Development of MIF/IL-1 β 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

Biosens Bioelectron. 2021 Sep 3;194:113608. doi: 10.1016/j.bios.2021.113608. Online ahead of print.ABSTRACTThere 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-1β) 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-1β potential targets with a low detection concentration as 1 pM and quantitative range from 1 pM to 10 nM. Surprisingly, through MIF/IL-1β biosensors, we angled 5-O-methylvisammioside, amygdalin, and cimicifugoside three CQAs. The strong interaction was discovered among three CQAs and MIF/IL-1β biosensors with almost all KD up to 10-11 M. Finally, interaction among three CQAs and MIF/IL-1β 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...
Source: Biosensors and Bioelectronics - Category: Biotechnology Authors: Source Type: research