Kim, Young-Sin;Choi, Se-Min;Kim, Hyung-Min;Youn, Chun-Song;Park, Kyu-Nam
Journal of The Korean Society of Clinical Toxicology
/
v.7
no.2
/
pp.113-120
/
2009
Purpose: Though caustic injury of the upper digestive tract can lead to severe sequelae, there are few clinical studies on this subject. This study was undertaken to evaluate the clinical characteristics, the endoscopic findings and the risk factors of the upper digestive lesions in patient with caustic ingestion injury. Methods: We retrospectively reviewed the medical records of 137 patients who ingested caustic materials and who visited to our emergency room from January, 2000 to June, 2009. Results: The most common ingested agent was sodium hypochlorite (44.5%), followed by acetic acid (19.7%), hydrochloric acid (11.7%) and lye (8.0%). Ingestion for suicidal attempt (62.0%) was more frequent than accidental ingestion (30.7%). Grade IIa injury was the most frequent finding on endoscopy of the esophagus and Grade 1 injury was the most frequent finding on endoscopy of the stomach. For the late sequelae, there were 9 cases (6.6%) of esophageal stricture and 2 cases (1.5%) of gastric outlet obstruction. The initial signs and symptoms did not correlate with the development of stricture, but leukocytosis, and grade III injury were related to the risk of developing stricture. Conclusion: Caustic injury of the upper gastrointestinal tract is frequently observed on early endoscopy and it can cause significant late sequelae such as stricture. Therefore, it is necessary to evaluate these patients with regular follow up endoscopic examinations for the management of late sequelae.
The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.
We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trintrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg.day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. also, colon weight as an index of tissue edema, which was mardedly increased in the IBD rats, became significantly lower after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also colon weitht as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taruine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. the taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.
Park, Jung-Soo;Ku, Jeong;Lee, Jun-Hee;Kim, Yun-Tae;Park, Jong-Hak;Ahn, Sik-Il;Mo, Jong-Hyun;Lee, Hai-Bang;Khang, Gil-Son
Journal of Pharmaceutical Investigation
/
v.38
no.2
/
pp.119-126
/
2008
Solid dispersions of poorly water-soluble drug, sibutramine, were prepared with hydrophilic polymer, poly-N-vinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC) and organic acid, citric acid, to improve the solubility of drug. Physicochemical variation and shape of microsphere were characterized by scanning electron microscopy (SEM), differential scanning calorimeter (DSC) and Fourier-transform infrared spectroscopy (FT-IR). Microspheres containing additives showed more spherical shape than non additive microspheres. In vitro release behavior of microspheres presented at simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The solid dispersion form transformed the drug into an amorphous state and dramatically improved its dissolution rate. These data suggest that the solid dispersion technique is an effective approach for developing the appetite depressant drug products and various pharmaceutical excipients are able to control the release behaviors.
Probiotics are living microorganisms that, when administered in adequate amounts, provide a health benefit to the host and are considered safe. Most probiotic strains that are beneficial to human health are included in the "Lactic acid bacteria" (LAB) group. The positive effects of probiotic bacteria on the host's health are species-specific and even strain-specific. Therefore, evaluating the probiotic potential of both wild and novel strains is essential. In this study, the probiotic characteristics of Lactobacillus brevis KT38-3 were determined. The strain identification was achieved by 16S rRNA sequencing. API-ZYM test kits were used to determine the enzymatic capacity of the strain. L. brevis KT38-3 was able to survive in conditions with a broad pH range (pH 2-7), range of bile salts (0.3%-1%) and conditions that simulated gastric juice and intestinal juice. The percentage of autoaggregation (59.4%), coaggregation with E. coli O157:H7 (37.4%) and hydrophobicity were determined to be 51.1%, 47.4%, and 52.7%, respectively. L. brevis KT38-3 produced β-galactosidase enzymes and was able ferment lactose. In addition, this strain was capable of producing antimicrobial peptides against the bacteria tested, including methicillin and/or vancomycin-resistant bacteria. The cell-free supernatants of the strain had high antioxidant activities (DPPH: 54.9% and ABTS: 48.7%). Therefore, considering these many essential in vitro probiotic properties, L. brevis KT38-3 has the potential to be used as a probiotic supplement. Supporting these findings with in vivo experiments to evaluate the potential health benefits will be the subject of our future work.
Shin, Jong-Il;Jeon, Yong-Joon;Lee, Sol;Lee, Yoon Gyeong;Kim, Ji Beom;Lee, Kyungho
Molecules and Cells
/
v.42
no.3
/
pp.252-261
/
2019
The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.
Background: Red ginseng (RG) extract, especially ginsenoside Rg1 and Rb1 fractions has been reported to have antithrombotic activities. However, gastric instability and low intestinal permeability are considered to be obstacles to its oral administration. We hypothesized that stability, permeability, and activities of RG might be improved by encapsulation within nanoparticles (NPs) prepared with antithrombotic coating materials. Methods: RG-loaded chitosan (CS) NPs (PF-NPs) were prepared by complex ionic gelation with the antithrombotic wall materials, polyglutamic acid (PGA), and fucoidan (Fu). The concentrations of PGA (mg/mL, X1) and Fu (mg/mL, X2) were optimized for the smallest particle size by response surface methodology. Antithrombotic activities of RG and PF-NPs were analyzed using ex vivo and in vivo antiplatelet activities, in vivo carrageenan-induced mouse tail, and arteriovenous shunt rat thrombosis models. Results: In accordance with a quadratic regression model, the smallest PF-NPs (286 ± 36.6 nm) were fabricated at 0.628 mg/mL PGA and 0.081 mg/mL Fu. The inhibitory activities of RG on ex vivo and in vivo platelet aggregation and thrombosis in in vivo arteriovenous shunt significantly (p < 0.05) increased to approximately 66.82%, 35.42%, and 38.95%, respectively, by encapsulation within PF-NPs. For an in vivo carrageenan-induced mouse tail thrombosis model, though RG had a weaker inhibitory effect, PF-NPs reduced thrombus significantly due to the presence of PGA and Fu. Conclusion: PF-NPs contributed to improve the activities of RG not only by nanoencapsulation but also by antithrombotic coating materials. Therefore, PG-NPs can be suggested as an efficient delivery system for oral administration of RG.
This study aimed to evaluate the potential allergenicity and oral toxicity of the phosphinothricin acetyltransferase (PAT) protein expressed in Zoysia japonica, a herbicide-tolerant genetically modified (GM) zoysiagrass. In silico analysis of PAT showed no similarities with any known allergenic or toxic proteins, with <35% amino acid sequence homology with known allergens across a length of 80 amino acids and no continuous eight amino acid identity with known allergens. The PAT protein expressed in Z. japonica degraded very rapidly in the simulated gastric fluid in the presence of pepsin, and, no glycosylation of PAT was observed. The oral toxicity test revealed no mortality or toxic effect in mice following PAT administration at 4,000 mg/kg body weight. Our findings indicate that the PAT protein expressed in Zoysia japonica does not exhibit allergenic or toxic properties.
Jong-Min Park;Young-Min Han;Migyeong Jeong;Eun Jin Go;Napapan Kangwan;Woo Sung Kim;Ki Baik Hahm
Journal of Digestive Cancer Research
/
v.4
no.1
/
pp.1-9
/
2016
The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.
Kim, Byoung-Mok;Jung, Jee-Hee;Lim, Ji-Hoon;Jung, Min-Jeong;Jeong, Jae-Whung;Choi, Yong-Suck;Sim, Jea-Man;Jeong, In-Hak;Kim, Young-Myoung
Journal of the Korean Society of Food Science and Nutrition
/
v.44
no.6
/
pp.862-873
/
2015
In this study, we investigated the physiochemical properties and biological activities of Gangwon-do endemic Makjang (MJ) products (12 types). The pH levels of all samples were in the range of 4.43 to 5.69, and MJ5 showed the highest pH (5.69). The salinities of all samples ranged from 11.1% to 16.9%. Hunter color values for L (lightness), a (redness), and b (yellowness) ranged from 26.2 to 36.9, 3.9 to 11.5, and 6.5 to 16.6, respectively. The amino nitrogen content of MJ2 was highest, whereas the total content of free amino acids of MJ11 (4,657.7 mg%) was highest. Total fatty acid contents of all samples ranged from 1,598.6 mg% to 2,874.4 mg%, with MJ10 showing the highest fatty acid content. The content of total polyphenolic compounds ranged from 401.48 to $746.67{\mu}g$ tannic acid equivalent/mL, with MJ11 showing the highest content. The 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) radical scavenging effects of MJ11, MJ8, and MJ4 were 51.30% and 82.5%, 41.29% and 67.0%, and 49.88% and 87.7%, respectively. MJ12 showed the strongest growth inhibitory effect on lung cancer A549 cells, whereas MJ5 showed the strongest growth inhibitory effect on AGS gastric cancer cell and MCF-7 breast cancer cell. MJ7 showed greater lipid accumulation inhibitory activity in HepG2 cells than the others. ACE inhibitory activity of MJ11 was the highest among the samples.
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