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024 7 |a 10.1016/j.clim.2023.109861  |2 doi 
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035 |a (DE-627)NLM365562033 
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041 |a eng 
100 1 |a Luo, Keke  |e verfasserin  |4 aut 
245 1 0 |a Huanglian Jiedu Wan intervened with "Shi-Re Shanghuo" syndrome through regulating immune balance mediated by biomarker succinate 
264 1 |c 2024 
336 |a Text  |b txt  |2 rdacontent 
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500 |a Date Completed 02.01.2024 
500 |a Date Revised 10.04.2024 
500 |a published: Print-Electronic 
500 |a Citation Status MEDLINE 
520 |a Copyright © 2023 Elsevier Inc. All rights reserved. 
520 |a With increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW 
650 4 |a Clinical Trial, Phase II 
650 4 |a Journal Article 
650 4 |a Multicenter Study 
650 4 |a Randomized Controlled Trial 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Huanglian Jiedu Wan 
650 4 |a Immune balance 
650 4 |a Inflammation-oxidative stress-energy metabolism 
650 4 |a Succinate 
650 4 |a “Shi-Re Shanghuo” syndrome 
650 7 |a 4-hydroxy-2-nonenal  |2 NLM 
650 7 |a K1CVM13F96  |2 NLM 
650 7 |a Arachidonic Acid  |2 NLM 
650 7 |a 27YG812J1I  |2 NLM 
650 7 |a Biomarkers  |2 NLM 
650 7 |a Drugs, Chinese Herbal  |2 NLM 
650 7 |a huanglian-jie-du decoction  |2 NLM 
650 7 |a Matrix Metalloproteinase 9  |2 NLM 
650 7 |a EC 3.4.24.35  |2 NLM 
650 7 |a Succinates  |2 NLM 
650 7 |a Succinic Acid  |2 NLM 
650 7 |a AB6MNQ6J6L  |2 NLM 
700 1 |a Zhao, Haiyu  |e verfasserin  |4 aut 
700 1 |a Wang, Mengxiao  |e verfasserin  |4 aut 
700 1 |a Tian, Mengyao  |e verfasserin  |4 aut 
700 1 |a Si, Nan  |e verfasserin  |4 aut 
700 1 |a Xia, Wen  |e verfasserin  |4 aut 
700 1 |a Song, Jianfang  |e verfasserin  |4 aut 
700 1 |a Chen, Yunqin  |e verfasserin  |4 aut 
700 1 |a Wang, Linna  |e verfasserin  |4 aut 
700 1 |a Zhang, Yan  |e verfasserin  |4 aut 
700 1 |a Wei, Xiaolu  |e verfasserin  |4 aut 
700 1 |a Li, Xing  |e verfasserin  |4 aut 
700 1 |a Qin, Guangyuan  |e verfasserin  |4 aut 
700 1 |a Yang, Jiaying  |e verfasserin  |4 aut 
700 1 |a Wang, Hongjie  |e verfasserin  |4 aut 
700 1 |a Bian, Baolin  |e verfasserin  |4 aut 
700 1 |a Zhou, Yanyan  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 258(2024) vom: 10. Jan., Seite 109861  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnas 
773 1 8 |g volume:258  |g year:2024  |g day:10  |g month:01  |g pages:109861 
856 4 0 |u http://dx.doi.org/10.1016/j.clim.2023.109861  |3 Volltext 
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