• Journal of Life Science
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• v.28 no.7
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• pp.765-771
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• 2018

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a key transcription factor that regulates adipogenesis, and epigenetic control of $PPAR{\gamma}$ is of great interest in obesity-inhibition research. Our previous study showed that CACUL1 (CDK2-associated cullin domain 1) acts as a corepressor that inhibits $PPAR{\gamma}$ transcriptional activity and adipocyte differentiation. Here, we investigated the roles of protein arginine methyltransferase 5 (PRMT5), a novel binding partner of CACUL1, in regulating $PPAR{\gamma}$. The interaction between PRMT5 and CACUL1 was shown by immunoprecipitation assay in vivo and GST pulldown assay in vitro. As shown by luciferase reporter assay, PRMT5 and CACUL1 cooperated to inhibit the transcriptional activity of $PPAR{\gamma}$. The suppressive role of PRMT5 in adipogenesis was examined by Oil Red O staining using 3T3-L1 cells, which stably overexpress or deplete PRMT5. Overexpression of PRMT5 suppresses $PPAR{\gamma}$-mediated adipogenesis, whereas PRMT5 knockdown increases lipid accumulation in 3T3-L1 cells. Consistently, PRMT5 attenuates the expression of Lpl and aP2, the target genes of $PPAR{\gamma}$, as demonstrated by RT-qPCR analysis. Overall, these results suggest that PRMT5 interacts with CACUL1 to impair the transcriptional activity of $PPAR{\gamma}$, leading to the inhibition of adipocyte differentiation. Therefore, the regulation of PRMT5 enzymatic activity may provide a clue to develop an anti-obesity drug.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.6
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• pp.147-156
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• 2016

The purpose of this study was to identify the factors associated with the improvement of metabolic syndrome, and provide basic data for the health management of clients. The subjects were 280 adults who were diagnosed with metabolic syndrome in 2013, and who were examined from January 2013 to December 2014. The data were analyzed by descriptive statistics, t-test, ${\chi}^2$-test, and logistic regression analysis with SPSS WIN 18. The change rate from 3 to 2 risk factors was 60.6% among those clients whose metabolic syndrome improved. The improvement group showed a decrease in their waist circumference, systolic blood pressure, triglycerides and increase in their HDL cholesterol in 2014 compared to 2013, as well as decreased drinking, increased exercise, proper calorie, protein and carbohydrate uptake, and increased consumption of a lipid lowering agent. Exercise, calorie uptake and maintenance of an oral hypoglycemic drug influenced the improvement of the metabolic syndrome. In conclusion, it is necessary to have an intervention program including exercise enhancement and diet modification and to reinforce the health education for continuing health management.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.5
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• pp.302-309
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• 2013

Purpose: This study evaluated the prognosis of conservative and surgical treatment according to the staging of bisphosphonate-related osteonecrosis of jaw (BRONJ) by American Association of Oral and Maxillofacial Surgeons and American Society for Bone and Mineral Research. Methods: We evaluated 53 patients of BRONJ who visited Department of Dentistry, Ajou University School of Medicine from May 2007 to February 2013. Twenty eight patients in stage 2, were divided into surgical and conservative groups with cessation of bisphosphonate therapy. Fifteen patients belonged to the conservative treatment group, in which mouth rinsing and antibiotics medication were done. Thirteen patients were treated with debridement or sequestrectomy, in the surgical treatment group. Each study list was analyzed by SPSS ver. 14.0 (SPSS Inc., USA) software and the favorable rate was verified by the Fisher exact test. P-values less than 0.05% were deemed significant. Results: Clinical outcome was evaluated on the basis of both clinical and radiographic findings. Of all the 28 patients of stage 2, 15 patients underwent conservative treatment and 13 patients received surgical treatment. In the surgical group, 9 of 13 (69.2%) showed good prognosis, 4 of 13 (30.7%) showed recurrence. In the conservative group, 13 of 15 (86.6%) showed no change duting the follow-up period. Two of 15 patients even showed a bad prognosis, such as pain and pus discharge, which are criteria for stage 3. P-value was 0.067 (>0.05). Conclusion: The results of the present study suggests that surgical intervention is good choice against the conservative treatment, after proper drug holidays period, while further investigation is needed for a definite solution to BRONJ.

• The Korea Journal of Herbology
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• v.22 no.3
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• pp.27-37
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• 2007

Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.

• The Journal of the Korean bone and joint tumor society
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• v.6 no.1
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• pp.41-46
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• 2000

We experienced the case of familiar hypercholesterolemia with multiple xanthomas which was treated by combined surgical and medical therapy. He was 26-year-old male patient of familiar hypercholesterolemia with multiple xanthomas in 22 sites on whole body, and was treated by 17 surgical excisions of the xanthomas and by medical therapy of the hypercholesterolemia. There was a normal healing process of the surgical wounds. Continual postoperative medical therapy of the hypercholesterolemia was done. There was no recurrence of the symptoms during more than 13 months of follow-up. But the serum level of the cholesterol was not lowered significantly, so we are treating him with drug therapy. Familial hypercholesterolemia is caused by a specific disorder of lipid metabolism, and is characterized by increased LDL cholesterol, tendon xanthomas, coronary disease associated with autosomal dominant transmission. Xanthomas usually appear in the second decade of life with familiar hypercholesterolemia which may have high risk for premature coronary atherosclerosis, which might be prevented with early diagnosis and medical treatment. So, orthopedic surgeons do not only excise the xanthomatosis surgically but also can diagnose the underlying hypercholesterolemia.

• Journal of Dental Anesthesia and Pain Medicine
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• v.15 no.3
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• pp.121-128
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• 2015

Background: The authors studied the hemodynamic effect influent by using the novel high concentration of lidocaine HCl for surgical removal impacted lower third molar. The objective of this study was to evaluate the hemodynamic change when using different concentrations of lidocaine in impacted lower third molar surgery. Methods: Split mouth single blind study comprising 31 healthy patients with a mean age of 23 years (range 19-33 years). Subjects had symmetrically impacted lower third molars as observed on panoramic radiograph. Each participant required 2 surgical interventions by the same surgeon with a 3-week washout period washout period. The participants were alternately assigned one of two types of local anesthetic (left or right) for the first surgery, then the other type of anesthetic for the second surgery. One solution was 4% lidocaine with 1:100,000 epinephrine and the other was 2% lidocaine with 1:100,000 epinephrine. A standard IANB with 1.8 ml volume was used. Any requirement for additional anesthetic and patient pain intra-operation was recorded. Post-operatively, patient was instructed to fill in the patient report form for any adverse effect and local anesthetic preference in terms of intra-operative pain. This form was collected at the seven day follow up appointment. Results: In the 4% lidocaine group, the heart rate increased during the first minute post-injection (P < 0.05). However, there was no significant change in arterial blood pressure during the operation. In the 2% lidocaine group, there was a significant increase in arterial blood pressure and heart rate in the first minute following injection for every procedure. When the hemodynamic changes in each group were compared, the 4% lidocaine group had significantly lower arterial blood pressure compared to the 2% lidocaine group following injection. Post-operatively, no adverse effects were observed by the operator and patient in either local anesthetic group. Patients reported less pain intra-operation in the 4% lidocaine group compared with the 2% lidocaine group (P < .05). Conclusions: Our results suggest that a 4% concentration of lidocaine HCl with 1:100,000 epinephrine has better clinical efficacy than 2% lidocaine HCl with 1:100,000 epinephrine when used for surgical extraction of lower third molars. Neither drug had any clinical adverse effects.

• Biomedical Science Letters
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• v.11 no.4
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• pp.455-463
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• 2005

Resistance to isoniazid (INH), which is one of the most important drugs in Mycobacterium tuberculosis chemotherapy, has been associated with mutations in genes encoding the mycobacterial catalse-peroxidase (katG), the enoyl acyl carrier protein (ACP) reductase (inhA), alkyl hydroperoxide reductase (ahpC), beta-ketoacyl acyl carrier protein synthase (kasA), and NADH dehydrogenase (ndh). In this study, we examined INH-resistance related genes in 50 INH-resistant and 24 INH-susceptible isolates by PCR-sequence analysis. In brief, mutations at the katG gene were found at codon 315 alone (2/50), at codon 463 alone (19/50), and both at 315 and 463 (29/50). However, while mutations at codon 315 were only detected in INH-resistant isolates, mutations at codon 463 were also detected in INH-susceptible isolates indicating mutations at 463 alone do not seem to confer resistance to INH. Similar to the case of katG 463, some of inhA mutations were also found among INH-susceptible isolates. For example, whereas mutations at 8 upstream of the start codon (UPS) and 15 UPS of the inhA gene were detected only in INH-resistant isolates, mutations at 101, 115, and 125 UPS were detected only in INH-susceptible isolates. Many different kinds of mutations were detected in INH­resistant isolates at ahpC, oxyR gene, and intergenic region of the oxyR-ahpC genes. Howerver, the mutations were not found oxyR and the intergenic regions in INH-susceptible isolates. No mutations were found at either kasA or at ndh gene among INH-resistant isolates. In conclusion, some of mutations such as katG 315, inhA promotor region, and oxyR-ahpC seem to be strongly related to INH-resistance. Currently we are developing a molecular diagnostic method based on these results.

• Biomedical Science Letters
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• v.11 no.4
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• pp.465-471
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• 2005

Ofloxacin has antimycobacterial activity that possibly contributes a pivotal role in the second-line drug regimens that are used for the treatment of multidrug-resistant tuberculosis. However, in some communities, the resistance rate of Mycobacterium tuberculosis to this agent is surging. Therefore, a rapid and accurate method that can be used to determine the resistance of M tuberculosis to the ofloxacin can be very useful for effective treatment of the patients. As an effort to develop such a method, this study was set up to reveal general types of mutations that are related to ofloxacin resistance of M tuberculosis. From previous studies, it has been well known that ofloxacin resistance is associated with mutations in a gene encoding the gyrase A subunit protein. In this study, we obtained 43 ofloxacin-resistant and 50 ofloxacin-susceptible M tuberculosis clinical isolates from Masan National TB Hospital, and sequences of DNA fragment of 320 bp, region of gyrA corresponding to the ofloxacin resistance-determining region were analyzed. In brief, the results showed that a total of seven mutation types were found at gyrA. Theses mutations were all clustered within nucleotides 2574 to 2586 of the gyrA gene (codons 88 to 94). Codon 94 was the most frequently substituted site. Twenty-four of the 43 isolates had mutations at this position resulting in a total of five different types of amino acid changes $(Asp{\to}Ala,\;Asp{\to}Gly,\;Asp{\to}His,\;Asp{\to}Tyr,\;and\;Asp{\to}Asn)$. Five isolates contained a mutation at codon 90 resulting $Ala{\to}Val$ change. Four isolates had mutations at codon 91 causing a $Ser{\to}Pro$ change at this site. Two isolates contained a mutation at codon 88 and each of them resulted in different types of amino acid changes $(Gly{\to}Cys,\;Gly{\to}Ala)$. On the other hand, polymorphic site at codon 95 was found in both ofloxacin-resistant and ofloxacin-susceptible isolates. From these results, we concluded that the rate of mutations present in gyrA among ofloxacin-resistant M. tuberculosis in Korea is similar to the general rates of mutations found throughout the world. Subsequently, an oligonucleotide probe was designed based on the results of sequence analysis and was used to develop a dot blot hybridization assay system to determine ofloxacin-resistance of M tuberculosis. To evaluate this probe, dot-blot hybridization was carried out using other 57 clinical isolates, and the results showed that the dot-blot hybridization assay is good for detecting sequence alterations atgyrA gene.

• Journal of Society of Preventive Korean Medicine
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• v.11 no.2
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• pp.23-39
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• 2007

Objectives : The aim of this study was to evaluate effects of herbal medicine and other associated factors for abnormal liver function tests(especially total bilirubin, AST, ALT, and ${\gamma}GT$) levels in outpatients at an oriental medical clinic. Methods : A cross-sectional study based on clinical records was conducted on 1,871 patients at one Oriental medical clinic in Seoul, Korea. 504 patients received a liver function tests for screening and 497 patients ranging from the age of 4 to 74 were chosen for the study. Patients with basal liver disease or DM were excluded during the screening process. Patients were classified into case(abnormal) and control(normal) groups by normal liver function test references. Results and Conclusions : In this study, 33.0% of the patients were females, and 67.0% were males. The mean age was $34.7{\pm}11.9$ years old. The mean total protein value was $6.78{\pm}0.66g/dL$(male $6.79{\pm}0.61$, female $6.76{\pm}0.76$), albumin $3.89{\pm}0.50g/dL$(male $3.94{\pm}0.47$, female $3.81{\pm}0.54$), total bilirubin $0.51{\pm}0.35mg/dL$(male $0.54{\pm}0.39$, female $0.45{\pm}0.23$), AST $23.31{\pm}18.22U/L$(male $26.37{\pm}20.73$, female $17.09{\pm}8.72$), ALT $33.49{\pm}36.36U/L$(male $40.56{\pm}41.77$, female $19.13{\pm}12.64$), LDH $258.07{\pm}74.84mg/dL$(male $263.68{\pm}73.77$, female $246.70{\pm}75.92$), and ${\gamma}GT$ $39.64{\pm}59.16U/L$(male $50.15{\pm}69.43$, female $17.83{\pm}8.36$). The percentage of abnormal total bilirubin levels(>1.0) in these patients was 2.6%, abnormal AST levels(>39m, >29f) 8.5%, ALT levels(>47m, >32f) 18.8%, and ${\gamma}GT$ (>50m, >40f) 19.9%.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1108-1117
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• 2007

To investigate the possible mechanism of ${\alpha}-spinasterol$ as a candidate of anti-cancer drug, I examined the effects of ${\alpha}-spinasterol$ on the apoptosis of U937 cells MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. ${\alpha}-spinasterol$ treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death. ${\alpha}-spinasterol$ treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. After treatment the level of Bcl-xL, anti-apoptotic gene expression was decreased and the level of ICE pro-apoptotic gene expression was increased. These findings suggest that ${\alpha}-spinasterol$ induced the apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.