• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.251-256
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• 2011

The prevalence of multi-drug resistant tuberculosis (MDR-TB), which is resistant to isoniazid and rifampin, has been increasing in Korea. And the side effects of 2nd line anti-tuberculosis medications, including drug-induced hepatitis, are well known. Although prothionamide (PTH) is one of the most useful anti-TB medications and although TB medication-induced acute hepatitis is a severe complication, there are only a few published case reports about prothionamide induced hepatitis. In this case report, a 22 year old male was diagnosed with pulmonary MDR-TB and was administered 2nd line anti-TB mediations, including PTH. Afterwards, he had a spiking fever and his liver enzymes were more than 5 times greater than the upper limit of the normal range. He was then diagnosed with drug-induced hepatitis by liver biopsy. His symptoms and liver enzyme elevation were improved after stopping PTH. Accordingly, we report this case of an association between PTH and acute hepatitis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.33 no.2
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• pp.93-97
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• 2007

Even in the moderately concentrated anionic surfactant system, some special encapsulation method can shield the papain enzyme from proteolytic attacks. The stabilization of enzyme has been a major issue for successful therapies. In this study, we first stabilized an enzyme, papain in the microcapsules by using polyols, polyethyleneglycol (PEG), poly-propyleneglycol (PPG), and PEG-PPG-PEG block copolymer. In the analysis of EDS and CLSM, it was demonstrated that polyols are effectively located in the interface of papain and polymer. Polyols located in the interface had an ability to buffer the external triggers by hydrophobic partitioning, preventing consequently the catalytic activity of papain in the micro-capsules. Second. we introduced multi-layer capsulation methods containing ion complex. Such a moderately concentrated anionic surfactant system as wash-off cleansers, surfactants and waters can cause instability of entrapped enzymes. Surfactants and water in our final products swell the surface of enzyme capsules and penetrate into the core so easily that we can not achieve the effect of enzyme, papain. In this case, the ion complex multi-layer capsule composed of sodium lauroyl sarcosinate and polyquaternium-6 could effectively prevent water from penetration into the core enzyme, followed by in vivo test, and evaluate the stratum corneum (SC) turn-over speed.

• Journal of Life Science
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• v.26 no.3
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• pp.282-288
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• 2016

Protein-protein interactions regulate the subcellular localization and function of receptors, enzymes, and cytoskeletal proteins. Proteins containing the postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domain have potential to act as scaffolding proteins and play a pivotal role in various processes, such as synaptic plasticity, neural guidance, and development, as well as in the pathophysiology of many diseases. Multi-PDZ domain protein 1 (MUPP1), which has 13 PDZ domains, has a scaffolding function in the clustering of surface receptors, organization of signaling complexes, and coordination of cytoskeletal dynamics. However, the cellular function of MUPP1 has not been fully elucidated. In the present study, a yeast two-hybrid system was used to identify proteins that interacted with the N-terminal PDZ domain of MUPP1. The results revealed an interaction between MUPP1 and Wdpcp (formerly known as Fritz). Wdpcp was identified as a planar cell polarity (PCP) effector, which is known to have a role in collective cell migration and cilia formation. Wdpcp bound to the PDZ1 domain but not to other PDZ domains of MUPP1. The C-terminal end of Wdpcp was essential for the interaction with MUPP1 in the yeast two-hybrid assay. This interaction was further confirmed in a glutathione S-transferase (GST) pull-down assay. When coexpressed in HEK-293T cells, Wdpcp was coimmunoprecipitated with MUPP1. In addition, MUPP1 colocalized with Wdpcp at the same subcellular region in cells. Collectively, these results suggest that the MUPP1-Wdpcp interaction could modulate actin cytoskeleton dynamics and polarized cell migration.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.327-337
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• 1999

Background: Reactive oxygen species are involved in multi-stage process of carcinogenesis. The moot of cancer cell lines and cancer cells in tumor tissue produce reactive oxygen species and on the other hand, the activities of catalase, Mn- and CuZn-superoxide dismutase in tumor cells are usually low. These persistent oxidative stress in tumor tissue facilitates tumor invasion and metastasis. 12-kDa thioredoxin, which regulates the intracellular redox potential with glutathione and glutaredoxin is involved in cell activation, proliferation, differentiation and redox-mediated apoptosis. It is also purified as 14-kDa and 10-kDa eooinophilic cytotoxic enhancing factor(ECEF) from human histiocytic cell(U937) and 10-kDa ECEF has more than 20 times eosinophilic stimulation activity than 14-kDa ECEF. It has been reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma show increased amounts of human thioredoxin and thioredoxin mRNA is increased in lung cancer. In this study, we investigated the expression of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue and the induction of thioredoxin in macrophage cells after treatment of oxidative stress and endotoxin Methods: We measured the amount of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue by immunoblot analysis and the induction of thioredoxin in mouse monocyte-macrophage cells(RAW 264.7) by treatment of 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin Results: On immunoblot analysis, the expression of 12-kDa thioredoxin was increased in lung cancer tissue compared to paired normal lung tissue. but the expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to paired normal tissue and the expression of glutathione peroxidase in lung cancer was variable. The expression of truncated thioredoxin was also increased in lung cancer. When mouse monocyte-macrophage cells were treated with 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin, the expression of thioredoxin was peaked at 12 hrs and sustained to 48 hrs. Conclusion: In contrast with other conventional antioxidants, the expression of 12-kDa and truncated thioredoxin in lung cancer were increased and it is closely associated with persistent oxidative stress in tumor microenvironment. Considering especially the biological functions of truncated thioredoxin, the increased amount of truncated thioredoxin has significant role in tumor growth through cell proliferation.

• Korean Journal of Community Nutrition
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• v.12 no.4
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• pp.396-404
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• 2007

Increased oxidative stress contributes to the progression of atherosclerosis. We measured serum antioxidant mineral concentrations, capacities of serum antioxidant enzymes and fasting lipid profile in 97 male patients with coronary artery disease (CAD) and 21 male controls. Nutrient intake was assessed by the semi-quantitative food frequency method. CAD patients were divided into single-vessel disease (SVD, n=66) and multi-vessel disease (MVD, n = 31) groups on the coronary angiography. The ratio of serum LDL- to HDL-cholesterol elevated with an increasing number of diseased vessels compared to the control (control < SVD < MVD, p < 0.05). Patients with SVD and MVD had higher levels of serum lipoprotein (a) than the control (p < 0.05). The mean intake of carbohydrate, protein and cholesterol was higher in MVD patients and the intakes of vitamins C and E were lower in MVD and SVD patients than in the control (p < 0.05). Serum copper (Cu) and zinc (Zn) levels were higher in MVD and SVD patients than in the control (Cu: control $75.8{\pm}5.07$, SVD $99.2{\pm}2.90$, MVD $100.1{\pm}2.32{\mu}g/dL$, p<0.01; Zn: $76.8{\pm}5.36$, $119.0{\pm}5.95$, $129.1{\pm}2.70{\mu}g/dL$, p < 0.01). And the ratio of Zn to Cu was higher in SVD and MVD patients than in the control (control $0.78{\pm}0.06$, SVD $0.88{\pm}0.05$, MVD $0.99{\pm}0.04$, P < 0.05). The activity of glutathione peroxidase (GSH-Px) was lower in MVD than in SVD and the control (control $35.13{\pm}1.34$, SVD $35.30{\pm}1.01$, MVD $31.00{\pm}1.04 U/mg$ protein, p < 0.05). The ratio of the activities of superoxide dismutase (SOD) to GSH-Px was higher in MVD than in control and SVD (p < 0.05). In groups with CAD, serum Cu and Zn concentrations and their ratio were changed compared to the control. GSH-Px activity was decreased and the ratio of SOD to GSH-Px was increased in the patients with MVD. The balances between the activities of SOD and GSH-Px should also be considered a risk factor in CAD patients.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.3
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• pp.148-154
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• 2016

A urea cycle disorder is a condition caused by a defect of the enzymes in the urea cycle, and deficiency of ornithine transcarbamylase (OTC), which converts carbamoyl phosphate and ornithine into citrulline, is the most common type of the disorder. OTC deficiency induces the accumulation of precursors of urea, ammonia, and glutamine, leading to neurological symptoms including hypotonia, respiratory failure, seizure, lethargy, and coma and sometimes to death. Because OTC deficiency is inherited in an X-linked manner, typical symptoms such as vomiting, poor feeding, and lethargy appear mainly in male neonates. We recently had a case that presented with neonatal onset lethargy, vomiting, and apnea in a 4-day-old boy. He was diagnosed with OTC deficiency by biochemical phenotype, including hyperammonemia and an increased orotic acid level in the urine. Genetic analysis of the OTC gene showed a novel mutation c.780_781insCAGGCAGTGT (p.Ile261Glnfs*35). He was treated for hyperammonemia using continuous venovenous hemofiltration (CVVH) at 118 hours after birth. After 4 days of CVVH, his consciousness and blood ammonia concentration were normalized, and he was discharged at the age of 53 days. At around 12 months of age, bilateral femur fractures and osteomyelitis occurred in this patient. Two months after the fracture, he died of septic shock, insulin-resistant hyperglycemia, and multi-organ failure.

• Genomics & Informatics
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• v.16 no.3
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• pp.52-58
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• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• Natural Product Sciences
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• v.26 no.4
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• pp.311-316
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• 2020

The chemical investigation of the methanolic crude extract of leaves of Diospyros iturensis gave us 15 known secondary metabolites identified as mixture of α-amyrenone (1) and β-amyrenone (2), β-amyrin (3), mixture of β-sitosterol (4) and stigmasterol (5), betulin (6), uvaol (7), betulinic acid (8), ursolic acid (9), corosolic acid (10), actinidic acid (11),11-O-p-hydroxybenzoylbergenin (12), bergenin (13) and mixture of stigmasterol glucoside (14) and β-sitosterol glucoside (15) respectively. The structures of secondary metabolites were elucidated with the help of NMR and mass spectral data and by comparison of their spectral data with literature. Among the fifteen isolated compounds, four compounds were identified for the first time in Diospyros genus. These included uvaol (7), corosolic acid (10), actinidic acid (11) and 11-O-p-hydroxybenzoylbergenin (12). Crude methanolic extract of leaves and four isolated compounds including betulin (6), betulinic acid (8), 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) were evaluated for their antiproliferative activity against two cancer cell lines CAL-27 and NCI-H460 by the MTT assay, antioxidant potential and inhibitory activity against the lipoxygenase and urease enzymes, respectively. The results indicated that the methanolic crude extract of leaves exhibited moderate antioxidant activity and was inactive against the two cancer cell lines. Betulin (6), 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) exhibited moderate antioxidant and lipoxygenase inhibition with IC50 = 65.8, 85.6, 82.5 μM and IC50 = 58.5, 95.2, 76.2 μM, respectively. Furthermore, 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) exhibited moderate urease inhibition activity with IC50 values of 45.6 μM and 49.8 μM, respectively.

• Animal Bioscience
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• v.35 no.10
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• pp.1575-1584
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• 2022

Objective: An experiment was conducted to evaluate the effects of partially replacing soybean meal (SBM) with sunflower meal (SFM) with added exogenous multienzymes (MEs) on various biological parameters in broilers. Methods: One week-old, 400 broiler chicks were randomly divided into four treatments (control, 3SFM, 6SFM, and 9SFM) with 5 replicates/treatment (20 chicks/replicate). Control diet was without SFM and MEs, while diets of 3SFM, 6SFM, and 9SFM treatments were prepared by replacing SBM with SFM at levels of 3%, 6%, and 9%, respectively, and were supplemented with MEs (100 mg/kg). Feeding trial was divided into grower (8 to 21 day) and finisher phases (22 to 35 day). External marker method was used to measure the nutrient digestibility. At the end of trial, twenty birds (one birds per replicate) with similar body weight were slaughtered for samples collection. Results: No significant effect of dietary treatments was found on all parameters of growth performance and carcass characteristics, except relative weight of bursa. Weight (25.0 g) and length (15.80 cm) of duodenum were significantly (p<0.05) higher in 3SFM than control. Lowest (p<0.05) villus height/crypt depth ratio was found in 3SFM and 9SFM than control. Most of meat quality parameters remained unaffected, however, highest pH of breast meat (6.16) and thigh meat (6.44) were observed in 9SFM and 3SFM, respectively. Lowest (p<0.05) cook loss of thigh meat was found in 6SFM (31.76%). Ileal digestibility of crude protein was significantly (p<0.05) higher in 3SFM (72.35%) than control (69.46%). In addition, amylase (16.87 U/mg) and protease (85.18 U/mg) activities were significantly (p<0.05) higher in 3SFM than control. However, cecal microbial count remained unaffected. Conclusion: Partial replacement (up to 9%) of SBM with SFM, with added MEs can help to improve the nutrient digestibility, intestinal morphology, and digestive enzyme activities without affecting cecal microbial count and growth performance in broilers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.8
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• pp.989-995
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• 2009

Extract yield of tartary buckwheat treated with water, 70% ethanol or methanol were about 13.6%, 7.0% and 6.6%, respectively. Extract yield was greatly increased by the treatment of $\alpha$-amylase indicating 95.1% yield. $RC_{50}$ value of DPPH radical scavenging activity with methanol and 70% ethanol extracts were 34.0 $\mu g$/mL, 40.5 $\mu g$/mL, respectively. The DPPH radical scavenging activity increased when it was treated with $\beta$-glucosidase and cellulase, showing $RC_{50}$ value of 24.7 $\mu g$/mL and 25.0 $\mu g$/mL, respectively. In ABTS radical scavenging activity, methanol extract (100 $\mu g$/mL) showed 30% inhibition. In DPPH or ABTS radical scavenging activities, the treatment of $\beta$-glucanase and $\alpha$-amylase shows the highest and the lowest activities, respectively. In $\alpha$-glucosidase inhibitory effect, 70% ethanol extract showed $RC_{50}$ value of 59.9 $\mu g$/mL, but water extract was not inhibitory effective. The $\alpha$-glucosidase inhibitory effect was the highest in multi enzyme treatment. Content of rutin and quercetin in methanol extract showed higher value with 4400.3 mg% and 71.9 mg%, respectively. The 70% ethanol extract of buckwheat contained rutin of 3459.8 mg% and quercetin of 56.9 mg%. In the treatment of $\beta$-glucanase, the rutin content of ethanol extract increased with 5057.4 mg% and multi-enzyme treatment resulted in the modification of rutin glycoside.