Structural Investigation of the Interaction Mechanism between Chlorogenic Acid and AMPA Receptor via In Silico Approaches

Chlorogenic acid (CGA), an important metabolite in natural plant medicines such as honeysuckle and eucommia, has been shown to have potent antinociceptive effects. Nevertheless, the mechanism by which CGA relieves chronic pain remains unclear. α-amino-3-hydroxy-5-methyl-4-isooxazolpropionic acid receptor (AMPAR) is a major ionotropic glutamate receptor that mediates rapid excitatory synaptic transmission and its glutamate ionotropic receptor AMPA type subunit 1 (GluA1) plays a key role in nociceptive transmission. In this study, we used Western blot, surface plasmon resonance (SPR) assay, and the molecular simulation technologies to investigate the mechanism of interaction between CGA and AMPAR to relieve chronic pain. Our results indicate that the protein expression level of GluA1 showed a dependent decrease as the concentration of CGA increased (0, 50, 100, and 200 μM). The SPR assay demonstrates that CGA can directly bind to GluA1 (K_D = 496 μM). Furthermore, CGA forms a stable binding interaction with GluA1, which is validated by molecular dynamics (MD) simulation. The binding free energy between CGA and GluA1 is −39.803 ± 14.772 kJ/mol, where van der Waals interaction and electrostatic interaction are the major contributors to the GluA1–CGA binding, and the key residues are identified (Val-32, Glu-33, Ala-36, Glu-37, Leu-48), which play a crucial role in the binding interaction. This study first reveals the structural basis of the stable interaction between CGA and GluA1 to form a binding complex for the relief of chronic pain. The research provides the structural basis to understand the treatment of chronic pain and is valuable to the design of novel drug molecules in the future.     

基于透明陶瓷材料的激光研究进展

陶瓷激光器是一种以透明陶瓷材料作为增益介质的激光器.与单晶相比,透明陶瓷具有制备周期短和烧结温度低等优势,在激活离子高掺杂浓度下能保证良好的光学均匀性,且容易制备成各种大尺寸复合结构.近年在高功率和超短超强激光输出方面得到广泛应用,产生了一系列研究成果.回顾了陶瓷激光器的发展历程,总结了透明陶瓷在高功率、超短超强脉冲激...     

基于永磁体间的磁性负刚度的分析与优化

为了有效地降低磁性负刚度结构的非线性程度,从简单三磁体结构出发,引入新型负刚度结构模型——五磁体对称结构,运用MATLAB建立新型负刚度结构的磁力学模型并应用Ansoft Maxwell进行仿真验证.研究永磁体间的相对位置参数对五磁体对称结构的负刚度曲线走势的影响,在微幅振动下对基于磁引力的负刚度曲线拟合后使用谐波平衡...     

Tolman length of simple droplet: Theoretical study and molecular dynamics simulation

In 1949, Tolman found the relation between the surface tension and Tolman length, which determines the dimensional effect of the surface tension. Tolman length is the difference between the equimolar surface and the surface of tension. In recent years, the magnitude, expression, and sign of the Tolman length remain an open question. An incompressible and homogeneous liquid droplet model is proposed and the approximate expression and sign for Tolman length are derived in this paper. We obtain the relation between Tolman length and the radius of the surface of tension(R_s) and found that they increase with the Rs decreasing. The Tolman length of plane surface tends to zero. Taking argon for example, molecular dynamics simulation is carried out by using the Lennard–Jones(LJ) potential between atoms at a temperature of 90 K. Five simulated systems are used, with numbers of argon atoms being 10140, 10935, 11760, 13500, and 15360, respectively. By methods of theoretical study and molecular dynamics simulation, we find that the calculated value of Tolman length is more than zero, and it decreases as the size is increased among the whole size range. The value of surface tension increases with the radius of the surface of tension increasing, which is consistent with Tolman’s theory. These conclusions are significant for studying the size dependence of the surface tension.     

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.     

Benzamides Substituted with Quinoline-Linked 1,2,4-Oxadiazole: Synthesis,Biological Activity and Toxicity to Zebrafish Embryo

To develop new compounds with high activity, broad spectrum and low-toxicity, 17 benzamides substituted with quinoline-linked 1,2,4-oxadiazole were designed using the splicing principle of active substructures and were synthesized. The biological activities were evaluated against 10 fungi, indicating that some of the synthetic compounds showed excellent fungicidal activities. For example, at 50 mg/L, the inhibitory activity of 13p (3-Cl-4-Cl substituted, 86.1%) against Sclerotinia sclerotiorum was superior to that of quinoxyfen (77.8%), and the inhibitory activity of 13f (3-CF₃ substituted, 77.8%) was comparable to that of quinoxyfen. The fungicidal activities of 13f and 13p to Sclerotinia sclerotiorum were better than that of quinoxyfen (14.19 mg/L), with EC₅₀ of 6.67 mg/L and 5.17 mg/L, respectively. Furthermore, the acute toxicity of 13p was 19.42 mg/L, classifying it as a low-toxic compound.     

Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers

Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (P_{app AP-BL}) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10⁻⁶ cm/s and (2.48 ± 0.18) × 10⁻⁶ cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins.     

Established Liposome-Coated IMB16-4 Polymeric Nanoparticles (LNPs) for Increasing Cellular Uptake and Anti-Fibrotic Effects In Vitro

As a global health problem, liver fibrosis still does not have approved treatment. It was proved that N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4) has anti-hepatic fibrosis activity. However, IMB16-4 displays poor water solubility and poor bioavailability. We are devoted to developing biodegraded liposome-coated polymeric nanoparticles (LNPs) as IMB16-4 delivery systems for improving aqueous solubility, cellular uptake, and anti-fibrotic effects. The physical states of IMB16-4−LNPs were analyzed using a transmission electron microscope (TEM), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). The results show that IMB16-4−LNPs increased the drug loading compared to liposomes and enhanced cellular uptake behavior compared with IMB16-4−NPs. In addition, IMB16-4−LNPs could repress the expression of hepatic fibrogenesis-associated proteins, indicating that IMB16-4−LNPs exhibited evident anti-fibrotic effects.     

The Extracts of Polygonum cuspidatum Root and Rhizome Block the Entry of SARS-CoV-2 Wild-Type and Omicron Pseudotyped Viruses via Inhibition of the S-Protein and 3CL Protease

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC₅₀ values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.     

Green Tea (Camellia sinensis): A Review of Its Phytochemistry,Pharmacology, and Toxicology

Objectives Green tea (Camellia sinensis) is a kind of unfermented tea that retains the natural substance in fresh leaves to a great extent. It is regarded as the second most popular drink in the world besides water. In this paper, the phytochemistry, pharmacology, and toxicology of green tea are reviewed systematically and comprehensively. Key findings Green tea has been demonstrated to be good for human health. Nowadays, multiple pharmacologically active components have been isolated and identified from green tea, including tea polyphenols, alkaloids, amino acids, polysaccharides, and volatile components. Recent studies have demonstrated that green tea shows versatile pharmacological activities, such as antioxidant, anticancer, hypoglycemic, antibacterial, antiviral, and neuroprotective. Studies on the toxic effects of green tea extract and its main ingredients have also raised concerns including hepatotoxicity and DNA damage. Summary Green tea can be used to assist the treatment of diabetes, Alzheimer’s disease, oral cancer, and dermatitis. Consequently, green tea has shown promising practical prospects in health care and disease prevention.