[Mechanism of Huangqi Simiao Decoction in treatment of type 2 diabetes mellitus based on network pharmacology and metabonomics].

This article analyzed the mechanism of Huangqi Simiao Decoction(HSD) for the treatment of type 2 diabetes mellitus(T2DM). The component targets of HSD and the related disease targets of T2DM were screened through network pharmacology. The protein-protein interaction(PPI) network of intersecting targets and the drug-component-intersecting target network were constructed to screen the potential active ingredients and targets. Molecular docking was performed using AutoDock Vina software to verify the interaction between potential components and core targets. The serum was tested by ultra performance liquid chromatography-tandem mass spectrometry, and multivariate statistical analyses, such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), were used to search for the differential metabolites and related metabolic pathways of each group by combining with the MetaboAnalyst database. The same metabolic pathways were analyzed by combining the screened differential metabolites with the intersecting targets screened by network pharmacology. Network pharmacology showed that the nine core components of HSD for the treatment of T2DM were quercetin, kaempferol, stigmasterol, baicalein, ß-sitosterol, flavodoxin, canthaxanthin, canthaxanthin, berberine, and berberine, and the five core targets included AKT1, TP53, TNF, IL6, and VEGFA. Molecular docking showed that the core components bound well to the target genes. Metabolomics showed that a total of 112 common differential metabolites were identified, of which 88 metabolites exhibited increased concentration and 24 metabolites decreased concentration after treatment with HSD. Enrichment analysis showed that HSD regulated the body metabolism of patients with T2DM, mainly related to seven metabolic pathways, such as amino acid metabolism and tricarboxylic acid cycle. The joint analysis of metabolomics and network pharmacology showed that both involved histidine metabolism, arginine and proline metabolic pathways. This study suggests that HSD has a good efficacy for T2DM. Based on the combined analysis of metabolomics and network pharmacology, it was found that the mechanism may be that the pharmacodynamic bases of quercetin, kaempferol, and stigmasterol in HSD enhance the effects on histidine metabolism, arginine and proline metabolic pathways by modulating a variety of metabolites, which provides the basis for further prevention and treatment of T2DM.

Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

[Study on interaction between heme-iron of myoglobin and metal ions by visible spectroscopy (I)].

Myoglobin (Mb) made up of a multipeptides train and a heme prosthetic group is a kind of protein taking charge of O2 stock and distribution in mammal cells, especially in muscle cells. The heme-iron plays a key role in O2 transfer and transport. In the present paper, the direct interaction between heme-iron of myoglobin and additional metal ions [Cu (II), Zn (II) and Co( II)] was studied by UV-Vis spectra. It was found that heme-iron of myoglobin directly interacted with additional Cu(II), Zn(II) and Co(II), these metal ions could drag iron ion out from heme prosthetic group of myoglobin, and subsequently myoglobin became myoglobin derivatives lacking iron ion. At the same time, the effect of the additional metal ions concentration on the direction interaction was studied. It was shown that the direct interaction increased gradually with the amount of external metal ions added. When the ratio of Mb and metal ions is 1 : 10, the interaction intension between the three metal ions and Mb is Co(II), Zn(II) and Cu(II) in turn. For the first time, the authors confirmed that the direct interaction has occurred between heme-iron of myoglobin and additional metal ions, and saw about how the metal ions intension affects the direct interaction.