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Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD

  • Zehong Yang;Yuanyuan Yu ;Nannan Sun;Limian Zhou;Dong Zhang;HaiXin Chen ;Wei Miao ;Weihang Gao ;Canyang Zhang ;Changhui Liu ;Xiaoying Yang ;Xiaojie Wu ;Yong Gao
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.376-384
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    • 2023
  • Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

Protective Effect of Betula Platyphylla on Ultraviolet B-irradiated HaCaT Keratinocytes (화피(樺皮) 에탄올 추출물의 Ultraviolet B로 자극한 피부 각질 세포 보호 작용)

  • Hag Soon Choi;Hyun Joo Kim;Hark Song Lee;Seung Won Paik;Ji Eun Kim;Yung Sun Song
    • The Journal of Korean Medicine
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    • v.44 no.2
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    • pp.119-131
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    • 2023
  • Objectives: Betula Platyphylla(BP) has been used as a analgesic, anti-microbial, anti-oxidant drug in Eastern Asia. However, it is still unknown whether BP ethanol extract could exhibit the inhibitory activities against ultraviolet B(UVB)-induced skin injury on human keratinocytes, HaCaT cells. This study was aimed to investigate the protective activity of BP ethanol extract on UVB-irradiated skin injury in HaCaT cells. Methods: The skin injury model of HaCaT cells was established under UVB stimulation. HaCaT keratinocyte cells were pre-treated with BP ethanol extract for 1 h, and then stimulated with UVB. Then, the cells were harvested to measure the cell viability, production of reactive oxygen species(ROS), pro-inflammatory cytokines such as interleukin(IL) 1-beta, IL-6, and tumor necrosis factor(TNF)-𝛼, hyaluronidase, type 1 collagen, matrix metalloproteinase(MMP)s. In addition, we examined the mitogen activated protein kinases(MAPKs) and inhibitory kappa B alpha(I𝜅;-B𝛼) as inhibitory mechanisms of BP ethanol extract. Results: The treatment of BP ethanol extract inhibited the UVBinduced cell death and ROS production in HaCaT cells. BP ethanol extract treatment inhibited the UVB-induced increase of IL-1beta, IL-6, and TNF-𝛼. BP ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. BP ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of BP ethanol extract could inhibit the UVB-induced skin injury via deactivation of MAPKs and nuclear factor kappa B(NF-𝜅B) in HaCaT cells. This study could suggest that BP ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells

  • Ning Song;Jun Luo;Lian Huang;Xiaoying Chen;Huimin Niu;Lu Zhu
    • Animal Bioscience
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    • v.36 no.10
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    • pp.1488-1498
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    • 2023
  • Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

The Effect of Dangguijakyak-san on Wound Healing (당귀작약산의 창상 회복에 대한 효과)

  • Yun-Jin Lee;Chang-Hoon Woo;Young-Jun Kim;Hyeon-Ji Kim;Hee-Duk An
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.3
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    • pp.47-65
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    • 2023
  • Objectives We evaluated the wound healing effects of Dangguijakyak-san (DJ) using C57BL/6 mice that were generated open wound. Methods The study was conducted with seven C57BL/6 mice assigned to each group, divided into the normal group, control group, vitamin E group, DJ low-dose group, DJ high-dose group. We measured total polyphenol, flavonoid contents, the size of the wound, liver function, pro-inflammatory cytokine activity in serum, inflammation-related proteins, adhesion molecules and chemokine proteins, collagen-related proteins in skin tissue and histopathological changes by H&E and Masson's staining. Results DJ treatment significantly reduced the area of the wound compared to the control group. Also, inflammatory cytokines were reduced and the expression of anti-inflammatory-related factors (interleukin-4 [IL-4] and IL-10) was significantly increased in the DJ treatment group. We identified that DJ treatment inhibits both pathways of inflammation, the mitogen-activated protein kinases and nuclear factor-κB pathway. Moreover, the protein expressions of Sirt1 (sirtuin 1), MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1) were decreased by DJ administration. Also, the expression of α-smooth muscle actin and collagen type I alpha 1, collagen-related proteins, that help skin recovery was significantly increased in the DJ treatment group. Histopathologically, a relatively thin epithelial layer could be observed in the DJ administration group, as well as an increase in fibroblasts and collagen fibers. Conclusions These data suggest that DJ treatment is effective in wound healing, suppressing inflammatory proteins, increasing skin repair factors and improving histopathological changes caused by wounds.

A study on the Antioxidative and Antimicrobial Activities of the Citrus Unshju peel Extracts (감귤과피 추출물의 항산화 및 항균 효과에 관한 연구)

  • Ahn, Myung-Soo;Seo, Mi-Sook;Kim, Hyun-Jeung
    • Journal of the Korean Society of Food Culture
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    • v.22 no.4
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    • pp.454-461
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    • 2007
  • Antioxidative and antimicrobial activities were carried out on the Citrus Unshju peel solvent extracts in order to discover new functional activities. The amounts of polyphenol in 70% metanol extract (MtEx) was measured as 836.8 mg% in Citrus Unshju peel. The EDA (electron donating ability) of 0.01, 0.02 and 0.1% MtEx in Citrus Unshju peel were measured as levels of 81.3, 86.0 and 89.6%. The nitrite scavenging effects of Citrus peel were also determined as the levels of 34.4% (pH 1.2) and 19.5% (pH 7.0). The pH of react solution was more acidic, the nitrite scavenging effect was more increased. The order of antioxidatives was shown as TBHQ > BHT > TOC > ChEx > EaEx > EtEx > WaEx > Control in corn germ oil and TBHQ > ChEx > EaEx > BHT > EtEx > WaEx > TOC > Control in canola oil. A number of the extracts were certified to have antimicrobial activities for a small number of micro-organisms, similar gram negative and positive micro-organisms. According to the results above, it was summerized that Citrus Unshju peel had the higher total polyphenol, EDA, nitrite scavenging effects and antimicrobial activities. Also isolated extract from ChEx and EaEx had high antioxidative, these effects were very similar to that of ${alpha}$-tocopherol and BHT. It would be proposed that Citrus peel can become a new natural source for antioxidative agents in future food industry.

Amelioration of DSS-induced colitis in mice by TNF-α-stimulated mesenchymal stem cells derived from feline adipose tissue via COX-2/PGE2 activation

  • Kyeongbo Kim;Ju-Hyun An;Su-Min Park;GaHyun Lim;Kyung-Won Seo;Hwa-Young Youn
    • Journal of Veterinary Science
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    • v.24 no.4
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    • pp.52.1-52.13
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    • 2023
  • Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b+CD206+ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.

Development of Health Status Scale for Abdominal Obesity Elderly (복부비만 노인의 건강수준 측정도구 개발)

  • Kim, Jeong Soo
    • 한국노년학
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    • v.30 no.4
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    • pp.1095-1106
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    • 2010
  • The purpose of this study was to develop a Abdominal Obesity Elderly(AOE) Health Status Scale to assess self rated health level. The subjects of this study were total 255(pretest 56, test 199) elderly over 65year. The data were collected between June to August, 2009. The method of this study as follow: items generation, test of validity and reliability, 5 panels of experts reviewed the preliminary questionnaire and then data were collected from elderly. Factor analysis, Cronbach's alpha, mean, standard deviation were analyzed the data by SPSS-Win 12.0 program. Results of factor analysis, 5 factors with a total of 16 items extracted that were Social level(Social participation 6 items, Physical Activity 2 items), Physical level(Disease Perception 4 items, Physical Index 2 items), Psychological level(Emotional Support 2 items). The reliability of the AOE health status scale was .868(Conbach's α). In the factor analysis Conbach's α correlations for the 5 factors ranged from .806 to .577. Therefore, Content validity, construct validity, reliability of the AOE health status scale were established. The AOE health status scale is a reliable and valid instrument which abdominal obesity elderly health status can be assessed.

Changes in Microbial Counts, Enzyme Activity and Quality of Foxtail Millet Yakju Treated with High Hydrostatic Pressure During Storage (초고압 처리한 좁쌀약주의 저장 중 미생물수, 효소활성 및 품질변화)

  • 임상빈;좌미경;목철균;박영서
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.576-581
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    • 2004
  • Foxtail Millet Yakju were treated with heat ($65^{\circ}C$/15 min) or high hydrostatic pressure ($25^{\circ}C$ (RT) and $65^{\circ}C$ (HT)/400 MPa/10 min), and stored for 64 days at l$0^{\circ}C$, $25^{\circ}C$ and 37$^{\circ}C$. Changes in microbial counts, enzyme activity and quality of Yakju during storage were measured. Total viable cells were about 10$^2$ CFU/mL, and remained almost constant during storage at l$0^{\circ}C$ and $25^{\circ}C$, while decreased significantly at 37$^{\circ}C$, and undetected after 55 days of storage in heat- and pressure(RT)-treated, but after 25 days in pressure(HT)-treated Yakju. Lactic acid bacteria and yeast in heat- and pressure-treated Yakju were not detected during storage. The relative activities of a -amylase in heat- and pressure(RT)-treated were more than 100%, while those in pressure(HT)-treated were less than 40% during storage of 64 days at l$0^{\circ}C$. However, at $25^{\circ}C$ and 37$^{\circ}C$ the relative activities in untreated and pressure(RT)-treated were decreased greatly and then reached at the point of the activities of heat- and pressure(HT)-treated. The relative activities of glucoamylase in untreated and pressure(RT)-treated were decreased as the increase of the storage temperature during storage, while those in heat- and pressure(HT)-treated increased slightly as the increase of storage period at 1$0^{\circ}C$ and $25^{\circ}C$, and had no change at 37$^{\circ}C$. pH in heat- and pressure-treated had almost no change. Turbidity and reducing sugar in heat- and pressure-treated increased as the increase of storage temperature during storage.

Effect of Mulberry (Morus alba L.) Extract on Blood Flow Improvement (오디 추출물(Morus alba L.)의 혈행개선 효과)

  • Park, Youn-Sil;Kang, Seong-Sun;Choi, Hyoung-Ja;Yang, Sung-Jun;Shon, Ho-Hyeong;Seo, Hyeong-Ho;Jeong, Jong-Moon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.4
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    • pp.498-506
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    • 2014
  • The objective of this study was to investigate the beneficial effects of mulberry extract (MBE) on blood flow improvement. The $SC_{50}$ value for the DPPH radical scavenging activity of MBE was $89.36{\pm}5.46{\mu}g/mL$. Analysis of the cellular toxicity of MBE on RAW 264.7 and HepG2 cells showed no toxicity under a concentration of 2,500 ${\mu}g/mL$. We found that MBE inhibited the enzyme activity of cyclooxygenase (COX)-2 as well as oxidation of human LDL. Western blotting analysis showed that MBE inhibited protein expression of COX-2 and 5-lipoxygenase in RAW 264.7 cells. In addition, MBE inhibited protein expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, MBE reduced the serum levels of total cholesterol and C-reactive protein in a concentration-dependent manner. These results both in vitro and in vivo suggest that MBE can be employed for the improvement of blood flow.

A Study on the Symptom Distress and Suffering of Five Major Cancer Patients (암질병에 따른 암환자의 불편감과 고통에 관한 연구)

  • Kwon, Mi-Hyoung;Kim, Boon-Han
    • Asian Oncology Nursing
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    • v.3 no.2
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    • pp.145-154
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    • 2003
  • Purpose: The study was to furnish basic raw materials that evaluate the efficacy of meatal care according to the form and the relative importance of symptom distress which most of cancer sufferers have been experienced. For that, an investigation of five diverse major cancer symptom distress made a comparison between symptom distress and degree of suffering. Method: Study subjects were 138 inpatients with stomach cancer, lung cancer, hepatocellular carcinoma(HCC), large intestine cancer and breast cancer, except those in the terminal-stage, in 'H' university hospital in Seoul and 'K' center in Ilsan gathered from November 20, 2002 to February 20, 2003. To measure the correlation between feeling of discomfort and agony caused by cancer, 5 point scale (from zero to four), stood on the basis of Symptom Distress Scale (SDS, Rodes & Watson, 1987), was used for this study and the Cronbach's coefficient alpha was 0.95. Accumulated data was analyzed with SPSS 10.0 for window, also used by ANOVA and Duncan's Multiple Range Test. Pearson's Correlation Analysis. Results: 1. Symptom distress of cancer patients was noted and defined in their severity-fatigue, anorexia, pain, depression, dyspepsia, changing appearance and nausea. The degree of symptom distress was fatigue, dyspepsia, depression, anorexia, pain, changing appearance and the degree of suffering was nausea, pain, anorexia, dyspepsia, vomiting, breathing difficulty, changing appearance and fatigue. 2. Examining the difference of degree of symptom distress in each cancer cases, it takes the precedence of them. First, in case of stomach cancer, depression, pain, vomiting and nausea were shown in sequence. In case of lung cancer depression, pain, sleeping problem, anxiety, changing appearance, inattentiveness and vomiting were showed in sequence, depression, changing appearance, sleeping problem, pain in case of HCC, depression, pain in case of large intestine cancer and lastly in case of breast cancer changing appearance, depression, pain and anxiety were shown in sequence. The category of the degree of symptom distress that has a signifiant difference was anorexia, activity discomfort, fatigue, constipation or diarrhea, breathing difficulty, dyspepsia, caughing, fever or chillness, scotoma and urinary disorder. Verifying the highest degree of symptom distress in each cancer cases, anorexia was 1.94(F=4.00, p<.01) in stomach cancer, activity discomfort was 0.97(F=3.08, p<.01) in lung cancer and HCC, fatigue was 2.32(F=4.64, p<.01) in HCC, constipation or diarrhea was 1.83(F=22.31, p<.001) in large intestine cancer, breathing difficulty was 1.83(F=4.00, p<.01) in lung cancer, dyspepsia was 2.69(F=9.98, p<.001) in stomach cancer, coughing was 1.53(F=20.49, p<.001) in lung cancer, fever or chillness was 1.23(F=6.88, p<.001) in lung cancer, scotoma was 1.20(F=3.02, p<.05) in lung cancer and urinary disorder was 1.54(F=11.56, p<.001) in HCC. 3. Examining the difference degree of suffering on cancer cases, the result was as follows; depression of lung cancer was 1.17(F=3.76, p<.01), anorexia of stomach cancer was 1.61(F=3.89, p<.01), constipation or diarrhea of large intestine cancer was 1.42(F=10.43, p<.001), changing appearance of breast cancer was 1.65(F=5.43, p<.001), breathing difficulty of lung cancer was 2.27(F=18.57, p<.001), dyspepsia of stomach cancer was 1.97(F=13.56, p<.001), coughing of lung cancer was 1.70(F=22.07, p<.001), fever or chillness of lung cancer was 1.13(F=4.41, p<.01), scotoma of lung cancer was 0.87(F=3.34, p<.05), anxiety of lung cancer was 0.87(F=4.50, p<.001) and urinary disorder of HCC was 1.43(F=16.71, p<.001). 4. In consequence, comparing between symptom distress and degree of suffering on cancer patients undergoing chemotherapy, lung cancer patients showed the highest feeling of discomfort following stomach cancer, HCC, breast cancer and large intestine cancer(F=2.88, p<.05). On those undergoing radiotherapy, lung cancer, HCC, breast cancer, large intestine cancer was in sequence(F=3.78, p<.05) and those resisting radiotherapy, lung cancer, HCC, stomach cancer, large intestine cancer and breast cancer was in sequence(F=2.72, p<.05). 5. Correlation between symptom distress and degree of suffering on cancer patients was generally significant. Conclusion: this study not only defines a significant correlation between symptom distress and degree of suffering but also proffers basic data to evaluate the efficient meatal care depending upon diverse spectrums of symptom distress and degree of suffering.

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