scholarly journals DNA methylation profiling in recurrent miscarriage

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8196
Author(s):  
Li Pi ◽  
Zhaofeng Zhang ◽  
Yan Gu ◽  
Xinyue Wang ◽  
Jianmei Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Candidate Genes ◽  
Recurrent Miscarriage ◽  
Enrichment Analysis ◽  
Type I ◽  
Diagnostic Biomarkers ◽  
Expression Levels ◽  
A Genome ◽  
Mrna Expression Levels

Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

scholarly journals Comprehensive analysis of inhibitor of differentiation/DNA-binding gene family in lung cancer using bioinformatics methods

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Suming Xu ◽  
Yaoqin Wang ◽  
Yanhong Li ◽  
Lei Zhang ◽  
Chunfang Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Dna Binding ◽  
Mrna Expression ◽  
Family Members ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genetic Mutations ◽  
Expression Levels ◽  
Mrna Expression Levels

Abstract The inhibitor of differentiation/DNA-binding (ID) is a member of the helix–loop–helix (HLH) transcription factor family, and plays a role in tumorigenesis, invasiveness and angiogenesis. The aims were to investigate the expression patterns and prognostic values of individual ID family members in lung cancer, and the potential functional roles. The expression levels of ID family were assessed using the Oncomine online database and GEPIA database. Furthermore, the prognostic value of ID family members was evaluated using the Kaplan–Meier plotter database. The genetic mutations of ID family members were investigated using the cBioPortal database. Moreover, enrichment analysis was performed using STRING database and Funrich software. It was found that all the ID family members were significantly down-regulated in lung cancer. Prognostic results indicated that low mRNA expression levels of ID1 or increased mRNA expression levels of ID2/3/4 were associated with improved overall survival, first progression and post progression survival. Additionally, genetic mutations of ID family members were identified in lung cancer, and it was suggested that amplification and deep deletion were the main mutation types. Furthermore, functional enrichment analysis results suggested that ID1/2/4 were significantly enriched in ‘regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism’ for biological process, ‘transcription factor activity’ for molecular function and ‘HLH domain’ for protein domain. However, it was found that ID3 was not enriched in the above functions. The aberrant expression of ID family members may affect the occurrence and prognosis of lung cancer, and may be related to cell metabolism and transcriptional regulation.

Expression of Ara-C Metabolizing Enzymes Mediates in Vitro Sensitivity to Ara-C in Primary AML Cells From Patients with Denovo AML,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3481-3481
Author(s):  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Ashok kumar Jayavelu ◽  
Shaji R Velayudhan ◽  
Rayaz Ahmed ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Candidate Genes ◽  
P Value ◽  
Mrna Levels ◽  
Wild Type ◽  
Mutation Status ◽  
Expression Levels ◽  
In Vitro Sensitivity ◽  
Mrna Expression Levels

Abstract Abstract 3481 Wide inter-individual variation in terms of treatment outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (ara-C) and daunorubicin. The pre-requisite for the cytotoxic action of pro-drug Ara-C is the enzymatic conversion to its active tri-phosphorylated form ara-CTP. Many drug activating (Deoxycytidine kinase (dCK) and human Equilibrative Nucleoside Transporter 1 (hENT1) and deactivating (Cytidine deaminase (CDA), 5'nucleotidase (NT5C2) genes and ribonucleoside reductase (RRM1), which are involved in transport and biotransformation of cytarabine contribute to the variation in ara-C sensitivity in AML patients. FLT3-ITD and NPM1 mutations act as major poor and good prognostic markers respectively in cytogenetically normal AML. The effect of these mutations in ara-C metabolism remains to be elucidated. The present study aims to determine independent as well as the combined effect of ara-C metabolizing genes mRNA expression on in-vitro ara-C cytotoxicity and the role of FLT3-ITD and NPM mutations on mRNA expression of these genes. Diagnostic bone marrow sample (median blasts 65%; range 21 – 98%) from 98 adult patients with de novo AML (other than AML-M3) were included in this study. mRNA expression levels for each target gene relative to housekeeping gene GAPDH was analyzed using Taqman based gene expression assays. In vitro cytotoxicity was assessed using MTT cell viability assay and IC-50 was calculated. In vitro sensitivity or resistance was classified on the basis of the IC-50 values <6uM and >6uM ara-C respectively. FLT3 ITD and NPM mutation status at diagnosis were determined through PCR followed by Genescan analysis using genomic DNA samples. Type of NPM mutation was identified by sequencing. When ara-C IC-50 values were compared with the mRNA expression levels of these candidate genes, Ara-C sensitive samples (n= 30; IC-50 < 6uM) showed significantly higher mRNA expression of dCK and hENT1 compared to those with Ara-C resistance (n=51) IC50 >6uM (median 314 (61.56 – 1232) vs. 180 (31.87 – 749.2); p = 0.0004 and median 172.1 (44.12 – 657.6) vs. 96.19 (37.49 – 432.4), p= 0.0008 respectively. RRM1 and NT5C2 did not show any association with in vitro Ara-C cytotoxicity, while CDA showed a trend towards association with lower CDA expression in ara-C sensitive samples. Based on these findings we put forward Ara-C resistance index (RI). RI is calculated by the formula RI = ΔCT (dCK X ENT1)/ ΔCT CDA. (Smaller ΔCT value= higher mRNA expression). RI values were significantly higher in resistant (IC50 >6uM) compared to sensitive cells (median: 6.084; range 1.89–11.82) vs. 3.702 (1.89–9.80); p=<0.0001). This association should now be validated in an independent cohort. Effects of NPM and FLT3 mutation status on Ara-C metabolizing genes were then evaluated. No significant association was found between FLT3-ITD status and the mRNA expression of these candidate genes. Interestingly, dCK mRNA levels were significantly higher in samples with NPM mutation (n=39) compared to NPM wild type (n=59); median 272.3 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.01. When analysed separately, patients with NPM type A mutation (n=27) showed significantly higher dCK expression (median 347.4 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.003 compared to those with wild type NPM1. This first report showing an association between expression profiles of ara-C metabolizing genes and NPM mutation should form the basis for evaluating their clinical correlations. Disclosures: No relevant conflicts of interest to declare.

Herpes simplex virus type I infection of mature dendritic cells leads to reduced LMP7-mRNA-expression levels

Immunobiology ◽  
2009 ◽  
Vol 214 (9-10) ◽  
pp. 861-867 ◽  
Author(s):  
Jutta Eisemann ◽  
Alexander T. Prechtel ◽  
Petra Mühl-Zürbes ◽  
Alexander Steinkasserer ◽  
Mirko Kummer
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mrna Expression ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Type I ◽  
Expression Levels ◽  
Simplex Virus ◽  
Mrna Expression Levels

Fragile X-related protein 1 (FXR1) regulates cyclooxygenase-2 (COX-2) expression at the maternal–fetal interface

2018 ◽  
Vol 30 (11) ◽  
pp. 1566 ◽  
Author(s):  
Xiao-Cui Li ◽  
Meng-fan Song ◽  
Feng Sun ◽  
Fu-Ju Tian ◽  
Yu-mei Wang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Recurrent Miscarriage ◽  
Fragile X ◽  
Firefly Luciferase ◽  
Cyclooxygenase 2 ◽  
Luciferase Reporter ◽  
Related Protein ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

Cyclooxygenase-2 (COX-2) is regulated post-transcriptionally by the AU-rich element (ARE) in the 3′-untranslated region (UTR) of its mRNA. However, the mechanism of COX-2 induction in infertility has not been thoroughly elucidated to date. The aim of this study was to examine the association between COX-2 and fragile X-related protein 1 (FXR1) in trophoblasts. Using quantitative reverse transcription polymerase chain reaction, our results showed that FXR1 mRNA expression levels were significantly decreased in trophoblasts from recurrent miscarriage patients compared with healthy controls; conversely, COX-2 mRNA expression levels were increased in patient samples. We also observed that FXR1 was highly expressed in human placental villi during early pregnancy. Furthermore, we used western blotting and immunofluorescence to analyse the expression levels of FXR1 and COX-2 in HTR-8 cells that were treated with tumour necrosis factor α; we observed that the expression of COX-2 was clearly increased in HTR-8 cells treated with FXR1 small interfering RNA, whereas the expression of COX-2 was effectively decreased in HTR-8 cells with FXR1 overexpressed via a plasmid. Importantly, bioinformatics analysis identified FXR1 binding sites in the 3′-UTR region of COX-2 and firefly luciferase reporter assay analysis verified that FXR1 binds directly to the 3′-UTR region of COX-2. ELISA assays showed that overexpression of FXR1 enhanced vascular endothelial growth factor-A and interleukin-8 expression in HTR-8 cells, whereas conversely, knockdown of FXR1 effectively repressed these effects. In conclusion, the results of this study indicate that FXR1 is a novel COX-2 regulatory factor.

scholarly journals Beta-defensins and analogs in Helicobacter pylori infections: mRNA expression levels, DNA methylation, and antibacterial activity

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222295 ◽  
Author(s):  
Raffaela Pero ◽  
Tiziana Angrisano ◽  
Mariarita Brancaccio ◽  
Annarita Falanga ◽  
Lucia Lombardi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Mrna Expression ◽  
Expression Levels ◽  
Beta Defensins ◽  
Mrna Expression Levels

scholarly journals DNA Methylation and SNPs of ABCA1 Gene Promoter Affect Gene Expression and Involve in the Pathological Mechanism of Ischemic Stroke

2021 ◽  
Author(s):  
Zhihao Li ◽  
Jun Wang ◽  
Baixue Zhou ◽  
Yang Liu ◽  
Zhaojing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Ischemic Stroke ◽  
Mrna Expression ◽  
Foam Cell ◽  
Gene Promoter ◽  
Control Group ◽  
Expression Levels ◽  
Pathological Mechanism ◽  
Mrna Expression Levels

Abstract ATP binding cassette subfamily A1 (ABCA1) is a key protein in the formation of mature high density lipoprotein (HDL), which plays a crucial role in atherosclerosis. Accumulating evidence has shown that the expression levels of the ABCA1 gene are upregulated in ischemic stroke (IS) patients. However, the mechanism remains elusive. We hypothesized that DNA methylation and SNPs of ABCA1 gene promoter affect the expression levels of ABCA1 gene and involve in the pathological mechanism of IS. 100 patients with IS and 100 healthy controls were enrolled in the present study. Initially, the mRNA expression levels of ABCA1 gene were examined by qPCR and the methylation levels was detected by MethyTarget sequencing. Then, rs1800976, rs1800977, rs2246298, rs2437817, rs2740483, rs539621172 in promoter region of ABCA1 gene were selected for genotyping. Finally, the relationship between the methylation of ABCA1 gene and gene expression was verified by constructing THP-1 foam cell model. The mRNA expression levels of ABCA1 gene in the IS group were significantly higher than those in controls (P<0.05). 17 CpG sites in the promoter of ABCA1 gene were analyzed and the DNA methylation levels of CpG1, CpG7 and CpG15 sites in IS group was significantly lower than control group (P<0.05). Rs2740483, rs1800977 and rs2437817 were significantly correlated with CpG1. Rs1800977 was significantly correlated with CpG3. In summary, DNA methylation and rs2740483, rs1800977, rs2437817 of ABCA1 gene promoter affect the expression levels of ABCA1 gene, change the clearance rate of intracellular lipids, and participate in the pathogenesis of IS.

scholarly journals Evaluation of mRNA Expression Levels of cyp51A and mdr1, Candidate Genes for Voriconazole Resistance in Aspergillus flavus

2015 ◽  
Vol 8 (12) ◽  
Author(s):  
Azam Fattahi ◽  
Farideh Zaini ◽  
Parivash Kordbacheh ◽  
Sasan Rezaie ◽  
Mahin Safara ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Candidate Genes ◽  
Aspergillus Flavus ◽  
Expression Levels ◽  
Mrna Expression Levels

scholarly journals In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilong Fang ◽  
Ling Yu ◽  
Da You ◽  
Nan Peng ◽  
Wanbei Guo ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Inflammatory Factors ◽  
Control Group ◽  
Therapeutic Effects ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α ◽  
Mrna Expression Levels

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

Sign in / Sign up

Export Citation Format

Share Document