Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Tang, Yan-Hui,Hu, Min,He, Xiao-Peng,Fahnbulleh, Sando,Li, Cui,Gao, Li-Xin,Sheng, Li,Tang, Yun,Li, Jia,Chen, Guo-Rong Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Yan-Hui Tang,Min Hu,Xiao-Peng He,Sando Fahnbulleh,Cui Li,Li-Xin Gao,Li Sheng,Yun Tang,Jia Li,Guo-Rong Chen 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold,whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged IC50 value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro

Xiao-Hui Zhang,Hong Wu,Shu Tang,Qiao-Ning Li,Jiao Xu,Miao Zhang,Ya-Nan Su,Bin Yin,Qi-Ling Zhao,Nicole Kemper,Joerg Hartung,Endong Bao 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.2

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken (Gallus gallus) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKa/b and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKa/b level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKa/b. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

The association of Hsp90 expression induced by aspirin with anti-stress damage in chicken myocardial cells

Xiao-hui Zhang,Huai-sen Zhu,Zhuang Qian,Shu Tang,Di Wu,Nicole Kemper,Joerg Hartung,Endong Bao 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.1

The protective effect of aspirin during exposure to heat stress in broiler chickens was investigated. We assayed pathological damage, expression and distribution of Hsp90 protein and hsp90 mRNA expression in chicken heart tissues after oral administration of aspirin following exposure to high temperature for varying times. Heat stress induced increases in plasma aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities while causing severe heart damage, which was characterized by granular and vacuolar degeneration, nuclear shrinkage and even myocardium fragmentation in cardiac muscle fibers. After aspirin administration, myocardial cells showed fewer pathological lesions than broilers treated with heat alone. A high positive Hsp90 signal was always detected in the nuclei of myocardial cells from broilers treated with aspirin, while in myocardial cells treated with heat alone, Hsp90 in the nuclei decreased, as did that in the cytoplasm. Aspirin induced rapid and significant synthesis of Hsp90 before and at the initial phase of heat stress, and significant expression of hsp90 mRNA was stimulated throughout the experiment when compared with cells exposed to heat stress alone. Thus, specific pre-induction of Hsp90 in cardiovascular tissue was useful for resisting heat stress damage because it produced stable damage-related enzymes and fewer pathologic changes.

CADMIUM TELLURIDE NANOCRYSTALS: SYNTHESIS, GROWTH MODE AND EFFECT OF REACTION TEMPERATURE ON CRYSTAL STRUCTURES

XIAO-YING QI,KAN-YI PU,QU-LI FAN,DUO-FENG TANG,GUI-AN WEN,FREDDY Y. C. BOEY,LIAN-HUI WANG,WEI HUANG,HUA ZHANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2008 NANO Vol.3 No.2

A series of cadmium telluride (CdTe) nanocrystals were synthesized by a modified organometallic synthesis method at various reaction temperatures ranging from 130 to 250°C. In this method, octadecylamine (ODA) was introduced as an additional coordinating component to the mixture of trioctylphosphine oxide (TOPO) and trioctylphosphine (TOP). CdO was used as a precursor. The prepared CdTe nanocrystals were studied by the absorption and emission spectra as well as the powder X-ray diffraction (XRD) patterns. The result shows that besides the traditional continuous-growth mode observed frequently at relatively high reaction temperature, a discontinuous-growth mode was confirmed at the initial growth stage of CdTe nanocrystals, arising from the change of the absorption spectra of CdTe nanocrystals with the reaction time at relatively low reaction temperature. The structures of CdTe nanocrystals, e.g., the cubic zinc blende structure at 160°C and the hexagonalwurtzite structure at 250°C, were characterized by XRD.

Follistatin N terminus differentially regulates muscle size and fat in vivo

Hui Zheng,Chunping Qiao,Ruhang Tang,Jianbin Li,Karen Bulaklak,Zhenhua Huang,Chunxia Zhao,Yi Dai,Juan Li,Xiao Xiao 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminusdeleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy.

Over-expression of StLCYb increases b-carotene accumulation in potato tubers

Xiao-yan Song,Wen-jiao Zhu,Rui-min Tang,Jing-hui Cai,Min Chen,Qing Yang 한국식물생명공학회 2016 Plant biotechnology reports Vol.10 No.2

Lycopene b-cyclase (LCYb) is involved in the first step of the b-branch synthetic pathway of carotenoids from lycopene in plants. In this study, to explore the possibility of regulating b-carotene synthesis via the b-branchspecific pathway in potato, StLCYb gene was first isolated from potato cultivar Desiree, and its open reading frame was 1503 bp long without intron. The protein sequence of StLCYb showed high similarity with that of LCYbs in other species such as SlLCYb1, CaLCYb, NtLCYb and ApLCYb. StLCYb was expressed in all tissues and the highest level was observed in tubers followed in flowers, and the lowest level was in roots. HPLC detected an about 1.5–1.9 times increase in b-carotene content of transgenic potato tubers, in which the gene StLCYb was overexpressed, compared with the wild-type control. Besides, the expression levels of carotenoid-related genes StPSY, StPDS, StZDS, StCHYb and StZEP transcripts in the transgenic lines were significantly higher than in the wild-type control, which implied a positive regulation in promoting carotenoid synthesis. All these results suggest that b-carotene content in potato tubers could be regulated by modulating StLCYb expression.

HGFK1 is Associated with a Better Prognostis and Reverses Inhibition by Gefitinib in NSCLC Cases

Zhou, Xiao-Hui,Tang, Li-Na,Yue, Lu,Min, Da-Liu,Yang, Yi,Huang, Jian-An,Shen, Zan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

Changes in Protein Phosphorylation during Salivary Gland Degeneration in Haemaphysalis longicornis

Qi Xiao,Yuhong Hu,Xiaohong Yang,Jianna Tang,Xiaoshuang Wang,Xiaomin Xue,Mengxue Li,Minjing Wang,Yinan Zhao,Jingze Liu,Hui Wang 대한기생충학ㆍ열대의학회 2020 The Korean Journal of Parasitology Vol.58 No.2

The ticks feed large amount of blood from their hosts and transmit pathogens to the victims. The salivary gland plays an important role in the blood feeding. When the female ticks are near engorgement, the salivary gland gradually loses its functions and begins to rapidly degenerate. In this study, data-independent acquisition quantitative proteomics was used to study changes in the phosphorylation modification of proteins during salivary gland degeneration in Haemaphysalis longicornis. In this quantitative study, 400 phosphorylated proteins and 850 phosphorylation modification sites were identified. Trough RNA interference experiments, we found that among the proteins with changes in phosphorylation, apoptosis-promoting Hippo protein played a role in salivary gland degeneration.

Overexpression of TRPM7 is Associated with Poor Prognosis in Human Ovarian Carcinoma

Wang, Jing,Xiao, Ling,Luo, Chen-Hui,Zhou, Hui,Hu, Jun,Tang, Yu-Xi,Fang, Kai-Ning,Zhang, Yi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

Background: The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that has been shown to promote tumor metastasis and progression. In this study, we determined the expression of TRPM7 in ovarian carcinomas and investigated its possible prognostic value. Materials and Methods: Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7 was assessed by real-time PCR and immunohistochemistry, expressed with reference to an established scoring system and related to clinical pathological factors. Kaplan-Meier survival analysis was applied to estimate disease-free survival (DFS) and overall survival (OS). Univariate and multivariate cox regression analyses were performed to correlate TRPM7 expression levels with DFS and OS. Results: TRPM7 was highly expressed in ovarian carcinoma and significantly associated with decreased disease-free survival (DFS: median 20 months vs. 42 months, P=0.0002) and overall survival (OS: median 27 months vs. 46 months, P<0.001). Conclusion: Overexpression of TRPM7 expression is significantly associated with poor prognosis in patients with ovarian cancer.