乙酰胆碱酯酶分子的原子力显微成像

本文研究了用原子力显微技术对乙酰胆碱酯酶进行成像的方法。在新鲜裂解的云一表面镀一层金膜,金膜与疏基丙酸（ＭＰＡ）的疏基形成Ｓ－Ａｕ键。使ＭＰＡ的游离羧基再通过碳二亚胺反应与ＡＣｈＥ的碱性氨基酸的氨基形成肽键连接,ＡＣｈＥ因而被固定于支持物表面,这样固定的ＡＣｈＥ可获得清晰成像而不脱落。     

Effects of DIMBOA on several enzymatic systems in Asian corn borer,Ostrinia furnacalis (Guenée)

By using spectrophotometric analysis and isoelectric focusing electrophoresis (IEF), we found inhibition of acetylcholinesterase (AChE), general esterase activity (Est), and lipase activity in larvae of the Asian corn borer (ACB),Ostrinia furnacalis (Guenée), fed on cabbage dipped in DIMBOA (400 ppm). Amylase was not influenced, while activity of cytochrome P-450 monooxygenase and glutathloneS-transferase was increased. The results indicate that DIMBOA influences activity levels of some nervous system and detoxication enzymes and inactivates some hydrolysis enzymes.     

Disorders of the Cholinergic System in COVID-19 Era—A Review of the Latest Research

The appearance of the SARS-CoV-2 virus initiated many studies on the effects of the virus on the human body. So far, its negative influence on the functioning of many morphological and physiological units, including the nervous system, has been demonstrated. Consequently, research has been conducted on the changes that SARS-CoV-2 may cause in the cholinergic system. The aim of this study is to review the latest research from the years 2020/2021 regarding disorders in the cholinergic system caused by the SARS-CoV-2 virus. As a result of the research, it was found that the presence of the COVID-19 virus disrupts the activity of the cholinergic system, for example, causing the development of myasthenia gravis or a change in acetylcholine activity. The SARS-CoV-2 spike protein has a sequence similar to neurotoxins, capable of binding nicotinic acetylcholine receptors (nAChR). This may be proof that SARS-CoV-2 can bind nAChR. Nicotine and caffeine have similar structures to antiviral drugs, capable of binding angiotensin-converting enzyme 2 (ACE 2) epitopes that are recognized by SARS-CoV-2, with the potential to inhibit the formation of the ACE 2/SARS-CoV-2 complex. The blocking is enhanced when nicotine and caffeine are used together with antiviral drugs. This is proof that nAChR agonists can be used along with antiviral drugs in COVID-19 therapy. As a result, it is possible to develop COVID-19 therapies that use these compounds to reduce cytokine production. Another promising therapy is non-invasive stimulation of the vagus nerve, which soothes the body’s cytokine storm. Research on the influence of COVID-19 on the cholinergic system is an area that should continue to be developed as there is a need for further research. It can be firmly stated that COVID-19 causes a dysregulation of the cholinergic system, which leads to a need for further research, because there are many promising therapies that will prevent the SARS-CoV-2 virus from binding to the nicotinic receptor. There is a need for further research, both in vitro and in vivo. It should be noted that in the functioning of the cholinergic system and its connection with the activity of the COVID-19 virus, there might be many promising dependencies and solutions.     

Novel Coumarin-Thiadiazole Hybrids and Their Cu(II) and Zn(II) Complexes as Potential Antimicrobial Agents and Acetylcholinesterase Inhibitors

A series of coumarin-thiadiazole hybrids and their corresponding Cu(II) and Zn(II) complexes were synthesized and characterized with the use of spectroscopic techniques. The results obtained indicate that all the coumarin-thiadiazole hybrids act as bidentate chelators of Cu(II) and Zn(II) ions. The complexes isolated differ in their ligand:metal ratio depending on the central metal. In most cases, the Zn(II) complexes are characteristic of a 1:1 ligand:metal ratio, while in the Cu(II) complexes the ligand:metal ratio is 2:1. All compounds were tested as potential antibacterial agents against Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains demonstrating activities notably lower than commercially available antibiotics. The more promising results were obtained from the assessment of antineurodegenerative potency as all compounds showed moderate acetylcholinesterase (AChE) inhibition activity     

乙酰胆碱酯酶在尼龙网上的固定化研究

以尼龙网为载体,分别用硫酸二甲酯和三乙基肟四氟化硼作烷基化试剂使尼龙网活化,然后将尼龙网浸入一定浓度的乙酰胆碱酯酶溶液中,置于4°C条件下进行固定化,获得了较好的固定化效果,酶膜活性分别达到4.2 U/cm2和11.1 U/cm2,固定化效率分别达到24.2%和64.1%,重现性好,稳定性好,5个月后活性无明显下降。     

计算机药物筛选方法探讨

本文论述了计算机药物筛选方法及其应用程序的开发,并通过建立乙酰胆碱酯酶(AchE)抑制剂的筛选模型,检测化合物样品的生物活性,比较生物活性结果与计算机筛选结果,检验了计算机药物筛选方法的可靠性.结果表明,计算机药物筛选方法在创新药物研究中具有重要意义,但需要进一步改进,并结合其他方法来提高它的可靠性.     

Characterization of a Bioactive Peptide T14 in the Human and Rodent Substantia Nigra: Implications for Neurodegenerative Disease

The substantia nigra is generally considered to show significant cell loss not only in Parkinson’s but also in Alzheimer’s disease, conditions that share several neuropathological traits. An interesting feature of this nucleus is that the pars compacta dopaminergic neurons contain acetylcholinesterase (AChE). Independent of its enzymatic role, this protein is released from pars reticulata dendrites, with effects that have been observed in vitro, ex vivo and in vivo. The part of the molecule responsible for these actions has been identified as a 14-mer peptide, T14, cleaved from the AChE C-terminus and acting at an allosteric site on alpha-7 nicotinic receptors, with consequences implicated in neurodegeneration. Here, we show that free T14 is co-localized with tyrosine hydroxylase in rodent pars compacta neurons. In brains with Alzheimer’s pathology, the T14 immunoreactivity in these neurons increases in density as their number decreases with the progression of the disease. To explore the functional implications of raised T14 levels in the substantia nigra, the effect of exogenous peptide on electrically evoked neuronal activation was tested in rat brain slices using optical imaging with a voltage-sensitive dye (Di-4-ANEPPS). A significant reduction in the activation response was observed; this was blocked by the cyclized variant of T14, NBP14. In contrast, no such effect of the peptide was seen in the striatum, a region lacking the T14 target, alpha-7 receptors. These findings add to the accumulating evidence that T14 is a key signaling molecule in neurodegenerative disorders and that its antagonist NBP14 has therapeutic potential.     

乙酰胆碱酯酶生物传感器及其研究进展

本实验介绍了乙酰胆碱酯酶生物传感器的基本原理,组成与分类。重点介绍了近年来国内外乙酰胆碱酯酶固定化技术和乙酰胆碱酯酶生物传感器研究进展,并分析了未来乙酰胆碱酯酶生物传感器的发展趋势。     

植物乳杆菌YS-1对活性炭诱导小鼠便秘的预防作用

检测植物乳杆菌YS-1(Lactobacillus plantarum YS-1,LP-YS1)对活性炭诱导便秘昆明小鼠的影响。结果表明LP-YS1的抗胃酸和胆盐能力强于保加利亚乳杆菌。LP-YS1能抑制便秘造成的小鼠体质量、粪便质量、颗粒数和含水量的下降。同时LP-YS1可以提高活性炭在小肠中的推进率和缩短排出首粒黑便的时间。LP-YS1还能使便秘小鼠的胃动素(motilin,MTL)、内皮素(endothelin,ET)、乙酰胆碱酯酶(acetylcholinesterase,ACh E)、P物质(substance P,SP)、血管活性肠肽(vasoactive intestinal peptide,VIP)水平提高和生长抑素(somatostatin,SS)水平下降。逆转录聚合酶链式反应实验进一步显示LP-YS1可以上调便秘小鼠小肠组织c-Kit(干细胞因子受体)、干细胞因子(stem cell factor,SCF)、胶质细胞源性神经营养因子(glial cellline-derived neurotrophic factor,GDNF)基因的m RNA表达和下调瞬时感受器电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1)、一氧化氮合酶(nitric oxide synthase,NOS)基因的表达。高浓度的LP-YS1显示出更好的作用,且显著优于保加利亚乳杆菌。这些实验结果证明LP-YS1可有效缓解便秘。