• Clinical and Experimental Pediatrics
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• v.52 no.9
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• pp.984-990
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• 2009

Purpose : Being small for gestational age (SGA) is a risk factor of short stature in children. Genetic background such as mid-parental height (MPH) is known to influence growth of children born SGA. We studied the relationship between growth of children born SGA and MPH and studied the effects of insulin-like growth factor (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) on postnatal growth in children born SGA according to MPH. Methods : Forty-nine neonates born SGA were included in this study. We defined corrected height standard deviation score (cHtSDS) by modified height SDS (HtSDS) based on their MPH. We categorized subjects into group 1 consisting of children with cHtSDS ${\geq}0$ (n=35) and group 2 consisting of children with cHtSDS <0 (n=14), and compared IGF-I and IGFBP-3 between the two groups. Results : The HtSDSs and cHtSDSs in groups 1 and 2 were $0.06{\pm}1.05$ vs. $-0.95{\pm}0.85$ (P=0.000) and $0.78{\pm}0.93$ vs. $-0.46{\pm}0.67$ (P=0.000), respectively. IGF-I SDS was higher in group 1 than in group 2 ($2.82{\pm}3.69$ vs. $0.23{\pm}2.42$, P=0.012). Total cHtSDS ($0.42{\pm}1.03$) was significantly higher than HtSDS ($-0.22{\pm}1.10$) (P=0.000). Conclusion : Our results show that cHtSDS differs significantly from HtSDS. Growth assessment by standardized growth curve does not uniformly show effects of genetic factors. A more accurate assessment of growth uses a personalized corrected growth curve that considers the genetic factor measured by MPH.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.4
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• pp.471-482
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• 2009

Nutrient availability may control muscle growth directly and indirectly through its influence on regulatory factors. We analyzed the effects of nutrient availability on the breast muscle insulin-like growth factor system. Real time RT-PCR was used to quantify the level of transcription in breast muscle from Langshan (LS) layer and Arbor Acres (AA) broiler chickens subjected to different feeding regimens during embryonic and postnatal development. The AA chickens were fed AA diet (AA, control group) while the LS chickens were either fed LS diet (LL) or AA diet (LA). According to our results, insulin-like growth factor (IGF)-II (embryonic day 16 (E16) - postnatal day 42 (P42)), IGF-I receptor (IGF-IR, E18-P42), and IGF binding protein (IGFBP)-2 (E18-P42), -5 (E16-P14), -7 (E12-P0), and -3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I. In comparison, IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E14-P0), and IGFBP-3 (E16-P0) were positively correlated with IGF-II, while IGF-IR (E10-E16) and IGFBP-3 (P0-P28) were negatively correlated with IGF-II. Moreover, IGFBP-2 (E16-P42), -7 (E10-E16), and -3 (E10-E16) were positively correlated with IGF-IR, while IGFBP-3 (P0-P28) was negatively correlated with IGF-IR. Finally, IGFBP-7 (E12-P0) was positively correlated with IGFBP-3, while IGFBP-2 (P0-P28) and -7 (P0-P42) were negatively correlated with IGFBP-3. Overall, the AA chickens exhibited higher levels of IGF-I, IGF-IR, and IGFBP-2 mRNA expression than the LL chickens, while the opposite was true for IGFBP-7. No strain differences in IGF-I, IGF-IR, and IGFBP-7 mRNA expression were detected between LA and AA chickens; however, a strain difference was observed for IGFBP-2. LA chickens exhibited higher levels of IGFBP-2 than LL chickens, while the opposite was true for IGFBP-7. Our data show the first evidence that certain genes may be correlated during specific developmental periods and that strain differences in the expression of those genes in LS and AA chickens are due to differential responses to the same diet.

• The Journal of Pediatrics of Korean Medicine
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• v.35 no.2
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• pp.11-20
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• 2021

Objectives The purpose of the study is to evaluate the safety of the Allium Fistulosum extract in children and its effectiveness in height growth. Methods This study is randomized, double-blind, placebo-controlled trial. The participants are children between the 3rd and 25th percentiles in height, and between the ages of 5 and 12 years. They are randomly assigned to treatment group or control group. The treatment group will take 5 g (1 g as Allium Fistulosum extract) for 24 weeks, 1 time a day. The control group will take the 5 g (0 g as Allium Fistulosum extract) of placebo for 24 weeks, 1 time a day. The primary outcome is change in height, and the secondary outcomes are growth rate, height standard deviations, Insulin-like growth factor-1 (IGF-1), Insulin-like growth factor binding protein-3 (IGFBP-3), IGF1-1/IGFBP-3 ratio, growth hormone, bone age, osteocalcin, and Z-score for growth. Results This protocol has been approved by the institutional review board (IRB) of Daejeon Korean Medicine Hospital of Daejeon University (IRB No. DJDSKH-20-BM-15), and registered in the Clinical Research Information Service (CRIS) (Registry No. KCT0005981). Conclusions This study will provide clinical information about the effectiveness and safety of Allium Fistulosum extract in children for their growth.

• The Journal of Pediatrics of Korean Medicine
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• v.37 no.3
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• pp.121-132
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• 2023

Objectives We aimed to confirm whether Humulus japonicus Extract Powder can enhance child height growth significantly and safely compared with a placebo. Methods A total of 150 children between the 3rd and 25th percentiles in height and between the ages of 6 and 9 years will be recruited to participate in this randomized, double-blind, placebo-controlled clinical trial. The participants will be randomly assigned to the treatment or placebo group. Participants in the treatment group will take one pack per day (700 mg of Humulus japonicus Extract Powder) for 24 weeks. Participants in the placebo group will take one package of placebo per day (0 mg of Humulus japonicus Extract Powder) for 24 weeks. The primary outcome will be a change in height after 12 weeks, and the secondary outcomes will be the height after 24 weeks, growth rate, height standard deviation, growth hormone, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), bone alkaline phosphatase (BALP), and osteocalcin after 12 and 24 weeks. Results This protocol was approved by the Institutional Review Board (IRB) of the Korean Medicine Hospital of Busan University (IRB No. PNUKHIRB-2023-03-002). Research participants will be recruited from June 2023 to December 2023. Conclusions The results of this study provide clinical information regarding the effectiveness and safety of the Humulus japonicus Extract Powder in increasing child height.

• Journal of Life Science
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• v.25 no.10
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• pp.1098-1102
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• 2015

FABPpm (plasma membrane-bound fatty acid binding protein ) is highly expressed in skeletal muscle. The principal role of this protein is modulating fatty acid uptake and metabolism. The influence of insulin-like growth factor-I (IGF-I), which is a major regulator of skeletal muscle cells, on FABPpm in skeletal muscle cells has not been investigated. To determine the effect of IGF-I on the expression of FABPpm, differentiated C2C12 murine skeletal muscle cells were treated with 20 ng/ml of IGF-I for different times. IGF-I increased the expression of FABPpm in a time-dependent manner. The mRNA level of FABPpm was measured by real-time quantitative PCR to determine whether the IGF-1-induced induction of FABPpm was regulated pretranslationally. The IGF-I treatment resulted in very rapid induction of the FABPpm mRNA transcript in the C2C12 myotubes. After 24 and 48 hr of the IGF-I treatment, FABPpm mRNA increased 130 and 179%, respectively. The increase in the protein expression returned to control levels after 72 hr of the IGF-I treatment, suggesting that IGF-1 regulated the FABPpm gene pretranslationally in skeletal muscle cells. This is the first evidence that IGF-I has a modulatory effect on the expression of FABPpm. In conclusion, IGF-I induced rapid transcriptional modification of the FABPpm gene in C2C12 skeletal muscle cells and exerted modulatory effects on FABPpm.

• Journal of Life Science
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• v.26 no.7
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• pp.758-763
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• 2016

Fatty acid transporters are key mediators of skeletal muscle lipid metabolism. Several protein groups have been implicated in cellular long-chain fatty acid uptake or oxidation, including fatty acid transporter proteins (FATPs), the plasma membrane fatty acid-binding protein (FABPpm), and the fatty acid translocase (FAT/CD36). FAT/CD36 is highly expressed in skeletal muscle and known to be regulated by various factors such as exercise and hormones. Insulin-like growth factor-I (IGF-I) is a well-known regulator of skeletal muscle cells. However, it has not been studied whether there is any interaction between IGF-I and FAT/CD36 in skeletal muscle cells. In this study, the effects of IGF-I treatment on FAT/CD36 induction were examined. Differentiated C2C12 cells were treated with 20 ng/ml of IGF-I at different time points. Treatment of C2C12 cells with IGF-I resulted in increased FAT/CD36 mRNA and protein expression. After 24 and 48 hr of IGF-I treatment, FAT/CD36 mRNA increased 89% and 24% respectively. The increase of both proteins returned to the control level after 72 hr of IGF-I treatment, suggesting that the FAT/CD36 gene is regulated pretranslationally by IGF-I in skeletal muscle cells. These results suggest that IGF-I can regulate the expression of FAT/CD36 in skeletal muscle cells. In conclusion, IGF-I induces a rapid transcriptional modification of the FAT/CD36 gene in C2C12 skeletal muscle cells and has modulating effects on fatty acid uptake proteins as well as oxidative proteins.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.45 no.5
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• pp.423-429
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• 2012

This study evaluated the effects of adding sea mustard Undaria pinnatifida glycoprotein to the diet of juvenile olive flounder Paralichthys olivaceus on its growth, and levels of insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs), and interleukins. Three experimental diets (U0, U0.5, and U1.0) were formulated that contained different amounts of an extract of U. pinnatifida (0, 0.5, and 1.0%, respectively). Experimental groups were established in triplicate (30 fish/group) and fed for 12 weeks. The experimental group fed 1.0% added U. pinnatifida glycoprotein had the greatest rate of weight gain, which differed significantly from the other experimental groups. SDS-PAGE of the plasma IGF-I and muscle protein showed that the experimental groups taking U. pinnatifida glycoprotein had significantly more IGF-I and a ca. 200 kDa protein, as compared to the control group. In addition, the amount of IGFBP-3 at ca. 43 kDa increased in the group given the U. pinnatifida extract, as compared to the control group. The interluekin-2, -4, -6, and -12 levels paralleled the level of growth factor in the groups given the U. pinnatifida extract. In conclusion, supplementing the diet of olive flounder with U. pinnatifida glycroprotein improved its growth and immunity.

• Journal of Embryo Transfer
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• v.12 no.3
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• pp.229-246
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• 1997

Implantation is a most important biological process during pregnancy whereby conceptus establishes its survival as well as maintenance of pregnancy. During the periimplantation period, both uterine endometriurn and conceptus synthesize and secrete a host of growth factors and cytokines which mediate the actions of estrogen and /or progesterone and also exert their steroid-independent actions. Growth factors expressed by the materno-conceptal unit en masse have important roles in cell migration, stimulation or inhibition of cell proliferation, cellular differentiation, maintenance of pregnancy and materno-conceptal communications in an autorcrine /paracrine manner. The present review focuses on the role of the intrauterine IGF system during periimplantation conceptus development. The IGF system comprises of IGF- I and IGF- II ligands, types I and II IGF receptors and six or more IGF-binding proteins(IGFBPs). IGFs and IGFBPs are expressed and secreted by uterine endometrium with tissue, pregnancy stage and species specificities under the influence of estrogen, progesterone and other growth factor(s). Conceptus also synthesizes components of the IGF system beginning from a period between 2-cell and blastocyst stages. Maternal IGFs are utilized by both maternal and conceptal tissues; conceptus-derived growth factors are believed to be taken up primarily by conceptus. IGFs enhance the development of both maternal and conceptal compartments in a wide range of biological processes. They stimulate proliferation and differentiation of endometrial cells and placental precursor cells including decidual transformation from stromal cells, placental formation and the synthesis of some steroid and protein hormones by differentiated endometrial cells or placenta. It is also well-documented in a number of experimental settings that both IGFs stimulate preimplantation embryo development. In slight contrast to these, prenatal mice carrying a null mutation of IGF and /or IGF receptor gene do not exhibit any apparent growth retardation until after implantation. Reason (s) for this discrepancy between the knock-out result and the in vitro ones, however, is not known. IGFBPs, in general, are believed to inhibit IGF action within the materno-conceptal unit, thereby allowing endometrial stromal cell differentiation as well as dampening ex cessive placental invasion into maternal tissue. There is evidence, however, indicating that IGFBP can enhance IGF action depending on environrnental conditions perhaps by directioning IGF ligand to the target cell. There is also a third possibility that certain IGFBPs and their proteolytic fragments may have their own biological activities independent of the IGF. In addition to IGFBPs, IGFBP proteases including those found within the uterine tissue or lumen are thought to enhance IGF bioavailability by degrading their substrates without affecting their bound ligand. In this regard, preliminary results in early pregnant pigs suggest that a partially characterized IGFBP protease activity in uterine luminal fluid enhances intrauterine IGF bioavailability during conceptus morphological development. In summary, a number of in vitro results indicate that IGFs stimulates the development of the rnaterno-conceptal unit during the periimplantation period. IGFBPs appear to inhibit IGF action by sequestering their ligands, whereas IGFBP proteases are thought to enhance intrauterine bioavailability of IGFs. Much is remaining to be clarified, however, regarding the roles of the individual IGF system components. These include in vivo evidence for the role of IGFs in early conceptus development, identification of IGF-regulated genes and their functions, specific roles for individual IGFBPs, identification and characterization of IGFBP proteases. The intrauterine IGF club house thus will be paying a lot of attention to forthcoming results in above and other areas, with its door wide-open!

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.366-371
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• 2010

Twelve Suffolk${\times}$Small-tail-Han male sheep (body weight 21-26 kg), aged four months, were used to study the effects of volatile fatty acids (VFA) on IGF-I (insulin-like growth factor-I), IGFBP-3 (insulin-like growth factor binding protein-3), GH (growth hormone), insulin and glucagon in plasma, and IGF-I and IGFBP-3 in different tissues. The sheep were randomly divided into four groups with 3 sheep in each group. The sheep were sustained by total intragastric infusions and four levels of mixed VFA (the molar proportion of acetic acid, propionic acid and butyric acid was 65:25:10), which supplied 333, 378, 423 and 468 KJ energy/kg $W^{0.75}$/d, were infused into the rumen as experimental Treatments I, II, III and IV, respectively. The experiment lasted 12 days, of which the first 8 days were for pretreatment and the last 4 days for collection of samples. At the end of the experiment, blood samples were taken and then the sheep were slaughtered and tissue samples from the rumen ventral sac, rumen dorsal sac, liver, duodenum and Longissimus dorsi muscle were obtained. IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in different tissues were analysed. Results showed that the concentration of IGF-I, IGFBP-3, GH, insulin or glucagon in plasma and the content of IGF-I and IGFBP-3 in the rumen dorsal sac, rumen ventral sac, liver or Longissimus dorsi muscle were increased with VFA infusion level (p<0.05). No significant differences were found in duodenum IGF-I between Treatments I and II and in rumen dorsal sac IGFBP-3 between Treatments II and III (p>0.05). It was concluded that IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in rumen dorsal sac, rumen ventral sac, liver and Longissimus dorsi muscle were increased significantly with increasing level of ruminal infusion of mixed VFA.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.120-128
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• 2005

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.