• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.507-516
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• 2023

Eradication of Helicobacter pylori infection is an essential strategy to decrease the risk of developing gastric cancer. However, the standard triple therapy has negative aspects associated with side effects and the emergence of antibiotic resistance. Therefore, alternative therapies are required to enhance the management of H. pylori infection effectively. In this study we examined the effect of emodin on the amelioration of inflammatory response due to H. pylori infection. Our results indicated that emodin treatment effectively decreased the expression of virulence genes, including sabA, vacA, cagL, cagA, sabA, and suppressed the adhesion ability of H. pylori to AGS cells. Emodin has been shown inhibitory effects on the inflammasome pathway through reductions in VacA translocation, lowering ROS stress, cleaved Caspase-1, NLRP3, and cleaved Gasdermin D levels, thereby lowered pyroptosis in infected cells. In summary, our study demonstrated that emodin has the ability to attenuate inflammation caused by H. pylori by modulating virulence gene expression and decreasing VacA translocation. Further study is required to evaluate the therapeutic efficacy of emodin in treating H. pylori infection and better understand the underlying mechanisms.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.175-181
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• 2018

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

• Food Science and Preservation
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• v.23 no.1
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• pp.104-109
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• 2016

The purpose of this study was to evaluate the inhibitory effect of commercial Makgeolli on tumor growth in human gastric adenocarcinoma cells (AGS) in a xenograft cancer model, transplanted with AGS cells. Commercial Makgeolli was first dealcoholized by evaporation and used as the test sample. We detected a significant increase in the volume and weight of tumor in nude mice (induction) that were transplanted with AGS cells. Administration of $100mg/kg{\cdot}day$ group (ML), and $500mg/kg{\cdot}day$ group (MH) dealcoholized commercial Makgeolli significantly decreased tumor growth. In this study, 5-FU $18mg/kg{\cdot}day$ was used as a positive control for tumor growth inhibition. Additionally, determination of the body weight of both the groups revealed no side effects after the administration of dealcoholized commercial Makgeolli. Using the cell culture system, we also evaluated the effect of dealcoholized commercial Makgeolli on caspase-3/7 activity in the AGS cells. Treatment with dealcoholized commercial Makgeolli increased the activation of caspase-3/7 and the apoptotic markers in AGS cells in a dose-dependent manner. Therefore, dealcoholized commercial Makgeolli can be used for cancer prevention.

• Journal of Life Science
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• v.18 no.3
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• pp.329-335
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• 2008

Korean Deep ground sea-like water (KDSW) has a similar mineral composition with deep sea water. KDSW has demonstrated its usefulness and attracted in the medical fields. KDSW and Danasoo (desalted deep ground sea-like water) intake improve antioxidant, antidiabetic activity and immunity. Antioxidant activities of KDSW and Dnansoo were measured by using 2,2-diphenyl-l-picryl-hydrazyl (DPPH) free radical, superoxide dismutase-like activity (SODA) and photochemiluminescence (PCL). DPPH radical scavenging and SOD-like activities of KDSW and Danasoo were remarkably increased in a dose-dependent manner. Antioxidant activities of KDSW and Danasoo 85.32 and 14.02 nmol of ascorbic acid equivalent/ml KDSW and Danasoo, respectively, using the PCL method. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages RAW264.7 cells was inhibited up to 30% by treatment with Danasoo (20%). NO is synthesized by the enzyme of nitric oxide synthase (NOS) and plays an important role tumor growth and angiogenesis. The anticancer effects of Danasoo on human gastric and lung cancer cells was performed by levels of inducible nitric oxide synthase (iNOS). Danasoo significantly reduced iNOS expression of human gastric cancer (SNU-l) and lung carcinoma (A549). The serum glucose level was significantly reduced by Danasoo (20%) diet in streptozotocin (STZ)-induced diabetic rats. These result suggest that KDSW has excellent biological activities and thus it has great potential as a source for natural health products.

• Journal of Life Science
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• v.17 no.12
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• pp.1723-1728
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• 2007

Rubus coreanus Miquel (RCM), a type of red raspberry, grows wild in Korea and China and its unripe fruit is used as a folk medicine for the treatment of impotence and as a diuretic. RCM was extracted with methanol and then further fractionated it into for different types. In this study, we investigated the antioxidant activity of a RCM extract (ext.) and its fraction (fr.). DPPH free radical scavenging activity assay, total polyphenols contents, total flavonoids contents assay were used to analyze antioxidant activity. The DPPH free radical scavenging activity $(RC_{50}:1.67{\mu}g/ml)$ and total polyphenols contents $(546.25{\mu}g/mg)$ were higher in butanol fraction than in other fr. And total flavonoids contents was higher in ethylacetate fr. $(141.78{\mu}g/mg)$. We applied comet assay to measure the DNA damage in the individual cells and exposed time course at $IC_{50}$. Comet assay is a rapid and sensitive fluorescent microscopic method to examine DNA damage and repair at individual cell level. The butanol fro from RCM significantly induced 54.12%, 57.95% of DNA damage after treated RCM for 8 hr. In conclus

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.267-272
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• 2003

Herpes simplex virus (HSV) thymidine kinase (TK) has been widely used for suicidal gene therapy in combination with nucleoside analogs such as ganciclovir (GCV). The use of HSV-TK is limited due to the side effect of GCV at high concentrations. Previous studies showed that stable transfectants of mutant HSV-TK with enhanced affinity to GCV were killed at lower GCV concentrations. In this study, we tested whether mutant HSV-TK can provide enhanced suicidal effect when transiently transfected with Epstein-Barr virus (EBV)-based plasmid. EBV-based plasmid which contains OriP and EBNA-1 sequence is well known for a stable episomal maintenance in human cells. Optimal transfection condition was assessed for SNU-638 gastric cancer cell line using polyetylnimine (PEI). Maximum transfection efficiency was achieved when DNA:PEI was 1:3 (w/v). Cytotoxicities of mutant and wild type HSV-TK were compared before and after partially selecting transfected cells. The cells were sensitive to $100\;{\mu}g/ml$ hygromycin. Following GCV treatment, more cells were killed after hygromycin selection than before selection. The mutant HSV-TK showed enhanced cytotoxicity compared with the wild type HSV-TK. Our results suggest that the EBV-based plasmid encoding mutant HSV-TK may be useful to treat the diseases caused by uncontrolled cell proliferation such as cancer and rheumatoid arthritis.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.76-81
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• 2007

Inhibitory effects of methanol extracts and several solvent fractions from meju on mutagenicity in vitro genotoxicity (SOS chromotest) and growth of human cancer cells (AGS gastric adenocarcinoma and Hep 3B hepatocellular cancinoma cells) were studied. The treatment of meju methanol extracts $(100{\mu}g/assay)$ to SOS chromotest system inhibited N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced mutagenicity by 36%. However, the ethylacetate and dichloromethane fractions from meju methanol extracts showed the stronger antimutagenic effects (91% and 91%, respectively) in SOS chromotest. In sulforhodamine B (SRB) assay, the treatments of ethylacetate and dichloromethane fractions (2 mg/assay) significantly inhibited the growth of AGS and Hep 3B cancer cells by 64% and 71%, respectively. These results indicated that meju had inhibitor)r effects on MNNG in SOS mutagenic system and growth of human cancer cells, suggesting that its antimutagenic effect may be relative to activity of doenjang.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9319-9325
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• 2014

Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1903-1907
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• 2016

Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.27-33
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• 1998

Purpose : To improve the therapeutic results of postoperative recurrent disease and inoperable disease of stomach cancer, we used the thermoradiotherapy. We conducted a retrospective analysis of the results and compared the results of hyperthermia before radiotherapy and those of hyperthermia after radiotherapy Materials and Methods : From July 1994 to November 1996, we treated twenty patients with locally advanced stomach cancer and recurrent stomach cancer with thermoradiotherapy. We divided those patients into two groups : hyperthermia before radiotherapy group (PreRT group : 13 Patients) and hyperthermia after radiotherapy group (PostRT group : 7 patients). We performed radiation therapy with the total tumor dose of 3000-5040cGy in a traction of 180-300cGy and 5 fractions per week. Hyperthermia was performed with 8 MHz radiofrequency apparatus. PreRT group patients were treated daily for 30 minutes before the radiation therapy within the interval of ten minutes. And PostRT group patients were treated with 1-2 sessions Per week for 40-60 minutes after the radiation therapy within the interval of 10 minutes. Results : Overall response rate was $33.3\%$. This response rate appeared the same in both groups. Mean survival and 1 rear survival rate were 10.3 months and $16.5\%$. In PreRT group, mean survival and 1 year survival rate were 6.8 months and $9.0\%$, and in PostRT group, mean survival and 1 year survival rate were 7.7 months and $34\%$. There were no statistically significant difference between the prognostic factors and therapeutic results. Conclusion : The thermoradiotherapy was a safe treatment method in advanced and recurrent gastric cancer when compared with other treatment. Because the number of patients we treated was small and the follow up period was short. we were not able to draw any conclusions about the therapeutic efficacy of the sequence of radiation therapy and hyperthermia. Therefore, further clinical trials of thermoradiotherauy for stomach cancer appear to be warranted.