Abstract
Cerebral ischemia has led to a high rate of both disability and mortality with massive healthcare costs. Although transcriptional regulation is typically mediated by different combinations of TFs, a combined regulatory unit to synergistically activate transcription has remained unclear in cerebral ischemia, especially in different drug treatments. In this study, TFs alterations after 6 h cerebral ischemic injury and repair were performed by a concatenated tandem array of consensus transcription factor response elements (catTFREs), and vital TFs were obtained by TFs-target imbalanced network. Drug intervention used Danhong injection (DHI) and BNC (BuChang NaoXinTong Capsules), which has been widely prescribed in Chinese herb medicine for the treatment of cerebrovascular and cardiovascular diseases. There were 198 TFs identified after 6 h MCAO operation, and six TFs (Sox2, Smad3, FoxO1, Creb1, Egr,1 and Smad4) were considered as critical TFs in response to cerebral ischemia. Moreover, Smad3 was identified as a hub TF among six vital TFs, and the transcription activity of Smad3 was further verified. These 6 TFs were all reversed by DHI or BNC, indicating different medications may regulate different transcription factors through TF synergy. Moreover, validation results indicated that Smad3 was a putative target TF for DHI and BNC-mediated protection against cerebral ischemia. The observations of the present study provide a fresh understanding of biomolecules and possible new avenues for therapeutic interventions, in addition to the new intervention pattern for different treatments for ischemia stroke.
Highlights
Cerebral ischemia, a serious neurological disease, has led to a high rate of both disability and mortality with massive healthcare costs [1]
And 1(c), mice in the model group showed a higher degree in infarction volume and infarction rate (28:25 ± 4:13), while the Danhong injection (DHI), BuChang NaoXinTong Capsules (BNC), and Ginaton group were observed to reduce the degree of infarction volume and infarction rate (DHI: 18:55 ± 3:05; BNC: 19:58 ± 5:53; Ginaton: 18:74 ± 3:46, respectively). All these results demonstrated the administration of Ginaton, DHI, and BNC contributes to improving neurologic function
Large-scale quantitative profiling and network pharmacology were used to construct the imbalanced network of transcription factors (TFs) after cerebral ischemia and critical TFs against cerebral ischemia by medication, BuChang NaoXinTong Capsules (BNC), and Danhong injection (DHI)
Summary
A serious neurological disease, has led to a high rate of both disability and mortality with massive healthcare costs [1]. Hypoxia-inducible factor-1α (HIF-1α) is involved in pathologic conditions such as hypoxia or ischemia and leads to severe cerebral injury [5]. N-Myc downstream-regulated gene-2 (NDRG2)) is upregulated after cerebral ischemia and is involved in inflammation [6]. Signal transducers and activators of transcription (STATs) were activated after cerebral ischemia promoted the expression of several critical proteins that induce brain injury [7]. Oligodendrocyte transcription factor 1 (Olig1) was found to be an important mediator during the differentiation and remyelination after focal cerebral ischemia [8]. Transcriptional regulation is typically mediated by distinct combinations of TFs, their combined regulatory cues to synergistically activate transcription have remained unclear in cerebral ischemia which indicated that there requires a need
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