• Korean Journal of Transplantation
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• v.31 no.4
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1331-1335
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• 2009

We have studied the anti-diabetic effects of medicinal plant water extracts on hepatic glucose-regulating enzymes such as glucokinase (GK) and acetyl-CoA carboxylase (ACC). $\alpha$-Glucosidase inhibitor is usually used to prevent and treat type II diabetes; thus, anti-$\alpha$-glucosidase activity of medicinal plant water extracts was assayed. The hepatic cytosol faction of a type II diabetic animal (Goto-Kakizaki rat) was used in GK and ACC activity assays. The medicinal plants were Lycium chinense (JGP), Discorea japonica Thunb. (SY), Pyrus pyrifolia (YSB), Cornus officinalis (SSY), Paeonia suffruticosa ANDR. (MDP), Cordyceps militaris (DCH), and Acanthopanax senticosus (GSO). JGP, SY, YSB, and SSY water extracts increased the hepatic GK activity and all medicinal plant water extracts led to an increase in hepatic ACC activity. YSB, SSY, MDP, and GSO water extracts showed significantly higher anti-$\alpha$-glucosidase activity than control samples. The highest anti-$\alpha$-glucosidase activity was observed in GSO water extract and the anti-$\alpha$-glucoside activity was higher than that of Acarbose (reference $\alpha$-glucosidase inhibitor). We suggest that JGP, SY, YSB, and SSY water extracts may exert an anti-diabetic effect by enhancing the glucose metabolism and that YSB, MDP and GSO may be used as natural $\alpha$-glucosidase inhibitors in type II diabetic conditions. Increased ACC activity by plant water extracts may provide additional anti-diabetic effect.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.11
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• pp.1293-1299
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• 2017

Obesity contributes to the development of diseases, such as type II diabetes, hypertension, coronary heart disease, and cancer. In addition, oxidative stress caused by reactive oxygen species (ROS) is recognized widely as a contributing factor in the development of chronic diseases. This study was examined the antioxidant and anti-adipogenic activities of epigallocatechin-3-gallate (EGCG) in 3T3-L1 preadipocytes. 3T3-L1 cells were differentiated with or without EGCG for 6 days. The production of glutathione (GSH) and the activities of the antioxidant enzymes, such as glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were measured. EGCG inhibited significantly the lipid accumulation and the expression of adipogenic specific proteins including CCAAT/enhancer binding protein ${\alpha}$ and adipocyte fatty acid binding protein. The production of intracellular ROS was decreased significantly by EGCG in 3T3-L1 cells. EGCG increased the GSH production and the activities of GPx, GR, CAT, and SOD. Moreover, EGCG increased the protein expression of glutamate-cysteine ligase and heme oxygenase-1 in 3T3-L1 cells. These results suggest that EGCG increased the activity and expression of antioxidant enzymes and suppressed the lipid accumulation in 3T3-L1 cells. Therefore, the use of phytochemicals that can maintain the GSH redox balance in adipose tissue could be promising for reducing obesity.

• Molecules and Cells
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• v.40 no.9
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• pp.667-676
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• 2017

Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/methylation during C2C12 myoblast differentiation. Our results indicated that the expression pattern of HDAC11 was substantially increased during myoblast differentiation. Furthermore, ectopic expression of HDAC11 completely inhibited myoblast differentiation, concomitant with reduced expression of key myogenic transcription factors. However, the catalytically inactive mutant of HDAC11 (H142/143A) did not impede myoblast differentiation. In addition, wild-type HDAC11, but not the inactive HDAC11 mutant, suppressed MyoD-induced promoter activities of MEF2C and MYOG (Myogenin), and reduced histone acetylation near the E-boxes, the MyoD binding site, of the MEF2C and MYOG promoters. Collectively, our results indicate that HDAC11 would suppress myoblast differentiation via regulation of MyoD-dependent transcription. These findings suggest that HDAC11 is a novel critical target for controlling myoblast differentiation.

• Journal of Yeungnam Medical Science
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• v.36 no.1
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.11
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• pp.1391-1398
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• 2007

We performed a randomized double-blind placebo-controlled trial to determine whether Laminaria japonica extract (LJE) supplement modulates blood glucose, serum lipids and antioxidant systems in type II diabetic patients. We also measured critical parameters assessing safety in liver and kidney functions after LJE supplement. A total of 37 patients (18 males and 19 females) were randomized to either LJE group or placebo group. The treatment group received four 350 mg of LJE capsules (1.4 g, total) per day for 12 weeks. The placebo group received the same dose of cellulose capsules. Baseline characteristics regarding general life style and dietary intake pattern were similar between the two groups. There were no significant influences of LJE supplement except for waist circumference on anthropometric parameters. As the whole, 12 weeks of LJE supplement resulted in a little decrease in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), but a significant decrease was not observed. Total cholesterol, LDL-cholesterol and triglyceride concentrations were significantly (p<0.05) lowered in LJE group. The antioxidant enzymes, glutathion peroxidase (GSH-px) and superoxide dismutase (SOD) levels were elevated in the LJE group (p<0.05) compared to the placebo. The increase of these enzymes was associated significantly with the decrease of MDA concentration (p<0.05). Furthermore, LJE supplement showed no adverse effects on the functions of liver and kidney. Findings from this study suggest that LJE supplement can help improve serum lipid status in type II diabetic subjects without adverse effects.

• Journal of Life Science
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• v.19 no.5
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• pp.680-683
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• 2009

Glycosidase inhibitors are major targets in the treatment of type II diabetes, cancer and viral infections. This study was carried out to investigate the glycosidase inhibitory substances from bamboo (Phyllostachys bambusoides). Bamboo was extracted with methanol and then further fractionated with n-hexane, chloroform, n-BuOH and aqueous to get an active fraction. All extracts were evaluated for ${\alpha}$-glucosidase inhibitory activities to identify the n-hexane fraction with 33.5 ${\mu}$g/ml of IC50 value. Active compound 1 in the n-hexane fraction was identified as linoleic acid, which exhibited inhibitory activity with 12.4 ${\mu}$M of IC50 value. Mechanistic analysis showed that linoleic acid exhibited noncompective inhibition. This is the first study in which bamboo is reported to show ${\alpha}$-glucosidase inhibitory activity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.5
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• pp.414-421
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• 2004

This is a reprospective study on the care of odontogenic infections in admission patients with geriatric diseases. The study was based on a series of 480 patients at Dong San Medical Center, Wonju Christian Hospital and Il San Health Insurance Hospital, From Jan. 1, 2000, to Dec. 31, 2002. The Obtained results were as follows: 1. The systemic malignant tumor was the most frequent cause of the geriatric diseases with odontogenic infectious diseases, and refractory lung disease, systemic heart disease, type II diabetes mellitus, cerebrovascular disease, bone & joint disease, senile psychologic disease were next in order of frequency. 2. Male prediction(57.5%) was existed in the odontogenic infectious patients with geriatric diseases. But, there were female prediction in senile psychologic disease, systemic heart disease and cerebrovascular disease. 3. The most common age group of the odontogenic infectious patient with geriatric disease was the sixty decade(47.9%), followed by the seventy & eighty decade in order. 4. In the contents of chief complaints on the odontogenic infectious patients with geriatric disease, peak incidence was occurred as toothache(52.7%), followed by extraction wish, tooth mobility, oral bleeding, oral ulcer, fracture of restoration, gingival swelling in order. 5. In the diagnosis group of odontogenic infectious diseases, periodontitis, pulpitis & periapical abscess were more common. 6. In the treatment group of odontogenic infectious diseases, the most frequent incidence(34.2%) was showed in primary endodontic treatment (pulp extirpation, occlusal reduction and canal opening drainage) and followed by scaling, incision & drainage, only drugs, pulp capping, restoration in order.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.12-20
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• 2015

Purpose: To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT) Materials and Methods: We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results: The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion: Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

• Journal of Life Science
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• v.27 no.6
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• pp.680-687
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• 2017

Recently, there has been a marked increase in the use of bioactive products resulting from the fermentation of natural substances by microorganisms. In this study, Opuntia humifusa (OH) was fermented using Lactobacillus plantarum (fermented Opuntia humifusa; fOH). We then examined the anti-obesity effect of fOH in mice fed a 45% Kcal high fat diet (HFD). In this study, mice were treated with fOH concentrations of 100, 200, and 400 mg/kg. The mice in the control group were treated with OH at a concentration of 400 mg/kg based on previous animal experiments. All of the mice given a continuous HFD showed an increase in their weight, the density of abdominal fat, and the accumulated periovaric and abdominal fat. All of these obesity-linked factors, however, were significantly decreased in the groups treated with fOH at concentrations of 200 and 400 mg/kg. Mice treated with fOH at 100 mg/kg did not show a significant decrease in these obesity-linked factors compared to the control group. It appears that fOH fermented by L. plantarum has a greater anti-obesity effect in HFD-supplied mice compared to unfermented OH. While further studies of fOH are needed to examine its effect on obesity, hyperlipidemia, hepatic steatosis, renal function, and type II diabetes with its relevant complications, fOH may have significant therapeutic potential in the treatment of metabolic syndrome.