INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2019
·Vol. 20
·期 6
·1469
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IF 4.183
Xuerong Zhou,Ling Zhao,Jie Luo,Huaqiao Tang,Min Xu,Yanyan Wang,Xiaoyu Yang,Helin Chen,Yinglun Li,Gang Ye,Fei Shi,Cheng Lv,Bo Jing
Research has shown that nano-copper (nano-Cu) can cause damage to the spleen and immune system yet their mechanisms of cytotoxicity are poorly understood. Our aim is to explore the potential immunotoxicity in the spleen of rats after nano-Cu exposure. The results of hematologic parameters, lymphocyte subsets, immunoglobulins, and histopathology indicated that copper obviously changed the immune function of the spleen. The levels of antioxidants (SOD, CAT, GSH-Px), oxidants (iNOS, NO, MDA), and anti-oxidative signalling pathway of Nrf2 (Nrf2 and HO-1) were strongly induced by nano-Cu. The expression of mRNA and protein of pro-/anti-inflammatory (IFN-γ, TNF-α, MIP-1α, MCP-1, MIF, IL-1/-2/-4/-6) cytokines were increased by nano-Cu. The expression of regulatory signal pathways, MAPKs and PI3-K/Akt were activated, which might be involved in the inflammatory responses and immunomodulatory processes of sub-acute nano-Cu exposure. The immune function of the spleen was repressed by nano-Cu induced oxidative stress and inflammation.Keywords:nano-Cu;rats;spleen injury;immune system;oxidative stress
研究领域:
毒理学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
·
IF 6.8
Qiang Li,Linmao Ke,Dandan Yu,Han Xu,Zixuan Zhang,Rilei Yu,Tao Jiang,Yue-Wei Guo,Mingzhi Su,Xin Jin
Mitogen-activated protein kinase-interacting protein kinases (MNKs) and phosphorylate eukaryotic initiation factor 4E (p-eIF4E) play a critical role in regulating mRNA translation and protein synthesis associated with the development of cancer, metabolism, and inflammation. This study undertakes the modification of a 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine structure, leading to the discovery of 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridine (D25) as a potent and selective MNK inhibitor. D25 demonstrated inhibitory activity, with IC50 values of 120.6 nM for MNK1 and 134.7 nM for MNK2, showing exceptional selectivity. D25 inhibited the expression of pro-inflammation cytokines in RAW264.7 cells, such as inducible NO synthase, cyclooxygenase-2, and interleukin-6 (IL-6). In the lipopolysaccharide-induced sepsis mouse model, D25 significantly reduced p-eIF4E in spleen tissue and decreased the expression of tumor necrosis factor α, interleukin-1β, and IL-6, and it also reduced the production of reactive oxygen species, resulting in improved organ injury caused by inflammation. This suggests that D25 may provide a potential treatment for sepsis and sepsis-associated acute spleen injury.
研究领域:
药理学
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免疫学
·
传染病
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Baoshi Xu,Rongrong Yang,Jingchao Qiang,Xuhui Xu,Mengyuan Zhou,Xiaomeng Ji,Yingzhi Lu,Zibo Dong
Background To investigate the effect of Gypenoside XLIX (Gyp-XLIX) on acute splenic injury (ASI) induced by cecal ligation and puncture (CLP) in septic mice, a study was conducted. Methods Sixty healthy mice were randomly divided into six groups: the NC group, the Sham group, the Sham + Gyp-XLIX group, the CLP group, the CLP + Gyp-XLIX group, and the CLP + Dexamethasone (DEX) group. The NC group did not undergo any operation, while the rest of the groups underwent CLP to establish the sepsis model. The Sham group only underwent open-abdominal suture surgery without cecum puncture. After the operation, the groups were immediately administered the drug for a total of 5 days. Various methods such as hematoxylin and eosin (HE) staining, biochemical kits, qRT-PCR, and reactive oxygen species (ROS) were used for analysis. Results The results demonstrated that Gyp-XLIX effectively mitigated the splenic histopathological damage, while reducing the malondialdehyde (MDA) lipid peroxidation index and enhancing the antioxidant activities of catalase (CAT), glutathione (GSH) and total antioxidant capacity (T-AOC). The utilization of Dihydroethidium (DHE) fluorescent probe revealed that Gyp-XLIX inhibited the acute splenic accumulation of ROS induced by CLP in septic mice. Further investigations revealed that Gyp-XLIX exhibited a down-regulatory effect on the protein levels of inflammatory mediators iNOS and COX-2, consequently leading to the suppression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Additionally, it up-regulated the expression of anti-inflammatory factor IL-10. Conclusion In conclusion, Gyp-XLIX was significantly effective in attenuating CLP-induced acute splenic inflammation and oxidative stress in septic mice.
研究领域:
药理学
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免疫学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
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