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α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

  • Kim, Myoungjae;Chin, Young-Won;Lee, Eun Joo
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.609-617
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    • 2017
  • Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

Adsorption of Heavy Metal Ions by Constituents of Bark (수피조성분에 의한 중금속 흡착)

  • Paik, Ki-Hyon;Choi, In-Gyu;Shin, Keum
    • Journal of the Korean Wood Science and Technology
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    • v.24 no.3
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    • pp.51-56
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    • 1996
  • The Bark lignin(alkali- and acid lignin), bark extractives(hot water-and $Na_2SO_3$ extractives) of Quercus acutissima and Pinus densiflora, and flavonoids were used to detect heavy metal adsorption. The adsorption ratio of heavy metals by lignin was assigned for 40 to 50%, but was not dependent on lignin kinds. However, in case of the addition of light metals such as $Ca^{++}$ and $Mg^{++}$ to lignin the adsorption ratio was increased by 20 to 40%, and $Pb^{++}$ was almost completely adsorbed. On hot water extractives, the adsorption ratio was very low because the substrate was water-soluble, so the substrate should be water-insoluble to adsorb the heavy metals. However, the adsorption ratios of $Cd^{++}$ and $Pb^{++}$ on $Na_2SO_3$ extractives were significantly increased, while those of $Zn^{++}$ and $Cu^{++}$, were similar to lignin. When four kinds of heavy metals were treated to $Na_2SO_3$ extractives together, more than 97% of $Pb^{++}$ and $Cu^{++}$ was adsorbed_ and $Zn^{++}$ was more adsorbed by 40%, and $Cd^{++}$ was not changed, comparing with the case that on kind of heavy metal was treated. There were differences between adsorption ratio of the kinds of flavonoids and heavy metals, and the adsorption ratio of heavy metals was assigned to 20 to 45% per 0.1g flavonoid.

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Quercetin, A Bioflavonoid, Protects Against Oxidative Stress-related Gastric Mucosal Damage in Rats

  • Rao, Ch.V.;Ojha, S.K.;Govindarajan, R.;Rawat, A.K.S.;Mehrotra, S.;Pushpangadan, P.
    • Natural Product Sciences
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    • v.9 no.2
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    • pp.68-72
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    • 2003
  • Quercetin and its sugar conjugates are the most abundantly distributed bioflavonoids and represent the largest proportion of flavonols in the plant kingdom. The present study was undertaken to demonstrate the effect of quercetin on the role of reactive oxygen species (ROS) in the development of gastric ulcers in rats. Administration of quercetin in doses of 50, 100 and $200\;mg\;kg^{-1}$ twice daily for 5 days, showed dose dependent significant protection against ethanol (EtOH), aspirin (ASP), cold-restraint stress (CRS) and pylorus ligation (PL) -induced gastric ulcer models and the results were comparable with those elicited by sucralfate. The thiobarbituric acid reactive substances in the stomach mucosa, an index of lipid peroxidation and regulation of plasma corticosterone were significantly increased in CRS-induced gastric ulceration. The queroetin $(100\;mg\;kg^{-1})$ and reduced glutathione effectively inhibited gastric lesions induced by CRS with a significant decrease in the lipid peroxidation and plasma corticosterone. These results indicate that quercetin a bioflavonoid exerts its antiulcer effect in light of free radical scavenging and plasma corticosterone in cold restraint stress ulcers.

Iontophoresis Enhances Transdermal Delivery of Methylene Blue in Rat Skin (I): The Effect of Current Application Duration

  • Lee, Jae-Hyoung;Choi, Eun-Young
    • The Journal of Korean Physical Therapy
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    • v.23 no.6
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    • pp.77-84
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    • 2011
  • Purpose: The objectives of this study were to determine the enhancing effect of iontophoresis method as it transdermally deliver methylene blue (MB) using visual examination, in terms of penetration depth and tissue distribution in the skin, and to determine the effect of application duration on the efficacy of iontophoresis. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into 5-, 10-, 20-, and 40-minute groups. These rats were exposed to either topical or anodic iontophoresis of 1% MB using a direct current of $0.5mA/cm^2$ for 5, 10, 20, and 40 minutes. Using cryosections of rat tissues, the penetration depth of MB was measured using light microscopy. Results: Significant differences in the penetration depth (F=54.20, p<0.001) were detected among the four groups. Post hoc comparisons of the penetration depth of MB data pooled across groups showed no significant difference between all topical application groups and 5-minute iontophoresis group, but did reveal a significant difference in the penetration depth between all topical application groups and 5-minute iontophoresis group versus 10-minute group, between the 10-minute and 20-minute group, and between the 20-minute and 40-minute iontophoresis group (p<0.05). Conclusion: The results demonstrate that iontophoresis enhances transdermal delivery of MB across stratum corneum of skin barrier by visual examination. Furthermore, the penetration depth of iontophoretic transdermal delivery of MB was dependent on the application duration. The duration of iontophoresis is one of the important factor in the efficacy of iontophoresis application.

Apoptosis and Autophagy Induction of A549 Human Lung Cancer Cells by Methylene Chloride Extracts of Morus alba L. (A549 인체폐암세포에서 상백피 메틸렌클로라이드 추출물에 의한 Apoptosis 및 Autophagy 유발)

  • Park, Shin-Hyoung;Chi, Gyoo-Yong;Choi, Yung-Hyun;Eom, Hyun-Sup
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.942-949
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    • 2010
  • Morus alba L., a kind of Oriental medicinal herbs, has been traditionally used to treat pulmonary asthma and congestion. According to recent studies, extracts of M. alba L. have showed anti-inflammatory, anti-oxidant, anti-tumor and hypoglycemic effects. However, the molecular mechanisms on how it acts as a death-inducer in cancer cells have not been fully understood. In this study, we investigated the cell death effects of methylene chloride extracts of M. alba L. (MEMA) in A549 human lung carcinoma cells. It was shown that MEMA induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. MEMA treatment induced the expression of death receptor-related proteins such as death receptor (DR) 4, DR5, Fas and FasL, which further triggered the activation of caspase-8 and the cleavage of Bid in a concentration-dependent manner. However, MEMA reduced anti-apoptotic Bcl-2 and Bcl-xL expression which contributed to the loss of mitochondrial membrane potential (MMP), and the activations of caspase-9 and caspase-3. Meanwhile, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in MEMA-treated cells. Furthermore, markers of autophagy, namely, the increased MDC-positive cells, conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Taken together, these findings demonstrated that MEMA triggered both autophagy and apoptosis in A549 cancer cells. They might suggest that M. alba L. could be a prospective clinical application to treat human lung cancers.

Prevalence of Malaria in Pregnant Women in Lagos, South-West Nigeria

  • Agomo, Chimere O.;Oyibo, Wellington A.;Anorlu, Rose I.;Agomo, Philip U.
    • Parasites, Hosts and Diseases
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    • v.47 no.2
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    • pp.179-183
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    • 2009
  • Prevalence rates reported for malaria in pregnancy in Nigeria vary considerably. The accuracy of results of malaria diagnosis is dependent on training, experience, and motivation of the microscopist as well as the laboratory facility available. Results of training programmes on malaria microscopy have shown low levels of sensitivity and specificity of those involved in malaria diagnosis routinely and for research. This study was done to ascertain the true prevalence of malaria in pregnancy in Lagos, South-West Nigeria. A total of 1,084 pregnant women were recruited into this study. Blood smears stained with Giemsa were used for malaria diagnosis by light microscopy. Malaria infection during pregnancy presents mostly as asymptomatic infection. The prevalence of malaria in this population was 7.7% (95% confidence interval; 6.2-9.4%). Factors identified to increase the risk of malaria infection include young maternal age (<20 years), and gravidity (primigravida). In conclusion, this study exposes the over-diagnosis of malaria in pregnancy and the need for training and retraining of laboratory staffs as well as establishing the malaria diagnosis quality assurance programme to ensure the accuracy of malaria microscopy results at all levels.

Effect of Soil Heating and Lateral Branching in White Spined Cucumbers (지중가온이 백침계 오이의 측지 발생에 미치는 영향)

  • Sang Gyu Lee;Ki Cheol Seong;Kwan Dal Ko;Kwang yong Kim
    • Journal of Bio-Environment Control
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    • v.10 no.3
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    • pp.155-158
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    • 2001
  • The cultivation area of white spined cucumbers for export has continuously increased up to 121 ha in 2000. Since white spined cucumbers set fruits on lateral shoots, fruit yield is dependent upon the development of lateral shoots. Unfortunately, the major cultivation period is during winter season, October to February, when temperature and light are limited for the development lateral shoots. This experiment was conducted to investigate the effect of soil heating on the development of lateral shoots in white spined cucumbers. Number of lateral shoots were 13.7 and 11.7 in the soil heated treatment and in the control, respectively. Number of marketable fruits per plant was 45 in the soil heated treatment as compared to 38 in the control. Fruit yield was 81 ton per ha, an 18% increase, in the soil heated treatment. Soil heating not only increased number of long lateral shoots but also decreased curved fruits.

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A Study on the Industry Food Service Management Practice in Chonbuk Province (산업체 단체급식소의 급식관리실태에 대한 조사연구)

  • 유정희
    • Korean journal of food and cookery science
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    • v.9 no.2
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    • pp.109-115
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    • 1993
  • This study was attempted to investigate the current status of industry food service management in Chonbuk province. The survey for the analysis was conducted through the questionaires to dietitian. The following results are to be noted. 1. Only one dietitian was employed regardless of feeding numbers and feeding times, and the average number of cooks comes to 5∼6 persons. Among 51 food service places for the study, 84.3% provided more than two meals a day. Feeding number were 200∼1000 people per one meal (64.7%) and feeding cost amounts to 700∼1000 won per meal per one person. 2. The food preferences and budget were primary considerations in menu planning. The type of menus was a non-selective menu with a seven-day cycle (83.7%). Most of dietitian (94.1%) had control of food purchasing, receiving and checking procedure and prefered placing orders by phone (94.5%) through the purveyors (86.4%). 3. In many food service places (70.5%), the mass food preparation was controlled of cooking method and standardized recipes were not undertaken by management Also, the food quality control such as flavor, texture, appearance and temperature was not fully established in food service system. 4. They used the method of manual dish washing operations (88%) and about 71.4% of them are dependent on boiling method of ultrabiolet light for disinfection of kitchen utensils. 5. The performance rates of dietitian management responsibility showed as nutritional management 100%, working management 72.4%, sanitary management 85.6%, personnel management 64.5% and nutrition education 40.7%, but they did not perform the objective and systematic their own responsibility as specialized dietitian because only few dietitian used basic check list and management tools. In addition, dietitian (21.6%) worked beyond their field. In the result, only 54.9% dietitian have satisfied their own occupation and most of them emphasized on practical working in educational curriculums.

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The Impacts of Private Health Insurance on Medical Institution Selection: Evidence from Outpatient Service Utilization among Arthritis Patients (민간의료보험이 의료기관 종별 선택에 미치는 영향: 관절염 환자의 외래 이용을 중심으로)

  • You, Chang Hoon;Kang, Sungwook;Choi, Ji Heon;Kwon, Young Dae
    • Korea Journal of Hospital Management
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    • v.22 no.2
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    • pp.58-69
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    • 2017
  • Recently, with the increase in the number of private health insurance subscribers, interest in overuse of the medical service is increasing. This study analyzed the impacts of private health insurance (PHI) on medical institution selection in outpatient service utilization among persons with arthritis. In order to control patients' health status, we extracted outpatient episodes with the same disease (KCD6, M13) from Korea Health Panel. The unit of analysis was an outpatient visit with arthritis in 2014 (n=23,363). In the light of insurance coverage, we redefined three type of private health insurance (ex, indemnity, fixed benefit, and non-insured) as a test variable and two type of medical institution (ex, hospital and physician visit) as a dependent variable. We conducted a probit regression analysis to identify the impacts of PHI on medical institution selection controlling for heteroscedasticity. The results of this study showed that the insured with indemnity were more likely to choose hospital departments than clinics (marginal effect=0.0475, p=0.000). The impact of participation of fixed benefit PHI was not as clear as that of indemnity type (marginal effect=0.0162, p=0.047). In conclusion, this study confirmed that PHI, particularly indemnity type has a significant impact on the selection of medical institutions. Healthcare policy makers should consider that PHI not only affects the overall quantitative increase in healthcare utilization, but also influences the selection of medical institutions.

The Srudy on the Relationship between blood Cyclosporin A level and Gingival Overgrowth in rats (Cyclosporin A 혈중농도와 백서 치은증식과의 관계)

  • Chung, Chan-Gill;Chung, Hyun-Ju
    • Journal of Periodontal and Implant Science
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    • v.28 no.1
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    • pp.71-86
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    • 1998
  • The purpose of this study was to evaluate clinically and histopathologically the effects to the periodontal tissue in rats after Cyclosporin A (CsA) administration and to determine whether there is a relationship between dosage of CsA or blood CsA level and the seventy of gingival overgrowth in rats. Twenty 6-week-old Sprauge-Dawley Fats were randomized into 4groups. The control group received olive oil only and the test group received daily CsA in olive oil via gastric feeding for 6weeks at a 3,10, and 30mg/kg. Rats were weighed to evaluate the systemic effect of drug and stone models were made from alginate impressions of upper and lover anterior region at 2 week interval. On completion of offal CsA administration, blood were collected and blood CsA levels were quantitated by TDxFLx analyzer. Rats were sacrificed an6 their upper and lower jaws were removed together with the surrounding gingiva and soft tissue for light microscopic examination. The results were as follows : 1. The weight gain of GsA-treated rats was much less than of the control group and central incisors were gradually displaced and separated in the test groups. 2. The extensive fibrovascular proliferation and scattered inflammatoy infiltrates in an edematous stroma were observed in enlarged gingiva of CsA-treated rats. 3. The increase in buccolingual, mesiodistal dimension of the anterior teeth and vertical height of the interdental papilla showed dose-dependent manner in CsA-treated rats. 4. Significant positive correlation exists between blood CsA level and the severity of gingival overgrowth in anterior teeth. This result indicates that the severity of gingival enlargement in CsA treated rats is correlated with dosage of CsA administration and blood CsA level.

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