Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

This study was conducted to develop rice cookies added with young persimmon fruits. Effects of varying amounts (0-12%) of the fruit powder from a young astringent persimmon fruit (picked at July) on the quality characteristics of rice cookies were studied. Ingredients [rice (Oryza sativa subsp. japonica ‘Ilpum’) flours, persimmon (Diospyros kaki Thunb. ‘Cheongdobansi’) powder, sugar, butter, salt, baking powder, egg] were mixed, cut (thickness 3 mm, diameter 35 mm), baked at 170-180℃ for 9 min, cooled, and packaged in polyethylene/nylon bags. The loss rate and spread factor after baking of cookies increased and then decreased with an increase in the amount of fruit powder added. The moisture content and color values (L* and a*) of cookies decreased with an increase in the amount of the persimmon powder added. Phenolic compounds content and DPPH radicals scavenging activity increased with an increase in persimmon powder content; in particular, the DPPH activity of the cookies sharply increased after the addition of 3% persimmon powder. These results suggest that the addition of the young persimmon fruit powder affected the quality characteristics of rice cookies and this fruit powder (approximately 3%) can be utilized as an additive during rice cookie processing.

Rubia cordifolia has been used to treat diseases for many years in China and India. Although the biological properties and major compounds of R. cordifolia have been extensively studied, the underlying mechanisms of its biological effects remain elusive. In terms of immunological effects, anti-inflammation effect of macrophage (Raw 264.7) simply has been reported. In this study, R. cordifolia was extracted in 70% ethanol and the extract did not affect to macrophage (Raw 264.7) pro-inflammation and T cell (Molt-4). However, in mast cell (RBL-2H3), it showed inhibition of degranulation. The inducing inhibitory effect on degranulation was related to concentration dependent variation in phosphorylation of ERK-1/2 and upregulating the JNK phosphorylation in RBL-2H3 cells. Based on these data, we concluded that R. cordifolia newly have anti-allergenic effects in RBL-2H3 and might be used as a therapeutic agent to treat or prevent allergic diseases such as asthma and atopic dermatitis.

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague–Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper’s glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

We present simulations of the optical-band images of high-redshift galaxies utilizing 845 near-ultraviolet (NUV) images of nearby galaxies obtained through the Galaxy Evolution Explorer (GALEX). We compute the concentration (C), asymmetry (A), Gini (G), and M20 parameters of the GALEX NUV/Sloan Digital Sky Survey r-band images at z ~ 0 and their artificially redshifted optical images at z = 0.9 and 1.6 in order to quantify the morphology of galaxies at local and high redshifts. The morphological properties of nearby galaxies in the NUV are presented using a combination of morphological parameters, in which early- type galaxies are well separated from late-type galaxies in the G–M20, C–M20, A–C, and A–M20 planes. Based on the distribution of galaxies in the A–C and G–M20 planes, we examine the morphological K-correction (i.e., cosmological distance effect and bandshift effect). The cosmological distance effect on the quantitative morphological parameters is found to be significant for early-type galaxies, while late-type galaxies are more greatly affected by the bandshift effect. Knowledge of the morphological K-correction will set the foundation for forthcoming studies on understanding the quantitative assessment of galaxy evolution.

In order to examine the effects of four different light spectra (i.e., white, red, green, blue) on the oocyte maturation in grass puffer, the change of reproductive parameters via brain-pituitary-gonad (BPG) axis were investigated in this study. After exposure to four different light spectra for 7 weeks, the abundance of gonadotropin-releasing hormone (GnRH) mRNA which is a type of seabream (sbGnRH) and two different of subunit of gonadotropin hormones mRNAs, follicle-stimulating hormone (fshβ) mRNA and luteinizing hormone (lhβ) mRNA, were analyzed in the brain and pituitary. Gonadosomatic index (GSI) and oocyte developmental stage were also investigated in the gonad based on anatomical- and histological observations. GSI value was significantly increased in the green spectrum-exposed group when compared to that of the other light-exposed groups (i.e., white, red, blue), with the presence of yolk stage oocytes (p˂0.05). The abundances of sbGnRHmRNA and fshβ mRNA in the green spectrum-exposed group were also significant higher than those of the other light spectra-exposed groups(p˂0.05). However, there was no significant difference between the abundances of lhβmRNA in all light spectra-exposed groups. These results indicate that the maturation of oocyte in grass puffercan be accelerated by exposure to the spectrum of green. The sbGnRHmRNA and fshβ mRNA may play an important reproductive parameters role in the initiation of maturation of oocyte. To better understand the molecular mechanism for the maturation of oocytein grass puffer, further study examining the relationship between oocyte development and its related genes (e.g., sbGnRHmRNA and fshβmRNA) is required.

In fish, light (photoperiod, intensity and spectra) is main regulator in many physiological actions including body growth. The present study was to investigate the effect of light spectra on the body growth in red spotted grouper Epinephelus akaara. Experiment performed from December, 2016 to March, 2017 and fish (n=200, body weight 6.9±0.1, total length 7.5±0.1) was reared under different light spectra (blue, green, red and white) for 15 week under 12 hour light and 12 hour dark photoperiod and natural water temperature (13.6~16.7℃). We examined the mRNA expression levels of growth hormone (GH) in the brain with pituitary and photoreceptors mRNA expression in the retina. Red spotted grouper of BW was no different in each for the four groups (light spectra of blue, green, red and white) to five week of rearing period, but BW of rearing blue light spectra group fish was significantly increased in ten week of rearing period. After that, in 15week of rearing period, BW of four group fish was no showed difference respectively. The total length (TL) of fish was no differed in four experimental groups under the experimental duration respectively. The gh mRNA was more highly expressed in rearing blue light spectra group fish than other experimental groups in 15 weeks. The short wavelength sensitive opsin (sws) mRNA was more increased in rearing blue light spectra group fish than other groups in 15 weeks. The middle wavelength sensitive opsin (mws) and rod opsin mRNA expression was no differed in four experimental groups under all experimental durations respectively. The long wavelength sensitive opsin (lws) mRNA expression was more increased in rearing red light spectra group fish than other groups in 15 weeks. Our present results suggest that somatic growth of red spotted grouper is induced under blue light condition under low water temperature duration. Also, these results are thought to be affected of the gh and sws mRNA expression blue wavelength. However, in this experiment we did not confirm the correlation between GH and photoreceptor. Therefore, further studies are needed to clarify the correlation of the light spectra and photoreceptor with body growth in red spotted grouper.

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and G2/M phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

Various bioactive substances are found in mistletoe, including viscumneoside III (1) and homoflavoyadorinin B (2), both which inhibit tyrosinase. These two compounds are mainly found in the EtOAc fraction of the mistletoe extract and demonstrate higher rates of tyrosinase inhibition than ascorbic acid, which was used as a control. Our results suggest that mistletoe extracts can be utilized in skin whitening cosmetics.

The purpose of this study was to investigate the improvement of growth in Israeli carp (Cyprinus carpio), and the cross experiment was carried out with two strains of Israeli carp. Four combinations of Israeli carp from Jeonbuk fisheries farm and Songpu mirror carp from Heilong Jiang, China (KK; Jeonbuk ♀ × Jeonbuk ♂, KC; Jeonbuk ♀ × China ♂, CC; China ♀ × China ♂ and CK; China ♀ × Jeonbuk ♂) were developed and reared. Body length, body weight and condition factor were determined at 20, 40, 60 and 170 days post-hatch (DPH). The results showed that there were differences in growth rate of the four groups. Body length of four groups were CK > CC > KC > KK and body weight were CC > CK > KC > KK at 170 DPH. The growth perfomance of four groups were statistically significant difference (P<0.05). During the rearing, CC group had longer length and higher weight at 170 DPH compared to other three groups and also condition factor was highest in the CC group, but there was no significant difference in a survival rate. These results indicated that the growth performance mainly depended upon brooder combination but survival rate could not significantly affect brooder.

Background : Acanthopanax sessiliflorus (Rupr. et Maxim) Seem, belonging to the Araliaceae family, is widely distributed in Korea, China, and Japan. The plants belonging to Acanthopanax species are traditionally used in Korea as anti-rheumatoid arthritis, anti-inflammatory and anti-diabetic drugs and are recognized to have ginseng-like activities. A simple and sensitive high-performance liquid chromatographic (HPLC) method was developed and validated for independent analysis of major compounds and chlorogenic acid in A. sessiliflorus fruits. Chlorogenic acid was reported that prevent cancer and cardiovascular disease in vivo. Also, it has antioxidant effect in vitro test. In the previous experiment, chlorogenic acid were found in A. sessiliflorus fruits. This study was performed to identification of the major compounds and investigate the method validation for the determination of chlorogenic acid in A. sessiliflorus fruits. Methods and Results : Three major compounds were recorded on a Varian Unity Inova AS-400 FT-NMR spectrometer and analyzed by the new HPLC analysis method. HPLC analysis was carried out using an Waters e2695 and PDA detector. The new analyasis method was validated by the measurement of intra-day, inter-day precision, accuracy, limit of detection (LOD, S/N=3), and limit of quantification (LOQ, S/N=10) of chlorogenic acid. The results showed that the correlation coefficient (R2) for the calibration curves of chlorogenic acid was 0.997 in terms of linearity. The limit of detection (LOD) and limit of quantification (LOQ) were 0.565 ㎍/ml and 2.88 ㎍/ml, respectively. There was no interfering peak observed each other and HPLC system was suitable for analysis showing goodness of peak and high precision. Conclusion : This method is suitable to detect and quantify major compounds in A. sessiliflorus fruits. Furthermore, the result will be applied to establish chlorogenic acid as an standard compound for A. sessiliflorus fruits.

Background : Bitter gourd (Momordica charantia) is a vegetable with pantropical distribution and contains the active ingredient, such as momordicine and charantin. Moreover, bitter gourd has been reported to exhibit antidiabetic, anticancer, cardiovascular-protective and antioxidant effects. But, the distinctive bitter taste of bitter gourd was not suitable for food preference. This study was conducted to evaluate the improvement effects of bitter taste of bitter gourd with natural fermentation and roasting process. Methods and Results : Bitter gourd fruits were obtained from Headeulnyeokae Co., Ltd.(Gang-Jin 59253, Repubilc Korea). Fruits of bitter gourd were prepared by natural fermentation process for 4h at 25℃. After natural fermentation, the fruits were dried in hot-air dryer for 15h at 49-55℃. The dried fruits were roasted in 500 g batches at 120℃ for 10 min in the electric rotisserie oven. After roasting, fruit pieces were extracted with hot water and cold water. One of them was cool-type, and the other was hot-type bitter gourd tea. In the sensory evaluation, hot tea and cold tea showed the high scores on color, flavor and overall acceptability. Conclusion : These mean that roasted bitter gourd had less bitter, and it could be utilized widely as drink and food material.

Background : Ginseng berry(GB) is useful not only just in growing source but also in functional food source. The ingredients of crops varies with the maturity. So, GB ingredients need to be analyse for optimal harvesting stage of GB against appropriate use. Methods and Results : This study was carried out to determine optimal harvesting stage of GB. GB was harvested 5 day periods from July 12, started harvesting when pollination was 50 days old, until August 1. GB was analysed color, ginsenosides and fatty acids using colorimeter, LC and GC, respectively. As the majority of GB increase, color of freeeze drying GB powder were changed that lightness and yellowness was increased, redness was decreased. Ginsenoside Re, Rb1 and Rb2, major ginsenoside in GB, were increased and Ginsenoside F1, Rk1 and Rg5, minor ginsenoside, were increased for a time and then decreased. Oleic acid, the main fatty acid in GB, was decreased, and linoleic acid and total fatty acid content was increased to July 27 and then decreased. Conclusion : Total ginsenosides content was the highest on August 1 and total fatty acid content was the highest July 27. As the majority of GB increase, ratio of oleic acid on total fatty acid was decreased and linoleic acid was increased. Thus, GB is that the longer a harvest period and the more useful for food source.

Background : Schizandra chinensis Baillon have five tastes and lately it is using a beverage broadly. Schizandra chinensis is one of the top producing medicinal plant in Korea. Mungyeong of Gyongbuk province produce almost of Schizandra chinensis. Maturity of Schizandra chinensis get 3 years and proliferation of Schizandra chinensis was not a manual. It is needed that a new cultivar has a big fruit and high quality chracteristics using processed food and beverage. Methods and Results : 105 lines of Schizandra chinensis were collected on Mungyeong, Yeongwol, Jinan. It were studied it’ characteristics especially it’s fruit trait. Fruit traits of Schizandra chinensis were researched on fruit length, fruit weight, maturity, number of fruit, male and female ratio, powdery mildew. Fruit length of Schizandra chinensis is relation of fruit weight. It were founded 15 lines of long fruit length. 5 lines were studied high fruit weight and it’s weight were 32 to 41g. Number of fruit has relation with fruit weight and high fruit weight gets many fruits. it’s numer of fruits were 3 to 41. Male and female ratio were very impotant characteristic. High level of female ratio has quantity of fruit. High level of female ratio were founded 2 lines. Finally It was selected 3 good breed lines of Schizandra chinensis. Conclusion : 105 lines of Schizandra chinensis Baillons were collected on Mungyeong, Yeongwol, Jinan. It were founded 15 lines of long fruit length and 5 lines were studied high fruit weight. High level of female ratio were founded 2 lines. 3 good breed lines of Schizandra chinensis were selected.

Background : ROS produced by oxidative stress damaged endothelial cells, and cause a variety of vascular complications. In diabetic hyperglycemia state, ROS increase. The polyol pathway occur in diabetic complications, the excess glucose is absorbed into the polyol pathway when aldose reductase increased, NADPH changes it to sorbitol. Glutathione (GSH) removes ROS. GSH level is reduced by glutathione reductase, using NADPH as an electron donor. Activation of the polyol pathway decrease NADPH, and GSH also reduced. As a result, ROS is increased. In diabetic hyperglycemia state, Glycolysis increases. Effects of increased glycolysis, protein kinase C (PKC) is increased. NAD(P)H oxidase, stimulated by PKC-dependent pathway, increases ROS in the cell. In this study, we measured the ROS scavenging activity of 5 natural products (Lycii fructus, Astragalus membranaceus, Cassia Tora, Polygonatum odoratum, Rubus Coreanus), to confirm the efficacy as diabetic antioxidants. Methods and Results : We extracted 5 natural product by distilled water and ethanol. DPPH radical scavenging activity was significantly higher in Lycii fructus, Rubus coreanus. ABTS radical scavenging activity was better Rubus coreanus, Lycii fructus, Cassia Tora. In addition to, Rubus coreanus, Cassia Tora, Lycii fructus was comparatively higher reducing power activity than other natural products. And total phenolic and flavonoid contents were much higher in Rubus coreanus compared with other extracts. Conclusion : These results suggest that Lycii fructus, Rubus coreanus can be applied as diabetic antioxidant that prevent vascular complications caused by ROS.

In this study, we investigated the characteristics of CCK-producing cells and mucus-secreting goblet cells with respect to stomach fish and stomachless fish of the Gobiidae in order to provide a basis for understanding the digestive physiology. Hairychin goby (Sagamia geneionema), which is stomachless fish, the numbers of mucus-secreting goblet cells is highest in the posterior intestine portion (P<0.05), while CCK-producing cells are scattered throughout the intestine. Gluttonous goby (Chasmichthys gulosus), which is stomach fish, mucus-secreting goblet cells are most abundant in the mid intestine portion (P<0.05), whereas CCK-producing cells are observed only in the anterior and mid intestine portion. Trident goby (Tridentiger obscurus) which is stomach fish, mucus-secreting goblet cells were most abundant in the mid intestine portion (P<0.05). CCK-producing cells are found in the anterior and mid intestine portion. Giurine goby, Rhinogobius giurinus which is also stomach fish, the largest number of mucus-secreting goblet cells showed in anterior intestine portion except for esophagus (P<0.05). CCK-producing cells are present only in the anterior and mid intestine portion. In S. geneionema, digestive action occurs in the posterior intestine portion to protect and functions to activate digestion. In contrast, in C. gulosus, T. obscurus and R. giurinus, their digestive action occurs in the anterior and mid intestine portion to protect and functions to activate digestion. Further studies of the modes of food ingestion by these fish, the contents of their digestive tracts, and the staining characteristics of the goblet cells need to be carried out.

This study was executed to evaluate the immune activity, nitrite scavenging activity and ABTS radical scavenging activity against extracts of various concentration of ethanol solvent from Codonopsis lanceolata cultured at 6 local regions. The immune responses from both human T and B cell line was significantly enhanced in the cell growth compared to control while the cell growth was influenced at a certain period of culture. The results revealed that the cell growth of both human T and B cell was altered in a time dependent manner. The nitrite scavenging activity of ethanol extracts from various solvent concentration of C. lanceolata were affected by pH. At a pH of 1.2, the nitrite scavenging effect of all of the extracts tested observed higher than that of the other two pH ranges. There was no distinct detection of nitrite scavenging effects of the pH range 6.0. The ABTS radical scavenging activity was progressively increased in a dose-dependent manner, and the activity was the highest in 100% ethanol extract. The result from this investigation suggests that the extract of Codonopsis lanceolata could be an addition to basic medicine for immune modulation and natural food additives.

This study describes results on sexual maturation and characteristics of natural spawned eggs to develop a method for the production of stable, healthy fertilized eggs from captive-reared yellowtail kingfish, Seriola lalandi. A total of 59 yellowtail kingfish were captured off the coast of Jeju Island, after which the broodstock was cultured in indoor culture tank (100 m3) until they were 6.1–14.9 kg in body weight. As part of the rearing management for induced sex maturation, the intensity of illumination was maintained at 130 lux. The photoperiod (light/dark; L/D) was set to a 12 L/12 D from October 2013 to January 2014, and 15 L/9 D from February 2014 to June 2014. Feeds comprised mainly EP (Extruded Pellets), with squid cuttlefish added for improvement of egg quality, and was given from April to June 2014. The first spawning of yellowtail kingfish occurred in May 3, 2014, at a water temperature of 17.0°C. Spawning continued until June 12, 2014, with the water temperature set at 20.5°C. Time of spawning was 26 times at this period. The total number of eggs that spawned during the spawning period was 4,449×103. The buoyant rate of spawning eggs and fertilization rate of buoyant eggs during the spawned period were 76.1% and 100%, respectively. The diameters of the egg and oil globule were 1.388 ± 0.041 mm and 0.378 ± 0.029 mm, respectively, which was higher in early eggs than in those from late during the spawned period.

In fish, light (photoperiod, intensity and spectra) is main regulator in many physiological actions including growth. We investigate the effect of light spectra on the somatic growth and growth-related gene expression in the rearing tiger puffer. Fish was reared under different light spectra (blue, green and red) for 8 weeks. Fish body weight and total length were promoted when reared under green light condition than red light condition. Expression of somatostatins (ss1 and ss2) in brain were showed higher expression under red light condition than green light condition. The ss3 mRNA was observed only higher expression in blue light condition. Expression of growth hormone (gh) in pituitary was detected no different levels between experimental groups. However, the fish of green light condition group was showed more high weight gain and feed efficiency than other light condition groups. Our present results suggest that somatic growth of tiger puffer is induced under green light condition because of inhibiting ss mRNA expression in brain by effect of green wavelength.

Molecular targeting for the altered signaling pathways has been proven to be effective for the treatment of many types of human cancer, including colorectal cancer (CRC). The dual phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 has shown to exhibit potent antitumor activity against solid tumors. Autophagy is a cellular lysosomal catabolic process to maintain metabolic homeostasis, which has been known to be induced in response to many therapeutic agents in cancer cells. This process is negatively regulated by mTOR and often acts as prosurvival or prodeath mechanism following cancer therapeutics. The current study was designed to investigate the antiproliferation activity of BEZ235 and to evaluate the role of autophagy induced by BEZ235 using HCT15 CRC cells bearing ras oncogene mutation. We found that BEZ235 decreases cell viability, which was mostly dependent on G1 arrest of cell cycle via suppression of cyclin A expression. BEZ235 affects PI3K/Akt/mTOR signaling pathway by increasing the phosphorylation of AKT at Ser473 and RAS/RAF/MEK/ERK pathway by decreasing the phosphorylation of ERK at Tyr204. BEZ235 also stimulated autophagy induction as evidenced by the increased expression of LC3-II and abundant acidic vesicular organelles (AVOs) in the cytoplasm. In addition, the combination of BEZ235 with autophagy inhibitor chloroquine, a known antagonist of autophagy, counteracted the antiproliferation effect of BEZ235. Thus, our study indicates that autophagy induced in response to BEZ235 treatment appears to act as cell death mechanism in HCT15 CRC cells.