PHYTOMEDICINE
·
2025
·
IF 8.3
Penghong Xu,Yuping Qian,Guo Xu,Jianlin Chu,Bingfang He
Background Inflammatory bowel disease (IBD), a chronic inflammatory condition categorized into ulcerative colitis (UC) and Crohn's disease (CD), affects a growing global patient population. Despite the prevalence, clinically there is a scarcity of effective therapeutic agents. Purpose This study investigated the therapeutic effects of fructosyl mangiferin (FM) on UC and elucidated its underlying mechanisms through in vivo and in vitro experiments. Methods In vivo , a UC model of C57BL/6J mice was established via dextran sulfate sodium (DSS) induction, and the therapeutic effects were assessed through intragastric administration. In vitro , the murine macrophage cell line RAW264.7 was stimulated with lipopolysaccharide (LPS) to establish an M1 polarization model and introduced to explore the role of FM in immune cells. Molecular docking was further employed to investigate the specific molecular mechanisms of FM. Results In vivo experimental findings indicate that FM, like mangiferin (M), preserves mucin secretion and the expression of occludin protein, and both significantly impede the progression of fibrosis associated with colitis. Additionally, FM effectively suppresses M1 macrophage polarization and exerts a pronounced inhibitory effect on the adaptive immune response, outperforming M in mitigating UC. In vitro results corroborate FM's inhibitory action on M1 polarization. Molecular docking studies identified FM as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor, aligning with western blot analyses from both in vivo and i n vitro experiments. Conclusion In conclusion, following fructosylation, FM exhibits remarkable anti-inflammatory and colonic protective effects. FM's ability to control the progression of UC offers a novel strategy for its potential treatment, warranting further investigation into its clinical application.
研究领域:
免疫学
·
药理学
·
消化病学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Tianying Bian,Hu li,Haohao Liu,Mudi Guo,Yiding Zhang,Pinli Hu,Meihua Chen
Objectives To explore the effects and biological mechanism of apabetalone on periodontal inflammation by regulating glycolysis and metabolites. Methods A ligature-induced periodontitis model was established in mice and apabetalone was administered on the ligation silk for two weeks. Inflammation levels and alveolar bone absorption were explored using micro-computed tomography and histopathological analysis. To observe the role of apabetalone in macrophage polarization and the macrophage-mediated immune microenvironment, a Luminex assay, quantitative real-time polymerase chain reaction, a conditioned medium experiment, a Seahorse extracellular flux assay and quantitative metabolomics were used for molecular biological analysis. Results Apabetalone-treated mice exhibited ameliorated alveolar bone loss and inflammatory infiltration in the periodontium. Furthermore, apabetalone significantly inhibited the production of proinflammatory cytokines and suppressed the levels of M1-specific biomarkers both in vivo and in vitro . Apabetalone also promoted the osteogenic potential of mouse periodontal ligament cells in a macrophage-mediated microenvironment. Apabetalone restrained LPS-induced glucose uptake and lactic acid production. Apabetalone inhibited glycolysis by suppressing the transcription and protein expression of hexokinase 2, glucose transporter 1 and phosphofructokinase-2/fructose-2,6- bisphosphatase 3 (PFKFB3) in a dose-dependent manner. Quantitative analysis of certain carbohydrates involved in energy metabolism revealed that apabetalone reserved the disruption of the tricarboxylic acid (TCA) cycle and inhibited glycolysis and the pentose phosphate pathway. In addition, apabetalone increased the oxygen consumption rate. Conclusion Collectively, these findings indicate that apabetalone improves the periodontal immune microenvironment by regulating metabolites in macrophages. Apabetalone exerts anti-inflammatory and osteo-protective effects by replenishing the broken TCA cycle and suppressing glycolysis. Apabetalone is a potential candidate for the treatment of periodontitis.
研究领域:
口腔医学
·
免疫学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2025
·
IF 3.8
Jiajia Chen,Huanle Liu,Yanfang Fu,Xiaolan Chen,Shiqin Zhang,Yongqi Yang,Shengwen Li,Guixiang Wang,Tian Lan
Background Chronic liver inflammation is a major cause of death in patients with liver fibrosis and cirrhosis, which pose a serious health threat worldwide, and there is no effective anti-hepatic fibrosis drug. Kaempferol (KA), a flavonoid polyphenol extracted from many edible plants and traditional Chinese medicine, has been reported to possess anti-inflammatory, antioxidant, and antitumor activities and has an ameliorating effect on liver fibrosis or other fibroproliferative diseases. However, the specific regulatory mechanism of KA-reversed macrophage M1 polarization is still obscure. This study aimed to investigate the protective effects of KA on carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice through M1 polarization. Methods C57BL/6 mice were intraperitoneally injected with CCl 4 twice weekly to induce liver fibrosis. Male mice were randomly divided into four groups (n = 5): the oil group, the CCl 4 group, the low-dose KA-treatment CCl 4 group (50 mg/kg/d KA), and the high-dose KA-treatment CCl 4 group (100 mg/kg/d KA). An equal amount of solvent was given to each group by intraperitoneal injection. Results The results indicated that KA decreased liver pathologic changes, hepatic macrophage recruitment, and serum alanine aminotransferase (ALT) levels. Notably, it reduced the activation of M1-type macrophages in the liver. The expression of proinflammatory cytokines and genes associated with M1 macrophages, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and inducible nitric oxide synthase (iNOS), was also decreased. The core targets, signaling pathways, and possible mechanisms related to the M1 polarization of KA were analyzed by network pharmacology and molecular docking. Further analysis revealed that KA regulated MAPK/NF-κB signaling pathways. Finally, the results indicated that KA regulates M1 macrophage activation by modulating the MAPK/NF-κB signaling pathways. Conclusions This study revealed that KA ameliorated liver injury, inflammation, and fibrosis by inhibiting macrophage M1 polarization through the MAPK/NF-ҡB signaling pathway, highlighting KA as a potential novel agent for the prevention and treatment of liver fibrosis.
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Zhixin Zhu,Lulu Jin,Qiaoxuan Wang,Haifei Shi,Ke Cheng,Zhengwei Mao
There is a desperate need for precise nanomedications to treat ischemic cerebral injury. Yet, the drawbacks of poor delivery efficiency and off-target toxicity in pathologic parenchyma for traditional antioxidants against ischemic stroke result in inadequate brain accumulation. M13 bacteriophages are highly phagocytosed by M1-polarized microglia and can be carried toward the neuroinflammatory sites. Here, a bio-active, inhalable, Ce 0.9 Zr 0.1 O 2 -backpacked-M13 phage (abbreviated as CZM) is developed and demonstrates how M13 bacteriophages are taken up by different phenotypes’ microglia. With the M1 microglia's proliferating and migrating, CZM can be extensively and specifically delivered to the site of the ischemic core and penumbra, where the surviving nerve cells need to be shielded from secondary oxidative stress and inflammatory cascade initiated by reactive oxygen species (ROS). With non-invasive administration, CZM effectively alleviates oxidative damage and apoptosis of neurons by eliminating ROS generated by hyperactive M1-polarized microglia. Here, a secure and effective strategy for the targeted therapy of neuroinflammatory maladies is offered by this research.
研究领域:
神经科学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 9
·2243
·
IF 5.4
Jiayi Zhang,Bing Gu,Shimiao Wu,Lin Liu,Ying Gao,Yucen Yao,Degong Yang,Juan Du,Chunrong Yang
Tumor hypoxia is considered one of the key causes of the ineffectiveness of various strategies for cancer treatment, and the non-specific effects of chemotherapy drugs on tumor treatment often lead to systemic toxicity. Thus, we designed M1 macrophage-biomimetic-targeted nanoparticles (DOX/CAT@PLGA-M1) which contain oxygen self-supplied enzyme (catalase, CAT) and chemo-therapeutic drug (doxorubicin, DOX). The particle size of DOX/CAT@PLGA-M1 was 202.32 ± 2.27 nm (PDI< 0.3). DOX/CAT@PLGA-M1 exhibited a characteristic core-shell bilayer membrane structure. The CAT activity of DOX/CAT@PLGA-M1 was 1000 (U/mL), which indicated that the formation of NPs did not significantly affect its enzymatic activity. And in vitro drug release showed that the cumulative release rate of DOX/CAT@PLGA-M1 was enhanced from 26.93% to 50.10% in the release medium of hydrogen peroxide, which was attributed to the reaction of CAT in the NPs. DOX/CAT@PLGA-M1 displayed a significantly higher uptake in 4T1 cells, because VCAM-1 in tumor cells interacted with specific integrin (α4 and β1), and thereby achieved tumor sites. And the tumor volume of the DOX/CAT@PLGA-M1 group was significantly reduced (0.22 cm3), which further proved the active targeting effect of the M1 macrophage membrane. Above all, a novel multifunctional nano-therapy was developed which improved tumor hypoxia and obtained tumor targeting activity.Keywords:tumor microenvironment;M1 macrophage;tumor hypoxia;catalase;cancer treatment
研究领域:
癌症生物学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Green Energy & Environment
·
2022
·
IF 12.781
Shuairen Qian,Yuxin Chen,Binhang Yan,Yi Cheng
High activity and productivity of MoVNbTeO x catalyst are challenging tasks in oxidative dehydrogenation of ethane (ODHE) for industrial application. In this work, phase-pure M1 with 30 wt% CeO 2 composite catalyst was treated by oxygen plasma to further enhance catalyst performance. The results show that the oxygen vacancies generated by the solid-state redox reaction between M1 and CeO 2 capture active oxygen species in gas and transform V 4+ to V 5+ without damage to M1 structure. The space-time yield of ethylene of the plasma-treated catalyst was significantly increased, in which the catalyst shows an enhancement near ∼100% than that of phase-pure M1 at 400 °C for ODHE process. Plasma treatment for catalysts demonstrates an effective way to convert electrical energy into chemical energy in catalyst materials. Energy conversion is achieved by using the catalyst as a medium.
研究领域:
催化化学
·
材料科学
·
能源转换
✓ 已验证
DOI
高影响因子
Emergency Medicine International
·
2021
·
IF 1.112
Chen Zongyun,Lin Bixia,Ding Fadian,Hong Xiaoping,Chen Hongbin,Deng Yu,Liu Qicai,Ye Xiaoyi,Zeng Kai
Introduction. The advances in cerebral ischemia treatment have resulted in a larger proportion of patients get the benefits of rebuilding blood flow to the brain. Then, ischemia-reperfusion injury has emerged as a new essential problem. Dectin-1 plays an important role in cerebral ischemia-reperfusion injury by regulating the function of immune cells. Methods. C57BL/6 was blindly divided into four groups including the sham-operated group and the three different kinds of middle cerebral artery occlusion (MCAO) groups (after 6 hours, 12 hours, and 24 hours after plug removal). The protein expression levels of dectin-1, proapoptosis molecule, and antiapoptosis molecule were measured by using western blot analysis. The brain tissue was analyzed by flow cytometry to detect the M1 macrophage levels. Results. The correlation analysis of dectin-1 and infarct areas showed that there was an obviously positive correlation in between them (R = 0.9603). Dectin-1, cleaved caspase-3, and Bax increased, while antiapoptosis molecule, Bcl-2, decreased at three appropriate time points (after 6 hours, 12 hours, and 24 hours). The level of M1 macrophages in the experimental group increased after ischemia-reperfusion injury compared to the control group. Conclusions. The high expression level of dectin-1 may affect M1 macrophage polarization and brain cell apoptosis in cerebral ischemia-reperfusion injury.
研究领域:
神经科学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
·
2017
·
IF 3.133
Meinan Wan,Baoshun Liu,Shuo Wang,Lingting Hu,Youjia He,Haizheng Tao,Xiujian Zhao
Monoclinic (M1) VO 2 film has potential applications in thermochromic modulators owing to the particular optical performance caused by phase transition. However, its controllable preparation is very difficult due to the multivalence of V element. Here, we studied a sol-gel process followed by annealing in a closed vaccum furnace containing NH 3 atmosphere, and discussed the formation mechanism of M1-phase VO 2 films. Thermochromic M1-phase VO 2 thin films can be fabricated under the base pressure of 600–2000 Pa with the annealing temperature at 470–590 °C for more than 0.5 h, and the optimal condition is at 1000–2000 Pa and 500–530 °C for 0.5 h, by synthetically considering their luminous transmittance ( T lum ), solar modulation efficiency ( ΔT sol ), and modulation efficiency at 2000 nm ( ΔT 2000nm ). The M1-phase VO 2 thin film generally exhibits the optical properties with T lum ≈ 39–41%, ΔT sol ≈ 7.7% and ΔT 2000nm ≈ 50%. A higher base pressure introduces more oxygen to remove polymers in precursors, enhancing the transparency of films. Improving the temperature or the duration promotes the growth of VO 2 crystallite with limits. However, inappropriate base pressure, temperature or duration will reduce or oxidize the VO 2 films, resulting in the inferior thermochromic properties. According to thermal and XPS analysis , NH 3 can act as a reductant to prevent oxidation of VO 2 films during the annealing process. This convenient heat treatment method to synthesize M1-VO 2 films may provide a useful and practical technique for the production of VO 2 -based smart window and optical devices.
研究领域:
材料科学
·
光学工程
✓ 已验证
DOI
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
DongXue Ma,YuXin Zhang,Jia Zhang,Jun Shi,ShanHu Gao,Fei Long,Xin Wang,XingYu Pu,Jiayao Sun,Shuang Liang,Richard D. Cannon,Silas Villas-Boas,Ting-Li Han
Introduction: Escherichia coli Nissle 1917 (EcN) is one of the most extensively studied nonpathogenic Gram-negative probiotic strains worldwide. Recent research has highlighted the ability of EcN outer membrane vesicles (OMVs) to enhance the phagocytosis and proliferation of RAW264.7 macrophages. However, the impact of EcN-OMVs on M1/M2 polarization and metabolic modulation remains unknown.Methods: In this study, we evaluated the metabolic effects of EcN-OMVs on RAW264.7 macrophage polarization using metabolomic, transcriptomic, and fluxomic approaches.Reuslts: We found that the RAW264.7 macrophages phagocytosed EcN-OMVs, triggering upregulation of the HIF-1, mTORC1, and NF-κB signaling pathways. This metabolic reprogramming enhanced glycolysis, suppressed the TCA cycle, elevated intracellular reactive oxygen species (ROS), TNF-α, IL-6, IL-1β, ATP, and nitric oxide (NO) production, and promoted macrophage proliferation, migration, invasion, and M1-type polarization.Discussion: In summary, this research establishes a theoretical foundation for utilizing probiotic OMVs in immunomodulatory therapeutic applications.
研究领域:
免疫学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Caiqi Xu,Yaoyao Wu,Sui Yang,Xuechun Zhao,Hao Zhang,Yunwen Yan,Jiemin Zhao,Wei Wei,Qian Meng,Yujuan Wang,Rui Zhang
DJ-1, also known as PARK7 (Parkinson's disease protein 7), which is involved in cell viability, apoptosis, transcriptional regulation, and oxidative stress adaptation, is also involved in the pathogenesis of various human diseases including carcinogenesis. Here, we aimed to determine the novel mechanism by which DJ-1 inhibition suppresses tumor growth. Our results showed that DJ-1 knockdown in cancer cells promoted the secretion of a significantly larger amount of mitochondrial transcription factor A (TFAM) into the cell culture medium. DJ-1 knockdown promotes p53 translocation to the mitochondria and stimulates the intrinsic mitochondrial apoptosis pathway, resulting in TFAM release. Moreover, DJ-1 knockdown induced the downregulation of sirtuin 3 (SIRT3), which increased the acetylation of TFAM and triggered its release. Furthermore, we found that extracellular TFAM played a critical role in antitumor activity by upregulating the expression of chemokine (C C motif) ligand 4 (CCL4) and chemokine (C-X-C motif) ligand 5 (CXCL5) in cancer cells, contributing to the promotion of M1 macrophage polarization in the tumor microenvironment (TME). Finally, we confirmed that the DJ-1 inhibitor suppressed tumor growth by increasing TFAM release from cancer cells and M1 macrophage polarization in vivo. These findings indicate that the depletion of DJ-1 stimulates apoptosis-dependent TFAM secretion that triggers M1 macrophage polarization, indicating a new therapeutic strategy by interfering with the DJ-1 function in cancer therapy.
研究领域:
肿瘤学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CATALYSIS
·
2022
·
IF 8.047
Yuxin Chen,Shuairen Qian,Kai Feng,Zhengwen Li,Binhang Yan,Yi Cheng
The original phase-pure M1 MoVNbTeO x catalyst was mechanically treated with stirring water for several days under ambient conditions to obtain particles with different sizes. The catalytic performance was significantly improved and stabilized after about 7 days of treatment. Among all the catalysts, the sample treated in water for 7 days can obtain 57.6 % ethane conversion and 0.79 kg C2H4 /kg cat /h ethylene productivity while the original phase-pure M1 catalyst was only 19.2 % and 0.27 kg C2H4 /kg cat /h at reaction temperature of 400 °C and contact time of 18.5 g cat ·h/mol C2H6 . Meanwhile, the catalyst was systematically characterized and the results showed that there was essentially no difference in microstructure between the original and treated catalysts. TEM and SEM morphological characterizations presented that the particle size and aspect ratio of the catalysts changed significantly, in which the particle size of the catalyst become smaller and the proportion of basal surface was enhanced. The activity and selectivity of the catalysts exhibited a correlation with the amount and proportion of basal surface. It can be deducted that the basal surface is the most active and selective surface during oxidative dehydrogenation of ethane (ODHE) process, and the intrinsic activity based on the basal (0 0 1) plane of the catalyst remains stable after the mechanical treatment. Samples treated in water for 7 days showed excellent long-term stability in a 200 h stability test at reaction temperature of 440 °C and contact time of 9.3 g cat ·h/mol C2H6 . The present work demonstrated that the differences in the catalytic properties of different M1 samples depend mainly on the amount and proportion of exposed basal surface, and the possibility of enhancing the activity of orthorhombic M1 phase by fragmentation method.
研究领域:
催化化学
·
材料科学
✓ 已验证
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Li An,Qianwen Zhai,Keyu Tao,Yingcai Xiong,Weiying Ou,Ziwei Yu,Xingyu Yang,Jianjian Ji,Mengjiang Lu
Background Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. Purpose This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. Methods BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. Results Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. Conclusion Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.
研究领域:
免疫学
·
药理学
·
病毒学
·
代谢组学
✓ 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）