ABSTRACT
Lactylation is a novel post-translational modification of proteins. Although the histone lactylation modification has been reported to be involved in glucose metabolism, its role and molecular pathways in gestational diabetes mellitus (GDM) are still unclear. This study aims to elucidate the histone lactylation modification landscapes of GDM patients and explore lactylation-modification-related genes involved in GDM. We employed a combination of RNA-seq analysis and chromatin immunoprecipitation sequencing (ChIP-seq) analysis to identify upregulated differentially expressed genes (DEGs) with hyperhistone lactylation modification in GDM. We demonstrated that the levels of lactate and histone lactylation were significantly elevated in GDM patients. DEGs were involved in diabetes-related pathways, such as the PI3K-Akt signaling pathway, Jak-STAT signaling pathway, and mTOR signaling pathway. ChIP-seq analysis indicated that histone lactylation modification in the promoter regions of the GDM group was significantly changed. By integrating the results of RNA-seq and ChIP-seq analysis, we found that CACNA2D1 is a key gene for histone lactylation modification and is involved in the progression of GDM by promoting cell vitality and proliferation. In conclusion, we identified the key gene CACNA2D1, which upregulated and exhibited hypermodification of histone lactylation in GDM. These findings establish a theoretical groundwork for the targeted therapy of GDM.
Subject(s)
Chromatin Immunoprecipitation Sequencing , Diabetes, Gestational , Histones , Protein Processing, Post-Translational , Diabetes, Gestational/genetics , Diabetes, Gestational/metabolism , Humans , Female , Pregnancy , Histones/metabolism , Histones/genetics , Signal Transduction/genetics , RNA-Seq , AdultABSTRACT
Pre-eclampsia is a serious multi-organ complication that severely threatens the safety of pregnant women and infants. To accurate and timely diagnose pre-eclampsia, point-of-care (POC) biosensing of the specific biomarkers is urgently required. However, one of the key biomarkers of pre-eclampsia, placental growth factor (PlGF), has a reduced level of expression in patients, which challenges the quantification capability and Limit-of-detection (LOD) of biosensors. Herein, we reported a microfiber Bragg grating biosensor for the quantification of PlGF in clinical serum samples. The Bragg grating was inscribed in a unilateral tapered fiber to generate the segmented Fabry-Perot spectrum for improving the capability of detection. Furthermore, a temperature-calibrated Bragg grating was added to enable dual parametric detection of PlGF and temperature simultaneously for removing the crosstalk. Finally, the biosensor was envisaged to be perfectly compatible with microfluidic chips, and thus dramatically reducing the sample consumption to as small as 10 µL. The proposed biosensor can respond to PlGF with concentrations ranging from 5 to 120 pg mL-1, attaining a LOD of 5 pg mL-1 of clinical relevance. More importantly, the biosensor achieved micro volume detection of clinical serum samples from patients, and the ROC curve with an AUC of 0.977 confirmed the viability of the device. Our study paves the way to a new idea for cost-effective and high-precision screening of patients with pre-eclampsia, and hence envisages a promising prospect for point-of-care (POC) diagnosis of patients with pre-eclampsia.