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Hwang, Ki-Jun,Chun, Moon-Woo,Jacobson, Kenneth A.,Jeong, Lak-Shin,Lee, Jeong-A,Moon, Hyung-Ryong,Kim, Hea-Ok,Kim, Kyung-Ran,Lee, Kang-Man,Kim, Bum-Tae 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16
On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a- d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating· lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-4, 6, and 7 did not show significant inhibitory activity against S-adenosylllolllocysteine hydrolase (SAH) up to 100 ㎛, maybe due to the absence of the secondary hydroxyl group at tile C3'-position, which should be oxidized by cofactor-bound NAD^(+). However, aplo-neplanocin A (5a) showed potent and highly selective binding affinity (K_(i), = 628 ± 69 nM) at the A_(3) adenosine receptor without any binding affinity at the A_(1) and A_(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugarsusing stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A_(3) adenosine receptor agonist, which play a great rote in developing new A_(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.
Design and Synthesis of A₃ Adenosine Receptor Ligands, 2´-Fluoro Analogues of Cl-IB-MECA
Kim, Hea Ok,Park, Jae Gyu,Moon, Hyung Ryong,Gunaga, Prashantha,Lim, Moo Hong,Chun, Moon Woo,Jacobson, Kenneth A.,Kim, Hee-Doo,Jeong, Lak Shin 梨花女子大學校 藥學硏究所 2003 藥學硏究論文集 Vol.- No.12
Synthesis of 2'-deoxy-2'-fluoro-N^(6) -substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A₃ adenosine receptor are described.
Antioxidant Activity of Extracts from Akebia quinata Decne
A-Ram Rim,Sun-Jung Kim,Kyung-Im Jeon,박은주,Hae-Ryong Park,Seung-Cheol Lee 한국식품영양과학회 2006 Preventive Nutrition and Food Science Vol.11 No.2
Antioxidant activity of Akebia quinata Decne was evaluated. Water extract (0.5 g/ 50 mL) of flowers and leaves of A. quinata were prepared and total phenol contents and radical scavenging activity of the extracts was determined for antioxidant activity. The total phenol contents of extracts from A. quinata flowers (FAQ) and leaves (LAQ) were 30.05 M and 20.23 M, while the radical scavenging activity of FAQ and LAQ were 60.51% and 52.97%, respectively. In addition, the effect of FAQ and LAQ extract on DNA damage induced by H2O2 in human lymphocytes was evaluated by comet assay. The FAQ and LAQ showed strong inhibitory effect against DNA damage induced by 200 M of H2O2. These results suggest that water extracts of A. quinata Decne flowers and leaves showed significant (p<0.05) antioxidant activity and protective effect against oxidative DNA damage.
Antioxidant Activity of Extracts from Akebia quinata Decne
A-Ram Rim,Sun-Jung Kim,Kyung-Im Jeon,Eunju Park,Hae-Ryong Park,Seung-Cheol Lee 한국식품영양과학회 2006 Preventive Nutrition and Food Science Vol.11 No.1
Antioxidant activity of Akebia quinata Decne was evaluated. Water extract (0.5 g/ 50 mL) of flowers and leaves of A. quinata were prepared and total phenol contents and radical scavenging activity of the extracts was determined for antioxidant activity. The total phenol contents of extracts from A. quinata flowers (FAQ) and leaves (LAQ) were 30.05 μM and 20.23 μM, while the radical scavenging activity of FAQ and LAQ were 60.51% and 52.97%, respectively. In addition, the effect of FAQ and LAQ extract on DNA damage induced by H₂O₂ in human lymphocytes was evaluated by comet assay. The FAQ and LAQ showed strong inhibitory effect against DNA damage induced by 200 μM of H₂O₂. These results suggest that water extracts of A. quinata Decne flowers and leaves showed significant (p<0.05) antioxidant activity and protective effect against oxidative DNA damage.
Antioxidant Activity of Extracts from Akebia quinata Decne
Rim, A-Ram,Kim, Sun-Jung,Jeon, Kyung-Im,Park, Eun-Ju,Park, Hae-Ryong,Lee, Seung-Cheol The Korean Society of Food Science and Nutrition 2006 Preventive Nutrition and Food Science Vol.11 No.1
Antioxidant activity of Akebia quinata Decne was evaluated. Water extract (0.5 g/50 mL) of flowers and leaves of A. quinata were prepared and total phenol contents and radical scavenging activity of the extracts was determined for antioxidant activity. The total phenol contents of extracts from A. quinata flowers (FAQ) and leaves (LAQ) were $30.05{\mu}M\;and\;20.23{\mu}M$, while the radical scavenging activity of FAQ and LAQ were 60.51 % and 52.97%, respectively. In addition, the effect of FAQ and LAQ extract on DNA damage induced by $H_2O_2$ in human lymphocytes was evaluated by comet assay. The FAQ and LAQ showed strong inhibitory effect against DNA damage induced by $200{\mu}M$ of $H_2O_2$. These results suggest that water extracts of A. quinata Decne flowers and leaves showed significant (p<0.05) antioxidant activity and protective effect against oxidative DNA damage.
Comparative Analysis of Human Epidermal and Peripheral Blood γδ T Cell Cytokine Profiles
( Kwangmi Kim1 ),( Jiyeon Han ),( Tae Ryong Lee ),( Dong Wook Shin ),( Hak Chang ),( A Ri Cho ),( Soon Jin Choi ),( Seong Jin Jo ),( Ohsang Kwon ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.3
Background: Human epidermal γδ T cells are known to play crucial roles in the defense and homeostasis of the skin. However, their precise mechanism of action in skin inflammation remains less clear. Objective: In this study, we analyzed the cytokine expression profile of human epidermal γδ T cells and compared it to that of peripheral blood γδ T cells to investigate the specific activity of epidermal γδ T cells in modulating skin inflammation. Methods: We isolated γδ T cells from epidermal tissue or peripheral blood obtained from healthy volunteers. Isolated γδ T cells were stimulated using immobilized anti-CD3 antibody and interleukin-2 plus phytohaemagglutinin, and were then analyzed using a cytokine array kit. Results: Both epidermal and peripheral blood γδ T cells produced comparable levels of granulocyte-macrophage colony-stimulating factor, I-309, interferon-γ, macrophage migration inhibitory factor, macrophage inflammatory protein-1α, and chemokine (C-C) ligand 5. The epidermal γδ T cells produced significantly higher levels of interleukin-4, -8, -13, and macrophage inflammatory protein-1β than the peripheral blood γδ T cells did. Notably, the epidermal γδ T cells produced several hundred-fold higher levels of interleukin- 13 than interleukin-4. Conclusion: These results suggest that the epidermal γδ T cells have a stronger potential to participate in the Th2-type response than the peripheral blood γδ T cells do. Furthermore, epidermal γδ T cells might play an important role in the pathogenesis of Th2-dominant skin diseases because of their active production of interleukin-13. (Ann Dermatol 26(3) 308∼313, 2014)
Jeong, Lak Shin,Choe, Seung Ah,Gunaga, Prashantha,Kim, Hea Ok,Lee, Hyuk Woo,Lee, Sang Kook,Tosh, Dilip K.,Patel, Amit,Palaniappan, Krishnan K.,Gao, Zhan-Guo,Jacobson, Kenneth A.,Moon, Hyung Ryong 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18
Truncated D-4'-thioadenosine derivatives lacking the 4'-hydroxymethylene moiety were synthesized starting from D-mannose, using cyclization to the 4-thiosugar and one-step conversion of the diol to the acetate as key steps At the human A₃ adenosine receptor (AR), N^(6)-substituted purine analogues bound potently and selectively and acted as antagonists in a cyclic AMP functional assay An N^(6)-(3-chlorobenzyl)purine analogue 9b displayed a K, value of 1 66 nM at the human A₃ AR Thus, truncated D-4'-thioadenosine is an excellent template for Ihe design of novel A₃ AR antagonists to act at both human and murine species.
Bae, Il-Hong,Lee, Sung Hoon,Oh, Soojung,Choi, Hyeongwon,Marinho, Paulo A.,Yoo, Jae Won,Ko, Jae Young,Lee, Eun-Soo,Lee, Tae Ryong,Lee, Chang Seok,Kim, Dae-Yong The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.2
Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma ($PPAR-{\gamma}$), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of $PPAR-{\gamma}$ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of $PPAR-{\gamma}$. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.
Jeong, Lak Shin,Shantanu Pal,Choe, Seung Ah,Choi, Won Jun,Kenneth A. Jacobson,Zhan-Guo Gao,Athena M. Klutz,Xiyan Hou,Kim, Hea Ok,Lee, Hyuk Woo,Lee, Sang Kook,Dilip K. Tosh,Moon, Hyung Ryong 이화여자대학교 약학연구소 2009 藥學硏究論文集 Vol.- No.19
Novel D- and L-4´-thioadenosine derivatives lacking the 4´-hydroxymethyl moiety were synthesized, starting from D-mannose and D-gulonic γ-lactone, respectively, as potent and selective species-independent A₃ adenosine receptor (AR) antagonists. Among the novel 4´-truncated 2-H nucleosides tested, a N^(6)-(3-chlorobenzyl) derivative 7c was the most potent at the human A₃ AR (K_(i) = 1.5 nM), but a N^(6)-(3-bromobenzyl) derivative 7d showed the optimal species-independent binding affinity.