• Biomolecules & Therapeutics
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• 제29권5호
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• pp.527-535
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• 2021

Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDX-MS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.

• 한국식품영양과학회지
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• 제15권2호
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• pp.191-200
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• 1986

It is now generally accepted that individuals at increased risk for cardiovascular disease may be identified by certain traits or habbits. The factors such as high blood pressure, elevated blood cholestrol, age, sex and obesity are associated with increseaed frequency of disease. The blood cholesterol level lowering will decrease cardiovascular disease risk. The regression of atherosclerosis can be achieved by lowering the level of circulating cholesterol. Those things are connected with the quantity and quality of protein, fats, carbohydrates, especially soluble and non-soluble fiber, magnesium and calcium. The lipoprotein and lipid metabolism are connected with the lipid transport. The factors on lipid absorption and blood serum lipid pattern of human are exist. The factors have a variety of materials with different chemical and physical properties. The soluble fiber diet make a low blood and liver lipids. Many kind of soluble fiber results in a lowering of blood cholesterol and triglyceride levels. The cholesterol lowering effects of dietery fiber may be a results of alterations of in intestinal handling of fats, hepatic metabolism of fatty acid or triglyceride acid metabolism of lipoprotein. It is investigated that the high density lipoprotein (HDL) is inversely related to coronary artery disease. It has been postulated that HDL may be an important factor in cholesterol efflux from the tissues, therby reducing the amount of cholesterol deposited there. Alternatively, the HDL may pick up cholestyl ester and phospholipid during normal VLDL lipolysis in the plasma. The HDL levels are relatively insensitive to diet. At present time, the cause-and -diet effect of HDL's inverse relation to CHD remains unclear.

• Asian-Australasian Journal of Animal Sciences
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• 제18권2호
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• pp.241-248
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• 2005

This study is aimed at understanding the role of arsenic in Roxarsone in causing fatty livers in mule ducks. One hundred 10-week-old mule ducks were randomly divided into 5 groups. Ducks received 2 weeks of various treatments followed by 2 weeks of withdrawal. The treatments were non-treatment (control), 300 mg/kg Roxarsone inclusion for 2 weeks ($1^{st}$ and $2^{nd}$ week), Roxarsone inclusion for one week ($2^{nd}$ week only), restrict feeding, or Roxarsone analogue (3-nitro-4-hydroxyphenyl acid) inclusion. Results showed that feed intake and body weight in the Roxarsone groups and the restrict feeding group decreased significantly during the treatment period. However only the liver and heart weights were significantly decreased (p<0.05) in the restrict feeding group. Fatty acid synthetase (FAS) activity showed a significant decrease (p<0.05) in the Roxarsone groups and the restrict feeding group, two-week-Roxarsone treatment significantly increased NADP-malic dehydrogenase (MDH) activity compared to the restrict (p<0.05). After 2 weeks drug withdrawal, the 1-week-Roxarsone or restrict feeding group showed significantly increased (p<0.05) glucose-6-phosphate dehydrogenase (G-6-PDH) activity (p<0.05). Two-week-Roxarsone treatment significantly decreased (p<0.05) the high density lipoprotein (HDL) and increased (p<0.05) the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) ratio. After drug withdrawal, the 1-week-Roxarsone or restrict feeding group showed significantly increased (p<0.05) creatine kinase (CK) activity. The 2-week-Roxarsone treatment group showed significantly increased (p<0.05) aspartate aminotransferase (AST) activity. The restrict feeding treatment group showed significantly decreased (p<0.05) total protein (TP) concentration. After drug withdrawal, the related enzyme activities in the blood that reflected the liver function were restored to the normal physiological range, except for the total bilirubin concentration and CK activity in the 1-week-Roxarsone group. This group showed a significant increase (p<0.05). Thus, the reasons for liver enlargement in the Roxarsone and restrict feeding groups were different.

• Asian-Australasian Journal of Animal Sciences
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• 제30권6호
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• pp.843-848
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• 2017

Objective: This experiment was conducted to evaluate the effects of a corn- or cassava- based diet on the production of meat-type ducks. Methods: Four hundred day-old ducks were used in this experiment. They were divided into five groups with each group replicated eight times. The ducks fed the corn-based diets served as the control group. The four other groups comprised different treatments, with each one given the cassava-based diet based on phase-feeding. Three treatments were fed the cassava-based diet from 16, 28, and 35 d; respectively up to 42 d of age and the other group was fed the cassava-based diet from 1 to 42 d of age. Results: The results indicated that ducks on either the corn- or cassava-based diets were similar in growth during 1 to 9 d of age. However, toward 35 to 42 d, the cassava-diet produced a higher weight gain (p<0.05). The cassava-based diet was better than the corn-based diet at increasing the outer and inner breast weights at 28, 35, or 42 d (p<0.05). In contrast, the corn-based diet was better at increasing abdominal fat (p<0.05). The two diets did not differ in their effects on the serum triglyceride, cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, very-low-density lipoprotein-cholesterol, and liver cholesterol. The corn-based diet, however, caused a highly significantly greater level of liver triglyceride (p<0.01). Conclusion: The results of this study suggest that both the cassava- and corn- based diets are similar in their effect on meat-type ducks during the starter stage but toward the finisher stage, the cassava-based diet has a better influence on weight gain and carcass characteristics.

• 한국축산식품학회지
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• 제38권2호
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• pp.259-272
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• 2018

This study aims to investigate the protective effects of kefir against myocardial infarction induced by isoproterenol (ISO). The rats were randomly divided into 4 groups, each group consisting of 8 rats. The control group, the kefir group (5 mL/kg/d kefir administered to rats as intra-gastric gavage for 60 d), the ISO group (100 mg/kg ISO was administered to rats, s.c. on 61. and 62. d), and kefir+ISO group (5 mL/kg/d kefir was administered to rats intra gastric gavage for 60 days prior to ISO, 100 mg/kg in two doses on day 61 and 62). 12 h after the last ISO dose, all rats were decapitated and their blood samples were collected. Cardiac tissue was reserved for histopathological examination. creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides, total cholesterol,very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and glucose were measured by autoanalyzer, whole blood malondialdehyde (MDA), glutathione (GSH) and plasma advanced oxidation protein products (AOPP) levels were measured spectrophotometrically. It was determined that in the group of kefir+ISO, the levels of AST (p<0.001), CK (p<0.001), LDH (p<0.001), MDA (p<0.001) and AOPP (p<0.001) were decreased, while the GSH (p<0.05) increased, compared to ISO group. There were no significant changes in lipid profile and glucose levels between these two groups. In conclusion, by examining cardiac enzymes and histopathological changes in cardiac tissue, it can be concluded that the administration of kefir in myocardial infarction induced by ISO can protect the heart with its antioxidant characteristic and minimize the toxic damage created by ISO.

• Nutrition Research and Practice
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• 제9권1호
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• pp.37-42
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• 2015

BACKGROUND/OBJECTIVES: Red grape seeds as functional food are a good source of important bioactive components such as phenolics and antioxidants, which decrease oxidative stress that contributes to the pathogenesis of hepatotoxicity. The current study was conducted in order to evaluate the protective effect of red grape dried seeds (RGDS) on antioxidant properties, lipid metabolism, and liver and kidney functions of rats with paracetamol (750 mg/kg) induced hepatotoxicity. MATERIALS/METHODS: RGDS was added to the basal diet at 5, 10, and 20%. Thirty five adult male rats were assigned to five groups (n = 7) for a six-week feeding period; group (1) normal control, group (2) induced control, groups (3, 4, and 5) fed a diet with RGPS at different levels, 5, 10, and 20%, respectively. At the end of the feeding period, animals' blood and tissues were collected for estimation of serum lipid profile, serum liver, and kidney biomarkers. The protection was measured by detecting lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT) (in liver tissues), and liver histological examination. RESULTS: The results showed a significant (P < 0.05) decrease in levels of serum cholesterol, triglycerides, low density lipoprotein (LDL-C), and very low density lipoprotein (VLDL-C), with a significant increase in level of high density lipoprotein (HDL-C) for RGDS groups compared to induced control. Rats administered a diet containing RGDS levels produced significant (P < 0.05) hepatoprotection by decreasing the activities of liver enzymes, kidney parameters, and lipid peroxidation, while levels of GSH, SOD, and CAT were increased significantly to near the normal levels. CONCLUSION: The RGDS 20% group was more effective than others against hepatotoxicity of paracetamol, which may be attributed to RGDS total phenols and antioxidant contents, which were 1.438 mg and 1.231 mg, respectively.

• Molecules and Cells
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• 제26권4호
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• pp.409-414
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• 2008

The cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism, has been shown to promote the transfer of triglycerides from very low density lipoprotein (VLDL) and low density lipoprotein (LDL) to high density lipoprotein (HDL) in exchange for cholesterol ester. Here we demonstrate that farnesoid X receptor ${\alpha}$ ($FXR{\alpha}$; NR1H4) down-regulates CETP expression in HepG2 cells. A $FXR{\alpha}$ ligand, chenodeoxycholic acid (CDCA), suppressed basal mRNA levels of the CETP gene in HepG2 cells in a dose-dependent manner. Using gel shift and chromatin immunoprecipitation (ChIP) assays, we found that $FXR{\alpha}$ could bind to the liver X receptor ${\alpha}$ ( $LXR{\alpha}$; NR1H3) binding site (LXRE; DR4RE) located within the CETP 5' promoter region. $FXR{\alpha}$ suppressed $LXR{\alpha}$-induced DR4RE-luciferase activity and this effect was mediated by a binding competition between $FXR{\alpha}$ and $LXR{\alpha}$ for DR4RE. Furthermore, the addition of CDCA together with a $LXR{\alpha}$ ligand, GW3965, to HepG2 cells was shown to substantially decrease mRNA levels of hepatic CETP gene, which is typically induced by GW3965. Together, our data demonstrate that $FXR{\alpha}$ down-regulates CETP gene expression via binding to the DR4RE sequence within the CETP 5' promoter and this $FXR{\alpha}$ binding is essential for $FXR{\alpha}$ inhibition of $LXR{\alpha}$-induced CETP expression.

• Clinical Nutrition Research
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• 제13권1호
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• pp.22-32
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• 2024

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder with widespread synovitis. Isoflavones, the main active component of soy, have been reported to have potent anti-inflammatory effects; the previous RA animal models showed the promising effect of soy supplementation. We aimed to evaluate the effect of soy bread on inflammatory markers and lipid profiles in RA patients. The present study was designed as a randomized controlled trial. RA patients were randomly allocated to obtain soy bread (n = 22) or placebo bread (n = 22) for 8 weeks. Fasting serum levels of lipid profile, total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and DAS28 were checked. Findings showed that there were no significant differences between the two groups in physical activity and dietary intake at the beginning of the study and the end of the study. There were no significant differences between the two groups in measured lipid profile markers, including high-density lipoprotein, low-density lipoprotein, total cholesterol, triglyceride, and very low-density lipoprotein, at the end of the trial. In addition, TAC and CRP also were not significant at the end of the trial between the 2 groups (0.66 and 0.12, respectively). However, the serum levels of TNF-α reduced significantly in the soy bread group at the end of the intervention (p < 0.000) and compared with the control group (p < 0.019). Soy bread consumption only decreased circulating TNF-α serum concentration. Other outcome measures were not changed following supplementation. Future long-term, well-designed studies are needed to confirm these findings.

• Preventive Nutrition and Food Science
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• 제16권3호
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• pp.195-201
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• 2011

Opuntia humifusa contains high levels of antioxidants including vitamin C, flavonoids and polyphenols, which may provide beneficial effects such as hypolipidemic activity and the reduction of atherosclerosis in postmenopausal women. This study was conducted to determine if the intake of O. humifusa seeds powder (OHS) regulates lipid concentrations, glutamate-oxaloacetate transaminase (GOT), and glutamate-pyruvate transaminase (GPT) in the serum of ovariectomized rats. Sprague-Dawley female rats were randomly assigned to either a sham-operated group (Sham) or one of the following four ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with 100, 200, and 500 mg/kg/day OHS (OHS100, OHS200, OHS500). Daily oral administration of OHS was initiated one week after ovariectomy and continued for seven weeks. Upon completion of treatments, organs were weighed and GOT, GPT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were determined enzymatically. No significant differences in feed intake and organ index were observed among the groups. Significant decreases in GPT, TC and LDL-C (p<0.05) were observed in all of the OHS groups (OHS100, 200 and 500), while no significant changes in HDL-C were observed. In addition, the OHS200 and OHS500 treatment groups exhibited a lower level of serum GOT compared to the OVX group. These results indicate that supplementation with O. humifusa seeds could induce favorable changes in serum lipoprotein and lipid profiles, which frequently worsen with inadequate estrogen availability.

• 한방재활의학과학회지
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• 제32권2호
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• pp.19-36
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• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.