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Background: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, with complex etiology, difficult treatment and poor prognosis. The objective of this study was to investigate the potential biomarkers for PAH based on bioinformatics analysis. Methods: The GSE117261 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by screening PAH patients and controls. Then the DEGs were analyzed using a Weighted Gene Co-expression Network Analysis (WGCNA) and the key modules were determined, and to further explore their potential biological functions via Gene Ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes Pathway analysis (KEGG), and Gene Set Enrichment Analysis (GSEA). Moreover, Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates in the key modules. Finally, real-time quantitative polymerase chain reaction was supplied to detect the expressions of hub genes in human pulmonary arterial smooth cells treated with cobalt chloride (COCl2) which was used to mimic hypoxia. Results: There were 2299 DEGs identified. WGCNA indicated that yellow module was the key one correlated with PAH. GO and KEGG analysis demonstrated that genes in the yellow module were mainly enriched in 'Pathways in cancer'. GSEA revealed that 'HALLMARK_MYC_TARGETS_V1' was remarkably enriched in PAH. Based on the PPI network, vascular endothelial growth factor A, proto-oncogene receptor tyrosine kinase (KIT), PNN interacting serine and arginine rich protein (PNISR) and heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) were identified as the hub genes. Additionally, the PCR indicated that the elevated expressions of PNISR and HNRNPH1 were in line with the bioinformatics analysis. ROC analysis determined that PNISR and HNRNPH1 may be potential biomarkers to provide better diagnosis of PAH. Conclusion: PNISR and HNRNPH1 were potential biomarkers to diagnosis PAH. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of PAH. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of fructo-oligosaccharide (FOS) supplementation intake of Taiping chickens (Gallus gallus domesticus) and its stimulating effects on ileum. 120 healthy chickens were randomly divided into two groups; control group (CT) and fructo-oligosaccharides group (FOS). At the 60th day of age, ileum mucosa of three chickens per group were collected and performed transcriptome profiling of Taiping chicken ileum mucosa using the Hiseq™ 2500 sequencing platform. Compared with CT group, 50 genes were differentially expressed in the FOS group. Ten of the differently expressed genes were further validated by RT-qPCR. In addition, gene ontology and Kyoto encyclopedia of genes and genomes analyses revealed that these differentially expressed genes were mainly enriched to drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, retinol metabolism, fat digestion and absorption, herpes simplex infection and valine, leucine and isoleucine biosynthesis. The results of this study provided the help to our understanding application of fructo-oligosaccharides in indigenous chicken production and provide a theoretical basis for the genetic development of indigenous chickens. [ABSTRACT FROM AUTHOR]

QKI is a vital regulator in RNA splicing and maturation, but its role in cervical cancer (CC) is little known. In this study, we found that QKI is decreased in human CC, and overexpression of QKI inhibits HeLa cell proliferation and promotes the apoptosis of cancer cells. We identified hundreds of endogenous QKI-regulated alternative splicing events (ASEs) and differentially expressed genes (DEGs) in QKI-overexpressed HeLa cells by RNA-seq and selectively validated their expression by quantitative reverse-transcription polymerase chain reaction. The gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that QKI-regulated ASEs and DEGs were closely related to cancer, apoptosis, and transcriptional regulatory functions. In short, QKI may affect the occurrence and development of CC by regulating gene expression through AS. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer (BC) is a malignant tumor which threat to women's physical and mental health. However, the mechanism of metabolism alteration in BC remains unclear. This study is intended to figure out the relationship between the alternation of metabolism and the progression of BC. Methods: In this study, metabolites of plasma in 60 BC patients and 40 healthy volunteers were detected using liquid chromatography mass spectrometer (LC‐MS). Transcriptomic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was performed to enrich the pathways. Results: A total of 97 metabolites have been identified and measured, of which 17 compounds exhibited the differential expression between tumor group and control group (p < 0.05; FDR < 0.05). Metabolites set enrichment analysis (MSEA) displayed that there were 12 significantly enriched pathways in all. Through the KEGG database, 382 genes were found closely correlated with the altered metabolic pathways. TCGA and GEO transcriptomic profiling revealed that 5,018 genes significantly changed between tumor group and control group. Integrating these genes with the transcriptomic data from the corresponding KEGG data set, we identified most of the differential expressed genes were related to purine metabolism. A total of 28 different expression genes were hub genes, wherein AMPD1 and RRM2 were significantly effective in the prediction of survival of BC patients, with 0.04 and 0.02, respectively. Conclusions: Combining with the transcriptomic and metabolomics data, we found that the dysregulation of purine metabolism pathway might affect the progression of BC. [ABSTRACT FROM AUTHOR]

Our previous study showed that knocking down integrin α5 (ITGA5) expression by using a lentiviral vector in human dental pulp stem cells (DPSCs) led to weakening proliferation and migration capacity while enhanced odontogenic differentiation. To seek for possible clinical application, we investigated the effect of the ITGA5 priming synthetic cyclic peptide (SCP; GA‐CRRETAWAC‐GA) on proliferation, migration, and the odontogenic differentiation of DPSCs. Remarkably, the involved mechanism was explored by isobaric tag for relative and absolute quantitation proteomic technique, and the in vivo effect of ITGA5 was investigated by nude mice subcutaneous transplantation of cell and hydroxyapatite/β‐tricalcium phosphate complex. Results showed that SCP weakened the proliferation and migration capacity while enhanced odontogenic differentiation of DPSCs as lentivirus. The phosphorylation of FAK, PI3K/AKT, and MEK1/2/ERK1/2, along with IGF2/IGFBP2 and Wnt/β‐catenin signaling pathway play an important role in this process. Proteomic Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the key role of extracellular matrix (ECM) and ECM‐receptor activity pathway were involved. ECM constituents, secreted protein acidic and cysteine‐rich (SPARC), lumican, vitronectin, prolargin, decorin, collagen type VI α1 chain (COL6A1), COL6A2, COL14A1, and COL5A1 were upregulated in the ITGA5‐silenced group. Inhibited expression of ITGA5 in DPSCs increased osteoid tissue formation and stronger related genes expression in vivo. In conclusion, the ITGA5 priming peptide could promote DPSCs odontogenic differentiation as lentivirus. Proteomics and bioinformatic analysis revealed that this may be due to the deposition of ECM and amplified ECM‐receptor activity, which could fuel the application process of utilizing priming ITGA5 on dental clinical practice. [ABSTRACT FROM AUTHOR]

Pristella maxillaris is known as the X-ray fish based on its translucent body. However, the morphological characteristics and the molecular regulatory mechanisms of these translucent bodies are still unknown. In this study, the following three phenotypes, a black-and-gray body color or wild-type (WT), a silvery-white body color defined as mutant I (MU1), and a fully transparent body with a visible visceral mass named as mutant II (MU2), were investigated to analyze their chromatophores and molecular mechanisms. The variety and distribution of pigment cells in the three phenotypes of P. maxillaris significantly differed by histological assessment. Three types of chromatophores (melanophores, iridophores, and xanthophores) were observed in the WT, whereas MU1 fish were deficient in melanophores, and MU2 fish lacked melanophores and iridophores. Transcriptome sequencing of the skin and peritoneal tissues of P. maxillaris identified a total of 166,089 unigenes. After comparing intergroup gene expression levels, more than 3,000 unigenes with significantly differential expression levels were identified among three strains. Functional annotation and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed genes (DEGs) identified a number of candidates melanophores and iridophores genes that influence body color. Some DEGs that were identified using transcriptome analysis were confirmed by quantitative real-time PCR. This study serves as a global survey of the morphological characteristics and molecular mechanism of different body colors observed in P. maxillaris and thus provides a valuable theoretical foundation for the molecular regulation of the transparent phenotype. [ABSTRACT FROM AUTHOR]

Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning (Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions. • A genome-wide DNA methylation profile for patients with coal-burning arsenic poisoning was showed by 850 K Beadchip. • Functional analysis (Gene ontology and Kyoto encyclopedia of genes) found 592 GO items and 131 KEGG pathways of coal-burning arsenic poisoning. • Five key genes((NAPRT1, NT5C3B, NEDD4L, SLC22A3, and RAB11B)) were screened by the online tool String and Cytoscape software. [ABSTRACT FROM AUTHOR]

Background: Excretory/secretory products (ESPs) released by parasites influence the development and functions of host dendritic cells (DCs). However, little is known about changes of DNA (hydroxy)methylation on DC development during Fasciola gigantica infection. The present study aimed to investigate whether F. gigantica ESPs (FgESPs) affects the development and functions of buffalo DCs through altering the DNA (hydroxy)methylation of DCs. Methods: Buffalo DCs were prepared from peripheral blood mononuclear cells (PBMCs) and characterized using scanning and transmission electron microscopy (SEM/TEM) and quantitative reverse transcriptional PCR (qRT-RCR). DCs were treated with 200 μg/ml of FgESPs in vitro, following DNA extraction. The DNA methylome and hydroxymethylome were profiled based on (hydroxy)methylated DNA immunoprecipitation sequencing [(h)MeDIP-Seq] and bioinformatics analyses. qRT-RCR was also performed to assess the gene transcription levels of interest. Results: FgESPs markedly suppressed DC maturation evidenced by morphological changes and downregulated gene expression of CD1a and MHC II. Totals of 5432 and 360 genes with significant changes in the 5-methylcytosine (5-mC) and the 5-hydroxymethylcytosine (5-hmC) levels, respectively, were identified in buffalo DCs in response to FgESPs challenge. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these differentially expressed genes were highly enriched in pathways associated with immune response. Some cancer-related pathways were also indicated. There were 111 genes demonstrating changes in both 5-mC and 5-hmC levels, 12 of which were interconnected and enriched in 12 pathways. The transcription of hypermethylated genes TLR2, TLR4 and IL-12B were downregulated or in a decreasing trend, while the mRNA level of high-hydroxymethylated TNF gene was upregulated in buffalo DCs post-exposure to FgESPs in vitro. Conclusions: To our knowledge, the present study provides for the first time a unique genome-wide profile of DNA (hydroxy)methylation for DCs that interact with FgESPs, and suggests a possible mechanism of FgESPs in suppressing DC maturation and functions that are involved in TLR signaling. [ABSTRACT FROM AUTHOR]

MiR-375, as a member of miRNA family, plays essential roles in prostate cancer (PC). We purpose to explore the expression and possible molecular mechanism of the miR-375 in PC using database analysis. First, Student's t -test, overall and subgroup meta-analyses with 20 eligible datasets in the Gene Expression Omnibus (GEO) database were performed to explore the expression of miR-375 in PC. Then the results of meta-analyses were verified in The Cancer Genome Atlas (TCGA) database by Student's t -test and Paired t -test. The candidate genes of miR-375 were predicted by four platforms. Protein-protein interaction (PPI) networks, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the potential molecular mechanism of miR-375 in PC. The overall meta-analysis showed the expression of miR-375 was significantly up-regulated in PC groups compared with non-cancerous group (SMD; 0.71; 95% CI: 0.38–1.04). In addition, the meta-analyses by subgroup showed the expression of miR-375 in PC tissues was higher than that in healthy prostate tissues and adjacent non-cancerous tissues. The results of TCGA database verified the expression of miR-375 in PC tissues was obviously higher than that in adjacent non-cancerous tissues. Moreover, GO and KEGG analysis revealed that the latent target genes were mainly involved in protein binding function and ubiquitin mediated proteolysis. PPI analysis identified JAK2, EHMT1 and QKI as the hub genes (highly connected genes with high degree in PPI). MiR-375 was up-regulated in PC tissues. Meanwhile, miR-375 may play an important role in aggressive PC by targeting its potential target genes. [ABSTRACT FROM AUTHOR]