• Title/Summary/Keyword: Induced resistance

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Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway

  • Choi, Eun-Ok;Cho, Eun-Ju;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Hwang, Hye-Jin;Moon, Sung-Kwon;Son, Chang Gue;Kim, Wun-Jae;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.213-221
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    • 2017
  • Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

Effects of Dietary Supplementation of a New Probiotic CS61 Culture on Performance in Broiler Chickens (새로운 생균제 CS61 배양액의 사료 내 급여가 육계의 생산성에 미치는 영향)

  • Kim, Sung-Hwan;Lee, In-Chul;Baek, Hyung-Seon;Kang, Seong-Soo;Kim, Hyoung-Chin;Yoo, Jin-Cheol;Kim, Jong-Choon
    • Journal of Life Science
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    • v.22 no.3
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    • pp.340-346
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    • 2012
  • Bacterial resistance to antibiotics and residues of antibiotics in poultry products have encouraged the use of probiotics, prebiotic substrates, and synbiotic combinations of prebiotics and probiotics as alternative approaches to the use of antibiotics in poultry. The present study was carried out to evaluate the effect of a new probiotic CS61 culture on growth performance, feed conversion efficiency, and safety in broiler chickens, and to evaluate its value as an alternative for antibiotics used as a feed additive. Two dosages of CS61 culture (0.1% and 1%) were fed to chickens for 28 days. The results showed that terminal body weight and daily weight gain in the treatment groups increased in a dose-dependent manner when compared with the control group. Dietary supplementation with CS61 culture also improved feed conversion rate compared to the control group. There were no treatment-related toxic effects in terms of clinical findings, mortality, necropsy findings, hematology, or serum biochemistry parameters in any group tested. The nitric oxide assay showed that CS61 peptide has a dose-dependent inhibitory effect on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. The results of this experiment indicated that dietary supplementation of CS61 culture may improve growth performance and feed conversion efficiency in chickens through its anti-inflammatory effect.

Gene Promoter Variation of Phosphoglycerate Kinase, a Glucose Metabolism Enzyme, is a Biomarker for Selection of Disease-resistant Sea Squirt, Halocynthia Roretzi (당 생합성 효소 PGK 유전자 프로모터 변이와 물렁증 저항성 멍게의 선별)

  • Cho, Hyun Kook;Hur, Young Baek;Cheong, Jae Hun
    • Journal of Life Science
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    • v.23 no.2
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    • pp.190-196
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    • 2013
  • The sea squirt, Halocynthia roretzi, has experienced mass mortality due to softness syndrome. The identification of disease-induced genes can provide insights into the development of this syndrome. To identify the genes, we performed differentially expressed gene (DEG) analysis. The expression of the phosphoglycerate kinase (HrPGK) gene was significantly decreased in diseased sea squirts compared to normal ones. We confirmed the result of the DEG analysis through RT-PCR and real-time PCR. In addition, we detected single nucleotide polymorphisms at position -106 (A/T) and -254 (G/T) in the HrPGK gene promoter by genotyping analysis. At the -106 site of the HrPGK gene, the frequency of the AA allele in disease-resistant sea squirts was about two-fold higher than that of sensitive ones, and the frequency of the TT allele in the disease-resistant sea squirts was about six-fold lower. At the -254 site of the HrPGK gene, the frequency of the GT and the GG allele was approximately two-fold higher and two-fold lower, respectively, in the disease-resistant sea squirts compared to the disease-sensitive ones. Analysis of the relationship between the genotypic variation at the -106/-254 promoter and the expression of HrPGK mRNA showed that HrPGK mRNA expression was higher in the -106/-254 AA/GT genotype samples than in the -106/254 TT/GG genotype ones. These results show that sea squirts harboring the AA/GT genotype may have more resistance to mortality than the sea squirts with other genotypes.

Effect of Dietary Herb Medical Stuff on the Non-specific Immune Response of Nile Tilapia, Oreochromis niloticus (나일틸라피아, Oreochromis niloticus의 비특이적 면역반응에 대한 생약재 투여 효과)

  • Hwang, Mi-Hye;Park, Soo-Il;Kim, Yi-Cheong
    • Journal of fish pathology
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    • v.12 no.1
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    • pp.7-15
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    • 1999
  • In order to investigate the immune response induced by supplementation of herb medical stuff in diet on the nile tilapia. Oreochromis niloticus, experiments were performed with feeding of four different experimental diets supplemented with 2% ginseng. Panax ginseng, 3% Kugija. Lycium chinense, 3% Hasuo, Polygonum multiflorum, 2% Omija, Schizandra chinensis, respectively, for 84 days. The non-specific immune responses changed during the feeding period were investigated at 2, 4, 6, 8, 10, 12 weeks in each group. Average body weight of the nile tilapia with supplemented diets was heavier than control group. The fish fed on diet supplemented with 3% Kugija showed the better growth than the other tested groups. Complement activity such as complete hemolytic activity ($CH_{50}$) and bactericidal activity against Escherichia coli tended to be increased by the supplementation of herb medical stuff. The lysozyme activity of serum and adherent phagocyte activity showed higher in the fish fec on diet supplemented with 3% kugija than the other tested groups. In respect to the RPS against experimental Edwardsiella tarda infection, all of the group fed on the herb medical stuff in diet appeared higher response compared with control group. From these results, herb medical stuff (Panax ginseng, Lycium chinense. Polygonum multiflorum, Schizandra chinensis) might be used a additives of diet for the increasing of non-specific immune response or resistance against bacterial fish diseases.

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Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

  • Zhou, Da;Chen, Yuan-Wen;Zhao, Ze-Hua;Yang, Rui-Xu;Xin, Feng-Zhi;Liu, Xiao-Lin;Pan, Qin;Zhou, Huiping;Fan, Jian-Gao
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.2.1-2.12
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    • 2018
  • Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

Estimation of Shear Plane at Failed Landfill Using Field and Laboratory Tests (현장 및 실내실험을 이용한 매립지 전단활동면 추정에 대한 연구)

  • Choi, Hoseong;Kim, Tae-Hyung;Kim, Sung-Wook
    • The Journal of Engineering Geology
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    • v.29 no.3
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    • pp.315-327
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    • 2019
  • Back analysis has been used to evaluate the factor of safety and circular failure plane at the landfill failure site. However, the estimated circular failure plane by back analysis is quite different from what is observed in the field. Thus, this study was conducted to estimate an actual shear failure plane inside the ground which gives a more accurate failure plane. Cone penetration test (CPT), boring test, soft X-ray image scan, density logging, and ultrasonic logging were conducted at the field and laboratory. The result of CPT showed significantly lower cone resistance, pore pressure, and undrained shear strength at a particular part. This part is a possible shear failure plane inside the ground. To validate, the soft X-ray scan images were analyzed and found the disturbed (inclined) bedding plane induced by shear activity at the estimated shear failure plane. Density and ultrasonic logging tests also found a similar result. Thus, the method in this study is possible to estimate the shear failure plane inside the ground.

Dichloroacetate Inhibits the Proliferation of a Human Anaplastic Thyroid Cancer Cell Line via a p53-independent Pathway (Dichloroacetate의 p53 비의존적 경로를 통한 인간 역분화 갑상선 암세포주의 성장억제 효과)

  • KC, Yam Bahadur;Poudel, Sunil;Jeon, Eon Ju;Shon, Ho Sang;Byun, Sung June;Jeoung, Nam Ho
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1469-1476
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    • 2018
  • Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.

A Study on the Ventilation Effects of the Shaft Development at a Local Limestone Mine (국내 석회석 광산 수갱 굴착에 의한 통기효과 분석 연구)

  • Lee, Changwoo;Nguyen, Van Duc;Kubuya, Kiro Rocky;Kim, Chang O
    • Tunnel and Underground Space
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    • v.28 no.6
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    • pp.609-619
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    • 2018
  • This study was carried out at a local limestone mine to analyze the ventilation efficiency of the shaft equipped with a main fan. The results show that its ventilation efficiency is clearly verified for the natural as well as the mechanical ventilation. The airflow rate of $11.7m^3/s$ was induced by the natural ventilation force and the maximum quantity is almost same as the airflow rate estimated by monitoring the average temperatures in the upcast and downcast air columns. Meanwhile, the airflow rate exhausted by the main fan through the shaft was $20.3{\sim}24.8m^3/s$; variation of the quantity was caused by the upward shift of the mine ventilation characteristic curve due to the frequent movement of the equipment. This indicates efforts are required to reduce the ventilation resistance and raise the quantity supplied by the main fan. The turbulent diffusion coefficients along the 1912 m long airway from the portal to the shaft bottom was estimated to be $15m^2/s$ and $18m^2/s$. Since these higher coefficients imply that contaminants will be dispersed at a faster velocity than the airflow, prompt exhaust method should be planned for the effective air quality control. The ventilation shaft and main fan are definitely what local limestone mines inevitably need for better working environment and sustainable development.

α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

  • Ittiudomrak, Teeranai;Puthong, Songchan;Roytrakul, Sittiruk;Chanchao, Chanpen
    • Toxicological Research
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    • v.35 no.2
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    • pp.167-179
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    • 2019
  • Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ${\alpha}$-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ${\alpha}$-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ${\alpha}$-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ${\alpha}$-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ${\alpha}$-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ${\alpha}$-mangostin and apigenin arrested the cell cycle at the $G_2/M$ phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ${\alpha}$-mangostin-treated SKOV-3 cells, respectively. ${\alpha}$-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ${\alpha}$-mangostin likely being involved with inflammation.

Effects of types of bridge decks on competitive relationships between aerostatic and flutter stability for a super long cable-stayed bridge

  • Hu, Chuanxin;Zhou, Zhiyong;Jiang, Baosong
    • Wind and Structures
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    • v.28 no.4
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    • pp.255-270
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    • 2019
  • Aerodynamic configurations of bridge decks have significant effects on the aerostatic torsional divergence and flutter forsuper long-span bridges, which are onset for selection of suitable bridge decksfor those bridges. Based on a cable-stayed bridge with double main spans of 1500 m, considering typical twin-box, stiffening truss and closed-box section, which are the most commonly used form of bridge decks and assumed that the rigidity of those section is completely equivalent, are utilized to investigate the effects of aerodynamic configurations of bridge decks on aerodynamic instability performance comprised of the aerostatic torsional divergence and flutter, by means of wind tunnel tests and numerical calculations, including three-dimensional (3D) multimode flutter analysis and nonlinear aerostatic analysis. Regarding the aerostatic torsional divergence, the results obtained in this study show twin-box section is the best, closed-box section the second-best, and the stiffening truss section the worst. Regarding the flutter, the flutter stability of the twin-box section is far better than that of the stiffening truss and closed-box section. Furthermore, wind-resistance design depends on the torsional divergence for the twin-box and stiffening truss section. However, there are obvious competitive relationships between the aerostatic torsional divergence and flutter for the closed-box section. Flutter occur before aerostatic instability at initial attack angle of $+3^{\circ}$ and $0^{\circ}$, while the aerostatic torsional divergence occur before flutter at initial attack angle of $-3^{\circ}$. The twin-box section is the best in terms of both aerostatic and flutter stability among those bridge decks. Then mechanisms of aerostatic torsional divergence are revealed by tracking the cable forces synchronous with deformation of the bridge decksin the instability process. It was also found that the onset wind velocities of these bridge decks are very similar at attack angle of $-3^{\circ}$. This indicatesthat a stable triangular structure made up of the cable planes, the tower, and the bridge deck greatly improves the aerostatic stability of the structure, while the aerodynamic effects associated with the aerodynamic configurations of the bridge decks have little effects on the aerostatic stability at initial attack angle of $-3^{\circ}$. In addition, instability patterns of the bridge depend on both the initial attack angles and aerodynamic configurations of the bridge decks. This study is helpful in determining bridge decksfor super long-span bridges in future.