• Microbiology and Biotechnology Letters
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• v.7 no.3
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• pp.127-133
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• 1979

By the treatment of several mutagens, a number of 5'-guanylic acid producing mutants from 5'-xan-thylic acid were obtained from Brevibacterium ammoniagenes ATCC 6871. The indispensensable genetic-characters of the mutants were adenine requirement, lack of GMP-reductase and mutation to adenosine resistance from adenosine sensitiveness. Main product from 5'-xanthylic acirl by strain BA-17-2 was 5'-guanulic acid, and was isolated in a crystalline form by the use of anion exchange resin, Duolite 102 D. The isolated crystalline was identified as 5'-guanylic acid by means of paper chromatography, ultrav-iolet absorption spectra, and infrared absorption spectrum.

• Biomedical Science Letters
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• v.16 no.4
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• pp.377-380
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• 2010

In this study, we investigated the effect of egg yolk lipids (EYL) on collagen ($10\;{\mu}g/ml$)-stimulated platelet aggregation in vivo. Dietary EYL significantly inhibited collagen-induced platelet aggregation, in addition, increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonist as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that EYL inhibits the collagen-induced platelet aggregation by up-regulating the cAMP and cGMP production. On the other hands, prothrombin time (PT) on extrinsic pathway of blood coagulation was potently prolonged by dietary EYL in vivo. These findings suggest that EYL prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that EYL may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

• Biomedical Science Letters
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• v.20 no.2
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• pp.70-76
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• 2014

In this study, we investigated the effect of DMSO, a highly dipolar organic liquid, in collagen ($5{\mu}g/ml$)-stimulated platelet aggregation. DMSO inhibited platelet aggregation at 0.5% by inhibiting production of thromboxane $A_2$ ($TXA_2$) which was associated with blocking cyclooxygenase (COX)-1 activity and $TXA_2$ synthase. In addition, DMSO significantly increased the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). On the other hand, DMSO (0.1~0.5% concentration) did not affect the LDH release which indicates the cytotoxicity. Based on these results, DMSO has anti-platelet effect by regulation of several platelet signaling pathways, therefore we suggest that DMSO could be a novel strategy on many thrombotic disorders.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.412-418
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• 1997

General pharmacological properties of AG 60 (mixture of acriflavine and guanosine (1:1, w/w)), which has anticancer effect, following intramuscular administration were examined in terms of effects on central nervous system, gastrointestinal system, cardiovascular system, respiratory system and autonomic nervous system in mice, rats, guinea-pigs and rabbits. AG 60 at the dose of 15 mgtg had no influences on pentobarbital sleeping time, spontaneous motor activity, chemoshock produced by pentylenetetrazole solution, writhing syndromes induced by 0.8% acetic acid solution, and motor coordination of mice. However, AG 60 at the dose of 7.5 and 15 mg/kg caused significant decrease of normal body temperature 1 and/or 2 h after the administration. No influence on body temperature was observed at 3.75 mg/kg in mice. Gastric secretion of rat and intestinal motility of mice were not influenced by the dose of 15 mg/kg. In terms of autonomic nervous system, AG 60 did not show direct effect and inhibitory or augmentative action of histamine- or acetylcholine-induced contractions at the concentration of 5 mg/L in the isolated ileum of guinea-pig. The administration of 15 mg/kg of AG 60 did not affect mean arterial blood pressure and heart rate in rat. AG 60 (15 mg/kg) given to anesthetized rabbits showed no effect on respiratory rate.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

• Journal of Veterinary Science
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• v.23 no.2
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• pp.28.1-28.18
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• 2022

Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhea in developing countries. However, sporadic outbreaks caused by this microorganism in developed countries are frequently reported recently. As an important zoonotic pathogen, EPEC is being monitored annually in several countries. Hallmark of EPEC infection is formation of attaching and effacing (A/E) lesions on the small intestine. To establish A/E lesions during a gastrointestinal tract (GIT) infeciton, EPEC must thrive in diverse GIT environments. A variety of stress responses by EPEC have been reported. These responses play significant roles in helping E. coli pass through GIT environments and establishing E. coli infection. Stringent response is one of those responses. It is mediated by guanosine tetraphosphate. Interestingly, previous studies have demonstrated that stringent response is a universal virulence regulatory mechanism present in many bacterial pathogens including EPEC. However, biological signficance of a bacterial stringent response in both EPEC and its interaction with the host during a GIT infection is unclear. It needs to be elucidated to broaden our insight to EPEC pathogenesis. In this review, diverse responses, including stringent response, of EPEC during a GIT infection are discussed to provide a new insight into EPEC pathophysiology in the GIT.

• Journal of Life Science
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• v.28 no.9
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• pp.1100-1117
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• 2018

The Ras superfamily of small G-proteins acts as a molecular switch on the intracellular signaling pathway. Upon ligand stimulation, inactive GTPases (Ras-GDP) are activated (Ras-GTP) using guanine nucleotide exchange factor (GEF) and transmit signals to their downstream effectors. Following signal transmission, active Ras-GTP become inactive Ras-GDP and cease signaling. However, the intrinsic GTPase activity of Ras proteins is weak, requiring Ras GTPase-activating protein (RasGAP) to efficiently convert RAS-GTP to Ras-GDP. Since deregulation of the Ras pathway is found in nearly 30% of all human cancers, it might be useful to clarify the structural and physiological roles of Ras GTPases. Recently, RasGAP has emerged as a new class of tumor-suppressor protein and a potential therapeutic target for cancer. Therefore, it is important to clarify the physiological roles of the individual GAPs in human diseases. The first RasGAP discovered was RASA1, also known as p120 RasGAP. RASA1 is widely expressed, independent of cell type and tissue distribution. Subsequently, neurofibromatosis type 1 (NF1) was discovered. The remaining GAPs are affiliated with the GAP1 and synaptic GAP (SynGAP) families. There are more than 170 Ras GTPases and 14 Ras GAP members in the human genome. This review focused on the current understanding of Ras GTPase and RasGAP in human diseases, including cancers.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.12
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• pp.298-305
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• 2019

Cudrania tricuspidata has been reported to have many biological activities, including anti-inflammatory, anti-cancer, and antioxidant properties. However, the effects of C. tricuspidata root extract (CTE) on human platelet aggregation induced by collagen as well as the signaling pathways involved remain unknown. In the present study, we investigated the effect of CTE on human platelets. CTE inhibited platelet aggregation via down-regulation of thromboxane A₂ (TXA₂) by blocking cyclooxygenase-1 (COX-1) activity and intracellular Ca²⁺ mobilization in collagen-induced platelets. CTE also reduced the phosphorylation of phospholipase C (PLC) γ2 and syk. CTE regulated platelet aggregation via cyclic guanosine monophosphate (cGMP)-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser²³⁹. In addition, administration of CTE (50 and 100 mg/kg) significantly reduced hyper-aggregated platelet aggregation by collagen (5 ㎍/mL) without hepatotoxicity in HFD (high fat diet)-fed rats. Taken together, these results suggest that CTE has anti-platelet effects both in vitro and in vivo. Therefore, CTE may be an effective therapeutic and preventive agent for cardiovascular disease, and is a safe and natural product.

• YAKHAK HOEJI
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• v.39 no.1
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• pp.78-84
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• 1995

Based on Computer graphics molecular modeling method, quinolone derivatives as DNA-gyrase inhibitors formed stable DNA-intercalation complex with deoxycytidilyl-3',5'-deoxy guanosine[d($C_{p}G)_{2}$] dinucleotide. When d($C_{p}G)_{2}$ and d($A_{p}T)_{2}$, were compared in order to find out which DNA could form more stable DNA-Drug complex based on interaction energy($\Delta$E) and DNA-Drug complex energy, d($C_{p}G)_{2}$ resulted in lower energy than d($A_{p}T)_{2}$.

• Bulletin of the Korean Chemical Society
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• v.12 no.2
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• pp.196-199
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• 1991

Attempts were made to develop new protecting groups for 1,6-lactam function of 2-N-acyl guanine in oligodeoxyribonucleotide synthesis. Several acyl groups, aryl groups, and carbamoyl groups were tested. Dimethylcarbamoyl and phenylacetyl groups are shown to be a good combination for guanine residue. 6-O-Di-methylcarbamoyl-2-N-pheylacetyl-2'-deoxy guanosine have been successfully used in the synthesis of d[AAGCTT], which is Hind Ⅲ recognition sequence.