• Title/Summary/Keyword: Molecular type

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Molecular Docking Study of Anti-diabetic Xanthones from Garcinia Xanthochymus

  • Babu, Sathya
    • Journal of Integrative Natural Science
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    • v.10 no.3
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    • pp.137-140
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    • 2017
  • Diabetes mellitus has become a major growing public health problem worldwide. More than 90% of all diabetes cases are classified as type 2 diabetes (T2D), which is also known as non-insulin dependent diabetes. Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin signal transduction pathway and has emerged as novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors enhance the sensibility of insulin receptor (IR) and have favorable curing effect for insulin resistance-related diseases. Recently twelve anti-diabetic xanthones were isolated from the bark of Garcinia xanthochymus. Hence, in the present study, molecular docking was carried out for these twelve xanthones. The objective of this work is to study the interaction of the newly isolated xanthones with PTP1B. The docking results showed that xanthones have good interactions and has better docking score with PTP1B and suggest LYS120 and ASP181 are the important residues involved in interaction between PTP1B enzyme and the xanthones.

Influences of Aldehyde Type and p-Substituent Type on Structural Characteristics of p-Alkylphenol Aldehyde Resins Using a Molecular Simulation

  • 최성신
    • Bulletin of the Korean Chemical Society
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    • v.20 no.2
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    • pp.203-210
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    • 1999
  • Structural characteristics of isotactic p-alkylphenol acetaldehyde novolak resins with methyl, t-butyl, and t-octyl as the p-substituent and p-t-butylphenol aldehyde novolak resins with methylene, ethylidene, and propylidene as the linkage were calculated using molecular mechanics and molecular dynamics. The five p-alkylphenol aldehyde resins were found to have common structural characteristics that hydroxyl groups of the p-alkylphenols cluster in the center of the molecule by intramolecular hydrogen bonds of hydroxyl groups of the adjacent p-alkylphenols and the alkyl groups are extended out. Distances between oxygen atoms and between p-carbon atoms of the adjacent p-alkylphenols become longer as the size of the p-substituent increases from methyl to toctyl. Bond angles of the linkage built between the adjacent p-alkylphenols become wider by increasing the p-substituent size and by decreasing the linkage size.

Molecular Subtyping of Methicillin-Resistant Staphylococcus aureus Isolated from Patients' Nasal Cavity (환자의 비강으로부터 분리된 메티실린 내성 황색 포도알균의 분자 아형 분석)

  • Kim, Sang-Ha;Park, Sung-Bae;Park, Heechul;Kim, Jun Seong;Kim, Jungho;Lee, Jiyoung;Lim, Jaewon;Kim, Young Kwon;Kim, Sunghyun
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.2
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    • pp.128-135
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    • 2020
  • Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body and causes skin and soft tissue infections (SSTI). The present study examined the antimicrobial resistance patterns and molecular epidemiological characteristics of MRSA isolated from nasal swabs in clinical patients. SCCmec type of MRSA isolates from clinical patients were analyzed: 24 cases were SCCmec type-II; two cases were type-II/IVa; one case was type-II/V; one case was type-IVa; 11 cases were not-typeable. The mec complex type of MRSA isolates from clinical patients were analyzed: 29 cases were mec complex type A, and 10 cases were not-typeable, but type B was not found in the present study. In conclusion, SCCmec type-II and mec complex type A were the most dominant MRSA subtypes among the MRSA isolates from a nasal swab of patients, and the results were similar to other studies on hospital-acquired MRSA (HA-MRSA). These results can not only provide basic data for hospital infection management but also be a good guideline for MRSA infections in the Republic of Korea.

mTOR signalling pathway - A root cause for idiopathic autism?

  • Ganesan, Harsha;Balasubramanian, Venkatesh;Iyer, Mahalaxmi;Venugopal, Anila;Subramaniam, Mohana Devi;Cho, Ssang-Goo;Vellingiri, Balachandar
    • BMB Reports
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    • v.52 no.7
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    • pp.424-433
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    • 2019
  • Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.

Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach

  • Jagadeb, Manaswini;Konkimalla, V. Badireenath;Rath, Surya Narayan;Das, Rohit Pritam
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.283-288
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    • 2014
  • Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, especially when the target is mutated. Mutations in the KCNJ11 gene, encoding the kir6.2 channel, are reported to be associated with congenital hyperinsulinism, having a major impact in causing type 1 diabetes, and due to the lack of its 3D structure, an attempt has been made to predict the structure of kir6.2, applying fold recognition methods. The current work is intended to investigate the affinity of four phytochemicals namely, curcumin (Curcuma longa), genistein (Genista tinctoria), piperine (Piper nigrum), and pterostilbene (Vitis vinifera) in a normal as well as in a mutant kir6.2 model by adopting a molecular docking methodology. The phytochemicals were docked in both wild and mutated kir6.2 models in two rounds: blind docking followed by ATP-binding pocket-specific docking. From the binding pockets, the common interacting amino acid residues participating strongly within the binding pocket were identified and compared. From the study, we conclude that these phytochemicals have strong affinity in both the normal and mutant kir6.2 model. This work would be helpful for further study of the phytochemicals above for the treatment of type 1 diabetes by targeting the kir6.2 channel.

Effect of chemical treatment and variations of the physical properties of waste water-soluble cutting oil (폐 수용성 절삭유의 화학처리효과 및 물성변화)

  • Sin, Chun Hwan;Jang, Jeong Guk
    • Journal of Environmental Science International
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    • v.13 no.4
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    • pp.403-412
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    • 2004
  • Waste water-soluble cutting oil was treated with WI type #1 and WI type #2. The properties of the original water-soluble cutting oil were pH=l0.4, viscosity=1.4cP, CODcr=44,750 ppm, and TOC=10,569 ppm. However, the properties of the oil used for more than 3 months were changed to pH=7.82, viscosity=2.1cP, CODcr=151,000 ppm, and TOC=74,556 ppm. It might be attributed to the fact that molecular chains were cut due to thermal oxidation and impurities such as metal chips were incorporated in to the oil during the operation processes. To prevent the putrefaction of oil, the sterilization effect of ozone and UV on the microorganism in the oil was investigated. Ozone treatment showed that 99.99% of the microorganism was annihilated with 30 minutes contact time and 60 minutes were necessary for the same effect when UV was used. Ozone treatment could cut molecular chains of the oil due to strong sterilization power, which was evidenced by the increase of TOC from 25,132 ppm at instantaneous contact to 28,888 ppm at 30 minutes contact time. However, UV treatment didn't show severe changes in TOC values and thus, seemed to cause of severe cut of molecular chains. When the activated carbon was used to treat the waste water-soluble cutting oil, TOC decreased to 25,417 ppm with 0.lg carbon and to 15,946 ppm with 5.0g carbon. This results indicated that the waste oil of small molecular chains could be eliminated by adsorption. From the results, it could be concluded that these treatment techniques could be proposed to remove the waste oil of small molecular chains resulting in the degradation of the oil properties. In addition, these experimental results could be used for the correlation with future works such as investigation of the molecular distribution according to the sizes, lengths, and molecular weight of the chains.

Protein-protein Interaction Network Analyses for Elucidating the Roles of LOXL2-delta72 in Esophageal Squamous Cell Carcinoma

  • Wu, Bing-Li;Zou, Hai-Ying;Lv, Guo-Qing;Du, Ze-Peng;Wu, Jian-Yi;Zhang, Pi-Xian;Xu, Li-Yan;Li, En-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2345-2351
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    • 2014
  • Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.

Molecular Typing of Acinetobacter Baumannii Strains by Randomly Amplified Polymorphic DNA (RAPD) Analysis (Randomly Amplified Polymorphic DNA (RAPD) 분석에 의한 Acinetobacter Baumannii 균주의 유전형 분류)

  • Oh, Jae-Young;Cho, Jae-Wee;Park, Jong-Chun;Lee, Je-Chul
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.2
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    • pp.129-139
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    • 2000
  • Acinetobacter baumannii strains are emerging pathogens of the nosocomial infection with an increasing frequency in recent years. The therapeutic difficulty due to the wide spread of multiple resistant strains was major problem in A. baumannii infection. It seems likely that high frequency of A. baumannii infection will be increasing epidemiological importance in the future. However, the current limited understanding of the epidemiology of A. baumannii infections is caused by lack of a rapid and practical method for the molecular characterization of A. baumannii strains. This study was undertaken to determine molecular types and genetic similarity among A. baumannii strains isolated from four hospitals by RAPD analysis. Eighty-five strains, including 40 from Chunnam University Hospital, 27 from Dankook University Hospital, 15 from Yonsei University Hospital, and 3 from Seonam University Hospital, were classified into three molecular types. Molecular type II was the most common pattern and included 72 strains. All strains from Dankook University Hospital and 40 strains from Chunnam University Hospital belonged to molecular type I or II. A. baumannii strains form Yonsei University Hospital were very distant similarity values. The range of genetic similarity values among 85 strains of A. baumannii was 0.26 to 1.00. Although phenotypes including biotype and antimicrobial resistance pattern of A. baumannii strains were same or very similar to each other, their RAPD patterns were quite different. Typing with phenotypes was found to be less reliable than molecular typing by RAPD analysis. These results suggest that RAPD analysis provides rapid and simple typing method of A. baumannii strains for epidemiological studies. This work is the first epidemiological report of A. baumannii infections in Korea and it is hoped that results of this work may contribute to a better understanding of the clinical importance and epidemiology of A. baumannii strains.

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Opposing Effects of Arkadia and Smurf on TGFβ1-induced IgA Isotype Expression

  • Choi, Seo-Hyun;Seo, Goo-Young;Nam, Eun-Hee;Jeon, Seong-Hyun;Kim, Hyun-A;Park, Jae-Bong;Kim, Pyeung-Hyeun
    • Molecules and Cells
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    • v.24 no.2
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    • pp.283-287
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    • 2007
  • $TGF-{\beta}1$ induces Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent class switching recombination (CSR) to IgA. In the present study, we investigated the roles of two E3-ubiquitin ligases, Smurfs (HECT type) and Arkadia (RING finger type) on $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Further, over-expression of Smurf1 and Smurf2 decreased both Smad3/4-mediated and Runx3-mediated $GL{\alpha}$ promoter activities, suggesting that the Smurfs can down-regulate the major $TGF-{\beta}1$ signaling pathway and decrease $GL{\alpha}$ gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts ($GLT_{\alpha}$, $PST_{\alpha}$, and $CT_{\alpha}$) and also $TGF{\beta}1$-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on $TGF{\beta}1$-induced $GLT_{\alpha}$ expression and IgA secretion. Similar results were obtained in the presence of over-expressed Smad7 and Smurf1. These results indicate that Arkadia can amplify $TGF{\beta}1$-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of $TGF{\beta}1$-induced IgA isotype expression.

Quercetin Inhibits the 5-Hydroxytryptamine Type 3 Receptor-mediated Ion Current by Interacting with Pre-Transmembrane Domain I

  • Lee, Byung-Hwan;Jung, Sang-Min;Lee, Jun-Ho;Kim, Jong-Hoon;Yoon, In-Soo;Lee, Joon-Hee;Choi, Sun-Hye;Lee, Sang-Mok;Chang, Choon-Gon;Kim, Hyung-Chun;Han, YeSun;Paik, Hyun-Dong;Kim, Yangmee;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.20 no.1
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    • pp.69-73
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    • 2005
  • The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 ($5-HT_{3A}$) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The $5-HT_{3A}$ receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with $5-HT_{3A}$ receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current ($I_{5-HT}$) with an $IC_{50}$ of $64.7{\pm}2.2{\mu}M$. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the $5-HT_{3A}$ receptor.