PHYTOMEDICINE
·
2024
·
IF 6.7
Xiaoliang Dong,Lu Qu,Bingxin Wang,Xiaowei Sha,Bo Wu,Yudong Sun,Xiaohua Pan,Juan Xiong,Jia Sun,Li-Long Pan
ABSTRACT Background Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. Purpose The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. Methods The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo , TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. Results Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. Conclusion : Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo , suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.
研究领域:
药理学
·
心血管疾病
·
炎症
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Huijuan Yu,Wen-Chao Geng,Zhe Zheng,Jie Gao,Dong-Sheng Guo,Yuefei Wang
Detection and quantification of trimethylamine N -oxide (TMAO), a metabolite from gut microbial, is important for the disease diagnosis such as atherosclerosis, thrombosis and colorectal cancer. In this study, a novel method was established for the sensing and quantitative detection of TMAO via molecular recognition of guanidinium-modified calixarene from complex matrix. Methods : Various macrocycles were tested for their abilities to serve as an artificial TMAO receptor. Using the optimized receptor, we developed an indicator displacement assay (IDA) for the facile fluorescence detection of TMAO. The quantification of TMAO was accomplished by the established calibration line after excluding the interference from the various interfering substances in artificial urine. Results : Among various macrocycles, water-soluble guanidinium-modified calix[5]arene (GC5A), which binds TMAO in submicromolar-level, was identified as the optimal artificial receptor for TMAO. With the aid of the GC5A•Fl (fluorescein) reporter pair, TMAO fluorescence “switch-on” sensing was achieved by IDA. The fluorescence intensity increased linearly with the elevated TMAO concentration. The detection was not significantly interfered by the various interfering substances. TMAO concentration in artificial urine was quantified using a calibration line with a detection limit of 28.88 ± 1.59 µM, within the biologically relevant low µM range. Furthermore, the GC5A•Fl reporter pair was successfully applied in analyzing human urine samples, by which a significant difference in fluorescence response was observed between the [normal + TMAO] and normal group. Conclusion: The proposed supramolecular approach provides a facile, low-cost and sensitive method for TMAO detection, which shows promise for tracking TMAO excretion in urine and studying chronic disease progression in humans.
研究领域:
分析化学
·
生物医学工程
·
分子生物学
·
临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Qiangwei Xin,Zhengxin Ma,Shiran Sun,Hongbo Zhang,Yan Zhang,Liangrui Zuo,Yifei Yang,Jing Xie,Chunmei Ding,Jianshu Li
In orthodontic treatment, orthodontic appliances are prone to bacterial infections, which pose a risk to oral health. Surface modification of orthodontic appliances has been explored to improve their antifouling properties and impart antibacterial capabilities, inhibiting initial bacterial adhesion and biofilm formation. However, coatings are susceptible to damage in the complex oral environment, leading to a loss of functionality. Here, we have prepared an antifouling self-healing coating based on supramolecular bonding by employing a simple spin coating method. The presence of the hydrophilic zwitterionic trimethylamine N-oxide (TMAO) and the hydrophobic antimicrobial moieties triclosan acrylate (TCSA) imparts to the polymers an amphiphilic structure and enhances the interaction with bacteria, resulting in excellent antimicrobial activity and surface antifouling properties. The multiple hydrogen bonds of ureido-pyrimidinone methacrylate (UPyMA) and ionic interactions contained in the polymers not only increased the adhesion of the coating to the material substrate (approximately 3 times) but also endowed the coating with the intrinsic self-healing ability to restore the antibiofouling properties at oral temperature and humidity. Finally, the polymer coating is biologically safe both in vitro and in vivo, showing no cytotoxic effects on cells and tissues. This research offers a promising avenue for improving the performance of orthodontic appliances and contributes to the maintenance and treatment of oral health.
研究领域:
牙科学
·
材料科学
·
生物材料
·
生物医学工程
✓ 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）