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The genomic landscape associated with resistance to aromatase inhibitors in breast cancer

  • Kirithika Sadasivam;Jeevitha Priya Manoharan;Hema Palanisamy;Subramanian Vidyalakshmi
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.20.1-20.10
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    • 2023
  • Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

Microbiome-metabolomics analysis of the effects of decreasing dietary crude protein content on goat rumen mictobiota and metabolites

  • Zhu, Wen;Liu, Tianwei;Deng, Jian;Wei, Cong Cong;Zhang, Zi Jun;Wang, Di Ming;Chen, Xing Yong
    • Animal Bioscience
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    • v.35 no.10
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    • pp.1535-1544
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    • 2022
  • Objective: The objective of this study was to investigate the effects of decreasing dietary crude protein content on rumen fermentation, mictobiota, and metabolites in goats. Methods: In an 84-day feeding trial, a total of twelve male Anhui white goat kids with initial body weight 15.9±1.13 kg were selected and randomly classified into two groups, feeding a normal crude protein diet (14.8% CP, NCP) or a low crude protein diet (12.0% CP, LCP). At the end of the experimental trial (on day 84), six animals were randomly selected from each group and were slaughtered to collect rumen fluid samples for the analysis of rumen fermentation parameters, microbiome, and metabolome. Results: The concentrations of ammonia-nitrogen, total volatile fatty acid, acetate, and propionate were decreased (p<0.05) in the LCP group in comparison with those in the NCP group. The abundances of genera Prevotella, Campylobacter, Synergistetes, and TG5, which were associated with nitrogen metabolism, were lower (p<0.05) in the LCP group compared with those in the NCP group. The levels of 78 metabolites (74 decreased, 4 increased) in the rumen fluid were altered (p<0.05) by the treatment. Most of the ruminal metabolites that showed decreased levels in the LCP group were substrates for microbial protein synthesis. Metabolic pathway analysis showed that vitamin B6 metabolism was significantly different (p<0.05) in rumen fluid between the two treatments. Conclusion: Decreased dietary protein level inhibited rumen fermentation through microbiome and metabolome shifts in goat kids. These results enhance our understanding of ruminal bacteria and metabolites of goat fed a low protein diet.

A Study of Serum Lipid, Blood Sugar, Blood Pressure of Buddhist Nuns in Vegetarians and Non-Vegetarians (III) - Based on Age - (채식인과 비채식 일반인의 혈중 지질, 혈당, 혈압에 관한 연구(III) -연령을 중심으로-)

  • Cha, Bok-Kyeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.8
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    • pp.1311-1319
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    • 2004
  • The purpose of this study was to compare the serum lipid level, blood sugar and blood pressure in vegetarians and non-vegetarians. The subjects of the study were 127 Buddhist nuns (age: 23∼79 y) from Oonmoon Temple in Choungdo district Gyeongsang Bookdo province and 118 Buddhist nuns practicing Zen meditation at Soodeok Temple in Yeosan district Chongcheong Namdo province. For control subjects, 235 healthy female adults (age: 23∼79 y) were selected. They were the nurses in the Gyeongsang National University Hospital, teachers and housekeepers living in Jinju, Gyeongsang Namdo province. The period of this study was from October 1996 to February 1997. The contents were consisted of food consumption survey, anthropometric measurement, estimated amount of energy expenditure, physical activity and clinical examination. The mean ages of the subjects were 44.2 y for vegetarians and 40.5 y for non-vegetarians, respectively. Average body mass index (BMI) of vegetarians and non-vegetarians were 22.47 and 21.08, WHR 0.85 and 0.84, percentage of body fat 28.79 and 26.55 respectively. The average duration of vegetarian diet of the vegetarians was 13.16 y. Levels of total cholesterol, LDL-cholesterol, atherogenic index (AI), diastolic blood pressure, blood sugar and HDL-cholesterol were significantly higher (p<0.01) in non-vegetarians than those of vegetarians. In both of subjects, levels of TG, total cholesterol, LDL-cholesterol, atherogenic index (AI) and systolic blood pressure were significantly higher (p<0.01) with an increment of age and the vegetarians showed a lower ratio of rise than the non-vegetarians. Levels of serum TG, LDL-cholesterol and AI were utmost in the 60 s and declined in the 70 s. Consequently, vegetarian diet can be considerably effective in reducing the level of the risk factors causing cardiovascular disease.

Relevance of Serum Vitamin D and Indices Related To Cardiovascular Disease Among Korean Adults (한국 성인의 혈청 비타민 D 수준과 심혈관 질환 관련 지표와의 관련성)

  • Kim, Han-Soo;Ryu, So-Yeon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.6
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    • pp.365-374
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    • 2018
  • This study investigated the relationship between Vitamin D levels and indices related to cardiovascular disease in Korean adults aged ${\geq}19years$. The data for analysis were obtained from the sixth Korea National Health Nutrition Examination Survey in 2013 and 2014. The results showed that the incidence of Vitamin D deficiency was 73.1% among Korean adults and that indices related to cardiovascular disease showed an increasing trend (55.6% of Korean adults). The relationship between Vitamin D levels and indices related to cardiovascular disease with controlled physical activity status was also studied. The odds ratios (ORs) for age were 1.72 for the 4-62 years age group (95% CI, 1.53-1.93) and 2.05 for the ${\geq}65years$ age group (95% CI, 1.71-2.45). For blood pressure, the OR for pre-hypertension was 1.30 (95% CI, 1.15-1.47) and that for hypertension was 1.31 (95% CI, 1.11-1.54). For body mass index (BMI), the OR was 1.36 (95% CI, 1.11-1.66) and that for waist circumference (WC) was 1.36 (95% CI, 1.11-1.66). For fasting blood sugar (FBS), the OR for impaired fasting glucose (IFG) was 1.37 (95% CI, 1.21-1.55) and that for diabetes mellitus (DM) was 1.31 (95% CI, 1.05-1.65). The OR for total cholesterol (TC) was 1.30 (95% CI, 1.11-1.52) and that for triglycerides (TG) was 1.20 (95% CI, 1.04-1.37) in Korean adults. There was a significant relationship between Vitamin D and indices related to cardiovascular disease in Korean adults with respect to age, blood pressure, FBS, BMI, TC and TG. Confirmation of a causal relationship between Vitamin D and indices related to cardiovascular disease may require further research consisting of more systematic cohort studies.

Hepatotoxicity Reducing Effect of Ethanol Extracts from Fermented Youngia denticulata Houtt Kitamura in Ethanol-treated Rats (발효 이고들빼기(Youngia denticulata Houtt Kitamura) 에탄올 추출물이 알코올 투여로 손상시킨 흰쥐의 간독성 해소 효과)

  • Kim, Mee-Jung;Lee, Hyun-Koo
    • Journal of the East Asian Society of Dietary Life
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    • v.26 no.5
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    • pp.389-399
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    • 2016
  • This study was performed to investigate the hepatotoxicity reducing effect of ethanol extracts from Youngia denticulata Houtt Kitamura (YD) fermented by Aspergillus oryzae, which is well known as a Korean traditional meju microbe. Experimental rats were divided into 4 diets groups (six rats/group) (NC: normal control group, EC: ethanol supplemented control group, ENY: ethanol extracts 0.5% supplemented diets of the non-fermented YD group, EFY: ethanol extracts 0.5% supplemented diets of the fermented YD group). After feeding them for four weeks, the activities GOT and GPT in serum, contents of neutral lipid, total cholesterol, LPO and GSH, and activities of XO (O type) enzyme, SOD and GST in liver tissue were observed. Compared to the NC group, the GOT and GPT activities in the EC group were markedly increased by 87.91% and 57.02%, and the contents of neutral lipid, total cholesterol and LPO were increased by 77.51%, 18.56% and 193.86%, respectively. On the other hand, the GSH content was decreased by 29.52%. The activities of SOD and GST which are anti-oxidation-related enzymes, were decreased by 42.78% and 0.94%, respectively, compared to the NC group, but the XO (O type) enzyme activity was significantly increased by 70.83%. These results confirmed that the liver tissue and anti-oxidation system of the EC group had been damaged. Compared to the EC group, the GOT and GPT activities of the ENY and EFY groups were significantly decreased by 24.73~41.99% and 22.91~30.11%, respectively. The contents of neutral lipid, total cholesterol and LPO were decreased by 16.65~33.33%, 22.44~23.11% and 63.34~66.13%, respectively, but the GSH content was significantly increased by 24.61~35.60%. The GST activity was not significantly affected, but the SOD activity was significantly increased by 214.94~261.19%. The XO (O type) enzyme activity was significantly decreased by 40.34~51.20%. Compared to the ENY group, the GOT and GPT activities of the EFY group were significantly decreased by 22.93% and 9.34%, respectively. The plasma contents of neutral lipid, total cholesterol and LPO were decreased by 20.01%, 0.86% and 7.59%, respectively. The SOD activity was significantly increased by 21.52%, and the XO (O type) enzyme activity was decreased by 18.19%. Given decreasde TG, total cholesterol, LPO contents of liver tissue, GOT, GPT and XO activity, and increased SOD activity, these study results that ethanol extracts from fermented Youngia denticulata Houtt Kitamura may be effective in reducing hepatotoxicity.

Green Tea Intake and Exercise Reduce Some Biochemical Markers of Obese Adolescents (녹차섭취와 운동에 의한 비만 청소년의 혈중 biochemical marker 함량 감소)

  • Yang, Jae-K.;Jung, Ji-Y.;Kang, Seol-J.;Cheong, Gang-W.;Kim, Jong-C.;Ko, Seong-K.;Jeong, So-B.
    • Journal of Life Science
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    • v.21 no.2
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    • pp.322-327
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    • 2011
  • The effects of green tea consumption and/or exercise for 12weeks on body weight and select biochemical markers in plasma were evaluated in obese adolescents with a fat ratio of greater than 25%. The subjects were randomly divided into a control group (n=9), green tea consumption group (n=9), exercise group (n=9) and green tea consumption with exercise group (n=9). Subjects in both green tea consumption group and green tea consumption with exercise group were given more than five cups of green tea extract in hot water ($90^{\circ}C$) daily, equivalent to 1.5-1.7 g dry green tea, for 12 weeks. Subjects in both the exercise group and green tea consumption with exercise group participated in a training program (HRmax 60-70%, 60 min/day) for 12 weeks. Control subjects were only given water equal to the quantity of green tea being given to the subjects of green tea consumption. No significant changes body weights were seen in any of these treatments, but the waist to hip ratio was reduced with treatments of both green tea and exercise. The control group showed no significant changes in TNF-$\alpha$, IL-6 and leptin levels. Green tea consumption reduced leptin (p<0.05), TNF-$\alpha$, and leptin levels. Exercise lowered TNF-$\alpha$ (p<0.05), IL-6 (p<0.01), and leptin (p<0.05) concentrations. Meanwhile, a combination of green tea consumption and exercise lowered TNF-$\alpha$, IL-6 (p<0.05) and leptin (p<0.05) levels. These results indicate that green tea consumption and exercise both had a positive effect on the reduction of inflammatory cytokines, TNF-$\alpha$, IL-6 and leptin, in obese adolescents, but no synergistic effect on the reduction of these cytokines.

Studios on Lipids in Fresh-Water Fishes 5. Distribution of Lipid Components in Various Tissues of Carp, Cyprynus carpio (담수어의 지질에 관한 연구 5. 잉어(Cyprynus carpio)의 부위별 지질성분의 분포)

  • CHOI Jin-Ho;RO Jae-Il;BYUN Dae-Seok;PYEUN Jae-Hyeung
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.18 no.2
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    • pp.149-156
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    • 1985
  • Distribution of lipid components in the tissue of meat, skin and viscera from carp(Cyprynus carpio) was analyzed using the techniques of column chromatography, thin layer chromatography and gas liquid chromatography according to the previous report(Choi, et al., 1984). Lipid content was varied by the portion such as $3.88\%$ in meat (free lipid, $2.47\%$ ; bound lipid, $1.41\%$), $8.02\%$ in skin(free lipid, $5.65\%$ ; bound lipid, $2.37\%$) and $6.18\%$ in viscera (free lipid, $3.54\%$ ; bound lipid, $2.64\%$). In the all portions of the body, free lipid was composed of $68\%\;to\;92\%$ in neutral lipid, $3\%\;to\;6\%$ in glycolipid and $4\%\;to\;18\%$ in phospholipid whereas bound lipid was composed of $8\%\;to\;20\%$ in neutral lipid, $2\%\;to\;7\%$ in glycolipid and $47\%\;to\;62\%$ in phospholipid. The free lipids of the tissues on the each portion were mostly represented by triglycerides and some diglycerides, but free lipids in viscera contained considerable amounts of free fatty acids. The bound lipids, on the other hand, commonly comprised appreciable amounts of esterified sterol and hydrocarbon, and triglycerides. The phospholipid was mainly consisted of phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl serine in the both free and bound lipids, and much more phosphatidyl choline in the bound lipid. The predominant fatty acids of free and bound lipids were $C_{16:0},\;C_{18:0},\;C_{20:4},\;C_{22:6}\;and\;C_{18:2}$ acids in polar lipids, and $C_{16:0},\;C_{16:1},\;C_{18:0},\;C_{18:1}\;and\;C_{18:2}$ acids in non-polar lipids, whereas those of neutral lipids were $C_{14:0}(2.54{\sim}6.98\%),\;C_{16:0}(11.20{\sim}21.13\%)$ and $C_{18:0}(1.58{\sim}12.76\%)$ of saturated acids, $C_{16:1}(7.06{\sim}20.70\%),\;C_{18:1}(21.68{\sim}30.50\%)$ and $C_{20:1}(1.76{\sim}6.27\%)$ of monoenoic acids, and $C_{18:2}(4.50{\sim}6.89\%),\;C_{20:4}(1.52{\sim}4.29\%)$ and $C_{22:6}(0.73{\sim}6.62\%)$, respectively. In conclusion, the fatty acid compositions revealed apparent differences between the free lipid and bound lipids in the tissues of body.

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Effects of Walking and Band Exercise on C-reactive Protein and Cardiovascular Disease Risk Factor in Overweight and Obese Children (걷기와 밴드운동이 과체중 및 비만아동의 C-반응성단백질 및 심혈관질환 위험인자의 변화에 미치는 영향)

  • Kim, Hyun-Jun;Kim, Tae-Un
    • Journal of Life Science
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    • v.18 no.2
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    • pp.193-199
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    • 2008
  • The purpose of this study was to demonstrate the effectiveness of walking and band exercise for 12 weeks on c-reactive protein and cardiovascular disease risk factor in overweight and obese children. Body composition, blood lipids, insulin sensitivity, c-reactive protein (CRP) were assessed before, after 4 weeks and after 12 weeks of combined exercise. Sixteen participants (BMI${\geq}$21.3) were randomly allocated to exercise group (n=8) and control group (n=8). The exercise group participated in 50 minutes of walking exercise and band exercises as resistance training two days a week for 12 weeks. There were significant different on weight (p<0.001), BMI (p<0.001), fat mass (p<0.001), fat percentage (p<0.001), LBM percentage (p<0.001), TG (p<0.05), HDL-C (p<0.01), insulin (p<0.05), HOMA-IR (p<0.05) in exercise group after intervention. And the change of weight (p<0.001), BMI (p<0.001), fat mass (p<0.001), fat percentage (p<0.001), LBM mass (p<0.05), LBM percentage (p<0.001), insulin (p<0.05), HOMA-IR (p<0.05) were significant difference between groups after intervention. These findings suggest that 12 weeks of walking and band exercise can be useful intervention in the improvement of cardiovascular disease risk factor in overweight and obese children. But c-reactive protein was no change.

Evaluation of the Risk of Metabolic Syndrome for the Young Adults in Korean Students of a University (한국인 대학생군 대상의 청.장년층 대사이상증후군 위험성 평가)

  • Chung, Jae-Hun;Lee, Bo-Reum;Lim, Sung-Jin;Jang, Je-Kwan;Lee, Myung-Koo;Lee, Chong-Kil;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.53 no.1
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    • pp.19-24
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    • 2009
  • Metabolic syndrome, defined as the clustering of several metabolic disorders including obesity (waist circumference ${\geq}90$ if male or ${\geq}80$ if female, cm), dyslipidemia ($TG{\geq}150$ or HDL-C<40 if male or <50 if female, mg/dl), hypertension ($BP{\geq}130/85mmHg$) and hyperglycemia (fasting plasma $glucose{\geq}110mg/dl$), increases the cardiovascular risk of the general population. Recently, risk of this syndrome arises in young adults world widely. Therefore, we randomly selected and evaluated the risk of metabolic syndrome of total 43 people (group I-22, group II-21) for 2 years. Group I was 22 peoples (15 males, 7 females) with age of 22 thru 35 year old (average 28 year old) and group II was 21 people (19 male, 2 female) with age of 22 thur 32 years old (average 24 year old) in Cheongju area from March 1st thru 30th of 2008 in Cheongju area from September 1st thru 30th of 2007 in order to find out how serious this phenomenon is in young adult of Korea. 13.95% (n=7) of total people has a metabolic syndrome by NCEP/ATPIII definition among this group (group I-6, group II-1). Those of 6 have 3 or over risk factor for metabolic syndrome such as obesity, hypertension, fasting blood glucose and hypetriglyceridemia at the same time (group I-5, group II-1). Group I have more risk factor because of more higher age than group II. Therefore we need aggressively to monitor and provide them for early diagnosis, educational programs and assistance for lifestyle changes in order to prevent metabolic syndrome among young adults.

Utilization of Fat Sources in Pigs Weaned at 21 Days of Age

  • Piao, X.S.;Jin, J.;Kim, J.H.;Kim, J.D.;Shin, I.S.;Han, In K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.9
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    • pp.1255-1262
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    • 2000
  • A total of 80 pigs ($5.68{\pm}0.61kg$ BW; 21 d of age) were used to evaluate the effect of fat sources in weaned pigs. Pigs were allotted into five treatments based on body weight, in a completely randomized block design. Treatments consisted of diets representing different ratio between soy oil or corn oil and tallow; 1) S100 (soy oil 100%), 2) S75 (soy oil:tallow=75:25), 3) S50 (soy oil:tallow=50:50), 4) C75 (corn oil:tallow=75:25), 5) C50 (corn oil:tallow=50:50). During d 0 to 14, pigs were fed diets containing 3,400 kcal ME, 23% crude protein, 1.65 % lysine and for the period of d 15 to 28, pigs were fed diets supplying 3,400 kcal ME, 20.5% crude protein, 1.355% lysine. For d 0 to 14, a significant differences in ADG and ADFI were observed among treatments, pigs fed animal-vegetable fat blends gained more than pigs fed the S100. As tallow addition was increased from 25% to 50% replacing soy or corn oil, ADG was improved from 6.32% to 28.38%. In phase II (d 15 to 28) period, ADG, ADFI and FCR were not significantly different among treatments. For overall period (d 0 to 28), pigs fed 50% animal:50% vegetable fat blends diets consumed more feed and grew faster than pigs fed control diet and 75% vegetable oil:25% tallow groups, but the differences was not significant among treatments. Apparent DM, CP and fat digestibility were increased with time postweaning for each treatment. There were no differences in digestibilities of total amino acid during overall period. The combination of soy oil or corn oil with tallow produced slightly higher serum triglycerides (TG) and total cholesterol (TC) combination compared with the soy oil alone. In conclusion, tallow:soy (or corn) oil blends diets improved growth rate and the ratio of 50% tallow plus 50% soy (or corn) oil blends diets were favorable for growth and nutrient digestibilities of weaned pigs.