Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
Tuberculosis and Respiratory Diseases
/
v.56
no.5
/
pp.465-484
/
2004
Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.
Jeon G. J.;Choy Y. H.;Cho K. H.;Kim M. J.;Kim H. C.;Choi J. G.;Lee C. W.;Hwang J. M.;Kim J. B.
Journal of Embryo Transfer
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v.20
no.3
/
pp.239-253
/
2005
Serum concentrations of Hanwoo steers and bulls as possible indicators of beef quality were analyzed to estimate their correlations with carcass traits. Blood samples were taken 2 months and right before shipping to abattoir and at the time of slaughter. And phenotypic correlation coefficients between serum concentrations and carcass traits were estimated. Beef yield index of steers was positively correlated with serum concentrations of total Protein (0.23), albumin (0.26), and calcium (0.31). But it was negatively co..elated with BUN (-0.30). Loin eye area was positively correlated with BUN (0.17) or with globulin (0.16). Back fat thickness was positively correlated with BUN (0.42) and inorganic phosphorus (0.20) being negatively correlated with total protein (-0.23), albumin (-0.33) and calcium (-0.33). Marbling score in the scale of 1 (scarcely marbled) through 9 (extremely marbled) was positively correlated with BUN (0.28) and negatively with IGF-I and calcium concentrations. Phenotype correlation coefficient of loin eye area with total protein concentration in the serum taken from steers right before shipment was estimated to be -0.16 and that with BUN was estimated to be -0.15. Serum concentrations of IGF, glucose, creatinine and on organic phosphorus from steers measured right before shipment were negatively correlated with respective correlation coefficient estimates as -0.21, -0.21, -0.19 and -0.18. Marbling score was negatively co..elated with serum creatinine (-0.16) measured at that time. Beef yield index of steers was positively correlated (0.31) with age adjusted calcium concentration in the serum taken at the time of slaughter. Correlation between body weight and BUN at slaughter was 0.17 At slaughter, loin eye area was negatively correlated with albumin (-0.19) and back fat thickness was also negatively correlated with age adjusted calcium concentration (-0.38). Marbling was negatively correlated with age adjusted calcium concentration(-0.17). Serum concentrations of testosterone, calcium and inorganic phosphorus taken in 2 months before slaughter were negatively but highly correlated with yield index(0.71, 0.67 and -0.71), respectively. Body weight at slaughter was positively was negatively correlated (0.67) with calcium level while dressing percentage was negatively (-0.69) correlated with serum glucose concentration, 2 months prior to slaughter. Correlation coefficients between back fat thickness and cortisol, between back fat thickness and inorganic phosphate were both positive (0.29 and 0.69). Marbling score was negatively correlated with creatinine (-0.81) and positively with BUN (0.87). Body weight loss during shipping was positively correlated with albumin and inorganic phosphate (0.77, 0.83). Yield index of bulls was positively correlated with serum testosterone concentration (0.66). Dressing percentage was positively and highly correlated with globulin (0.73). Back fat thickness of bulls, however, was negatively correlated with testosterone (-0.60). Loin eye area of bull carcasses was positively correlated with testosterone (0.40). Mar-blaine was negatively co..elated with creatinine (-0.55). Yield index of bulls and age adjusted HDLC concentration at slaughter was negatively correlated (-0.71). Dressing percentage of bulls was positively and highly correlated with globulin concentration (0.70). Back fat thickness was also positively correlated with HDLC (0.69) in the serum taken at slaughter. Correlation coefficients between carcass weight and triglyceride, between loin eye are and testosterone and between marbling score and creatinine or glucose were 0.51, -0.91 and -0.58, respectively.
Effects of recombinant bovine somatotropin (bST) on plasma hormonal concentration, embryo quality, and pregnancy rate were examined during the superovulation and synchronization treatment in donor and recipient cows. Hanwoos (Korean native beef cattle) were treated with controlled internal drug release (CIDR) combined with bST (CIDR+bST) or without bST (CIDR) as donor cows. The embryos recovered from donors were transferred into Holstein recipient heifers treated with bST (CIDR+bST) or without bST (CIDR) for synchronization. The correlation between IGF-I and P4 showed a positive pattern in the CIDR+bST group (r=0.44, p<0.01), but a negative pattern was shown in the CIDR group (r = -0.59, p<0.02) at day 7 of estrous cycles. Although the number of recovered, transferable, and degenerated embryos was not different, quantities of grade 1 (excellent) embryos in CIDR+bST group were significantly higher than those of the CIDR group (p<0.01). The pregnancy rate was higher in the CIDR+bST recipient group compared to CIDR group (p<0.05), when the embryos were recovered from the donors treated with CIDR. However, the pregnancy was maintained highly in both recipient groups, when the embryos were produced by CIDR+bST treated donors. It can be concluded that bST administration combined with CIDR is an effective method for superovulation and synchronization treatment to stabilize plasma hormonal levels, to obtain excellent quality of embryos, and to get higher pregnancy rate.
The study was conducted to investigate the effects of different levels of xylanase on performance, blood parameters, intestinal morphology, microflora and digestive enzyme activities of broilers. The wheat-based diets were supplemented with 0, 500, 1,000, 5,000 U/kg xylanase. Xylanase supplementation significantly (p<0.05) improved the feed:gain ratio of broilers from 1 to 21 d and 1 to 42 d. Supplementing 500 U/kg and 1,000 U/kg xylanase improved (p<0.05) the villus height and the ratio of villus height to crypt depth in the small intestine. Excess supplementation of xylanase (5,000 U/kg) increased the villus height in the ileum (p<0.01) and the ratio of villus height to crypt depth in the duodenum and ileum (p<0.05). The microflora in the ileum and caecum, digestive enzyme activities in the small intestine and the concentrations of serum glucose, uric acid, insulin and IGF-I were not affected by the supplementation of xylanase. Excess level of xylanase (5,000 U/kg) had a tendency to induce the multiplication of E. coli and total aerobes. The results suggested that supplementing 500 U/kg and 1,000 U/kg xylanase was beneficial for broilers and excess xylanase supplementation resulted in no further improvement or negative effects.
This research was designed to investigate the effects of Estromon including FGF271 (Female Growth Factor 271) which was developed as a phytoestrogen for post- and pre-menopausal syndrome (PMS). The oral administration of two capsules of Estromon twice a day for 3 months significantly improved PMS (Post-/Premenopausal Syndrome) about 5 times more than placebo group (OR=5.04, 95% C.1. 1.40-18.14). In the group of 24 patients having taken Estromon, the concentration of alkaline phosphatase asn the bone marker decreased by -9.3${\pm}$9.5 IU/L after 3 months with a statistic significance. Since the concentration of osteocalcin as the other bone marker also decreased in more patients in Estromon group than in placebo group, the bone density might be expected to be improved in long-term treatment. Serum human growth hormone level increased in 17 out of 24 patients. Triglycerides decreased by -8.0${\pm}$40 (mg%) after 1 month and by -4.4${\pm}$36 (mg%) after 3 months in Estomon group while triglycerides increased in both cases in placebo group (p.0.01). Therefore, PMS patients might benefit from Estromon as a phytoestrogen supplement without any serious side effects.
The objective of this study was to evaluate the effects of adding essential oils to the diet of weaned pigs on performance, nutrient utilization, immune response and intestinal health. A total of 96 weaning pigs ($8.37{\pm}1.58$ kg) were allotted to one of three dietary treatments. The treatments consisted of an unsupplemented basal diet (negative control, NC) or similar diets supplemented with 0.01% of an essential oil product which contained 18% thymol and cinnamaldehyde (EOD) as well as a diet supplemented with 0.19% of an antibiotic mixture which provided 150 ppm chlortetracycline, 80 ppm colistin sulfate and 50 ppm kitasamycin (positive control, PC). Each treatment was provided to eight pens of pigs with four pigs per pen. Over the entire 35 d experiment, ADG and fecal score were improved (p<0.05) for pigs fed the PC and EOD compared with the NC. Dry matter and crude protein digestibility as well as lymphocyte proliferation for pigs fed the PC and EOD diets were increased significantly compared with NC (p<0.05). IGF-I levels in plasma were significantly increased (p<0.05) in pigs fed the PC diet compared with pigs fed the NC diet. Interleukin-6 concentration was lower (p<0.05) and the tumor necrosis factor-${\alpha}$ level was higher (p<0.05) in the plasma of pigs fed the EOD diet than the NC diet. Plasma total antioxidant capacity level increased (p<0.05) in pigs fed the EOD diet compared with pigs fed the NC. Villus height to crypt depth ratio in the jejunum was greater (p<0.05) in pigs fed the PC and EOD diets than the NC. The numbers of E. coli in the cecum, colon and rectum were reduced (p<0.05) in pigs fed the PC and EOD diets compared with the control. In the colon, the ratio of Lactobacilli to E. coli was increased (p<0.05) in pigs fed the EOD diet compared with NC diet. Total aerobe numbers in the rectum were decreased (p<0.05) in pigs fed the PC and EOD diets compared with the control. Collectively, these results indicate that blends of essential oils could be a candidate for use as an alternative to traditional antibiotics in weaning pig diets.
Kim, Su Jin;Cho, Joong Bum;Kwak, Min Jung;Paik, Kyung Hoon;Kwon, Eun Kyung;Jin, Dong-Kyu
Clinical and Experimental Pediatrics
/
v.51
no.7
/
pp.742-746
/
2008
Purpose : The objective of this study was to evaluate the effects and adverse side-effects of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). Methods : Forty-one patients who had been treated with GH for more than two years (24 boys and 17 girls, mean age $7.3{\pm}3.3$ years during treatment initiation) were enrolled for this study. Results : After 2 years of GH therapy, the height and weight standard deviation scores (SDS) increased significantly ($-1.19{\pm}1.37$ vs. $-0.02{\pm}1.45$, and $1.02{\pm}2.42$ vs. $1.63{\pm}2.22$, P<0.002); however the percentage body fat decreased ($44.6{\pm}9.9%$ vs. $38.1{\pm}10.5%$, P<0.001). Further, no change was observed in the thyroid and serum glucose levels, but the total cholesterol level decreased. GH therapy did not impact glucose control in the patients with diabetes. The most common adverse effects of GH therapy were the progression of scoliosis and adenoid hypertrophy. Conclusion : GH therapy improved the height SDS and body composition in patients with PWS. However, GH should be used with caution in patients with scoliosis and adenoid hypertrophy.
Periodontal ligament (PDL) cells have been known as multipotential cells, and as playing an important rolesin periodontal regeneration. The PDL cells are composed of heterogeneous cell populations which have the capacity to differentiate into either cementoblasts or osteoblasts, depending on needs and conditions. Therefore, PDL cells have the capacity to produce mineralized nodules in vitro in mineralization medium which include ascorbic acid, ${\beta}$-glycerophosphate and dexamethasone. In spite of these well-known osteoblast like properties of PDL cells, very little is known about the molecules involved in the formation of the mineralized nodules in the PDL cells. In the present study, we analysed gene-expression profiles during the mineralization process of cultured PDL cells by means of a cDNA microarray consisting of 3063 genes. Nodules of mineralized matrix were strongly stained with alizarin red S on the PDL cells cultured in the media with mineralization supplements. Among 3,063 genes analyzed, 35 were up-regulated more than two-fold at one or more time points in cells that developed matrix mineralization nodules, and 38 were down-regulated to less than half their normal level of expression. In accord with the morphological change we observed, several genes related to calcium-related or mineral metabolism were induced in PDL cells during osteogenesis, such as IGF-II and IGFBP-2. Proteogycan 1, fibulin-5, keratin 5, ,${\beta}$-actin, ${\alpha}$-smooth muscle actin and capping protein, and cytoskeleton and extracellular matrix proteins were up-regulated during mineralization. Several genes encoding proteins related to apoptosis weredifferentially expressed in PDL cells cultured in the medium containing mineralization supplements. Dkk-I and Nip3, which are apoptosis-inducing agents, were up-regulated, and Btf and TAXlBP1, which have an anti-apoptosis activity, were down-regulated during mineralization. Also periostin and S100 calciumbinding protein A4 were down-regulated during mineralization.
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