibited the ear edema at the doses of 20 and 50 mg/kg. Compound 11c, inhibited edema by 49.59
% at the dose of 20 mg/kg, was comparable to the reference drug dexamethasone at the same dose (with an inhibition of 50.49 %). To understand the binding pattern, molecular docking of representative 7b and 11c was performed, which demonstrated that both compounds have a forceful binding with
the TNF-α, and that the phenyl and hydrazide moieties of them play a significant role in binding with the target site.
研究领域:
药物化学
·
炎症研究
·
分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Benyue Sun,Wenwen Xie,Xuejiao Li,Taohua Liu,Jingjing Bai,Yuan Yao,Long Ma,Shuli Man
Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria , while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.
研究领域:
肿瘤学
·
微生物学
·
免疫学
·
药理学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）