• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.31 no.3
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• pp.154-160
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• 2020

Objectives: It remains unclear whether methylphenidate (MPH) has yadverse effects on growth in children. This study aimed to investigate the association of MPH with serum biological markers of growth in children with attention-deficit/hyperactivity disorder (ADHD). Methods: The present study included 103 children with ADHD (64 drug-naive children, 39 MPH-treated children) and 112 control subjects. Children with ADHD were diagnosed on the basis of a semi-structured interview. Levels of biochemical markers of growth, including insulin-like growth factor-I, thyroid stimulating hormone (TSH), free T₄, calcium, phosphorus, alkaline phosphatase, vitamin D, hemoglobin, total protein, albumin, total cholesterol, and hematocrit were measured in these individuals. Results: Except in case of TSH, no intergroup differences were found in the levels of the growth markers. The levels of TSH were found to be lower in the MPH-treated boys with ADHD than in the drug-naive and control groups (p<0.05), although the levels of TSH in all the groups were within normal limits. Conclusion: In this cross-sectional study, no significant association was found between MPH and growth markers. This calls for the need to carry out prospective longitudinal research studies in the future that investigate the effect of MPH on the growth trajectory in children.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.103-111
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• 2006

Objectives : Deer antler Water Extract(DAE), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immuno-suppressive and immuno-activating Korean herbal-acupuncture, is thought to play an important role in human bone remodeling. Methods : To determine whether DAE can induce the differentiation of resting zone chondrocytes(RC) or not, confluent cell cultures were pretreated for 24, 36, 48, 72, and 120hrs with DAE. At the end of pretreatment, the media were replaced with new media containing $10^{-10}{\sim}10^{-8}M\;1,25-(OH)_2D_3$ and the cells incubated for an additional 24hrs. Results : This second treatment was chosen because prior studies had shown that only the more mature growth zone chondrocytes(GC) respond to this vitamin $D_3$ metabolite. The effect of DAE pretreatment on cell maturation was confirmed by measuring alkaline phosphatase (ALPase)-specific activity. Changes in matrix protein synthesis were examined by measuring collagen synthesis, as well as $^{35}SO_4$ incorporation into proteoglycans. When RC cells were pretreated for 120h with DAE, treatment with $1,25-(OH)_2D_3$ caused a dose-dependent increase in ALPase-specific activity and collagen synthesis, however, the proteoglycan production was not affected. RC cells pretreated with $1,25-(OH)_2D_3$ responded like RC cells that had not received any pretreatment. Conclusion : These results indicate that DAE directly regulates the maturation of RC chondrocytes into GC chondrocytes. Therefore it was indicated that DAE may play a significant role in regulating chondrocyte maturation during endochondral ossification.

• International Journal of Oral Biology
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• v.45 no.1
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• pp.15-24
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• 2020

The fruit of Chaenomeles sinensis (Thouin) Koehne (Chaenomelis Fructus) known as "Mo-Gua" in Korea has been commonly used in traditional medicine to treat inflammatory diseases, such as sore throat. However, its effect on bone metabolism has not been elucidated yet. Here, we examined the effect of Chaenomelis Fructus ethanol extract (CF-E) on receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation and formation. CF-E considerably inhibited osteoclast differentiation and tartrate-resistant acid phosphatase-positive multinuclear cell formation from bone marrow-derived macrophages and osteoclast precursor cells in a dose-dependent manner. In addition, the formation of actin rings and resorption pits were significantly suppressed in CF-E-treated osteoclasts as compared with the findings in non-treated control cells. Consistent with these phenotypic inhibitory results, the expressions of osteoclast differentiation marker genes (Acp5, Atp6v0d2, Oscar, CtsK, and Tm7sf4) and Nfatc1, a pivotal transcription factor for osteoclastogenesis, were markedly decreased by CF-E treatment. The inhibitory effect of CF-E on RANKL-induced osteoclastogenesis was associated with the suppression of NFATc1 expression, not by regulation of mitogen-activated protein kinases and NF-κB activation but by the inactivation of phospholipase C gamma 1 and 2. These results indicate that CF-E has an inhibitory effect on osteoclast differentiation and formation, and they suggest the possibility of CF-E as a traditional therapeutic agent against bone-resorptive diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.2
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• pp.153-164
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• 2020

Objectives This study is designed to evaluate the safety of Soshihotang soft extract in healthy male volunteers. Methods 12 healthy male volunteers were recruited and this study was carried out by a single center. Laboratory test results, vital signs of the volunteers were collected to evaluate safety. According to registration order, the 12 subjects were allocated by serial number. To evaluate safety, blood samples were taken and vital signs were checked 4 times-screening, pre administration, post administration and follow up-during the whole trial. The incidence of all adverse effects are shown in percentage. The mean and standard deviation were used to to describe and summarize continuous data. To evalate the effectiveness of the intervention, data of blood tests was analyzed by Wilcoxon signed rank test or paired T-test (p<0.05). Results In the case of red blood cell, hemoglobin, hematocrit, neutrophils, protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase values, the normality test result of the variable for the difference value before and after the dosing has a significance level <0.05. But most of values did not deviate from the normal range, and the deviation from the normal range could not be regarded as the significance associated with this clinical trial. And adverse event wasn't observed associated with the clinical trial drug. Conclusions Soshihotang soft extract were considered to be safe for healthy male volunteers.

• Journal of the East Asian Society of Dietary Life
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• v.20 no.5
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• pp.680-686
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• 2010

Silk sericin protein was hydrolyzed by seven proteolytic enzymes in order to examine the effectiveness of the hydrolysates in binding calcium. The amino acid nitrogen content of hydrolysates from Flavourzyme was higher than that for other enzymes, and its calcium binding capacity showed a dose-dependent increase. We examined the effects of calcium binding peptide from sericin hydolysates on the bioavailability of Ca-deficient rats. Three-week-old male rats were fed an Ca-deficient diet for three weeks. Rats were divided into four groups (DD: non-treated group on calcium deficient diet; DD+MC: milk-calcium treated group; DD+OC: organic calcium made using sericin hydolysates; and DD+IC: inorganic calcium ($CaCl_2$). After oral administration of calcium supplements for one week, the calcium content of the serum and liver were significantly higher in DD+OC ($101.7{\mu}g$/mL and $49.3{\mu}g$/mL) and DD+MC ($83.6{\mu}g$/mL and $42.8{\mu}g$/mL) than DD ($86.3{\mu}g$/mL and $43.4{\mu}g$/mL). The alkaline phosphatase (ALP) content in the treated groups was significantly lower than DD, but no significant difference among groups was shown. Aspartate aminotransferase (AST) levels did not show any significant difference between groups. Alanine aminotransferase (ALT) levels were significantly reduced compared to the DD group. In conclusion, binding calcium to peptides from sericin hydrolysates seems to improve its bioavailability, and to hasten the cure of calcium deficiency in experimental rats.

• Journal of Dental Rehabilitation and Applied Science
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• v.19 no.3
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• pp.185-193
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• 2003

The object of this study is to observe the effects of magnetism on the osteoblasts using a neodymium magnet. The osteoblasts was cultured under magnetic fields of varying intensities to evaluate the effect of magnetism on the activity and alkaline phosphatase acitivty of the osteoblasts. Osteoblasts were cultured in the cell density of $10^4$ for the evaluation of cell proliferation and 105/ml for the evaluation of ALP activity under 0. 10, 100, 500, 1000, 2000, 4000 gauss for 24 hour. For evaluation of osteoblast morphologic changes under magnetic, osteoblasts were observed by inverted microscope and TEM. To elucidate if IGF-receptors are increased under the magnetic field, we investigated osteoblasts by immunofluoroscence staining. The results were as follows: In the varying intensities of magnetic fields, the degree of cell proliferation was the highest in the magnetic field of 10 gauss and this gradually decreased up to 1000 gauss. In the magnetic fields stronger than 1000 gauss, the degree of the cell proliferation decreased to an even lower level than that of the control group. The ALP activity and protein synthesis showed a similar increase pattern as the degree of cell proliferation compared to the control group but showed little difference. Under the microscope, morphological change of the cells ( decrease in length and increase in roundness) were observed but no peculiarity of cell distribution could be found according to the magnetic field line. In the proper intensity of magnetic fields (10 gauss), the cultured cells showed increase in number of IGF Receptors compared to that of the control group.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.299-305
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• 2012

Endochondral bone formation is the process by which mesenchymal cells condense to become chondrocytes, which ultimately form new bone. The process of chondrogenic differentiation and hypertrophy is critical for bone formation and as such is regulated by many factors. In this study, we aimed to indentify novel factors that regulate chondrogenesis. We investigated the possible role of isopsoralen in induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were stained more intensely with Alcian blue than control cells, suggesting that isopsoralen increases the synthesis of matrix proteoglycans. Similarly, isopsoralen markedly induced the activation of alkaline phosphatase activity compared with control cells. Isopsoralen enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time-dependent manner. Furthermore, isopsoralen induced the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c-jun N-terminal kinase (JNK). Isopsoralen significantly enhanced the protein expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors of ERK and p38 MAPK, respectively, decreased the number of stained cells treated with isopsoralen. Taken together, these results suggest that isopsoralen mediates a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore a possible therapeutic agent for bone growth disorders.

• Molecules and Cells
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• v.28 no.5
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• pp.455-461
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• 2009

Calcineurin is a $Ca^{2+}$/Calmodulin activated Ser/Thr phosphatase that is well conserved from yeast to human. It is composed of catalytic subunit A (CnA) and regulatory subunit B (CnB). C. elegans homolog of CnA and CnB has been annotated to tax-6 and cnb-1, respectively and in vivo function of both genes has been intensively studied. In C. elegans, calcineurin play roles in various signaling pathways such as fertility, movement, body size regulation and serotonin-mediated egg laying. In order to understand additional signaling pathway(s) in which calcineurin functions, we screened for binding proteins of TAX-6 and found a novel binding protein, HLH-11. The HLH-11, a member of basic helix-loop-helix (bHLH) proteins, is a putative counterpart of human AP4 transcription factor. Previously bHLH transcription factors have been implicated to regulate many developmental processes such as cell proliferation and differentiation, sex determination and myogenesis. However, the in vivo function of hlh-11 is largely unknown. Here, we show that hlh-11 is expressed in pharynx, intestine, nerve cords, anal depressor and vuvla muscles where calcineurin is also expressed. Mutant analyses reveal that hlh-11 may have role(s) in regulating body size and reproduction. More interestingly, genetic epistasis suggests that hlh-11 may function to regulate serotoninmediated egg laying at the downstream of tax-6.

• Journal of Nutrition and Health
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• v.51 no.1
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• pp.23-30
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• 2018

Purpose: Runx2 (runt-related transcription factor 2), a bone-specific transcription factor, is a key regulator of osteoblast differentiation and its expression is induced by the activation of BMP-2 signaling. This study examined whether zinc modulates BMP-2 signaling and therefore stimulates Runx2 and osteoblast differentiation gene expression. Methods: Two osteoblastic MC3T3-E1 cell lines (subclones 4 as a high osteoblast differentiation and subclone 24 as a low osteoblastic differentiation) were cultured in an osteogenic medium (OSM) as the normal control, Zn-($1{\mu}M$ Zn) or Zn+($15{\mu}M$ Zn) for 24 h. The genes and proteins for BMP-2 signaling (BMP-2, Smad-1/p-Smad-1), transcription factors (Runx2, osterix), and osteoblast differentiation marker proteins were assessed. Results: In both cell lines, BMP-2 mRAN and protein expression and extracellular BMP-2 secretion all decreased in Zn-. The expression of Smad-1 (downstream regulator of BMP-2 signaling) and p-Smad-1 (phosphorylated Smad-1) also downregulated in Zn-. Furthermore, the expression of the bone-specific transcription factors, Runx2 and osterix, decreased in Zn-, which might be due to the decreased BMP-2 expression and Smad-1 activation (p-Smad-1) by Zn-, because Runx2 and osterix both are downstream in BMP-2 signaling. Bone marker gene expression, such as alkaline phosphatase (ALP), collagen type I (COLI), osteocalcin, and osteopontin were also downregulated in Zn-. Conclusion: The results suggest that a zinc deficiency in osteoblasts suppresses the BMP-2 signaling pathway via the suppression of Smad-1 activation, and this suppressed BMP-2 signaling can cause poor osteoblast differentiation.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.86-97
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• 2021

Background: Panax ginseng Meyer has been used as a nourishing edible herb in East Asia for thousands of years. 25-OH-PPT was first discovered as a natural rare triterpenoid saponin in ginseng stems and leaves by our group. Research found that it showed strong inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B, and protected cardiocytes (H9c2) through PI3K/Akt pathway. Methods: In the research, in order to optimize the 25-OH-PPT enrichment process, optimal macroporous resins and optimal purification conditions were studied. Meanwhile, the hypoglycemic effect and mechanism of 25-OH-PPT were evaluated by using STZ to establish insulin-dependent diabetic mice and the spontaneous type 2 diabetes DB/DB mice. Results and Conclusion: Research found that 25-OH-PPT can reduce blood glucose and enhance glucose tolerance in STZ model mice. It increases insulin sensitivity by upregulating GLUT4 and AMPK in skeletal muscle, and activating insulin signaling pathways. In DB/DB mice, 25-OH-PPT achieves hypoglycemic effects mainly by activating the insulin signaling pathway. Meanwhile, through the influence of liver inflammatory factors and lipids in serum, it can be seen that 25-OH-PPT has obvious anti-inflammatory and lipid-lowering effects. These results provide new insights into the study of ginseng as a functional food.