• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.221-227
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• 2004

Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.242-253
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• 2008

It is a common clinical practice to recommend taking iron supplements for pregnant women during gestation. Although it is required to ensure adequate iron stores during pregnancy, there has been some debate over the interference effects of excessive iron load, because it is possible to compete in the transport in the intestine and placenta and in binding to serum proteins of other trace minerals. In this study, maternal and neonatal serum concentrations of Fe, Zn, Cu, Se, Cr, Mn, and Co were assessed along with maternal Fe intakes. A total of 124 pregnant women and their term neonates participated voluntarily in this research. The women were divided into one of the three groups {high Fe intake (HFI), median Fe intake (MFI), and low Fe intake (LFI)} by their total Fe intakes and one of the two groups (Anemic and Normal) by their Fe nutritional status. All the data were compared among the three groups and between the two groups also. Total Fe intakes of HFI, MFI, and LFI groups were 140.8 ${\pm}$ 76.1, 68.0 ${\pm}$ 11.2, and 30.2 ${\pm}$ 8.6 mg/day, respectively. Those of Anemic and Normal groups were 90.1 ${\pm}$ 74.8 and 86.6 ${\pm}$ 46.8 mg/day, respectively. Maternal Hb concentration and Hct were not significantly different among HFI, MFI, and LFI groups but those were significantly different between Anemic and Normal groups. However, neonatal Hb concentration was not significantly different among HFI, MFI, and LFI groups and between Anemic and Normal groups either. Maternal serum Fe concentrations of the three groups, HFI, MFI, and LFI, were similar but that of Anemic group was significantly lower compared to Normal group. However, there was no significant difference in neonatal serum Fe concentrations among the three groups and between the two groups either. Serum concentrations of the other trace minerals in both mothers and neonates were not significantly different among HFI, MFI, and LFI groups and between Anemic and Normal groups. In addition, in the maternal serum, Fe concentration was positively correlated to Zn and Se concentration, respectively. As for the neonatal serum, Fe concentration showed a positive correlation to Zn, Cu, Mn, Se, and Co concentration, respectively. No trace mineral concentration was found to correlate negatively to Fe concentration in both maternal and neonatal serum, The results in this study indicate that Fe intakes of pregnant women, even if it is considerably above the level of estimated average requirement (EAR), may not affect serum Fe concentration in both mothers and neonates. In addition it might not influence adversely on the availability of other trace minerals including Zn and Cu in both mothers and neonates.

• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.