What Is the Mechanism Driving the Reduction of Cardiovascular Events from Glucagon-like Peptide-1 Receptor Agonists?—A Mini Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are considered the standard of care for type 2 diabetes in many countries worldwide. These molecules have profound anti-hyperglycaemic actions with a favourable safety profile. They are now being considered for their robust cardiovascular (CV) protective qualities in diabetic patients. Most recent CV outcome trials have reported that GLP-1 RAs reduce major adverse cardiovascular events (MACE). Furthermore, the GLP-1 RAs seem to target the atherosclerotic CV disease processes preferentially. GLP-1 RAs also improve a wide range of routinely measured surrogate markers associated with CV risk. However, mediation analysis suggests these modest improvements may contribute indirectly to the overall anti-atherogenic profile of the molecules but fall short in accounting for the significant reduction in MACE. This review explores the body of literature to understand the possible mechanisms that contribute to the CV protective profile of GLP-1 RAs.     

光谱法研究纳米二氧化硅(SiO_2)催化超声波照射对牛血清白蛋白(BSA)的损伤

利用紫外-可见(Uv-Vis)光谱和荧光光谱研究了超声波照射激活纳米二氧化硅(SiO2)粒子对牛血清白蛋白(BSA)分子的损伤,并考查了超声波照射时间、纳米SiO2粉末加入量、溶液酸度和超声波照射功率等因素对BSA分子损伤程度的影响.结果表明,对于体系温度为(37.0±0.2)℃和浓度为1.0×10-5mol·-1的BSA溶液,UV-Vis光谱显示,随着超声波照射时间,纳米SiO2粉末加入量,溶液pH值和照射功率的增大呈现出越来越明显的增色效应.然而,BSA溶液的荧光光谱却随着上述因素的增大呈现出越来越明显的猝灭现象.此外,还初步探讨了超声波照射激活纳米siO2粒子对BSA分子损伤的机理,认为是声致发光或高热激发使纳米siO2粒子产生·OH自由基,进而损伤溶液中的BSA分子.这一研究结果对声催化方法应用于临床治疗肿瘤以及纳米药物的开发具有一定的指导意义.     

3-环丙基卟吩f-3甲酯与转铁蛋白的相互作用

用荧光光谱法、分光光度法研究了3-环丙基卟吩f-3甲酯（Mf3-3）与转铁蛋白（Transferrin,Tf）的相互结合反应。计算了反应的表观平衡常数、结合位点数,获得了不同温度下两者结合的热力学常数,推测了二者之间的主要作用力。     

头孢他啶与牛血清白蛋白(BSA)的相互作用

采用荧光、紫外及红外光谱法研究了头孢他啶与牛血清白蛋白(BSA)的结合反应.头孢他啶对BSA的色氨酸残基和酪氨酸残基均具有猝灭作用,其猝灭机理为静态猝灭,两者之间形成新的复合物是导致BSA荧光猝灭的主要原因.获取了复合物的结合常数(298K:1.27×10~4L·mol~(-1);310K:1.33×10~41·mol~(-1)).BSA Ⅱ A结构域的site I位点是其唯一可能结合位点.同步荧光光谱表明头孢他啶造成BSA的酪氨酸残基的极性增强.红外光谱表明头孢他啶引起了BSA二级结构的改变,使其α-螺旋含量降低.     

Multi-components of T2 relaxation in ex vivo cartilage and tendon

The multi-components of T₂ relaxation in cartilage and tendon were investigated by microscopic MRI (μMRI) at 13 and 26 μm transverse resolutions. Two imaging protocols were used to quantify T₂ relaxation in the specimens, a 5-point sampling and a 60-point sampling. Both multi-exponential and non-negative-least-square (NNLS) fitting methods were used to analyze the μMRI signal. When the imaging voxel size was 6.76 × 10⁻⁴ mm³ and within the limit of practical signal-to-noise ratio (SNR) in microscopic imaging experiments, we found that (1) canine tendon has multiple T₂ components; (2) bovine nasal cartilage has a single T₂ component; and (3) canine articular cartilage has a single T₂ component. The T₂ profiles from both 5-point and 60-point methods were found to be consistent in articular cartilage. In addition, the depletion of the glycosaminoglycan component in cartilage by the trypsin digestion method was found to result in a 9.81–20.52% increase in T₂ relaxation in articular cartilage, depending upon the angle at which the tissue specimen was oriented in the magnetic field.     

Characterization of x-ray diffraction and electron spin resonance: Effects of sintering time and temperature on bovine hydroxyapatite

The physical and chemical properties of a hydroxyapatite produced by the sintering of bovine bone were investigated by powder x-ray diffraction (PXRD), electron spin resonance (ESR), energy dispersive x-ray spectroscopy (EDX), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and differential thermal analysis (DTA). A bovine bone powder was sintered at different temperatures ranging from 500 to 1400 °C. The influences of post-irradiation storage on the radiation ESR response of the bovine bone powder before and after sintering were also studied. The results indicate that the sintered bovine bone powder contained hydroxyapatite. Diffraction patterns were sharp and clear based on the (211), (300), and (202) reflections corresponding to bovine hydroxyapatite (BHA), which confirmed the phase purity and high crystalline grade of the BHA produced. The PXRD profile of BHA was dependent on sintering temperatures and times. The molecular formula of BHA was determined by Rietveld analysis showed a similar structure and composition to calcium hydroxyapatite in hexagonal P6₃/m space group a=b=9.435 Å and c=6.895 Å. ESR data showed that the sintering process can decrease the number of free radicals in BHA; it also revealed that the number of free radicals is constant during long storage periods (75 days). The sintering technique described in this study may be used to extract hydroxyapatite from biowaste bovine bone, leading to its application as a bone filler.     

蛋白质-POEGMA结合体的合成与表征

首先利用5'-磷酸吡哆醛酯(PLP)对牛血清白蛋白(BSA)的氮端进行定位活化,之后与2-溴-2甲基丙酸-2-氨氧基乙酯(ABM)反应形成大分子引发剂(BSA-Br).最后以寡聚乙二醇甲基丙烯酸酯(OEGMA)为单体,通过原子转移自由基聚合法(ATRP)制备带有2条POEGMA高分子链的蛋白质高分子结合体(BSAPOEGMA).利用红外(FTIR)、核磁共振谱(1H-NMR)、紫外分光光度计(UV-Vis)、基质辅助激光解析串联飞行时间质谱仪(MALDI-TOF-MS)等分析技术对所合成化合物进行表征.实验结果表明各步骤的化合物及最终的蛋白质高分子结合体都具有预期结构.     

A combined tryptic peptide and winged peptide internal standard approach for the determination of α‐lactalbumin in dairy products by ultra high performance liquid chromatography with tandem mass spectrometry

A robust ultra high performance liquid chromatography with tandem mass spectrometry method at peptide level was established for measuring α‐lactalbumin in various dairy products. An isotope‐labeled winged peptide (VKKILDKVG*I NYW*L AHKALCSEKL) with extra amino acids of the sequence of signature peptide concatenated at each end as the internal standard was spiked in samples to participate in the whole tryptic digestion process. The peptide VG*I NYW*L AHK that resulted from the isotope‐labeled winged peptide was used as the final isotopically labeled internal standard of the α‐lactalbumin signature peptide (VGINYWLAHK) during the quantitative analysis. The contents of α‐lactalbumin in samples were calculated based on the equimolar relationship between the α‐lactalbumin protein and signature peptide. The optimized molar ratio of trypsin to protein (1:60) and enzymatic digestion time (5 h) could not only improve the digestion efficiency and reduce the cost, but also minimize the period of sample pretreatment. Considering the robustness of the current method using the isotopically labeled internal standard and acceptable measurement cost, its application may promote the development of nutrient investigation and quality control of α‐lactalbumin in dairy products. This protein analysis method might provide a new reference strategy for food analysis and quantitative protein analysis.