PMID- 34500224 OWN - NLM STAT- MEDLINE DCOM- 20211019 LR - 20211019 IS - 1873-4235 (Electronic) IS - 0956-5663 (Linking) VI - 194 DP - 2021 Dec 15 TI - Development of MIF/IL-1beta biosensors for discovery of critical quality attributes and potential allergic rhinitis targets from clinical real-world data by intelligent algorithm coupled with in vitro and vivo mechanism validation. PG - 113608 LID - S0956-5663(21)00645-X [pii] LID - 10.1016/j.bios.2021.113608 [doi] AB - There are still huge challenges from clinical real-world data to accurate targets and critical quality attributes (CQAs) for effective treatment of allergic rhinitis (AR). Here, we present a novel integrated strategy that biosensors and intelligent algorithms were used to angle AR targets and CQAs from clinical real world. Firstly, bagging and boosting partial least squares discrimination analysis (PLS-DA) and Monte-Carlo sampling were proposed to screen accurate AR targets. Macrophage migration inhibitory factor (MIF) and Interleukin-1beta (IL-1beta) potential targets were obtained based on large-scale analysis of one thousand proteins and in-depth precise screening of seventy proteins. Furthermore, high electron mobility transistor (HEMT) biosensors were fabricated and successfully modified by MIF and IL-1beta potential targets with a low detection concentration as 1 pM and quantitative range from 1 pM to 10 nM. Surprisingly, through MIF/IL-1beta biosensors, we angled 5-O-methylvisammioside, amygdalin, and cimicifugoside three CQAs. The strong interaction was discovered among three CQAs and MIF/IL-1beta biosensors with almost all K(D) up to 10(-11) M. Finally, interaction among three CQAs and MIF/IL-1beta biosensors were evaluated by in vitro and vivo experiments. In this paper, two critical potential targets and three effective CQAs for AR treatment were discovered and validated by biosensor and advanced algorithms. It provides a superior integrated idea for angling critical targets and CQAs from clinical real-world data by biosensors and informatics. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Ma, Lijuan AU - Ma L AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Zheng, Yanfei AU - Zheng Y AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China. FAU - Wang, Ji AU - Wang J AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China. FAU - Li, Qianqian AU - Li Q AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Zeng, Jingqi AU - Zeng J AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Wang, Zijian AU - Wang Z AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Hou, Tingjun AU - Hou T AD - Zhejiang University, College of Pharmaceutical Sciences, Zhejiang, 310058, China. FAU - Zhang, Yang AU - Zhang Y AD - Chinese Academy of Sciences, Institute of Semiconductors, Beijing, 100083, China. FAU - Li, Mingshuang AU - Li M AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Shen, Rongmin AU - Shen R AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China. FAU - Chen, Xuemei AU - Chen X AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China. FAU - Qin, Jingbo AU - Qin J AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China. FAU - Lei, Leting AU - Lei L AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China. FAU - Xia, Qing AU - Xia Q AD - Biology Institute of Shandong Academy of Sciences, Shandong, 250014, China. FAU - Wang, Qi AU - Wang Q AD - Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing, 102488, China; Pharmaceutical Engineering and New Drug Development of TCM of Ministry of Education, Beijing, 102488, China. Electronic address: wangqi710@126.com. FAU - Qiao, Yanjiang AU - Qiao Y AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China; Pharmaceutical Engineering and New Drug Development of TCM of Ministry of Education, Beijing, 102488, China. Electronic address: yjqiao@bucm.edu.cn. FAU - Wu, Zhisheng AU - Wu Z AD - Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing, 102488, China; Pharmaceutical Engineering and New Drug Development of TCM of Ministry of Education, Beijing, 102488, China. Electronic address: wzs@bucm.edu.cn. LA - eng PT - Journal Article DEP - 20210903 PL - England TA - Biosens Bioelectron JT - Biosensors & bioelectronics JID - 9001289 RN - 0 (Interleukin-1beta) RN - 0 (Macrophage Migration-Inhibitory Factors) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.2.1 (MIF protein, human) SB - IM MH - Algorithms MH - *Biosensing Techniques MH - Humans MH - Interleukin-1beta MH - Intramolecular Oxidoreductases MH - *Macrophage Migration-Inhibitory Factors MH - *Rhinitis, Allergic/diagnosis/drug therapy OTO - NOTNLM OT - Allergic rhinitis OT - Clinical real-world data OT - High electron mobility transistor biosensor OT - Intelligent algorithm OT - Interleukin-1beta OT - Macrophage migration inhibitory factor EDAT- 2021/09/10 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/09/09 20:20 PHST- 2021/07/23 00:00 [received] PHST- 2021/08/23 00:00 [revised] PHST- 2021/08/29 00:00 [accepted] PHST- 2021/09/10 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/09/09 20:20 [entrez] AID - S0956-5663(21)00645-X [pii] AID - 10.1016/j.bios.2021.113608 [doi] PST - ppublish SO - Biosens Bioelectron. 2021 Dec 15;194:113608. doi: 10.1016/j.bios.2021.113608. Epub 2021 Sep 3.