• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.6
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• pp.558-566
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• 2020

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion: The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2147-2150
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• 2010

c-Jun N-terminal kinase 1 (JNK1) is involved in apoptosis, cell differentiation and proliferation. It has been reported that a flavonol, quercetin, induces cell apoptosis and JNK inhibition. In order to understand the interactions of quercetin and JNK1, we performed receptor-oriented pharmacophore based in silico screening and determined a binding model of human JNK1 and quercetin at the ATP binding site of JNK1. 5-OH of A-ring and carbonyl oxygen of C-ring of quercetin participated in hydrogen bonding interactions with backbone of E109 and M111. Additionally, 3'-OH of quercetin formed a hydrogen bond with backbone of I32. One hydrophobic interaction is related on the binding of quercetin to JNK1 with I32, N114, and V158. Based on this model, we conducted a docking study with other 8 flavonols to find possible flavonoids inhibitors of JNK1. We proposed that one flavonols, rhamnetin, can be a potent inhibitor of JNK and 5-OH of A-ring and 3'-OH of B-ring of flavonols are the essential features for JNK1 inhibition.

• The Journal of Dong Guk Oriental Medicine
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• v.8 no.1
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• pp.93-106
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• 1999

For the purpose of investigate the inhibition effects of Injinchunggantang on Hepatitis and C Virus. The inhibition experiments were as follows : 1. The inhibition effects of Hepatitis B surface antigen production was remarkably increased in the pretreated group of Injinchunggantang compared with control group. 2. Amplified PCR products of HBV-DNA in culture media was considerably decreased in the pretreated group of Injinchunggantang compared with control group. 3. Results of ATP quantitation and ATPase inhibition percent was increased pretreated group of Injinchunggantang. Also ATPase activity of HCV helicase inhibition assay was increased with a dose dependent manner. These results may suggest that Injinchunggantang will have the inhibition effects of Hepatitis B and C Virus.

• Journal of Plant Biotechnology
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• v.46 no.3
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• pp.189-204
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• 2019

In this study, we analyzed the changes in glucosinolate content and gene expression in TO1000DH3 and Early big seedling upon methyl jasmonate (MeJA) treatment. Analysis of glucosinolate contents after MeJA treatment at $200{\mu}M$ concentration showed that the total glucosinolate content increased by 1.3-1.5 fold in TO1000DH3 and 1.3-3.8 fold in Early big compared to those before treatment. Aliphatic glucosinolates, progoitrin and gluconapin, were detected only in TO1000DH3, and the changes in the content of neoglucobrassicin were the greatest at 48 hours after MeJA treatment in TO1000DH3 and Early big. The transcriptomic analysis showed that transcripts involved in stress or defense reactions, or those related to growth were specifically expressed in TO1000DH3, while transcripts related to nucleosides or ATP biosynthesis were specifically expressed in Early big. GO analysis on transcripts with more than two-fold change in expression upon MeJA treatment, corresponding to 12,020 transcripts in TO1000DH3 and 13,510 transcripts in Early big, showed that the expression of transcripts that react to stimulus and chemical increased in TO1000DH3 and Early big, while those related to single-organism and ribosome synthesis decreased. In particular, the expression increased for all transcripts related to indole glucosinolate biosynthesis, which is associated with increase in glucobrassicin and neoglucobrassicin contents. Upon MeJA treatment, the expression of AOP3 (Bo9g006220, Bo9g006240), TGG1 (Bo14804s010) increased only in TO1000DH3, while the expression of Dof1.1 (Bo5g008360), UGT74C1 (Bo4g177540), and GSL-OH (Bo4g173560, Bo4g173550, Bo4g173530) increased specifically in Early big.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.1-11
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• 1996

Since it has been reported that the depolarization-induced norepinephrine (NE) release is inhibited by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus, a large body of experimental data on the post-receptor mechanism of this process has been accumulated. But, the post-receptor mechanism of presynaptic $A_1-adenosine$ receptor on the NE release has not been clearly elucidated yet. Therefore, it was attempted to clarify the post-receptor mechanisms of the $A_1-adenosine$ receptor-mediated control of NE release in this study. Slices from rat hippocampus were equilibrated with $^3H-norepinephrine$ and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 $Vcm^{-1}$, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Adenosine, in concentrations ranging from $1{\sim}30{\mu}M$, decreased the NE release in a dose-dependent manner, without affecting the basal rate of release. The adenosine effects were significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, $2{\mu}M$), a selective $A_1-receptor$ antagonist. The responses to N-ethylmaleimide (NEM, 10 & $30{\mu}M$), a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the basal release, and the adenosine effects were completely abolished by NEM pretreatment. $4{\beta}-Phorbol$ 12,13-dibutyrate (PDB, $1{\mu}M$), a specific protein kinase C (PKC) activator, increased the evoked NE release, whereas polymyxin B sulfate (PMB,0.1 mg), a PKC inhibitor, decreased the release, and the adenosine effects were inhibited by these agents. Nifedipine $(1{\mu}M)$, a $Ca^{2+}-channel$ blocker of dihydropyridine analogue, did not affect the adenosine effect. Tetraethylammonium (TEA, 3 mM) increased the evoked NE release, and inhibited the adenosine effects, but glibenclamide, a ATP dependent $K^+-channel$ blocker, did not. Finally, 8-bromo cyclic AMP (100 & $300{\mu}M$), a membrane-permeable analogue of cAMP, did not alter the NE release, but adenosine effects were inhibited by pretreatment with 8br-cAMP. These results suggest that the decrement of the evoked NE-release by $A_1-adenosine$ receptor is mediated by the C-protein, which is coupled to protein kinase C, adenylate cyclase system and TEA sensitive $K^+-channel$, and that nifedipine-sensitive $Ca^{2+}-channel$ and glibenclamide-sensitive $K^+-channel$ are not involved in this process.

• Genomics & Informatics
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• v.8 no.3
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• pp.103-107
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• 2010

The imputation of untyped SNPs enables researchers to validate association findings across SNP arrays and also enables them to test a large number of SNPs to reveal the fine structure of the association peak, facilitating interpretation of the results and the location of causal polymorphisms. In this study, we applied the imputation method to a genomewide association study and recapitulated the previously associated gene loci of blood pressure traits in Korean cohorts. A total of 1,827,004 SNPs were imputed by the IMPUTE program, and we conducted a genomewide association study for systolic and diastolic blood pressure. While no SNPs passed the Bonferroni correction p-value (p=$2.74{\times}10^{-8}$ for 1,827,004 SNPs), 12 novel loci for systolic blood pressure and 16 novel loci for diastolic blood pressure were detected by imputed SNPs, with $10^{-5}$ < p-value < $10^{-4}$. Moreover, 7 regions (ATP2B1, 10p15.1, ARHGEF12, ALX4, LIPC, 7q31.1, and TCF7L2) out of 14 genetic loci that were previously reported revealed that the imputed SNPs had lower p-values than those of genotyped SNPs. Moreover, a nonsynonymous SNP in the CSMD1 gene, one of the 14 genes, was found to be associated with systolic blood pressure (p<0.05). These results suggest that the imputation method can facilitate the discovery of novel SNPs as well as enhance the fine structure of the association peak in the loci.

• The Journal of Internal Korean Medicine
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• v.43 no.6
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• pp.1162-1185
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• 2022

Purpose: We examined the effects of Dansam (Salvia miltiorrhiza Bunge, SM) and Dansam-eum (DSE) on gastroesophageal reflux disease (GERD) and reflux esophagitis by comparing the inhibitory effects of SM and DSE with the representative treatment of PPI Omeprazole to determine if the effects of the prescription DSE based on Korean medicine are better than those of a single-use of SM. Methods: We performed experiments using both animal models and cancer cells. Results: Comparison of SM and DSE with PPI in the animal model tests revealed that the effects were superior for SM and DSE than for PPI in all categories (8-OHdG, p-IκB, PAR2, COX-1, cathelicidin, p-JNK, Caspase 3, ATP6V1B1, GRPR, serotonin, and NPY). In three categories (COX-1, serotonin, and NPY), SM and DSE showed superior results over the Controls. In the animal model tests, DSE was superior to SM in all categories except for serotonin. The anti-cancer effects observed in cancer cell tests revealed that SM and DSE had meaningful results in terms of cytotoxicity and cell movement rate, as well as in cancer cell apoptosis. Conclusions: We confirmed that SM and DSE can have effects on reflux esophagitis through the regulation of oxidative stress, inflammation, mucosal protection, apoptosis, proton pumping, and the enteroendocrine system in the stomach and esophagus. We also confirmed that SM and DSE have superior effects to those of PPI on all aspects, especially gastric mucosa protection and enteroendocrine system control. We also confirmed that SM and DSE have anti-cancer effects. Above all, we confirmed that DSE has superior effects on almost all aspects compared to using SM alone.

• Korean Journal of Food Science and Technology
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• v.35 no.1
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• pp.97-102
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• 2003

Raw and washed spinaches were tested to evaluate the incidences of Aeromonas hydrophila, Escherichia coli O157:H7, Plesiomonas shigelloides, Pseudomonas aeruginosa, Salmonella spp., Shigella spp., Yersinia enterocolitica, Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Listeria monocytogenes, and Staphylococcus aureus. Four pathogenic bacteria were isolated from spinach samples, and identified by morphological and biochemical methods, including API and ATB identification systems. Isolates from MacConkey, Cereus Selective, Clostridium Perfringens, and Baird-Parker agar media were in 99.9, 99.8, 99.9, and 97.8% agreements with A. hydrophila, B. cereus, C. perfringens, and S. aureus at the species level, respectively. SET-RPLA revealed, among the five strains of S. aureus isolates, two produced type A enterotoxin. All five strains of B. cereus isolates produced enterotoxin as revealed with CRET-RPLA.

• Animal Bioscience
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• v.35 no.1
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• pp.96-104
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• 2022

Objective: Sarcoplasmic proteins include proteins that play critical roles in biological processes of living organisms. How seasons influence biological processes and meat quality of postmortem muscles through the regulation of protein phosphorylation remain to be investigated. In this study, the phosphorylation of sarcoplasmic proteins in pork longissimus muscle was investigated in four seasons. Methods: Sarcoplasmic proteins were extracted from 40 pork carcasses (10 for each season) and analyzed through ProQ Diamond staining for phosphorylation labeling and Sypro Ruby staining for total protein labeling. The pH of muscle, contents of glycogen and ATP were measured at 45 min, 3 h, and 9 h postmortem and the water (P_2b, P₂₁, and P₂₂) was measured at 3 h and 9 h. Results: A total of 21 bands were detected. Band 8 (heat shock cognate 71 kDa protein; heat shock 70 kDa protein 1B) had higher phosphorylation level in summer than that in other seasons at 45 min postmortem. The phosphorylation levels of 3 Bands were significantly different between fast and normal pH decline groups (p<0.05). The phosphorylation levels of 4 bands showed negative associations with immobilized water (P₂₁) and positive association with free water (P₂₂). Conclusion: The phosphorylation levels of sarcoplasmic proteins involved in energy metabolism and heat stress response at early postmortem time differed depending on the seasons. These proteins include heat shock protein 70, pyruvate kinase, phosphoglucomutase-1, glucose-6-phosphate isomerase, and carbonic anhydrase 3. High temperatures in summer might result in the phosphorylation of those proteins, leading to pH decline and low water holding capacity.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.683-689
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• 2022

Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl₃ (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H₂O₂) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B₂ production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H₂O₂ cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B₂ production, and granule release, but also in delaying blood coagulation, FeCl₃-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.