Rational molecular targeting of the inter-subunit interaction between human cardiac troponin hcTnC and hcTnI using switch peptide-competitive biogenic medicines

The human cardiac troponin (hcTn) has been implicated in diverse cardiovascular diseases (CDs). The protein function is regulated by the inter-subunit interaction between the N-terminal domain of hcTnC and the C-terminal switch peptide of hcTnI; disruption of the interaction has been recognized as a potential therapeutic strategy for CDs. Here, we report use of biogenic medicines as small-molecule competitors to directly disrupt the protein–protein interaction by competitively targeting the core binding site (CBS) of hcTnC NTD domain. A multistep virtual screening protocol is performed against a biogenic compound library to identify competitor candidates and competition assay is employed to verify the screening results. Consequently, two compounds Collismycin and Compound e are identified as strong competitors (CC₅₀ < 10 μM) with hcTnI for hcTnC CBS site, while other tested compounds are found to have moderate (CC₅₀ = 10–100 μM), low (CC₅₀ > 100 μM) or no (CC₅₀ = N.D.) potency. The competitor ligands are anchored at the core groove of hcTnC CBS site through aromatic and hydrophobic interactions, while few peripheral hydrogen bonds are formed to further confer specificity for domain–compound recognition. These molecular-level findings would benefit from further in vitro and in vivo studies at cellular and animal levels, which can help to practice the ultimate therapeutic purpose.     

黑龙骨中两个新强心苷的结构鉴定

系统研究黑龙骨Periploca forrestii Schltr.中的化学成分, 利用各种色谱技术进行分离, 得到2个新类型的强心苷,黑龙骨苷甲和乙. 并通过化学和光谱方法(MS, ¹H, ¹³C NMR和2D NMR)鉴定其结构为: 5β-羟基-8,14β-环氧-强心 甾- 20(22)-烯-3-O-β-D-磁麻吡喃糖苷(1)和5β-羟基-8,14β-环氧-强心甾-20(22)-烯-3-O-β-D-葡萄吡喃糖基-(1→4)-β-D-磁麻吡喃糖苷(2).     

基于双醛基功能化离子液体构建电化学免疫传感器

合成了含双醛基的离子液体,此离子液体一端的醛基与修饰在电极表面的氨基发生共价键作用,将离子液体修饰在电极表面,另一端的醛基可用来固定抗体,构建电化学免疫传感器,实现对心肌肌钙蛋白I(cTnI)的检测。离子液体通过共价键作用固定在电极表面,不仅减少了从电极表面向检测溶液的渗透,提高传感器的稳定性,而且还可以直接固定抗体,不需要使用其他交联试剂;同时,离子液体可增强传感界面的导电性,提高传感器的灵敏度。在优化的实验条件下,传感器的线性范围为0.1~40 ng/mL,检出限为0.06 ng/mL。     

量子点偶联抗体型夹心免疫传感法检测心肌肌钙蛋白I

将纳米量子点(QD)的放大作用与夹心免疫传感技术相结合, 首次应用量子点标记抗体和表面等离子体共振生物传感器(SPR)对心肌肌钙蛋白I(cTn I)进行特异性定量检测. 利用N-羟基琥珀酰(NHS)和1-乙基-3-(3-二甲氨基丙基)碳二亚胺盐酸盐(EDC)将量子点偶联到cTn I的单克隆抗体2F11上, 再利用SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)验证偶联是否成功, 膜印迹法证明标记后的2F11具有良好的生物学和免疫学活性, 最后以蛋白A为基底膜、特异性抗心肌肌钙蛋白I多克隆抗体为第一抗体(捕捉抗体)、QD标记的抗心肌肌钙蛋白I单克隆抗体2F11为第二抗体(检测抗体), 用表面等离子体共振生物传感器构建了对心肌肌钙蛋白I具有特异性的夹心免疫传感法, 并成功用于检测心肌肌钙蛋白I. 本法的检测范围为0.4~15 μg/L, 检出限为0.4 μg/L, 较未标记夹心法和直接法分别提高了约2倍和10倍.     

Fine Needle Aspiration: A Novel Application in Laryngology

Fine needle aspiration (FNA) has had an early start in medicine and has been heavily used in the United States since the 1980s. It is regarded as a highly effective means to sample mass lesions, serving as the first diagnostic procedure in many instances. FNA is safe, less invasive than biopsy, and reduces the risk of scar formation. Its main limitations can be overcome through effective training and practiced technique. In laryngology, the development of new and diversified therapeutic and diagnostic strategies depends on the development of equally appropriate diagnostic tools. FNA has the potential to be a relatively easy procedure that can be performed under local anesthesia, increasing the otolaryngologist's armamentarium. Combining the FNA procedure with technology now available, secondary to advances in genomic science, rather than cytology and H&E stains, provides the means of obtaining clinically useful information about benign and malignant disease for clinicians and researchers. This paper provides a review of the traditional FNA procedure. It offers an introduction to the future applicability of FNA to office-based laryngology. Lastly, this paper familiarizes the reader with the genomic principles being used for this procedure.     

A laser fluorimeter for direct cardiac metabolism investigation

We have developed a device which includes two laser sources (nitrogen and dye lasers), an optical system, an optical fibre able to transmit both ultra-violet and infra-red light, photoreceivers, and an analogue circuit feeding a microcomputer in order to perform an in situ and on line study of NADH/NAD ratios by fluorimetry.The paper includes the scientific basis of the method, the characteristics of each part of the apparatus and possible applications to the study of cardiac metabolism or any organ that can be reached through catheterism, fibrescopy or simple transcutaneous puncture. Examples of experiments carried out to appreciate the effects of anoxia or ischemia on the tissular NADH level are presented.     

Canards in a rheodynamic model of cardiac pressure pulsations

This paper reports on the canard phenomenon occurring in a rheodynamic model of cardiac pressure pulsations. By singular perturbation techniques the corresponding parameter value at which canards exist is obtained. The physiological significance of canards in this model is given.     

用多克隆抗体构建的夹心免疫传感器检测心肌肌钙蛋白I

用表面等离子体子共振生物传感器构建对心肌肌钙蛋白I特异性的免疫传感器检测心肌肌钙蛋白I,并建立两种检测方法:直接法的最低检测限为2.5μg/L,基于传感膜上的夹心免疫法的灵敏度为0.5μg/L,检测范围为0.5～20μg/L,批内及批间精密度分别为3.5%～4.9%,6.1%～7.4%;用夹心法及国外试剂盒对40名健康献血者和20例急性心肌梗死患者血清心肌肌钙蛋白I水平进行检测,两者符合率为95%.     

Comparative neuroprotective effects of native curcumin and its galactomannoside formulation in carbofuran-induced neurotoxicity model

Abstract

Toxicity of the pesticide carbofuran (CF) can be alleviated by curcumin, if not for its poor bioavailability. Hence, we investigated the effect of a bioavailable curcumin-galactomannan complex (CGM) on CF-induced neurotoxicity in rats in comparison to that of unformulated standard curcumin (CS). The CF (5?mg/kg b.wt/day) treatment for 90?days produced chronicity model which were treated with either CS or CGM (100?mg/kg b.wt and 250?mg/kg b.wt/day) for another 30?days. Improvement in CF-induced behaviour was evident in endurance, motor co-ordination and pain response on both CS (p?<?0.01) and CGM (p?<?0.001) supplementation. Amelioration of CF-induced toxicity parameters, oxidative stress, and mitochondrial dysfunction on CS (p?<?0.01) and CGM (p?<?0.001) supplementation was further confirmed by histopathology of brain and liver tissues. But, CGM was more effective in mitigating CF toxicity, with results comparable to that of normal. Hence, CGM might be superior in toxicity management against CF.