KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Glioma is one of the most common types of human brain tumor, with high mortality in high-grade gliomas (HGG). Low-grade gliomas (LGG) can progress into HGG, leading to poor prognosis. However, it is unclear what factors affect the progression of LGG to HGG. This study aims to explore the function of the crosstalk genes on the progression and prognosis of LGG using bioinformatics analysis. Integrated transcriptome analysis was used to screen differentially expressed genes (DEGs). Then, gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the association between DEGs and gene functions and pathways by ClusterProfiler package and ClueGO plug-in. Protein-protein interaction (PPI) network analysis was applied to explore the connection between genes and biological processes. Subsequently, the gene clusters were analyzed using the Centiscape and molecular complex detection (MCODE) plug-in in Cytoscape software, where the crosstalk genes were identified for further study. Ultimately, the UALCAN website and Gene Expression Profiling Interactive Analysis (GEPIA) website were performed to visualize the expression levels and survival curves of genes, respectively. There were 74 DEGs identified in glioma, including 55 upregulated genes and 19 downregulated genes, which mainly were enriched in extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and so on. Then, six crosstalk genes were selected, including COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 genes. Overall survival (OS) analysis of crosstalk genes was conducted on the GEPIA website. High expression levels of crosstalk genes were closely related to the low survival rate of patients with LGG. The overexpressed crosstalk genes, such as COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 may participate in the progression and poor prognosis of LGG through the ECM-receptor interaction pathway.

Identification of genes related to low-grade glioma progression and prognosis based on integrated transcriptome analysis.

MicroRNAs (miRNAs) have been proven to play a crucial role in postmenopausal osteoporosis (PMO), and studies on their diagnostic value have been increasing. In our study, we aim to identify the key miRNAs in the PMO that might be potential biomarkers. A comprehensive systematic literature search was conducted by searching PubMed, Web of Science, Embase and Cochrane Library databases. In the total of 16 independent miRNA expression studies which contained 327 PMO patients and 328 postmenopausal (PM) healthy control samples, miRNAs were evaluated by using robust rank aggregation (RRA) method. A statistically significant meta-signature of up-regulated hsa-miR-133a-3p (P = 1.38e-03) was determined. Then bioinformatics analysis to recruit putative target genes prediction of hsa-miR-133a-3p and pathway enrichment analysis to reveal what biological processes this miRNA may affect were conducted. It was indicated that pathways were commonly associated with adrenergic signaling in cardiomyocytes, adherens junction, PI3K-Akt signaling pathway and AMPK signaling pathway. Furthermore, STRING and Cytoscape tools were used to visualize the interactions between target genes of hsa-miR-133a-3p. Six genes were detected as hub genes among 576 targets which were CDC42, RHOA, EGFR, VAMP2, PIK3R2 and FN1. After Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was detected that these hub genes were mostly enriched in signaling pathways and cancer. In this meta-analysis, it is stated that circulating hsa-miR-133a-3p may serve as a potential non-invasive biomarker and therapeutic target in PMO.

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Differentially expressed circulating miRNAs in postmenopausal osteoporosis: a meta-analysis

Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng, can regulate autophagy via AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway AMPK/mTOR signaling and autophagy have been reported to be involved in osteogenesis Here, the effect of Rg3 on ovariectomy (OVX)-induced osteoporosis is explored In vivo, rats were treated with 20 mg/kg Rg3 after OVX and the body weight (BW) was monitored Bone mineral density (BMD), hematoxylin-eosin staining of femur tissues, osteogenesis, autophagy, and AMPK/mTOR signaling were analyzed In vitro, MC3T3-E1 cells were treated with 0, 1, 5, 10, 20, and 100 μmol/L Rg3 10 and 20 μmol/L Rg3, which had no significant effect on cell viability and significantly affected AMPK/mTOR signaling, were chosen for further analysis Then osteogenic differentiation was induced with Rg3 or/and AMPK inhibitor (Compound C) AMPK/mTOR signaling, autophagy, osteogenic differentiation, and mineralization by Alizarin Red staining were analyzed The expression or activity of AMPK/mTOR signaling-related proteins, autophagy markers, and osteogenesis markers was measured by western blotting or commercial kits, and cell viability by cell counting kit-8 assay kits Rg3 significantly alleviated OVX-induced BW increases, BMD declines and histological changes of femur tissues, promoted osteogenesis, autophagy, and AMPK signaling, but inhibited mTOR signaling in vivo Moreover, Rg3 significantly enhanced AMPK signaling, autophagy, osteogenic differentiation, and mineralization, but suppressed mTOR signaling in vitro However, Compound C significantly reversed Rg3-induced alterations in vitro, indicating that Rg3 regulated autophagy, osteogenic differentiation, and mineralization via AMPK/mTOR signaling Hence, it was speculated that Rg3 might attenuate OVX-induced osteoporosis via AMPK/mTOR signaling pathway

Ginsenoside Rg3 attenuates ovariectomy-induced osteoporosis via AMPK/mTOR signaling pathway.

Efficacy of Chinese patent medicine for primary osteoporosis: A network meta-analysis.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

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A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by β2AR

Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus. Network topological parameters were determined using NetworkAnalyzer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and ClueGO. Cytoscape with the Search Tool for the Retrieval of Interacting Genes and Molecular Complex Detection plug-in was used to visualize protein-protein interactions (PPIs). Additionally, miRNA-gene regulatory modules were predicted using CyTargetLinker in order to guide future research. In total, 915 DEGs were identified, including 774 upregulated and 141 downregulated genes. Enriched GO terms and pathways were determined, including 'nervous system development', 'regulation of molecular function', 'glutamatergic synapse pathway' and 'pathways in cancer'. The node degrees of DEGs followed power-law distributions. A PPI network with 541 nodes and 1,431 edges was obtained. Overall, 3 important modules were identified from the PPI network. The following 10 genes were identified as core genes based on high degrees of connectivity: Albumin, PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2), DNA topoisomerase 2-α, kininogen 1 (KNG1), interleukin 2 (IL2), leucine-rich repeats and guanylate kinase domain containing, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), leptin, transferrin and RNA polymerase II subunit A (POLR2A). Additionally, 15 miRNA-target interactions were obtained using CyTargetLinker. Overall, 7 miRNAs co-regulated IL2, 3 regulated PHLPP2, 3 regulated KNG1, 1 regulated PIK3CG and 1 modulated POLR2A. These results indicate potential biomarkers in the pathogenesis of OP and therapeutic targets.

/pdf/identification-of-core-genes-and-prediction-of-mirnas-2xrieap9eq.pdf

Qiaoling Fan

Papers

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by β2AR

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach