• Title/Summary/Keyword: protein-protein network

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Identification of Differentially-Methylated Genes and Pathways in Patients with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage

  • Kim, Bong Jun;Youn, Dong Hyuk;Chang, In Bok;Kang, Keunsoo;Jeon, Jin Pyeong
    • Journal of Korean Neurosurgical Society
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    • v.65 no.1
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    • pp.4-12
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    • 2022
  • Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

Methyl Linderone Suppresses TPA-Stimulated IL-8 and MMP-9 Expression Via the ERK/STAT3 Pathway in MCF-7 Breast Cancer Cells

  • Yoon, Jae-Hwan;Pham, Thu-Huyen;Lee, Jintak;Lee, Jiyon;Ryu, Hyung-Won;Oh, Sei-Ryang;Oh, Jae-Wook;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.325-332
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    • 2020
  • Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

Systematic Approach for Analyzing Drug Combination by Using Target-Enzyme Distance

  • Park, Jaesub;Lee, Sunjae;Kim, Kiseong;Lee, Doheon
    • Interdisciplinary Bio Central
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    • v.5 no.2
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    • pp.3.1-3.7
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    • 2013
  • Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.

Network pharmacoligical analysis for selection between Saposhnikoviae Radix and Glehniae Radix focusing on ischemic stroke (방풍(防風)과 해방풍(海防風) 중 뇌경색 연구에 더욱 적합한 약재 선정을 위한 네트워크 약리학적 분석)

  • Jin Yejin;Lim Sehyun;Cho Suin
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.171-182
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    • 2023
  • Objectives : Saposhnikoviae Radix (SR) and Glehniae Radix (GR) have been frequently used in traditional medicine to treat diseases related to 'wind' syndrome, but there have been cases where it has been mixed in a state where the plant of origin is not clear. In this study, to select materials for conducting preclinical cerebral infarction research, the network pharmacology analysis method was used to select suitable medicinal materials for the study. Methods : In this study, a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) based network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3 were applied, then networks of bioactive compounds, target proteins, and target diseases was constructed. STRING database was used to construct a protein-protein interaction network. Results : It was confirmed that SR rather than GR has various target proteins and target diseases based on network pharmacological analysis using TCMSP database. And it was analyzed that the bioactive compounds only in SR act more on neurovascular diseases, and both drugs are expected to be effectively used for cardiovascular diseases. Conclusions : In our future study, SR will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

A New Function of Skp1 in the Mitotic Exit of Budding Yeast Saccharomyces cerevisiae

  • Kim, Na-Mil;Yoon, Ha-Young;Lee, Eun-Hwa;Song, Ki-Won
    • Journal of Microbiology
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    • v.44 no.6
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    • pp.641-648
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    • 2006
  • We previously reported that Skp1, a component of the Skp1-Cullin-F-box protein (SCF) complex essential for the timely degradation of cell cycle proteins by ubiquitination, physically interacts with Bfa1, which is a key negative regulator of the mitotic exit network (MEN) in response to diverse checkpoint-activating stresses in budding yeast. In this study, we initially investigated whether the interaction of Skp1 and Bfa1 is involved in the regulation of the Bfa1 protein level during the cell cycle, especially by mediating its degradation. However, the profile of the Bfa1 protein did not change during the cell cycle in skp1-11, which is a SKP1 mutant allele in which the function of Skp1 as a part of SCF is completely impaired, thus indicating that Skp1 does not affect the degradation of Bfa1. On the other hand, we found that the skp1-12 mutant allele, previously reported to block G2-M transition, showed defects in mitotic exit and cytokinesis. The skp1-12 mutant allele also revealed a specific genetic interaction with ${\Delta}bfa1$. Bfa1 interacted with Skp1 via its 184 C-terminal residues (Bfa1-D8) that are responsible for its function in mitotic exit. In addition, the interaction between Bfa1 and the Skp1-12 mutant protein was stronger than that of Bfa1 and the wild type Skp1. We suggest a novel function of Skp1 in mitotic exit and cytokinesis, independent of its function as a part of the SCF complex. The interaction of Skp1 and Bfa1 may contribute to the function of Skp1 in the mitotic exit.

Low-Temperature FTIR Spectroscopy of Bacteriorhodopsin and Phoborhodopsin

  • Kandori, Hideki;Furutani, Yuji;Shimono, Kazumi;Iwamoto, Masayuki;Sudo, Yuki;Shichida, Yoshinori;Kamo, Naoki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.106-109
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    • 2002
  • Archaeal rhodopsins possess retinal molecule as their chromophores, and their light-energy and light-signal conversions are triggered by all-trans to 13-cis isomerization of the retinal chromophore. Relaxation through structural changes of protein then leads to functional processes, proton pump in bacteriorhodopsin (bR) and transducer activation in phoborhodopsin (pR). It is known that sensory rhodopsins can pump protons in the absence of their transducers. Thus, there should be common and specific features in their protein structural changes for function. In this paper, our r ecent studies on pR from Natronobacterium pharaonis (ppR) by means of low-temperature Fourier-transform infrared (FTIR) spectroscopy are compared with those of bR. In particular, protein structural changes upon retinal photoisomerization are studied. Comparative investigation of ppR and bR revealed the similar structures of the polyene chain of the chromophore and water-containing hydrogen-bonding network, whereas the structural changes upon photoisomerization were more extended in ppR than in bR. Extended protein structural changes were clearly shown by the assignment of the C=O stretch of Asnl05. FTIR studies of a ppR mutant with the same retinal binding site as in bR revealed that the Schiff base region is important to determine their colors.

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Gel Color and Texture of Surimi-like Pork from Muscles at Different Rigor States Post-mortem

  • Kang, Geun-Ho;Yang, Han-Sul;Jeong, Jin-Yeon;Moon, Sang-Hoon;Hur, Sun-Jin;Park, Gu-Boo;Joo, Seon-Tea
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.7
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    • pp.1127-1134
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    • 2007
  • Gels were made from surimi-like pork (SLP) made from muscles obtained at 1, 24 and 72 h post-mortem. The SLP from pre-rigor muscle had higher pH and moisture percentage compared to in- or post-rigor muscles. Also, SLP from pre-rigor muscle showed higher concentration of water-soluble protein that was washed out during the process. Gel from post-rigor muscle exhibited higher a* and b* value, and also resulted in higher Chroma and lower hue values. The dark color of gel from post-rigor muscle was related to higher concentration of sarcoplasmic protein in SLP and denser structure in the gel matrix. SDS-PAGE showed higher intensity of the phosphorylase in the sarcoplasmic protein fraction from pre-rigor muscle. Gel from post-rigor muscle showed higher hardness and sensory firmness, and the greater firmness was related to higher concentration of protein in SLP, and a compact network with smaller pockets in the gel matrix.