Rapid Diagnosis of Type II Diabetes Using Fourier Transform Mid-Infrared Attenuated Total Reflection Spectroscopy Combined with Support Vector Machine

Type II diabetes was diagnosed by Fourier transform mid-infrared (FTMIR) attenuated total reflection (ATR) spectroscopy in combination with support vector machine (SVM). Spectra of serum samples from 65 patients with clinical confirmed type II diabetes mellitus and 55 healthy volunteers were acquired using ATR-FTMIR and were first pretreated by three pretreatments (Savitzky–Golay smoothing, multiple scattering correction, and wavelet transforms algorithms) to reduce the interfering information before establishing the SVM models. The parameters of SVM (penalty factor C and kernel function parameter gamma) were optimized to improve the generalization abilities of the models. A grid search method (GS), genetic algorithm (GA), and particle swarm optimization (PSO) algorithm, were used to find out the optimal parameter values. The results showed that the maximum accuracies were 95.74, 97.87, and 89.36% for the optimized GS, GA, and PSO algorithms. The maximum sensitivities were 96, 100, and 92, and the maximum specificity were 95.45, 95.45, and 86.36%, respectively. The results indicated that the accuracy of type II diabetes was improved using the GS, GA, and PSO algorithms for optimizing the SVM parameters. The GA was found to be slightly better than the GS and PSO. The results of the experiment confirmed that the combination of the ATR-FTMIR spectroscopy and SVM was able to rapidly and accurately diagnose type II diabetes without reagents.     

Alpha-glucosidase inhibitory activity of ethanol extract,fractions and purified compounds from the wood of Albizia myriophylla

Albizia myriophylla Benth. is a medicinal herb which is used as a traditional remedy for various ailments including diabetes in Thailand. In our continued investigation of the biological activity of A. myriophylla, the ethanol extract, fractions and the isolated compounds from the wood of this plant were evaluated for in vitro α-glucosidase inhibition using spectrophotometric method. The plant ethanol extract and its different fractions possessed α-glucosidase inhibitory activity in a concentration-dependent manner. Dichloromethane fraction of the wood ethanol extract exhibited the highest percent inhibition against α-glucosidase (69.30%) among all fractions. Subsequent α-glucosidase inhibition assay proved that indenoic acid (1), 8-methoxy-7, 3′,4′-trihydroxyflavone (2) and 3,4,7,3′-tetrahydroxyflavan (3) were partially rational for antidiabetic effect of this plant species. Among these compounds, 3 (IC₅₀ 98.59 μg/mL) exhibited potent inhibition of α-glucosidase, compared with a positive control acarbose (IC₅₀ 125 μg/mL). The inhibitory effect towards α-glucosidase of compounds 1–3 was reported herein for the first time.     

Detection of acetone in the human breath as diabetes biomarker based on PPy/WO3 nanocomposite sensor by FFT continuous cyclic voltammetry method

This research represents a novel detection method of acetone level in the exhaled breath samples (RH=88 %) based on polypyrrole/tungsten oxide (PPy/WO₃) nanocomposite sensor. The PPy/WO₃ sensor was fabricated by the deposition of nanocomposite on/between interdigitated electrodes (IDEs) through electrospray coating and was then characterized by FE-SEM imaging. In this detection method, the coulometric signal of the sensor was calculated using Fast Fourier Continuous Cyclic Voltammetry (FFTCCV), where cyclic voltammetry (CV) was applied to the sensor in the defined potential rang and then charge changes of the sensor was obtained by integration of the current in all scanned potential ranges. FFTCCV method enhances the sensitivity of the sensor when exposed to the gas mixtures containing acetone. In addition to its fast coulometric response time (≤5 s) in the two linear ranges of 0.7–2.8 ppm and 2.8–28.2 ppm (R²=0.99), FFTCCV method provides the low detection limit of 70 ppb, and high sensitivity toward acetone at the optimum values of the parameters. The fabricated sensor showed great selectivity toward acetone when exposed to humid air and some exhaled gas like carbon dioxide, ammonia, methanol, ethanol and alkyl amines. The results were very satisfying as the sensor was capable to detect different acetone levels in human exhaled breath as non-invasive diagnosis of diabetes with a good correlation (R²≃0.9) to the routine blood sugar test taken by different commercial glucometers results.     

Synthesis of urea acetates as potential PPARα/γ,dual agonists

In the quest for novel PPARα/γ dual agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia,we designed and synthesized a series of urea acetates as potential PPARα/γ dual agonists.The structure of the target compounds,intermediates were characterized by 1H NMR,HRMS.     

pH-temperature Responsive Hydrogel-Mediated Delivery of Exendin-4 Encapsulated Chitosan Nanospheres for Sustained Therapeutic Efficacy in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like peptide-1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half-life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience. To address this issue, an injectable hydrogel system is developed that can provide sustained EX release at the injection site, reducing the need for daily injections. In this study, the electrospray technique is examine to form EX@CS nanospheres by electrostatic interaction between cationic chitosan (CS) and negatively charged EX. These nanospheres are uniformly dispersed in a pH-temperature responsive pentablock copolymer, which forms micelles and undergoes sol-to-gel transition at physiological conditions. Following injection, the hydrogel gradually degraded, exhibiting excellent biocompatibility. The EX@CS nanospheres are subsequently released, maintaining therapeutic levels for over 72 h compared to free EX solution. The findings demonstrate that the pH-temperature responsive hydrogel system containing EX@CS nanospheres can be a promising platform for the treatment of T2D.     

A Modular Method for the High‐Yield Synthesis of Site‐Specific Protein–Polymer Therapeutics

A versatile method is described to engineer precisely defined protein/peptide–polymer therapeutics by a modular approach that consists of three steps: 1) fusion of a protein/peptide of interest with an elastin‐like polypeptide that enables facile purification and high yields; 2) installation of a clickable group at the C terminus of the recombinant protein/peptide with almost complete conversion by enzyme‐mediated ligation; and 3) attachment of a polymer by a click reaction with near‐quantitative conversion. We demonstrate that this modular approach is applicable to various protein/peptide drugs and used it to conjugate them to structurally diverse water‐soluble polymers that prolong the plasma circulation duration of these proteins. The protein/peptide–polymer conjugates exhibited significantly improved pharmacokinetics and therapeutic effects over the native protein/peptide upon administration to mice. The studies reported here provide a facile method for the synthesis of protein/peptide–polymer conjugates for therapeutic use and other applications.     

Assessment of silver(I) complexes of salicylaldehyde derivatives—histidine Schiff base as novel α-glucosidase inhibitors

In this study, a novel class of histidine Schiff base silver (I) complexes derived from salicylaldehyde, 1a-9a, was found to be an effective inhibitor of α-glucosidase. The results of this study showed that the newly synthesized complexes inhibited α-glucosidase through noncompetitive mechanisms; the IC₅₀ values were ranging from 0.00431 μmol L^-1 to 0.492 μmol L^-1. The structure-activity relationship was established as well. These results demonstrated that compound 7a, 5-nitro salicylaldehyde Schiff base silver complex, is the most promising α-glucosidase inhibitor with the lowest IC₅₀ value, which could be exploited as a drug candidate to alleviate postprandial hyperglycemia in the treatment of type Ⅱ diabetes mellitus. This research provided a catalyst-free, simple, and environmentally benign reaction to synthesize compounds using mechanochemistry.     

糖尿病综合症新药Epalrestat的光敏异构化研究

Epalrestat是一种治疗糖尿病晚期综合症的新药。它可以缓解糖尿病型视网膜病变,运动神经传导阻滞等症状。绕丹宁乙酸与α-甲基肉桂醛在乙酸中缩合得到了Epalrestat,并利用了高压液相色谱,X衍射,高分辨率核磁共振,对它的立体异构进行了研究,还研究了它的保存条件。发现Epalrestat的四个立体异构体中(Z,E)构型占96.5%。见光后易发生异构化,产物中(Z,Z)构型的含量可达到37.7%。而避光保存一年后(Z,E)仍能保持93.6%的含量。     

Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells

Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes.     

内皮调节对小动脉管腔运动影响的模型分析1）

微循环是血液和组织之间发生物质交换的主要场所,它可以通过改变管径实现对血压、血流量的局部调节.血管内皮层对小动脉运动有重要的调节作用.本文基于连续介质假设,建立了内皮调节过程中主要活性物质在管壁中的扩散--反应动力学模型,并分析了非线性黏弹性血管的径向运动特性.利用该模型首先得到了内皮舒张因子一氧化氮（NO）、平滑肌细胞内钙离子（Ca²⁺）以及磷酸化肌球蛋白（actin-myosin complexes,AMC）在管壁内的的径向浓度分布;为分析内皮调节的动态过程,进一步对小动脉的被动舒张、血流量发生扰动时的管径响应分别进行了模拟.研究结果显示：当没有活性物质参与调节小动脉被动舒张时,管径无振荡发生;当血流量变化引起内皮调节时,内皮舒张因子NO浓度和管径均出现衰减振荡,振荡周期约60 s.分析认为内皮调节对壁面剪切力的反馈控制,可能是NO浓度和管径产生周期性振荡的原因.内皮调节过程呈现的频谱特征可以为血管内皮功能障碍的诊断提供帮助.