• Title/Summary/Keyword: 4EBP1

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Using of the "Consolidated Standards of Reporting Trials:CONSORT" to heighten quality of Medical Education study (의학교육연구의 질을 향상시키기 위한 '연구보고의 표준' 의 활용)

  • Yoo, Ji-Soo
    • Korean Medical Education Review
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    • v.10 no.2
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    • pp.25-44
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    • 2008
  • Objectives: Through using of the strong research method like a Randomized Controlled Trial: RCT, we have to heighten quality of Medical Education study. I'd like to introduce "CONSORT", which stands for Consolidated Standards of Reporting Trials. Contents: Preventive Service Task Force(200l) in USA proposed Levels of evidence for enlarging evidence-based Practice: EBP. And the CONSORT was introduced, which encompasses various initiatives developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials (RCTs). the CONSORT has 13 guides like these: 1. How participants were allocated to interventions 2. Scientific background and explanation of rationale 3. Eligibility criteria for participants. The settings and locations where the data were collected. 4. Precise details of the interventions intended for each group and how and when they were actually administered 5. Specific objectives and hypotheses 6. Clearly defined primary and secondary outcome measures, When applicable. any methods to enhance the quality of measurements (e.g., multiple observations, training of assessors) 7. How sample size was determined. When applicable, explanation of any interim analyses and stopping rules 8. Method used to generate the random allocation sequence, Details of any restriction [of randomization] 9. Method used to implement the random allocation sequence 10. Who generated the allocation sequence, who enrolled participants. and who assigned participants to their groups 11. Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment. If done, how the success of blinding was evaluated 12. Statistical methods used to compare groups for primary outcome(s), Methods for additional analyses, such as subgroup analyses and adjusted analyses 13. Flow of participants through each stage (a diagram is strongly recommended) Specifically, for each group report the numbers of participants randomly assigned. receiving intended treatment, completing the study protocol. and analyzed for the primary outcome. Results and Conclusion: Randomized Controlled Trial: RCT guided of CONSORT will contribute to do stronger evidence-based medical studies.

G-Protein-Coupled Receptor 120 Mediates DHA-Induced Apoptosis by Regulating IP3R, ROS and, ER Stress Levels in Cisplatin-Resistant Cancer Cells

  • Shin, Jong-Il;Jeon, Yong-Joon;Lee, Sol;Lee, Yoon Gyeong;Kim, Ji Beom;Lee, Kyungho
    • Molecules and Cells
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    • v.42 no.3
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    • pp.252-261
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    • 2019
  • The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

Inhibitory Effects of Allium senescens L. Methanol Extracts on Reactive Oxygen Species Production and Lipid Accumulation during Differentiation in 3T3-L1 Cells (두메부추(Allium senescens L.) 메탄올 추출물의 지방세포 내 활성산소종 생성 및 지질축적 억제 효능)

  • Choi, Hye-Young;Kim, Gun-Hee
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.498-504
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    • 2014
  • Allium senescens L. is perennial plant of the Liliaceae family that grows throughout Korea. In this study, we investigated the effect of Allium senescens L. methanol extracts on reactive oxygen species (ROS) production and lipid accumulation during adipogenesis. Our results indicated that 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of Allium senescens L. methanol extracts increased in a dose-dependent manner. Allium senescens L. methanol extracts suppressed ROS production and lipid accumulation during adipogenesis. In addition, Allium senescens L. methanol extracts inhibited the mRNA expression of the pro-oxidant enzyme, such as G6PDH and lead to a reduction in the mRNA levels of the transcription factors, such as sterol regulatory element binding proteins 1c, peroxisome proliferator-activated receptor ${\gamma}$, and CCAAT/enhancer-binding proteins ${\alpha}$. These results indicate that Allium senescens L. methanol extracts inhibit adipogenesis by modulating ROS production associated with ROS-regulating genes and directly down-regulating adipogenic transcription factors.

Inhibitory effect of by Ojeok-san lipid accumulation in high fat diet-induced obesity mice and 3T3-L1 adipocytes (오적산 (五積散)의 고지방식이 마우스 지방축적억제 및 3T3-L1지방세포에서의 비만 조절 기전에 관한 연구)

  • Choi, Hye-Min;Moon, Sung-Ok;Lee, Hee-Hyun;이, 화동
    • The Korea Journal of Herbology
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    • v.30 no.4
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    • pp.121-128
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    • 2015
  • Objectives : Ojeok-san (OJS), an oriental herbal formula, has been used in Asian countries including Korea, China and Japan to treat the common cold and illnesses including fatigue and gastrointestinal disorders. The purpose of this study was to examine the anti-obesity effect and molecular mechanism of OJS, on adipogenesis in 3T3-L1 cells. Also, the effects of OJS in obese mice fed a high-fat diet on adiposity were examined.Methods : Preferentially, we analyzed the component of OJS and measured the stability of its component in OJS according to study periods using high performance liquid chromatography (HPLC). In vitro, 3T3-L1 cells were treated with OJS (50 to 200 μg/mL) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining. The expressions of genes related to adipogenesis were measured by RT-PCR and Western blot analyses. For anti-obesty effect in vivo, we experimented for 8 weeks with four group (normal diet (CON), high-fat diet (HF), high-fat diet with OJS (HF+OJS) and high-fat diet with Bang-pung-tong-sung-san (HF+BTS) in comparison group HF+OJS).Results : OJS showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affect cell toxicity as assessed by measuring fat accumulation and adipogenesis. In addition, OJS significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ(PPAR-γ) and CCAAT/enhancer-binding protein-α(C/EBP-α). Also OJS-administered mice showed significant inhibitory of body weights and abdominal adipose tissue weights.Conclusions : This study showed that traditional medicine OJS has an anti-obesity effect in vitro and in vivo. Thus, OJS could be developed as a supplement for reduction of body weight gain induced by an obesity.

Sequencing of cDNA Clones Expressed in Adipose Tissues of Korean Cattle

  • Bong, J.J.;Tong, K.;Cho, K.K.;Baik, M.G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.4
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    • pp.483-489
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    • 2005
  • To understand the molecular mechanisms that regulate intramuscular fat deposition and its release, cDNA clones expressed in adipose tissues of Korean cattle were identified by differential screening from adipose tissue cDNA library. By partial nucleotide sequencing of 486 clones and a search for sequence similarity in NCBI nucleotide databases, 245 clones revealed unique clones. By a functional grouping of the clones, 14% of the clones were categorized to metabolism and enzyme-related group (stearoyl CoA desaturase, lactate dehydrogenase, fatty acid synthase, ATP citrate lyase, lipoprotein lipase, acetyl CoA synthetase, etc), and 6% to signal transduction/cell cycle-related group (C/EBP, cAMP-regulated phosphoprotein, calmodulin, cyclin G1, cyclin H, etc), and 4% to cytoskeleton and extracellular matrix components (vimentin, ankyrin 2, gelosin, syntenin, talin, prefoldin 5). The obtained 245 clones will be useful to study lipid metabolism and signal transduction pathway in adipose tissues and to study obesity in human. Some clones were subjected to full-sequencing containing open reading frame. The cDNA clone of bovine homolog of human prefoldin 5 gene had a total length of 959 nucleotides coding for 139 amino acids. Comparison of the deduced amino acid sequences of bovine prefoldin 5 with those of human and mouse showed over 95% identity. The cDNA clone of bovine homolog of human ubiquitin-like/S30 ribosomal fusion protein gene had a total length of 484 nucleotides coding for 133 amino acids. Comparison of the deduced amino acid sequences of bovine ubiquitin-like/S30 ribosomal fusion protein gene with those of human, rat and mouse showed over 97% identity. The cDNA clone of bovine homolog of human proteolipid protein 2 mRNA had a total length of 928 nucleotides coding for 152 amino acids. Comparison of the deduced amino acid sequences of bovine proteolipid protein 2 with those of human and mouse showed 87.5% similarity. The cDNA clone of bovine homolog of rat thymosin beta 4 had a total length of 602 nucleotides coding for 44 amino acids. Comparison of the deduced amino acid sequences of bovine thymosin beta 4 gene with those of human, mouse and rat showed 93.1% similarity. The cDNA clone of bovine homolog of human myotrophin mRNA had a total length of 790 nucleotides coding for 118 amino acids. Comparison of the deduced amino acid sequences of bovine myotrophin gene with those of human, mouse and rat showed 83.9% similarity. The functional role of these clones in adipose tissues needs to be established.

Effects of Extracts of Five Species of Korean Native Forest Plants on Lipid Accumulation and Reactive Oxygen Species Production during Differentiation of 3T3-L1 Preadipocytes (3T3-L1 세포분화 중 지방축적 및 활성산소종 생성에 대한 국내 산림자원 5종 추출물의 효과)

  • Choi, Sun-Il;Lee, Jong Seok;Lee, Sarah;Lee, Hye Jin;Yeo, Joohong;Cho, Bong-Yeon;Lee, Jin-Ha;Kim, Jae-Min;Jung, Tae-Dong;Choi, Seung-Hyun;Kim, Jong-Yea;Kang, Suk-Nam;Lee, Ok-Hwan
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.523-528
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    • 2017
  • This study investigate the effects of extracts of five species of Korean native forest plants on lipid accumulation and reactive oxygen species (ROS) production during the differentiation of 3T3-L1 cells. Our results show that Korean native forest plants extracts significantly reduced lipid accumulation and ROS production during adipogenesis in 3T3-L1 cells. Especially, Rubus coreanus Miq. was most effective in the inhibition of lipid accumulation and ROS production at a concentration of $100{\mu}g/mL$. Moreover, Rubus coreanus Miq. extracts significantly inhibited adipocyte differentiation, which is dependent on down-regulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and adipocyte-specific fatty acid binding protein, a key adipogenic transcription factor. Therefore, these results suggest that Rubus coreanus Miq. might be a valuable source of bioactive compounds with anti-adipogenic activity.

Anti-obesity Effects of African Mango (Irvingia gabonesis, IGOB 131TM) Extract in Leptin-deficient Obese Mice (유전성 비만 마우스에 대한 아프리칸 망고 추출물의 항비만 효과)

  • Lee, Minhee;Nam, Da-Eun;Kim, Ok Kyung;Shim, Tae Jin;Kim, Ji Hoon;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.10
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    • pp.1477-1483
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    • 2014
  • This study investigated the anti-obesity effects of African mango (Irvingia gabonesis, IGOB $131^{TM}$) extract in leptin-deficient obese mice. Experimental groups were treated with two different doses of IGOB $131^{TM}$ (1% and 2% in each AIN93G supplement) for 8 weeks. Treatment of obese mice with both low and high dose of IGOB $131^{TM}$ significantly reduced body weight gain by 10.9% and 13.3%, respectively, compared to control obese mice. Subcutaneous adipose tissue weight of mice was significantly reduced by 18% by low-dose and 23% by high-dose supplementation. This result was supported by micro-CT analysis around the abdominal regions of mice, indicating that the adipose tissue area and volume were significantly reduced by treatment with IGOB $131^{TM}$. Serum levels of triglycerides in the low- and high-dose groups were reduced by 36.5% and 43.8%, respectively, upon treatment with IGOB $131^{TM}$, whereas total cholesterol levels were reduced by 31.8% and 35.4%. Interestingly, the serum LDL level decreased upon treatment with IGOB $131^{TM}$ while the serum level of HDL dramatically increased upon high-dose treatment with IGOB $131^{TM}$, resulting in a significant reduction in the LDL to HDL ratio of 59.2%. These results were supported by the expression levels of enzymes and proteins related to lipid metabolism assessed by real-time PCR. There was a significant increase of in adiponectin expression as well as significant decreases in the expression of FAS, LPL, and lipid regulatory transcription factors such as PPAR-${\gamma}$, C/EBP, and SREBP upon both low- and high-dose IGOB $131^{TM}$ treatment. However, there was no statistical difference between low- and high-dose treatments. These results suggest that IGOB $131^{TM}$ is able to regulate the serum lipid profiles by reducing triglyceride and increasing HDL levels as well as regulate expression of lipid metabolic factors, resulting in reduction of a weight gain in leptin-deficient obese mice.

Enzymatically Modified Isoquercitrin Attenuates High-Fat Diet-Induced Obesity (효소 처리된 Isoquercitrin이 고지방식이에 의해 비만이 유도된 마우스의 체중감소에 미치는 영향)

  • Min, Yeojin;Park, Taesun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.4
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    • pp.474-483
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    • 2016
  • Enzymatically modified isoquercitrin (EMIQ) is a mixture of quercetin glycodsides consisting of isoquercitrin and its ${\alpha}-glucosylated$ derivatives containing one to seven additional linear glucose moieties. The aim of this study was to assess whether or not EMIQ attenuates high-fat diet (HFD)-induced body weight gain and changes in plasma indices of obesity in mice. Male C57BL/6N mice were fed chow diet, HFD, and HFD containing 1.2% EMIQ for 10 weeks. EMIQ significantly (P<0.05) reduced body weight gain (-21%), total visceral fat-pad weights (-31%), and plasma levels of triglycerides (-17%), total cholesterol (-19%), and free fatty acids (-26%) in HFD-fed mice. EMIQ significantly increased protein kinase A (PKA) expression in the epididymal adipose tissue of HFD-fed mice. Expression of adipogenesis-related genes significantly decreased, whereas expression of fatty acid oxidation-related and thermogenesis-related genes increased in epididymal adipose tissue of EMIQ-fed mice compared with HFD-fed mice. These results suggest that the protective effects of EMIQ against HFD-induced adiposity in mice appear to be associated with PKA-mediated signaling cascades involved in adipogenesis, fatty acid oxidation, and thermogenesis in adipose tissue.

Association of β-Catenin with Fat Accumulation in 3T3-L1 Adipocytes and Human Population (β-catenin 유전자의 3T3-L1 지방세포 및 인체에서의 지방축적 연관성 연구)

  • Bae, Sung-Min;Lee, Hae-Yong;Chae, Soo-Ahn;Oh, Dong-Jin;Park, Suk-Won;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.21 no.9
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    • pp.1301-1309
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    • 2011
  • The major function of adipocytes is to store fat in the form of triglycerides. One of the signaling pathways known to affect adipogenesis, i.e. fat formation, is the WNT/${\beta}$-catenin pathway which inhibits the expression and activity of key regulators of adipogenesis. The purpose of this research is to find genes among the WNT/${\beta}$-catenin pathway which regulate adipogenesis by using small interfering (si) RNA and to find the association of single nucleotide polymorphisms (SNPs) of the gene with serum triglyceride levels in the human population. To elucidate the effects of ${\beta}$-catenin siRNA on adipogenesis key factors, PPAR${\gamma}$ and C/EBP${\alpha}$, we performed real-time PCR and western blotting experiments for the analyses of mRNA and protein levels. It was found that the siRNA-mediated knockdown of ${\beta}$-catenin upregulates adipogenesis key factors. However, upstream regulators of the WNT/${\beta}$-catenin pathway, such as DVL2 and LRP6, had no significant effects compared to ${\beta}$-catenin. These results indicate that ${\beta}$-catenin is a candidate gene for human fat accumulation. In general, serum triglyceride level is a good indicator of fat accumulation in humans. According to statistical analyses of the association between serum triglyceride level and SNPs of ${\beta}$-catenin, -10,288 C>T SNP (rs7630377) in the promoter region was significantly associated with serum triglyceride levels (p<0.05) in 290 Korean subjects. On the other hand, serum cholesterol levels were not significantly associated with SNPs of the ${\beta}$-catenin gene. The results of this study showed that ${\beta}$-catenin is associated with fat accumulation both in vitro and in the human population.

Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/β-Catenin Pathway in Dermal Papilla Cells

  • Kang, Jung-Il;Choi, Youn Kyung;Koh, Young-Sang;Hyun, Jin-Won;Kang, Ji-Hoon;Lee, Kwang Sik;Lee, Chun Mong;Yoo, Eun-Sook;Kang, Hee-Kyoung
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.354-360
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    • 2020
  • The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.