Background: Function of Dhrs3 and importance of the upstream metabolism of retinoic acid are not well understood in early embryonic development. Results: Dhrs3 attenuates retinoic acid synthesis and is required for embryonic patterning. Conclusion: dhrs3 is involved in maintaining balance of retinoic acid signaling and therefore regulates body axis formation. Significance: This is the first functional study of Xenopus dhrs3 in embryonic development.
Background: A proper level of BMP signal is essential for the maintenance of neural crest cells. Results: Ets1 cooperates with HDAC1 to down-regulate BMP signaling output and reduce id3 expression. Conclusion: Ets1 regulates neural crest development through epigenetic control of BMP signaling. Significance: This is the first study linking Ets1 to BMP signaling.
Background:The function of Hspa5 in early embryonic development is not well understood. Results: Hspa5 is involved in mediating retinoic acid signaling and is required for pronephros. Conclusion: Hspa5 is essential for pronephros formation by mediating retinoic acid signaling. Significance: This is the first report on the cross-talk between physiological ER stress and transduction of retinoic acid signaling.
Puerarin is an isoflavonoid isolated from the root of Pueraria lobata (Gegen in Chinese) that has been widely used to treat cardiovascular and cerebrovascular diseases in China. Here, we investigated the hypotensive effects and mechanisms of puerarin in spontaneously hypertensive rats. The qPCR array technique was used to determine the expression of hypertension-related genes. Then, the differentially expressed genes were analyzed using the STRING database. The systolic blood pressure and diastolic blood pressure of rats decreased after the administration of puerarin for nine weeks. Puerarin, but not losartan, also slowed the heart rate of rats. NO and cGMP levels were improved by puerarin. Eighteen differentially expressed hypertension-related genes were identified by comparing the model group with the control group and the high-dose puerarin group with the model group. NO and cGMP levels were increased by high-dose puerarin. High-dose puerarin increased the levels of the phosphorylated eNOS protein and decreased AT1 and Cav1 levels. Based on our results, eNOS was a key target in the mechanism by which puerarin reduced blood pressure, and puerarin represents a potential antihypertensive agent.
Mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been shown to effectively limit the infarct area in numerous clinical and preclinical studies. However, the primary mechanism associated with this activity in MSC transplantation therapy remains unclear. Blood supply is fundamental for the survival of myocardial tissue, and the formation of an efficient vascular network is a prerequisite for blood flow. The paracrine function of MSCs, which is throughout the neovascularization process, including MSC mobilization, migration, homing, adhesion and retention, regulates angiogenesis and vasculogenesis through existing endothelial cells (ECs) and endothelial progenitor cells (EPCs). Additionally, MSCs have the ability to differentiate into multiple cell lineages and can be mobilized and migrate to ischemic tissue to differentiate into ECs, pericytes and smooth muscle cells in some degree, which are necessary components of blood vessels. These characteristics of MSCs support the view that these cells improve ischemic myocardium through angiogenesis and vasculogenesis. In this review, the results of recent clinical and preclinical studies are discussed to illustrate the processes and mechanisms of neovascularization in ischemic heart disease.
BackgroundsDown syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidies. The main characteristic of DS patients is intellectual disability. MicroRNAs (miRNAs) play important regulatory roles in various biological processes, such as embryonic development, cell differentiation, proliferation and apoptosis. Several miRNAs have shown association with DS. However, the role of miRNAs in DS patients has not been well elaborated.MethodsIn this research, total RNA extracted from fetal hippocampal tissues was used to analyze miRNA and mRNA expression via Affymetrix miRNA 4.0 and PrimeView Human Gene Expression Array, respectively. Then miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their predicted target mRNAs. Microarray data were further validated by real-time PCR. Regulation of zeste homolog 2 (EZH2) expression by hsa-miR-138 was determined by luciferase reporter assay.ResultsWe analyzed microRNA expression profile in hippocampal tissues from DS fetal using miRNA microarray. Further with the use of mRNA microarray data, we integrate miRNA expression and mRNA expression in hippocampus of trisomy 21 fetus to elucidate the mechanism that underlying DS abnormalities. We characterized the repertoire of specific miRNAs involved in hippocampus in trisomy 21 patients, highlighting hsa-miR-138 and hsa-miR-409, in particular the importance of hsa-miR-138, especially the -5p strand. Furthermore, the expression level of predicted target genes of hsa-miR-138-5p in trisomy 21 fetus, including zeste homolog 2 (EZH2) were further confirmed. In addition, luciferase assay indicated that EZH2 was a direct target of hsa-miR-138 in HEK293T cells.ConclusionThe function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-016-0265-0) contains supplementary material, which is available to authorized users.
Effectively improving myocardial blood flow and controlling atherosclerotic plaque have always been key and difficult points in the prevention and treatment of coronary artery disease (CAD). Although “therapeutic angiogenesis” is regarded as a promising approach for ischemic heart disease by improving blood flow, angiogenesis itself can induce the destabilization of atherosclerotic plaque, which reflects the double-edged role of angiogenesis. Modulating the balance of angiogenesis can be an important target for CAD treatment. Traditional Chinese medicine (TCM) emphasizes the holistic view and dynamic balance of the body. Furthermore, the principle of activating blood circulation and removing blood stasis (ABCRS) is closely connected with angiogenesis and CAD. Recent research suggests that Chinese herbal medicines for ABCRS are effective in balancing the regulation of angiogenesis. This review presents the progress of recent research on the angiogenesis regulation with Chinese herbal medicines for ABCRS in CAD. Moreover, this review demonstrates that Chinese herbal medicines for ABCRS can not only promote angiogenesis in the ischemic area to improve myocardial blood flow but also alleviate angiogenesis to stabilize plaque in atherosclerosis, which reflects the holistic regulatory role in CAD treatment.
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