含肉桂酰胺类化合物的合成及α-糖苷酶抑制活性

合成了4个未见报道的含肉桂酰胺类化合物9a～9b, 初步评价了它们的α-糖苷酶抑制活性. 这些化合物均具有α-糖苷酶抑制活性, 是一类结构新颖的α-糖苷酶抑制活性化合物, 其中, 化合物9b和9c的活性高于阳性对照药物阿卡波糖.     

Structure-based prediction of free energy changes of binding of PTP1B inhibitors

The goals were (1) to understand the driving forces in the binding of small molecule inhibitors to the active site of PTP1B and (2) to develop a molecular mechanics-based empirical free energy function for compound potency prediction. A set of compounds with known activities was docked onto the active site. The related energy components and molecular surface areas were calculated. The bridging water molecules were identified and their contributions were considered. Linear relationships were explored between the above terms and the binding free energies of compounds derived based on experimental inhibition constants. We found that minimally three terms are required to give rise to a good correlation (0.86) with predictive power in five-group cross-validation test (q2 = 0.70). The dominant terms are the electrostatic energy and non-electrostatic energy stemming from the intra- and intermolecular interactions of solutes and from those of bridging water molecules in complexes.     

Carbohydrates from camel's milk and shubat near the Aral Sea

Camel's milk and shubat are demonstrated experimentally to differ quantitatively in carbohydrate content. Shubat is recommended as a food source for Fe-deficient anemics and diabetics because of its low content of carbohydrates and high content of Fe and Zn.Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 212–213, May–June, 2000.     

A Review on Bioengineering Approaches to Insulin Delivery: A Pharmaceutical and Engineering Perspective

Diabetes mellitus (DM) is the most prevalent non‐contagious disease, which has affected a large number of people all over the world. Among all treatments known to have a positive influence in the control of DM, insulin therapy is the most common and effective one. Nowadays, various methods of insulin delivery are under investigation, which are able to reach a plausible bioavailability with ignorable side effects instead of insulin injection. This article presents a comprehensive review of the insulin therapy approach with a focus on modified methods in insulin delivery strategies and current advances in engineered insulin delivery systems.     

糖尿病大鼠视神经病变方向性扩散加权MRI表现

利用扩散加权磁共振成像技术研究了链脲佐菌素（STZ）诱导大鼠糖尿病4周时视神经的病理改变. 测量平行和垂直于视神经方向上的水质子的表观扩散系数,分别用ADC_∥和ADC_⊥来表示. 初步结果显示模型组左右侧视神经ADC_∥没有出现一致的改变,而ADC_⊥都有下降的趋势,但没有达到统计显著性. 该结果提示STZ诱导4周后扩散成像测量参数ADC_⊥的改变可能反映了糖尿病引起的视神经轴突损伤.     

糖尿病患者红细胞镁和蛋白酪氨酸磷酸酶的关系

目的探讨了糖尿病患者红细胞镁、蛋白酪氨酸磷酸酶(PTP)和血糖的关系．方法用葡萄糖氧化酶法和放免法分别测定30例糖尿病患者(DM)和20例正常对照组(NT)空腹血糖(FGP)胰岛素浓度(FINS),等离子体原子发射光谱法测定红细胞镁,酶联免疫法测定红细胞胞浆PTP活性．结果DM组年龄,体重和体重指数(BMI)与NT组相比无显著性;年龄(岁)(57．33±7．21)vs(58．35±7．71);体重(kg)(61．00±8．29)vs(61．95±6．96);BMI(kg．m-2)(23．50±2．50)vs(23．40±2．70);收缩压(kPa)(16．41±0．95vs(16．76±0．98);舒张压(kPa)(9．96±0．66)vs(10．28±0．73),DM组FGP和PTP活性显著高于NT组(FGP(mmol-L-1)(10．03±2．01)vs(5．16±0．70),P<0．001;PTP活性(U)(8．40±1．99)vs(6．17±2．84),P<0．05);DM组红细胞镁显著低于NT组(Mg(μmo1．g-1)(5．48±0．66)vs(6．47±0．63),P<0．001)．相关分析显示红细胞镁与PTP活性呈显著负相关(γ=-0．58,P<0．01),PTP活性与空腹血糖呈显著正相关(γ=0．81,P<0．01)．结论红细胞内低镁和高PTP活性与糖尿病患者高血糖状态密切相关．     

Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes

Increased secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), is often associated with adipose tissue dysregulation, which often accompanies obesity. High levels of TNFα have been linked to the development of insulin resistance in several tissues and organs, including skeletal muscle and the liver. In this study, we examined the complex regulatory roles of TNFα in murine hepatocytes utilizing a combination of global proteomic and phosphoproteomic analyses. Our results show that TNFα promotes extensive changes not only of protein levels, but also the dynamics of their downstream phosphorylation signaling. We provide evidence that TNFα induces DNA replication and promotes G1/S transition through activation of the MAPK pathway. Our data also highlight several other novel proteins, many of which are regulated by phosphorylation and play a role in the progression and development of insulin resistance in hepatocytes.     

柯尔克孜族和维吾尔族ACE基因多态性与2型糖尿病的关联研究

探讨新疆柯尔克孜族和维吾尔族人群血管紧张素转化酶（ACE）基因rs1799752位点插入或缺失（I/D）多态性及其与2型糖尿病（TypeⅡdiabetes mellitus,T2DM）的关系．方法采用病例-对照的研究设计．采集无血缘关系、年龄性别匹配的新疆柯尔克孜族样本117例、维吾尔族样本127例,分为2型糖尿病组（T2DM）、糖耐量异常组（impaired glucose tolerance, IGT）和糖耐量正常组（normal glucose tolerance, NGT）,以Hardy-Weinberg平衡检验确认研究样本的群体代表性,采用PCR技术检测ACE基因I/D多态性．结果（1）病例组与对照组ACE基因多态性的分布符合Hardy-Weinberg平衡定律,所选人群具有代表性;（2）柯尔克孜族DD型42.74%,ID型31.58%,II型26.50%,D和I 等位基因频率分别为58.115%和41.876%;维吾尔族DD型35.43%,ID型28.35%,II型36.22%,D和I 等位基因频率分别为49.626%和50.387%．（3）ACE基因频率差异在柯尔克孜族（χ2=70.11,P 〈0.01）,维吾尔族（χ^2=35.11,P〈0.01）的糖调节异常组与糖耐量正常组间,分别具有统计学意义．在维吾尔族T2DM组中携带DD、ID、ID＋DD基因型的个体较携带II基因型的个体发生糖代谢异常（T2DM＋IGT）的危险性增加（OR=7.812,95%CI=3.135-19.607;OR=4.854,95%CI=1.835-12.821;OR=6.410,95%CI=2.865-14.286,携带D等位基因的个体较携带I等位基因的个体发生糖代谢异常（T2DM＋IGT）的危险性增加（OR=4.444,95%CI=2.617-7.576）,而柯尔克孜族DD、ID＋DD基因型和D等位基因性对糖代谢异常（T2DM＋IGT）的发病风险降低．结论ACE基因I/D多态性与新疆两个少数民族T2DM相关,ACE基因I/D多态性可能是维吾尔族T2DM的危险因素,柯尔克孜族的保护因素．     

壳聚糖及其衍生物应用于肥胖治疗的研究进展

肥胖是并发高血脂、脂肪肝、糖尿病和心脑血管损害等疾病的主要危险因子,减肥药物（食品）是一种有效的控制体重的手段。壳聚糖对脂肪和胆固醇具有良好的吸附性能,正在成为一种新型的减肥药物（食品）。结合本课题研究方向,综述了药用壳聚糖及其衍生物在治疗肥胖及其并发症方面应用的研究进展。通过在壳聚糖C6住-OH上改性制备了水溶性、油溶性和两亲性良好的壳聚糖衍生物,并通过动物试验研究了其减肥功效。     

Influence of In Vitro Human Digestion Simulation on the Phenolics Contents and Biological Activities of the Aqueous Extracts from Turkish Cistus Species

Oxidative stress is one of the significant precursors of various metabolic diseases such as diabetes, Parkinson’s disease, cardiovascular diseases, cancer, etc. Various scientific reports have indicated that secondary plant metabolites play an important role in preventing oxidative stress and its harmful effects. In this respect, this study was planned to investigate the phenolic profile and antioxidant and antidiabetic potentials of the aqueous extracts from Turkish Cistus species by employing in vitro methods. In vitro digestion simulation procedure was applied to all extracts to estimate the bioavailability of their phenolic contents. Total phenolic, flavonoid, phenolic acid and proanthocyanidin contents were determined for all phases of digestion. In addition, changes in the quantity of the assigned marker flavonoids (tiliroside, hyperoside and quercitrin) were monitored by High-Performance Thin Layer Chromatography (HPTLC) analysis. The antioxidant activity potentials of the extracts were studied by various methods to reveal their detailed activity profiles. On the other hand, in vitro α-amylase and α-glucosidase enzymes and advanced-glycation end product (AGE) inhibitory activities of the extracts were determined to evaluate the antidiabetic potentials of extracts. The results showed that aqueous extracts obtained from the aerial parts of Turkish Cistus species have rich phenolic contents and potential antioxidant and antidiabetic activities; however, their bioactivity profiles and marker flavonoid concentrations might significantly be affected by human digestion. The results exhibited that total phenolic contents, antioxidant activities and diabetes-related enzyme inhibitions of the bioavailable samples were lower than non-digested samples in all extracts.