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        Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for Cerebral Palsy

        Kang, Mino,Min, Kyunghoon,Jang, Joonyoung,Kim, Seung Chan,Kang, Myung Seo,Jang, Su Jin,Lee, Ji Young,Kim, Sang Heum,Kim, Moon Kyu,An, SeongSoo A.,Kim, MinYoung Mary Ann Liebert 2015 STEM CELLS AND DEVELOPMENT Vol.24 No.19

        <P>This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.</P>

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        Characterizing affinity epitopes between prion protein and b-amyloid using an epitope mapping immunoassay

        Mino Kang,Su Yeon Kim,안성수,Young Ran JU3 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.8

        Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that b-amyloid1–42 oligomer causes neurotoxicity associated with Alzheimer’s disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimer’s disease;therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in b-amyloid. Residues 23–39 and 93–119 in the prion protein were involved in binding to b-amyloid1–40 and 1–42, and monomers of this protein interacted with prion protein residues 93–113 and 123–166. Furthermore, b-amyloid antibodies against the C-terminus detected bound b-amyloid1–42 at residues 23–40, 104–122 and 159–175. b-Amyloid epitopes necessary for the interaction with prion protein were not determined. In conclusion, charged clusters and hydrophobic regions of the prion protein were involved in binding to b-amyloid1–40 and 1–42. The 3D structure appears to be necessary for b-amyloid to interact with prion protein. In the future, these binding sites may be utilized for 3D structure modeling, as well as for the pharmaceutical intervention of Alzheimer’s disease.

      • Slow relaxation dynamics of a mononuclear Er(iii) complex surrounded by a ligand environment with anisotropic charge density

        Lim, Kwang Soo,Kang, Dong Won,Song, Jeong Hwa,Lee, Han Geul,Yang, Mino,Hong, Chang Seop The Royal Society of Chemistry 2017 Dalton Transactions Vol.46 No.3

        <▼1><P>The Er complex containing a nitrate ligand exhibits typical single-ion magnet behavior, while slow relaxation is not visible in the Er complex containing neutral water molecules.</P></▼1><▼2><P>Two sets of isostructural mononuclear compounds, [Ln(LOMe)2(H2O)2](PF6) [1, Ln = Er; 3, Ln = Gd; LOMe = CpCo{P(O)(O(CH3))2}3] and Ln(LOMe)2(NO3) (2, Ln = Er and 4, Ln = Gd), are synthesized by self-assembly of the respective lanthanide ions and tripodal chelate ligands. The Ln ions are encircled by two LOMe ligands, and two water molecules or one nitrate anion. Each octacoordinated Ln center adopts a distorted square antiprism geometry. The Er complex (2) chelated by a nitrate anion shows slow dynamics in magnetic relaxation, diagnostic of a single-ion magnet. Quantum tunneling in 2 is effectively blocked by application of an external field. Weak intermolecular magnetic interactions occur in 2, and are supported by the magnetic behavior of 4. Chemical dilution of Er with the diamagnetic Y ion can nullify magnetic interactions and suppress quantum tunneling. Generation of slow relaxation dynamics in the Er system is related to the anisotropic charge distribution supplied by the coordination of ligands with different charge densities, as observed in the Dy analogue. This suggests that magnetic anisotropy arises in a coordination system when an anisotropic lanthanide ion (Dy and Er) is surrounded by a ligand environment with anisotropic charge density, resulting in slow magnetic relaxation.</P></▼2>

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