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Lee, M.,Ryu, Y.H.,Cho, W.G.,Jeon, T.J.,Lyoo, C.H.,Kang, Y.W.,Lee, S.J.,Kim, C.H.,Kim, D.G.,Kang, J.H.,Seo, Y.B.,Yi, C.H.,Lee, K.,Choi, T.H.,Choi, J.Y. Pergamon Press 2014 Applied radiation and isotopes Vol.94 No.-
The purpose of the present study is to investigate the relationship between dopaminergic neuron destruction and 5-HT system changes in a hemiparkinsonian rat model. We performed PET imaging studies with trans-[<SUP>18</SUP>F]Mefway in a hemiparkinsonian model of unilateral 6-hydroxydopamine (6-OHDA) rats. Region-of-interests (ROIs) were drawn in the hippocampus (HP) and cerebellum (CB). HP uptake, the ratios of specific binding to non-specific binding in the HP, and non-displaceable binding potential (BP<SUB>ND</SUB>) in the HP were compared between 6-OHDA and control rats. As a result, unilateral 6-OHDA-lesioned rats exhibited significant bilateral reduction of HP uptake and trans-[<SUP>18</SUP>F]Mefway BP<SUB>ND</SUB> compared to the intact control group. Therefore, the results demonstrate that destruction of the dopaminergic system causes the reduction of the serotonergic system.
Lee, M.,Kim, Y.,Ryu, J.H.,Kim, K.,Han, Y.M.,Lee, H. Elsevier BV 2016 ACTA BIOMATERIALIA Vol.32 No.-
For practical applications of human embryonic stem cells (hESCs) in regenerative medicine, hESCs should be cultured on a large scale, and at the same time their properties have to be maintained in a controllable manner. Here, we report a chemically defined, scalable culture platform involving co-immobilization of heparin-catechol (HepC) and collagen type-1 (Col) for the long-term maintenance (>18 passages) of hESCs in a feeder-free condition. This platform utilizes a wet-adhesive, mussel-inspired heparin-catechol conjugate as a key component. We hypothesized that the heparin's affinity toward a wide range of proteins, might support undifferentiated in vitro growth of hESC. In fact, on the HepC-coated substrate, most hESC clumps were adhered (~78% at passage 2 (P2)) and expressed pluripotency markers (Fig. 2). Although HepC alone wasn't able to support long-term maintenance of hESCs in a feeder-free system due to decrease in the adhesion rate of hESCs on HepC coating (~ 44% at P4) during the repeated passaging processes, we found that when collagen type I was co-immobilized in the process of HepC coating, the long-term maintenance (passage 18 or more) of hESCs could be achieved with 100% adhesion efficiency (Fig. 4). One remarkable observation is that hESCs on collagen type-I underwent spontaneous differentiation after P6 (Fig. 3), which implied co-immobilized HepC played a role to suppress differentiation of hESCs. This study suggests that unlike the previous studies using proteins, peptides, or synthetic polymers, a polysaccharide, heparin, can be used as a cost-effective component for chemically defined, feeder-free culture of hESC. Statement of Significance: Towards practical applications of human embryonic stem cells (hESCs) in regenerative medicine, hESCs should be cultured on a large scale, and their pluripotent property has to be maintained in a controllable manner. To address these issues, studies that develop chemically defined culture substrates have been explored to replace the widely used, complex, and undefined culture materials represented by Matrigel. Most reports have focused on utilizing proteins, peptides and/or synthetic polymers. However, there have not yet been studies on using polysaccharides as two-dimensional coating materials to potentially replace Matrigel coating. Here, we report that heparin is an effective polysaccharide for the feeder-free, two dimensional culture of hESCs. Our study implies that use of polysaccharides or a polysaccharide/ECM combination can be a new, alternative design principle for hESC culture systems.
The bond survival time variation of polymorphic amyloid fibrils in the mechanical insight
Lee, M.,Baek, I.,Chang, H.J.,Yoon, G.,Na, S. North Holland 2014 Chemical physics letters Vol.600 No.-
The structure-property relationships of biological materials such as amyloid fibrils are important to developing therapeutic strategies for amyloid-related diseases. The mechanical characterization of biological materials can provide insight into such relationships. In this study, polymorphic human islet polypeptide (hIAPP) fibrils were constructed with molecular modeling, and a constant-force bending simulation was performed to characterize the different mechanical behaviors of polymorphic hIAPP protofibrils. Our simulation results showed that, owing to their different intramolecular interactions, the fracture times of polymorphic hIAPP protofibrils depend on polymorphic structures.