• Journal of Korean Neurosurgical Society
• /
• v.63 no.4
• /
• pp.444-454
• /
• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

• Journal of the Korea Society of Computer and Information
• /
• v.18 no.5
• /
• pp.95-102
• /
• 2013

In metabolomics, metabolic pathway is represented by well-displayed graph. Metabolic pathways, especially, have a complex binding structure, which makes the graphical representation hard to visualize. There is a problem that edge crossings exponentially increase as the number of nodes grows. To apply automatic graph layout techniques to the genome-scale metabolic flow of metabolism domains, it is very important to reduce unnecessary edge crossing on a metabolic pathway layout. we proposed a metabolic pathway layout algorithm based on 2-layer layout. Our algorithm searches any meaningful component existing in a pathway, such as circular components, highly connected nodes, and the components are drawn in upper layer. Then the remaining subgraphs except meaningful components are drawn in lower layer by utilizing a new radial layout algorithm. It reduces ultimately reduced the number of edge crossings. This algorithm is the basis of flexible analysis for metabolic pathways.

• Advances in nano research
• /
• v.12 no.3
• /
• pp.301-317
• /
• 2022

Many studies have shown that Mg-Nd-Zn-Zr (abbreviated as JDBM) alloy has good biocompatibility and biodegradability as well as promotion of cell adhesion, proliferation and differentiation, and Wnt/β-catenin signaling pathway may play a unique role in joint tissue by controlling the function of chondrocytes, osteoblasts and synoviocytes. However, it is not clear whether the JDBM alloy induces osteochondral repair through Wnt/β-catenin signaling pathway. This study aims to verify that JDBM alloy can repair osteochondral defects in rats, which is realized by Wnt/β-catenin signaling pathway. In this study, the osteochondral defect model of the right femoral condyle non-weight-bearing area in rats was established and randomly divided into three groups: Control group, JDBM alloy implantation group and JDBM alloy implantation combined with signaling pathway inhibitor drug ICRT3 injection. It was found that after JDBM alloy implantation, the bone volume fraction (BVF) became larger, the bone trabeculae were increased, the relative expression of osteogenesis gene Runx2, Bmp2, Opn, Ocn and chondrogenesis gene Collagen II, Aggrecan were increased, and the tissue repair was obvious by HE and Masson staining, which could be inhibited by ICRT3.

• Horticultural Science & Technology
• /
• v.28 no.5
• /
• pp.750-756
• /
• 2010

This study was performed to investigate the role of phytohormones in the bulbing of garlic in order to assess the yield and quality. The effect on endogenous plant hormones such as gibberellin (GA) content was also examined during growth stage i.e. clove differentiation to bulbing in garlic. More than 18 gibberellins in garlic were identified with extensive gas chromatograph-mass spectrometry-selected ion monitoring (GC-MS-SIM) quantitative analysis. The results showed that GAs were biosynthesized by both non C-13 hydroxylation pathway (NCH) and early C-13 hydroxylation pathway (ECH) in garlic plant. It was also revealed that NCH pathway leading to synthesis of bioactive $GA_4$ was the more prominent GA biosynthesis pathway than ECH pathway in which bioactive $GA_1$ was synthesized. Total GAs level was gradually increased from clove differentiation to bulbing and later decreased, which portrays the active role of GA in differentiation. The biosynthesis ratio of bioactive $GA_4$ and $GA_1$ concentration was similar to that of total GAs content, which was closely related with bulb development in garlic.

• Genomics & Informatics
• /
• v.20 no.2
• /
• pp.20.1-20.13
• /
• 2022

Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.21 no.3
• /
• pp.36-51
• /
• 2008

Objective : This study investigated the effects of PR(Pinelliae Rhizoma) on gene expression of lung tissue resected from asthma induced mice using intra-nasal instillation. Methods : Gene expression levels were measured using a microarray technique, and a functional analysis on these genes was conducted. Results : A total of 3270 genes were up-regulated or down-regulated, 860 genes which were lowered by induction of asthma were restored to those of naive animals, Furthermore hand, 1235 genes were lowered to normal levels, which were elevated by induction of asthma. Most of changed genes were involved in signalling pathways. Genes in which expression levels were restored by oral administration of PR were involved in MAPK pathway, focal adhesion, and regulation of actin cytoskeleton etc. Genes of which expression levels were lowered by oral administration of PR were involved in rhodopsin-like receptor activity, zinc ion binding and ATP binding. These genes were also involved in neuroactive ligand receptor interaction, the JAK-STAT signaling pathway and also the T-cell receptor signaling pathway. Conclusion : These results demonstrate the strong possibility that the mechanisms of PR on asthma are involved in neuroactive ligand receptor interaction pathway or related molecules.

• Journal of Korean Academy of Nursing
• /
• v.34 no.7
• /
• pp.1255-1264
• /
• 2004

Purpose: The purpose of this study was to determine the effect of a 3-week somatosensory stimulation program on the integrity of the somatosensory pathway of patients with brain damage. Method: The sample consisted of two groups of patients with brain damage matched by Glasgow Coma Scale (GCS) scores and age:8 patients with a mean age of 56.75 years who were treated with somatosensory stimulation, and 8 patients with a mean age of 58.88 years, who were not treated with sensory intervention program. A repeated measures matched-control group design was used to assess functional recovery of the brain. The instrument used in this study was SSEP (somatosensory evoked potentials), a neurophysiological parameter, for the integrity of the somatosensory pathway. Results: The hypothesis that patients with brain damage who were treated with the somatosensory stimulation program will show higher SSEP wave form scores than the non-treatment group was supported (3rd week.: U=13.000, p=.014). Additional repeated measures analysis showed that there were no significant differences in recovery trends between the groups (F=1.945, p=.159). Conclusion: This study demonstrates that a somatosensory stimulation program is effective in promoting recovery of the integrity of the somatosensory pathway of patients with brain damage.

• BMB Reports
• /
• v.50 no.11
• /
• pp.539-545
• /
• 2017

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

• BMB Reports
• /
• v.44 no.9
• /
• pp.584-589
• /
• 2011

The mammalian ste20-like kinase (MST) pathway is important in the regulation of apoptosis and cell cycle and emerges as a novel tumor suppressor pathway. MST-induced phosphorylation of Salvador homolog 1 (SAV1), which is a scaffold protein, has not been evaluated in detail. We performed a mass spectrometric analysis of the SAV1 protein that was co-expressed with MST2. Phosphorylation was detected at Thr-26, Ser-27, Ser-36 and Ser-269. Although single or double mutations had little effects, the mutation of all four residues in SAV1 to Ala (SAV1-4A) had inhibitory effects on the MST pathway. MST2-mediated induction of SAV1-4A protein levels, SAV1-4A interaction with MST2 and the self-dimerization of SAV1-4A were weaker compared to those of wild-type SAV1. SAV1-4A inhibited MST2- and K-RasG12V-induced cell death of MCF7 cells. These results suggest that MST-mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway.

• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2004.11a
• /
• pp.124-130
• /
• 2004

Microarray expression datasets are incessantly cumulated with the aid of recent technological advances. One of the first steps for analyzing these data under various experimental conditions is determining differentially expressed genes (DEGs) in each condition. Reasonable choices of thresholds for determining differentially expressed genes are used for the next -step-analysis with suitable statistical significances. We present a model for identifying DEGs using pathway information based on the global connectivity structure. Pathway information can be regarded as a collection of biological knowledge, thus we are tying to determine the optimal threshold so that the consequential connectivity structure can be the most compatible with the existing pathway information. The significant feature of our model is that it uses established knowledge as a reference to determine the direction of analyzing microarray dataset. In the most of previous work, only intrinsic information in the miroarray is used for the identifying DEGs. We hope that our proposed method could contribute to construct biologically meaningful network structure from microarray datasets.