• Journal of Gastric Cancer
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• 제13권4호
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• pp.232-241
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• 2013

Purpose: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. Materials and Methods: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. Results: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. Conclusions: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.

• 대한약침학회지
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• 제17권3호
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• pp.40-49
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• 2014

Objectives: The gastric ulcer is a common disorder of the stomach and duodenum. The basic physiopathology of a gastric ulcer results from an imbalance between some endogenous aggressive and cytoprotective factors. This study examined whether Ganoderma lucidum pharmacopuncture (GLP) would provide protection against acute gastric ulcers in rats. Methods: Sprague-Dawley rats were divided randomly into 4 groups of 8 rats each: normal, control, normal saline (NP) and GLP groups. The experimental acute gastric ulcer was induced by using an EtOH/HCl solution and the normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated once with injections of saline and GLP, respectively. Two local acupoints were used: CV12 (中脘) which is the alarm point of the Stomach Meridian, and ST36 (足三里), which is the sea point of the Stomach Meridian. The stomachs from the rats in each group were collected and analyzed for gross appearance and histology. Also, immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$ was performed. Results: Histological observations of the gastric lesions in the control group showed comparatively extensive damage of the gastric mucosa and necrotic lesions had penetrated deeply into the mucosa. The lesions were long, hemorrhagic, and confined to the glandular portions. The lesions were measured microscopically by using the clear depth of penetration into the gastric mucosal surface. The length and the width of the ulcer were measured and the inhibition percentage was calculated. Wound healing of the acute gastric ulcer was promoted by using GLP, and significant alterations of indices in gastric mucosa were observed. Such protection was shown by gross appearance, histology and immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$. Conclusion: These results suggest that GLP administered at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol-induced acute gastric ulcer.

• 대한약침학회지
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• 제18권1호
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• pp.72-78
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• 2015

Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP) on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP) and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘) and ST36 (足三里) were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX), B-cell lymphoma 2 (Bcl-2) and Transforming growth factor-beta 1 (TGF-${\beta}1$). Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

• Journal of Cancer Prevention
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• 제22권1호
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• pp.33-39
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• 2017

Background: MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods: Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n = 8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results: A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions: miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권sup1호
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• pp.83-92
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• 2008

Helicobacter pylori is the causative agent of chronic gastritis and has a role in the pathogenesis of peptic ulcer diseases, and gastric cancer. There have been reports suggesting a close link between these gastroduodenal disorders and a state of vitamin C deficiency. In this paper, the past, present and future perspectives on H. pylori infection and vitamin C will be discussed under the following view points. Since the ecological niche of H. pylori is the mucus layer and intercellular junctions of the gastric epithelium, the various kinds of host inflammatory cells motivated by the local and systemic immune responses cannot eliminate the microorganisms. When the invading foreign body is not removed, despite full activation of defense mechanisms, adverse consequences of the immune responses develop on the host gastric mucosa. The reasons for the body vitamin C depletion could be explained as follows; 1) the increased vitamin C consumption by increased oxygen free radical production through the prolonged hypersensitivity reactions in the gastric mucosa, 2) the increased vitamin C oxidation by the nitrite which is formed from nitrate reduction by the intragastric bacteria proliferated in the hypochlorhydric gastric cavity, 3) the strong ${\gamma}$-glutamyltranspeptidase activity of H. pylori which depletes the glutathiones in gastric mucosa. Depletion of glutathiones in the stomach favors irreversible oxidative destruction of ascorbic acid. Both persistent inflammatory burdens in the stomach by H. pylori and resultant vitamin C depletions synergistically and uninhibitedly might aggravate the hypothetical sequence of gastric carcinogenesis: atrophic gastritis${\rightarrow}$intestinal metaplasia${\rightarrow}$dysplasia${\rightarrow}$gastric adenocarcinoma. High intake of vitamin C could reverse the hypothetical sequence of the gastric carcinogenesis via direct and indirect effects on H. pylori and host-parasite relationships.

• Clinical Endoscopy
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• 제55권1호
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• pp.136-140
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• 2022

Eradication of Helicobacter pylori is the first-line treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphomas; however, lesions may persist in 20% of patients after initial treatment, thereby necessitating the use of an additional therapeutic approach. Other treatment options include radiation therapy, chemotherapy, endoscopic resection, rituximab therapy, or watchful waiting. We present a case of localized gastric MALT lymphoma that did not respond to H. pylori eradication therapy. The patient waited for 12 months but the tumor showed no signs of regression endoscopically. Histologic examination revealed residual MALT lymphoma. The tumor was then successfully treated using endoscopic submucosal dissection and the patient remained disease-free for 4 years. To our knowledge, this is the first case in which a gastric MALT lymphoma was treated with endoscopic submucosal dissection. In conclusion, endoscopic resection may be recommended as second-line therapy for properly selected patients with gastric MALT lymphoma as it is effective and minimally invasive.

• Journal of Nutrition and Health
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• 제30권8호
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• pp.920-929
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• 1997

This study examined the effect of dietary salt levels on the incidence and cure of gastric ulcer in rats. Two sets of experiment were conducted . In the first experiment, the rats were divided into 3 groups. The 3 groups were fed 0%, 4%, and 8% NaCl diets respectively for 20days. The rats were given water -immersion restraint stress at the end of the dietary period , and sacrificed. The ulcer index by histological test was higher in rats fed the 8% NaCl diet than those in the other groups. The hexosamine and glutathione levels were significantly lower in the rats fed the 8% NaCl diet. Hematocrit and total iron binding capacity(TIBC) showed lower values caused by bleeding of gastric mucosa. The second experiment was designed to determine the effect of soldium concentration on the cure of gastric ulcer . As the gastric ulcer was recovered, ulcer length was gradually deceased in the control group but not changed in the 8% NaCl diet group. The gastric hexosamine and hepatic glutathione were increased in the control group but decreased in the 8% NaCl diet group. The hematologic indices of stressed rats showed the same tendency. As a result, dietary salt per se did not cause gastric ulcer . Once an ulcer is formed by stress or any other factor, higher levels of dietary salt may be detrimental to gastric mucosa, thereby delaying the healing of the ulcer. It is recommended that dietary salt intake be reduced in stress-prone people.

• 대한한방내과학회지
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• 제40권4호
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• pp.697-708
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• 2019

Objective: The aim of this study was to introduce gastric dysmotility as a common cause in patients with concurrent functional dyspepsia and chronic atrophic gastritis. Method: Dyspeptic symptoms, the Rydoraku score, gastric motility (electrogastrography, bowel sound analysis), gastric mucosa (gastroendoscopy), and blood and blood chemistry were all evaluated. For the treatment method, Pyengwi-san (solution) and Banwhasashim-tang (extract) were used as herbal drugs. Both ST36 electrical stimulation and simple immersion stimulation of CV11, 12, and 13 in the abdomen were applied. Results: Dyspeptic symptoms including indigestion, headache, and insomnia were all relieved. Gastric myoelectrical activity and gastric pyloric function were additionally improved. The condition of the gastric mucosa was changed from atrophic to erosive. Other side-effects of the treatment were not noted. Conclusion: The traditional Korean treatment showed effectiveness in the relief of dyspeptic symptoms and mucosal improvement of chronic atrophic gastritis. Gastric dysmotility is a common cause of the condition being concurrent with both functional dyspepsia and chronic atrophic gastritis without Helicobacter pylori infection.

• Natural Product Sciences
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• 제26권4호
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• pp.268-278
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• 2020

In this study, we investigated the chemical profile and effects of RW0117 (Artemisia argyi 65 .5 % ethanol extract) on gastric lesions in rats. We optimized and validated a method to obtain the chemical profile of RW0117. We then investigated the antioxidant and anti-inflammatory effects in vitro, and the protective effects on gastric lesions in vivo. The IC50 of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging considering the antioxidant effects of RW0117 was 166.55 ㎍/mL, and the IC50 of nitric oxide scavenging considering the anti-inflammatory effects was 41.16 ㎍/mL. Oral administration of RW0117 at lower concentrations (25, 50, 100 mg/kg) had similar or greater effects than the daily intake conversion concentration (115mg/kg) of a health functional food (Avexol®) in the acetic acid-induced ulcer and the ethanol-induced gastric injury rat models. In addition, oral administration of RW0117 increased the expression of prostaglandin E2, which enhances the protective effect in the gastric mucosa in the ethanol-induced gastric injury rat model. These results suggest that RW0117 may have potential therapeutic uses in the protection of the gastric mucosa.

• Journal of Ginseng Research
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• 제25권4호
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• pp.141-149
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• 2001

The effect of ginseng on gastric ulcer and gastric acid secretion was investigated in pylorus-ligated rats. Methods: Sprague-Dawley strain rats were used after 24 hours fast. Pylorus-ligation was performed under light ether anaesthesia, then gastric mucosal damage was evoked in conscious pylorus-ligated rats by the administration of subcutaneous (s.c.) indomethancin (20mg/kg), s.c. histamine (150mg/kg) or by pylorus-ligation (Shay ulcer). Ginseng was given by intragastric (i.g.) or intraperitoneal (i.p.) route simultaneously with the ulcerogens. Rats were killed after 3h (indomethacin) and histamine models) or after 18h (Shay ulcer), when the gastric secretory responses, the number and severity of gastric mucosal lesions and mucosal mucus content deetermined. the effect of i.p. ginseng on basal gastric acid secretion and on gastric acide secretion in indomethacin (20mg/kg, s.c.)-treated rats was also investigated in urethane anesthetized rats. Gastric acid secretion was measured by flushing of the gastric lumen with saline every 15min through an oesophageal cannula. Results: In conscious pylorus-ligated rats, i.g. ginseng(12.5-50mg/$m\ell$; 50-200mg/kg) protected against gastric mucosal lesions evoked by s.c. indomethacin or s.c. histanmine in the d3-h pylorus-lighted rat, withoutmodifying gastric acid secretory responses. Ginseng given i.p. (150 or 200mg/kg) did not reduce the gastric lesions produced by histamine or by ligating the pylorus (Shay ulcer) Ginseng given orally in 50mg/$m\ell$ (200mg/kg) increased gastric mucus secretion in saline- and indomethacin-treated conscious pylorus-ligated rats. In anaesthetized rats ginseng (50 or 200mg/kg) did not modify basal gastric acid secretion or gastric acid secretion in the indomethacin-treated rats. Conclusions: ginseng given orally exerts gastroprotective effects in the rat stomach. Such anti-ulcer effect does not involve changes in gastric acid secretory responses. In addition, ginseng possesses stimulatory effect on gastric mucus secretion, which could be one mechanism by which the compound exerts its antiulcer effect. Our data are in favor for a beneficial effect for topically applied ginseng on the gastric mucosa.