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Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Production of Dendropanax morbiferus extract containing multi-functional ingredients by serial fermentation using Bacillus subtilis HA and Lactobacillus plantarum KS2020 (고초균-젖산균의 순차적 복합 발효를 통한 복합 기능성 물질 함유 황칠나무 추출물의 생산)

  • Su-Jin Son;Hye-Mi Kang;Yun-Ho Park;Mi-Hyang Hwangbo;Sam-Pin Lee
    • Food Science and Preservation
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    • v.31 no.1
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    • pp.138-148
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    • 2024
  • The production of poly-γ-glutamic acid (γ-PGA) and γ-aminobutyric acid (GABA) was optimized by serial fermentation of Dendropanax morbiferus extract (DME) using Bacillus subtilis HA and Lactobacillus plantarum KS2020. The 1st alkaline fermentation was performed on 60% DME including 2% glucose and 10% monosodium ʟ-glutamate (MSG) as a precursor. The 1st fermented DME had 57 mg% tyrosine. Consequently, the 2nd lactic acid fermentation for 5 days increased the tyrosine content of 106 mg%. The mucilage containing γ-PGA showed a high content of 3.50% on the first day of alkaline fermentation and then increased to 4.10% after 2 days. The precursor (MSG) remaining in the 1st fermented DME was efficiently converted to GABA by the 2nd lactic acid fermentation in the presence of 5% skim milk, 1.5% glucose and 0.5% yeast extract, resulting in the production of 18.29 mg/mL GABA. The viable cells of lactic acid bacteria increased and indicated 9.49 log CFU/mL on the fermentation for 5 days, and the acidity of co-fermented DME indicated the highest value of 1.55%. Conclusively, the serial fermented DME has multi-functional ingredients containing γ-PGA, GABA, peptides and probiotics.

Prodigiosin Production From Serratia sp. PDGS120915 Isolated From Daeyeon Stream Water in Busan (하천에서 분리한 Serratia sp. PDGS120915의 프로디지오신 생산)

  • Keunho Ji;Young Tae Kim
    • Journal of Life Science
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    • v.34 no.6
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    • pp.377-384
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    • 2024
  • Prodigiosin is a red pigment characterized by a common pyrrolylpyrromethane skeleton. It is produced by Serratia marcescens, Vibrio psychroerythrus, Hahella chejuensis, etc. Prodigiosin has been reported to possess anticancer, immunosuppressant, antifungal antimalarial, and algicidal activities. However, despite prodigiosin's diverse range of activities, its production rate is significantly low and biosynthesis conditions are difficult. Consequently, the selling price is high, and its usability is limited. This study aimed to increase the efficiency of prodigiosin production according to the culture conditions of Serratia. In this study, a bacterial strain PDGS120915 producing prodigiosin was isolated from lightly contaminated stream water in Busan and identified as a strain of Serratia sp. based on 16S rDNA gene sequence analysis and physiological characteristics. The reddish pigment from PDGS120915 was directly extracted using acidified ethanol, and a characterization analysis confirmed that it was a prodigiosin compound. The optimal conditions for pigment production were 25℃, pH 7, and 0% NaCl concentration for a duration of 14 hr. Furthermore, by treating carbon and nitrogen sources, such as fructose and beef extract, respectively, prodigiosin production increased approximately six-fold and four-fold. Among the minerals tested, 0.1% KCl was found to be the most effective for prodigiosin production. Moreover, casein was identified as the most suitable source for prodigiosin production.

Incubation Conditions Affecting Bacteriocin Production of Lactobacillus plantarum K11 Isolated from Dongchimi (동치미에서 분리된 Lactobacillus plantarum K11의 박테리오신 생산에 영향을 미치는 배양 조건)

  • Lim, Sung-Mee;Lee, Gun-Ja;Park, Sun-Mee;Im, Dong-Soon
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.113-120
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    • 2008
  • The influence of incubation temperature, pH and media components on bacteriocin production by Lactobacillus plantarum K11 were investigated. The highest activity was observed in MRS broth, but no bacteriocin activity was obtained in TSB. The bacteriocin was produced from the exponential growth phase and its activity also reached a maximum in MRS broth, but then dropped after 16 hr because of degradation by extracellular proteolytic enzymes or exhaustion of medium nutrients. The optimal temperature and pH for production of bacteriocin were $37^{\circ}C$ and pH 7.0 in MRS broth, respectively. The addition of 0.5 or 1.0% glucose and $0.5{\sim}1.5%$ lactose to MRS resulted in the increase of the bacteriocin production. With 0.5% NaCl and $K_2HPO_4$, the activities were significantly higher than that of control, respectively. However, increasing nitrogen sources such as beef extract, casein, and tryptone and salts such as $NH_4PO_4$, $MgSO_47H_2O$, and $MnSO_4H_2O$, had detected a negative influence upon the bacteriocin production. Consequently, because the bacteriocin produced by L. plantarum K11 was affected by various incubation conditions, the bacteriocin activity of L. plantarum K11 applied in food as a novel starter will be dependent on environmental factors such as fermentation conditions and food ingredients.

The Development of Imitated Cheese Using Whole Milk Powder and Fermented Milk (전지분유와 발효유를 이용한 치즈 유사품개발)

  • Jo, Ae-Ri;Noh, Hae-Won;Kim, Kee-Sung;Chung, Keun-Hee;Jeon, Woo-Min
    • Food Science of Animal Resources
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    • v.30 no.1
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    • pp.102-109
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    • 2010
  • Imitated cheese was prepared from whole milk powder and fermented milk and the moisture content, general components, noncasein nitrogen, nonprotein nitrogen and free amino acids were analyzed to determine the optimal ripening conditions needed to produce imitated cheese that was similar to natural cheese. The moisture content of the imitated cheese was 40.27% one day after being produced. The cheese was ripened using two different methods; at $12^{\circ}C$ with vacuum sealing and at $12^{\circ}C$ and 95% RH with a spray of Penicillium camemberti. The lactose content decreased rapidly from 24.64 to 5.43% at the $4^{th}$ wk of ripening when it was ripened with Penicillium camemberti. The degradation of protein by mold ripening in the imitated cheese was more rapid than that of vacuum sealing. The flavor and body texture were optimal at the $4^{th}$ wk ripening. The noncasein nitrogen and nonprotein nitrogen content increased from 28.10 to 54.05, and from 6.58 to 23.06 mg/mL, respectively, when ripened with P. camemberti. When the cheese was ripened at $12^{\circ}C$, 95% R.H with P. camemberti after 4 wks, all free amino acids increased significantly except asparagines. The total free amino acid and bitter amino acid concentrations increased from 8.40 to 34.87, and from 1.53 to 10.02 nmol/mg, respectively. When the imitated cheese was prepared, the protein degradation and flavor of the cheese was better when ripened with P. camemberti.

Effects of Fermented Soybean Paste Chungkukjang on the Immunoreactivity in Ovariectomized Mice (청국장이 난소적출 마우스의 면역 기능에 미치는 영향)

  • Park, Hyunjin;Yoon, Leena;Kim, Hyun-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.12
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    • pp.1930-1939
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    • 2013
  • It has been reported that Chungkukjang, one of Korean traditional fermented soybean products, may improve hypertension, diabetes, and hyperlipidemia. In this study, we sought to investigate the immunoenhancing effects of Chungkukjang in ovariectomized mice. For the first period, female SLC ddy mice were either sham-operated (Sham; n=27) or ovariectomized (OVX; n=27). As a basal diet, ovariectomized mice were fed low-calcium diet for faster induction of osteoporosis for six weeks, and those in the Sham group were fed AIN-76 diet. For the second period, half of the OVX group (n=9) and the Sham group (n=9) were fed a Chungkukjang-based diet (CKJ); whereas the other half (OVX; n=9/ Sham; n=9) were fed a casein-based diet (CSI) for 8 weeks. After a second period, we collected the blood via heart puncture and measured the splenocytes proliferation, T lymphocyte subsets by flowcytometry, and levels of serum cytokines (IL-2, IL-4, IL-6, IL-10, IFN-${\gamma}$ and TNF-${\alpha}$) by ELISA assay. The OVX+CKJ group showed higher splenocytes proliferation, higher ratio of CD4/CD8, and lower levels of IL-6 and TNF-${\alpha}$ cytokines compared to the OVX+CSI group. The Sham+CKJ group showed cytokine productions, such as higher levels of IL-10 and IFN-${\gamma}$, and lower levels of IL-6 and TNF-${\alpha}$ compared to the Sham+CSI group. The result of this study suggests that Chungkukjang may lower the proinflammatory cytokine levels in both the OVX and Sham groups. In addition, Chungkukjang could make a balance of T cell subset proliferations and enhance the splenocyte proliferations in the OVX group.

Effect of the Various Sources of Dietary Additives on Growth, Body Composition and Shell Color of Abalone Haliotis discus hannai (다양한 원료의 사료첨가제가 전복의 성장, 체조성 및 패각 색채에 미치는 영향)

  • Cho, Sung-Hwoan;Park, Jung-Eun;Kim, Chung-Il;Yoo, Jin-Hyung;Lee, Sang-Min;Choi, Cheol-Young
    • Journal of Aquaculture
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    • v.19 no.4
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    • pp.275-280
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    • 2006
  • Effect of the various sources of dietary additives on growth, body composition and shell color of abalone Haliotis discus hannai was investigated for 16 weeks. Forty juvenile abalone averaging 13.5 g were randomly stocked into 21 of 50 L plastic rectangular containers each. Eight kinds of additives were prepared for this study: four commercially available microalgae [Haeatococcus (Hae), Isochrysis galbana (Iso), Shizochytrium (Sch) and Spirulina (Spi)], three crustacean meals [krill meal (KM), shrimp head meal (Shm) and red crab meal (Rcm)], and green tea by-product (Gre). In addition, dry sea tangle (Dst), Laminaria japonica, as a control, was prepared. Casein, dextrin and a mixture corn oil and fish oil was protein, carbohydrate and lipid sources, respectively, in the experimental diets. The 2% each additive was included into the experimental diets. The experimental diets were fed to abalone once a day at the ratio of $1.5{\sim}2.0%$ total biomass of abalone with a little leftover throughout the 16-week feeding trial. Survival of abalone was not significantly (P>0.05) affected by the experimental diets. However, weight gain of abalone fed the all experimental diets containing the various sources of additives was significantly (P<0.05) higher than that of abalone fed the Dst diet. Weight gain of abalone fed the Spi diet was highest and Shi, KM and Iso diets in order. Shell length and the ratio of soft body weight to body weight of abalone was not significantly (P>0.05) affected by the experimental diets. However, shell width of abalone fed the all experimental diets containing the various sources of additives was significantly (P<0.05) higher than that of abalone fed the Dst diet. The shell color of abalone fed the Spi diet was improved the most distinctively and similar to that of natural abalone. Therefore, it can be concluded that the experimental diets with the various sources of additives (microalgae and crustacean meals) was effective to improve growth of abalone and dietary inclusion of Spirulina was most effective to improve shell color of abalone.

A Study of Synthesis and Biological Function on DL-1-Aminoethylphosphonic Acid (DL-1-Aminoethylphosphonic acid의 생물학적(生物學的) 기능연구(機能硏究))

  • Kim, Sook-He;Cho, Jung-Nam;Kim, Yong-Joon
    • Journal of Nutrition and Health
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    • v.2 no.4
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    • pp.173-181
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    • 1969
  • Since 1959 ${\beta}-aminoethylphosphonic$ acid was discovered in the living organism, the biosynthesis and biological functions of aminophosphonic acids have been extensively studied. The author designed and carried out this study for 14 weeks to find out the metabolic function of Ethylaminophosphonic acid (AEP) and it's utilization in the living body. Sixty rats, thirty males and thirty females aged $40{\pm}5$ days were divided into two parts, one for alanine supplemented as control group and the other for AEP as experimental group to compare metabolic pathway of ordinary amino acid with that of AEP. Both alamine and AEP group were divived into two subgroups according to the level of supplements, 0.1% and 0.2% of the diet. The major components of the diet in this study were composed of 20% casein, 72% Sugar, 4% fat, 4% salt Mixture, and all kind of Uitamins in adeguate amount. For comparision of biological values between experimental and control group in terms of body weight, uninary nitrogen, creatinine excretion and final orgam weight, there were no statically significant difference in these respects. This meant AEP could be utilized in the body as much as alanine could. Urinary phosphorus excretion was determined by developing the blue color to read on the Spectronic 20. Statistically insignificance in the urinary phosphorus excretion between experimental and control group was observed in spite of the supplementation of phosphorus of AEP for experimental group in the diet. The level of blood phosphorus was higher in experimental group than that in control group this result supported above result. In the analysis of fat and nitrogen contents in the liver, AEP group showed slightly higher than control in both respects. But it was noteworthy 0.2% AEP group in both sex were higher than 0.1% AEP in liver fat content. Histological examinal of internal organs liiver, lung, spleen, heart, kindey, adrenal and sex organs showed no changes in all groups included in this study. The group supplemented higher level of diet. by alanine 0.2% and AEP 0.2% stayed on less body weight gain and lower liver weight. This result could be interpreted that amino acid imbalanced condition was arose in the body.

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Studies on Bacterial Contamination of Domestic Chicken Breeding Farm (국내 종계장에 있어서 미생물 오염에 관한 연구)

  • 김기석;이희수;김상희;박근식
    • Korean Journal of Poultry Science
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    • v.18 no.3
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    • pp.151-159
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    • 1991
  • As a part of investigation on causes of drop in egg production in domestic chicken breeding farm, bacteriological contamination on air, feed, drinking water and artificial insemination instruments of randomly selected three farms was surveyed. Total bacterial population in the air was very high in all of the chicken houses tested and was not significantly different among these farms . However, total bacterial counts in the air of the problem house having egg drop problem and colibacillosis was higher than normal house within the problem farm. Bacterial population in the assorted feed was low before or after administration on the normal farm while it was much more increased after administration than before administration on the problem farm. Bacterial population of the drinking water in the source of water supply was very low and has no differences among farms tested. Also, bacterial population in the normal farm was not significantly different between source of water supply and after administration. However, population of total bacteria and coliform bacteria after administration was increased. Bacterial population was much higher in the artificial insemination instrument of problem farm than normal farm. However, this bacterial population in the problem farm was decreased to those of normal farm after these instruments were sanitized.

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Design and Implementation of Game Server using the Efficient Load Balancing Technology based on CPU Utilization (게임서버의 CPU 사용율 기반 효율적인 부하균등화 기술의 설계 및 구현)

  • Myung, Won-Shig;Han, Jun-Tak
    • Journal of Korea Game Society
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    • v.4 no.4
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    • pp.11-18
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    • 2004
  • The on-line games in the past were played by only two persons exchanging data based on one-to-one connections, whereas recent ones (e.g. MMORPG: Massively Multi-player Online Role-playings Game) enable tens of thousands of people to be connected simultaneously. Specifically, Korea has established an excellent network infrastructure that can't be found anywhere in the world. Almost every household has a high-speed Internet access. What made this possible was, in part, high density of population that has accelerated the formation of good Internet infrastructure. However, this rapid increase in the use of on-line games may lead to surging traffics exceeding the limited Internet communication capacity so that the connection to the games is unstable or the server fails. expanding the servers though this measure is very costly could solve this problem. To deal with this problem, the present study proposes the load distribution technology that connects in the form of local clustering the game servers divided by their contents used in each on-line game reduces the loads of specific servers using the load balancer, and enhances performance of sewer for their efficient operation. In this paper, a cluster system is proposed where each Game server in the system has different contents service and loads are distributed efficiently using the game server resource information such as CPU utilization. Game sewers having different contents are mutually connected and managed with a network file system to maintain information consistency required to support resource information updates, deletions, and additions. Simulation studies show that our method performs better than other traditional methods. In terms of response time, our method shows shorter latency than RR (Round Robin) and LC (Least Connection) by about 12%, 10% respectively.

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