摘要：
Type 2 diabetes mellitus (T2DM) is a chronic degenerative endocrine and metabolic disease with high mortality and morbidity, yet lacks effective therapeutics. We recently generated a novel fusion peptide INSR-IgG4Fc, Yiminsu (YMS), to facilitate the high-affinity binding and transportation of insulin. Thus, the aim of the present study was to determine whether the novel recombinant peptide, YMS, could contribute to restoring insulin sensitivity and glycaemic control in insulin resistance models and revealing its underlying mechanism. Palmitic acid (PA)-treated LO2 cells and high fat diet (HFD)-fed mice were treated with YMS. Therapeutic effects of YMS were measured using Western blotting, ELISA, qPCR, Histology and transmission electron microscopy. We observed that YMS treatment effectively improved insulin signaling in PA-treated LO2 cells and HFD-fed mice. Notably, YMS could significantly reduce serum levels of glucose, triglycerides, fatty acids and cholesterol without affecting the serum insulin levels. Moreover, our data demonstrated that YMS could restore glucose and lipid homeostasis via facilitating insulin transportation and reactivating PI3K/Akt signaling in both PA-treated cells and liver, gastrocnemius and brown fat of HFD-fed mice. Additionally, we noticed that the therapeutic effects of YMS was similar as rosiglitazone, a well-recognized insulin sensitizer. Our findings suggested that YMS is a potentially candidate for pharmacotherapy for metabolic disorders associated with insulin resistance, particularly in T2DM.
作者机构：
[让蔚清; 付由户; 刘洋; 翦耀文; 杨慧仙] Department of Center for Disease Control and Evaluation, University of South China, Hengyang, 421001, China;[熊文婧] Traditional Chinese Medicine Hospital of Hengyang, Hengyang, 421001, China
通讯机构：
[Rang, W.] D;Department of Center for Disease Control and Evaluation, China
作者：
Wang, J.;Zou, T.;Yang, H. X.;Gong, Y. Z.;Xie, X. J.;...
期刊：
Genetics and Molecular Research,2015年14(3):8819-8828 ISSN：1676-5680
通讯作者：
Liu, HY
作者机构：
[Yang, H. X.; Wang, J.] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang, Hunan, Peoples R China.;[Yang, H. X.; Wang, J.] Univ South China, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[Zou, T.] Univ South China, Affiliated Hosp 1, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Gong, Y. Z.; Xie, X. J.; Liao, D. F.] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.;[Liu, H. Y.; Liu, HY] Metammune LLC, Morrisville, NC 27560 USA.
通讯机构：
[Liu, HY ] M;Metammune LLC, Morrisville, NC 27560 USA.
摘要：
Insulin resistance is a key feature of obesity and type 2 diabetes mellitus (T2DM). Interaction of insulin with the insulin receptor (IR) leads to both its auto-phosphorylation and phosphorylation of tyrosine residues on the IR substrate (IRS) proteins, initiating the activation of intracellular signaling cascades. The metabolic effects of IRS are known to be mediated through pathways involving phosphatidyl-inositol 3-kinase (PI-3K), which result in the activation of Akt signaling. The C-terminal region of the IR ectodomain is required to facilitate the conformational changes that are required for high-affinity binding to insulin. Furthermore, the CH2 and CH3 domains in the Fc fragments of immunoglobulins are responsible for their binding to the Fc receptor, which triggers transcytosis. In this study, we created a fusion peptide of the C-terminal end of the human IR ectodomain with the IgG4 Fc fragment, including an intervening polyG fragment to ensure enough space for insulin binding. We named this new peptide "Yiminsu", meaning an insulin sensitizer. The results of our analyses show that Yiminsu significantly facilitates insulin signaling via the activation of Akt in hepatocytes in a dose- and time-dependent manner. Further studies are required to determine whether Yiminsu can act as an insulin sensitizer.
作者：
Yang Sheng-yuan;Xu Xiao-na*;Yu Jun-hui;Yang Hui-xian;Hu Cheng-lan
期刊：
光谱学与光谱分析,2015年35(12):3471-3474 ISSN：1000-0593
通讯作者：
Xu Xiao-na
作者机构：
[Yu Jun-hui; Yang Hui-xian; Yang Sheng-yuan; Xu Xiao-na; Hu Cheng-lan] Univ South China, Coll Publ Hlth, Hengyang 421001, Peoples R China.
通讯机构：
[Xu Xiao-na] U;Univ South China, Coll Publ Hlth, Hengyang 421001, Peoples R China.
关键词：
核酸探针;共振光散射
摘要：
根据目标物诱导核酸分子构象发生变化, 导致体系共振光散射强度增大的原理建立了检测Hg2+的新方法。 当溶液中有Hg2+ 存在时, 基于 “T-Hg2+-T” 特异性结合作用, 促使Hg2+特异核酸探针的构象发生变化, 由单链状态变为刚性双链结构, 使体系共振光散射强度增大。 在波长566 nm处, 当汞离子浓度在7.2×10-9～9×10-8mol·L-1范围内时, 体系的共振光散射增强程度ΔI与汞离子的浓度(c)具有良好的线性关系。 其线性方程为ΔI=5.12c+3.55(r=0.999 5)。 将该方法用于环境水样中汞离子的测定, 相对标准偏差(RSD)小于1.9%; 样品加标回收率为99.4％～104.3％。 该方法以Hg2+的高度特异性核酸探针作为识别元件, 通过控制Hg2+浓度的变化调节共振光散射强度的变化, 将Hg2+的检测转化为对DNA分子构象变化的检测, 该转化有利于增强体系共振光散射强度, 提高方法灵敏度, 该共振光散射检测方法能检测到浓度为2.16×10-9mol·L-1的Hg2+。 同时, 由于“T-T” 错配碱基对对Hg2+的特异结合能力, 显著提高了该分析方法对Hg2+的选择性。 另外, 该方法操作简便、 不需标记。 A new label-free resonance light scattering method for the highly selective and sensitive detection of mercury ion was designed. This strategy makes use of the target-induced DNA conformational change to enhance the resonance light scattering intensity leading to an amplified optical signal. The Hg2+ ion, which possesses a unique property to bind specifically to two DNA thymine (T) bases, in the presence of Hg2+, the specific oligonucleotide probes form a conformational reorganization of the oligonucleotide probes from single-chain structure to duplex-like complexes, which can greatly enhance the resonance light scattering intensity. Under the optimum experimental conditions, the enhanced resonance light scattering intensity at 566 nm was in proportion of mercury ion concentration in the range 7.2×10-9～9×10-8mol·L-1 with the linear regression equation was ΔI=5.12c+3.55(r=0.999 5). This method was successfully applied to detection of Hg2+ in enviro nmental water samples, the RSD were less than 1.9% and recoveries were 99.4％～104.3％. This label-free strategy uses the mercury specific oligonucleotide probes as recognition elements and control the strength of resonance light scattering by changing the concentration of Hg2+. It translating the small molecule detection into the DNA hybridization behavior leading to an amplified resonance light scattering signal can well enhance the sensitive detection of Hg2+. With amplification by DNA hybridization behavior, the sensitivity for the detection of Hg2+ can achieve 2.16×10-9mol·L-1. In this study, the stacked T-Hg2+-Tfunctioned not only as amplification property but also as an selective recognition. The highly specific detection of Hg2+ is attributed to the formation of a stable T-Hg2+-T complex.
摘要：
目的：优化五味子抗氧化物的提取条件；分析湖北产和辽宁产五味子提取物的 DPPH清除能力。方法以 DPPH自由基的清除能力为参考指标，采用单因素实验的方法，考察溶剂种类、乙醇浓度、料液比、提取时间、提取次数和提取方法等因素对五味子提取物抗氧化作用的影响。结果五味子抗氧化物的最优提取条件为：以60％的乙醇为提取溶剂，超声法提取，料液比为1∶30（ g? mL －1），提取次数3次，每次提取20min，室温提取；湖北产和辽宁产五味子提取物清除DPPH自由基的IC50分别为3．79mg? mL －1和7．60mg? mL －1。结论五味子提取物具有较强的抗氧化作用，且湖北产五味子提取物的抗氧化作用比辽宁产五味子的强。
