Kim, Young-Hwan;Lee, Min-Ja;Lee, Hye-Sook;Kim, Jung-Guk;Park, Won-Hwan
Journal of Physiology & Pathology in Korean Medicine
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v.25
no.1
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pp.92-99
/
2011
Topical natural antioxidants are a useful strategy for the prevention of oxidative stress mediated cardiovascular disease including atherosclerosis. From the viewpoint of this underlying principle, the screening of natural plant extracts with scavenging activity for pro-oxidant reactive species is a primary requirement for the development of new topical antioxidant formulations. Euryale ferox Salisbury (EF) is botanical name and it's pharmaceutical name is EURYALES SEMEN (ES). The stems and branchs of EF have been used as a traditional herbal medicine for the treatment of dysentery, diarrhea, leucorrhoea, incontinence and paralysis of joint. In this study, the antioxidant activity of extract from EF was studied in vitro methods by measuring the antioxidant activity and free radical scavenging activity by TEAC and DPPH, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$-induced human LDL oxidation. The EF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation. In conclusion, the EF extracts have antioxidative effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and chronic degenerative disease such as atherosclerosis.
Proceedings of the Korean Society for Bioinformatics Conference
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2000.11a
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pp.74-82
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2000
Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.
Olarte, Elizabeth Iglesias;Herrera, Annabelle Aliga;Villasenor, Irene Manese;Jacinto, Sonia Donaldo
Asian Pacific Journal of Cancer Prevention
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v.14
no.5
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pp.3191-3196
/
2013
Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.
The purposes of this investigations were survey of the occurred bacterial diseases, development of new animal health drug, guidance to formers on the treatment and control methods of diseases. Some series of investigations have been carried out by microbiological, pathological and serological examinations. The results could be summarized as follows. 1. A total of 953 cases of outbreaked swine diseases have been diagnosed in Clinical pathology laboratories, Bayer Vet Res Institute during 8 years (from 1986 to 1993). The high incidence diseases were colibacillosis, pleuropneumonia, streptococcal infection and pasteurellosis in decreasing order. 2. Pleuropneumonia caused by Actinobacillus pleuropneumoniae was the most important respiratory diseases and pasteurellosis by Pasteurella multocide could be confirmed in several cases. 3. Actinobacillus pleuropneumoniae 50 strains were isolated and identified by biochemical and serological tests. In serotyping test, 22 isolated strains were serotype 5, 21 strains as serotype 2, each 2 strains as serotype 3 and 7 by the coagglutination test. 4. Colibacillosis and edema discase caused by Escherichia coli has been the most predominant outbreaked disease in this investigations. The 100 isolates of E coli strains were sensitive to amikacin, colistin, enrofloxacin, gentamycin and trimethoprim -sulfamethoxazole. 5. Swine erysipelas caused by Erysipelothrix rhusiopathiae was confirmed 25 cases as acute septicemic forms. Isolates of E rhusiopathiae were highly sensitive to ampicillin, cephalothin, enrofloxcin, penicillin and tetracycline. 6. The 49 cases of hemorrhagic and necrotic enteritis in piglets were observed and 13 strains of Clostridium perfringens could be isolated and confirmed by biological and serological test. Isolates of Clostridium perfringens type C were highly sensitive to ampicillin, cephalothin, enrofloxacin, penicillin and trimethoprim- sulfamethoxazole. 7. The 14 strains of Streptococcus suis type II could be isolated from meningitis of piplets. 8. Polyserositis caused by Haemophilus parasuis and salmonellosis were observed and confirmed. Also Corynebacterial infections and several parasitosis have been also observed in this investigations.
The preventive hypolipidemic effect of the aqueous extracts of Picrorrhiza Rhizoma (PR) was observed in a high fat diet (HFD) feeding hyperlipidemic mouse with their hepatoprotective effects. PR extracts (50, 100 and 200mg/kg) were orally dosed once a day for 12 weeks initiated with HFD supply, and changes on body weight and gains, liver weight, serum aspartate transferase (AST) and alanine transferase (ALT) levels were monitored with serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels. The efficacy of test articles was compared to that of 10mg/kg of simvastatin (SIMVA). Dramatic decrease of both absolute and relative liver weight was dose-dependently observed in all PR extract dosing groups as compared with HFD control group. The serum AST and ALT levels were dose-dependently decreased in PR extract dosing groups. The serum LDL, triglyceride and total cholesterol levels were dose-dependently decreased in PR extract dosing groups compared to that of HFD control group. The serum HDL levels were slightly but dose-dependently increased in PR extract dosing groups as compared with control group. The efficacy on the serum lipid levels of PR extracts was slighter than that of SIMVA. Based on these results, it is concluded that water extract of PR has a relatively good favorable preventive effects on the HFD inducing hyperlipidemia and hepatopathy.
Choi, Eun Kyoung;Park, Eun Jung;Phan, Tien Thuy;Kim, Hea Dong;Hoe, Kwang-Lae;Kim, Dong-Uk
Biomolecules & Therapeutics
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v.28
no.4
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pp.370-379
/
2020
Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.
To differentiate between frozen-thawed and fresh broiler breast fillets, different methods such as optical microscopy and measurement of drip loss, pH, torrymeter and K-value were performed. A total of 10 samples of fresh and frozen-thawed breast fillets were stored in a refrigerator ($4^{\circ}C$) for 5 d. Optical microscopy of the frozen-thawed breast fillets found structural changes caused by ice crystals, which may have significantly increased drip loss compared to fresh breast fillet. The pH and K-value could not be distinguished between the two breast fillets during storage. However, the torrymeter values of the fresh and frozen-thawed breast fillets were significantly different (p<0.05). The results indicate that both optical microscopy and torrymeter measurement can be effective methods for differentiating between fresh and frozen-thawed breast fillets. However, optical microscopy may be difficult to implement in the marketplace since it requires much time and effort. Thus, the determination of the torrymeter value is the easiest and most rapid instrumental method among those tested for the differentiation of frozen-thawed chicken breast fillet from fresh one.
Journal of Physiology & Pathology in Korean Medicine
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v.21
no.2
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pp.491-497
/
2007
Hyeonggaeyeongyo-tang (HYT; Jingjielianqiao-tang), is known to be effective in lowering wind-heat blended as a pathogen of kidney. HYT has been traditionally used for the treatment of a syndrome in kidney meridian, due to invasion of pathogenic wind and heat. Nowadays, this prescription is used to treat diseases marked by excessive wind and heat in the kidney meridian, such as acute otitis media, empyema, hypertrophic rhinitis, nasal bleeding, nasal obstruction, acne and tonsillitis. The present study was conducted to evaluate the effect of HYT on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of HYT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX-2_ and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. The production of No was significantly inhibited by pre-treatment (1h) with HYT(0.1-0.3 mg/ml) on LPS-activated Raw264.7 cells. The expression of iNOS and COX-2 protein were up-regulated by LPS, but the increased levels of iNOS and COX-2 were inhibited by pre-treatment of HYT (0.3-1.0 mg/ml), respectively. And the level of interleukin-6 (IL-6), cytokine released from macrophage, was reduced by HYT pre-treatment (0.3-1.0 mg/ml). Thus, the present data suggest that HYT may play an important role in adjunctive therapy in Gram-negative bacterial infections.
The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.
Gleditsiae Semen (GS) has been used in both Korea and China as herbal medicine for the treatment of cephalalgia, catharsis, and other diseases. However, the apoptosis of GS against human cancer cells has not previously been investigated. The primary objective of this study was to determine the mechanisms inherent in GS-induced cytotoxicity and apoptosis, using methanolic extract of GS (GSE) in HT-29 human colon carcinoma cells. We found that GSE induced cytotoxicity in HT-29 cells in a dose-dependent manner, and this effect was verified via a lactate dehydrogenase release assay and a colony formation assay. In particular, HT-29 cells showed extensive cell death when treated with $50\;{\mu}g/mL$ of GSE; the calculated $IC_{50}$ value was $20\;{\mu}g/mL$. It induced characteristic apoptotic signs in HT-29 cells, including chromatin condensation and DNA fragmentation, occurring within 6-24 hr when the cells were treated at a concentration of $50\;{\mu}g/mL$. Interestingly, we detected the activation of caspase-3 and -9, but not caspase-8, and apoptotic bodies in GSE-treated HT-29 cells. Collectively, our results indicate that GSE induces apoptosis via a mitochondria-mediated apoptotic pathway, and these findings may be significant with regard to the development of a new drug for the treatment of human colon carcinoma cells.
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