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( Xian Li ),( Yue Lu ),( Ye Jin ),( Jong Keun Son ),( Seung Ho Lee ),( Hyeun Wook Chang ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.1
Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cγ1 (PLCγ1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
( Xian Li ),( Yue Lu ),( Ye Jin ),( Jong Keun Son ),( Seung Ho Lee ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0
Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca(2+) influx via phospholipase Cγ1 (PLCγ1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
( Xian Li ),( Ju Hye Yang ),( Ye Jin ),( Fansi Jin ),( Dong Young Kim ),( Jae Hoon Chang ),( Jung Ae Kim ),( Jong Keun Son ),( Tae Chul Moon ),( Kun Ho Son ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
Ethnopharmacological relevance: 15,16-Dihydrotanshinone I (DHT-I), isolated from the dried root of Salvia miltiorrhiza Bung, which is traditionally used to treat cardiovascular and inflammatory diseases agent in Chinese medicine. DHT-I has been reported to have a broad range of biological activities, including antibacterial activity, and has been used to treat circulatory disorders, hepatitis, inflammation, cancer, and neurodegenerative diseases. Aim of the study: The aim of this study was to evaluate the anti-allergic inflammatory effects of DHT-I on degranulation and on the generation of eicosanoids, such as, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4), in IgE/Ag-stimulated bone marrow-derived mast cells (BMMCs). Materials and methods: The anti-allergic inflammatory activity of DHT-I was evaluated using BMMCs. The effects of DHT-I on mast cell activation were investigated by following degranulation and eicosanoid generation using ELISA and immunoblotting and immunoprecipitation techniques. Results: DHT-I at a concentration of 20 μM markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of FcεRI-mediated signaling pathways demonstrated that DHT-I inhibited the phosphorylations of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT), and inhibited downstream signaling process, including [Ca2þ]i mobilization induced by the phosphorylation of phospholipase Cγ1 (PLCγ1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-κB (NF-κB) pathway. Conclusions: DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a FcεRI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases. & 2015 Elsevier Ireland Ltd. All rights reserved.
Nan Zhong,Xian Li,Huan Hu,Yawen Huang,Xu Ye,Junxiao Yang 한국고분자학회 2019 Macromolecular Research Vol.27 No.12
All-benzocyclobutene functionalized polycarbosilanes and the derived copolymers were successfully synthesized by ring-opening polymerization (ROP) of 1,1-dibenzocyclobutene-1-silacyclobutane (DBCBSCB) and 1,1-diphenylsiletane (DPSCB) using Karstedt’s catalyst. Adjusting the copolymerization ratio of DBCBSCB and DPSCB could afford to control the ultimate properties of the cured resins. The linear polycarbosilanes containing dibenzocyclobutene were directly cross-linked upon high temperature. With increasing the copolymerization ratio of DBCBSCB and DPSCB, the 5% weight loss temperature (T5%) of cured resins is increased from 450 °C to 506 °C under a nitrogen atmosphere, while the dielectric constant (k) is decreased from 2.60 to 2.42 at 10 MHz. The excellent thermostability and low-dielectric performance make such thermosets have potential application in the microelectronic industry.
Yueqin Shen,Xian Li,Yawen Huang,Guanjun Chang,Ke Cao,Junxiao Yang,Renyi Zhang,Xueying Sheng,Xu Ye 한국고분자학회 2016 Macromolecular Research Vol.24 No.7
pH and redox dual stimuli-responsive injectable hydrogels were prepared by cross-linking oxidized carboxymethyl cellulose (oxi-CMC) with 3,3'-dithiobis (propionohydrazide) (DTP) via Schiff base reaction under physiological condition. The hydrogels showed good performance such as tunable gelling time, appropriate rheology properties, high swelling ratio and low degradation rate. In vitro release studies confirmed that bovine serum albumin (BSA) as a model drug exhibited a sustainable release at pH 7.4 and an accelerated release under a lower pH 5.0 and/or reducing environments. The results signified that oxi-CMC/DTP hydrogels could be an attractive candidate for drug delivery system, tissue engineering or cell scaffold materials.
Su, Long,Li, Xian,Gao, Su-Jun,Yu, Ping,Liu, Xiao-Liang,Tan, Ye-Hui,Liu, Ying-Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2
Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.
Hwang, Seung-Lark,Li, Xian,Lu, Yue,Jin, Ye,Jeong, Yong-Tae,Kim, Yong Deuk,Lee, In-Kyu,Taketomi, Yoshitaka,Sato, Hiroyasu,Cho, You Sook,Murakami, Makoto,Chang, Hyeun Wook Elsevier 2013 The Journal of allergy and clinical immunology Vol.132 No.3
<P><B>Background</B></P> <P>Aggregation of FcεRI activates a cascade of signaling events leading to mast cell activation, followed by inhibitory signals that turn off the activating signals. However, the overall view of negative signals in mast cells is still incomplete. Although AMP-activated protein kinase (AMPK), which is generally known as a regulator of energy metabolism, is also associated with anti-inflammation, little is known about the role of AMPK in mast cells.</P> <P><B>Objectives</B></P> <P>We investigated the role of AMPK and its regulatory mechanism in mast cells.</P> <P><B>Method</B></P> <P>The roles of AMPK in FcεRI-dependent activation of bone marrow–derived mast cells (BMMCs) were evaluated by using chemical agents, small interfering RNAs (siRNAs), or adenovirus that modulated the activity or expression of AMPK signaling components. In addition, <I>AMPKα2</I> <SUP>−/−</SUP> mice were used to verify the role of AMPK in anaphylactic models.</P> <P><B>Results</B></P> <P>FcεRI signaling and associated effector functions in BMMCs were suppressed by the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) and were conversely augmented by siRNA knockdown of AMPKα2 or liver kinase B1 (LKB1), an upstream kinase of AMPK. Furthermore, <I>AMPKα2</I> deficiency led to increased FcεRI-mediated BMMC activation and anaphylaxis that were insensitive to AICAR, whereas enforced expression of AMPKα2 in <I>AMPKα2</I> <SUP>−/−</SUP> BMMCs reversed the hypersensitive FcεRI signaling to normal levels. Pharmacologic inhibition or siRNA knockdown of Fyn mimicked AMPK activation, suggesting that Fyn counterregulates the LKB1-AMPK axis. Mechanistically, Fyn controlled AMPK activity by regulating LKB1 localization.</P> <P><B>Conclusions</B></P> <P>The Fyn-regulated LKB1-AMPK axis acts as a novel inhibitory module for mast cell activation, which points to AMPK activators as therapeutic drugs for allergic diseases.</P>
( Yun Deng ),( Yong Qing Li ),( Xiong Wei Fan ),( Wu Zhou Yuan ),( Hua Ping Xie ),( Xiao Yang Mo ),( Yan Yan ),( Jun Mei Zhou ),( Yue Qun Wang ),( Xian Li Ye ),( Yong Qi Wan ),( Xiu Shan Wu ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.6
LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes αB-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with αB-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, αB-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or αB-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both αB-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and αB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21. [BMB reports 2010; 43(6): 432-437]