Identification of the Disrupted Pathways Associated with Periodontitis Based on Human Pathway Network

Objective: The objective of this work is to search for a novel method to explore the disrupted pathways associated with periodontitis(PD) based on the network level.Methods: Firstly, the differential expression genes(DEGs) between PD patients and cognitively normal subjects were inferred based on LIMMA package. Then, the proteinprotein interactions(PPI) in each pathway were explored by Empirical Bayesian(EB) coexpression program. Specifically, we determined the 100 th weight value as the threshold value of the disrupted pathways of PPI by constructing the randomly model and confirmed the weight value of each pathway. Meanwhile, we dissected the disrupted pathways under the weight value > the threshold value. Pathways enrichment analyses of DEGs were carried out based on Expression Analysis Systematic Explored(EASE) test. Finally, the better method was selected based on the more rich and significant obtained pathways by comparing the two methods. Results: After the calculation of LIMMA package, we estimated 524 DEGs in all. Then we determined 0.115222 as the threshold value of the disrupted pathways of PPI. When the weight value>0.115222, there were 258 disrupted pathways of PPI enriched in. Additionally, we observed those 524 DEGs that were enriched in 4 pathways under EASE=0.1.Conclusion: We proposed a novel network method inferring the disrupted pathway for PD. The disrupted pathways might be underlying biomarkers for treatment associated with PD.

In vitro assessment of thyroid hormone receptor activity of four organophosphate esters

Previous animal experiments have implied that organophosphate esters（OPEs） have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone（TH） nuclear receptor（TR） using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that tris（2-chloro-1-（chloromethyl）ethyl）phosphate（TDCPP） could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TRβ, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRβ, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR.