RESUMO
The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.
Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
A large number of studies have argued that aberrant CpG methylation is associated with some human cancers. One possible mechanism of the cancer caused by CpG methylation is the gene repression, which is a binding-inhibition of the sequence-specific transcription factors bound to specific DNA-binding sites. Exploring the effects of CpG methylation on the structure and the thermodynamic property of DNA-binding transcription factors will help to gain an insight into how CpG methylation affects the repression of gene transcription in cancer. We have performed molecular dynamics (MD) simulations and free energy calculations of the protein bound to the native or the methylated DNA, in which the solution structure of the K50-class homeodomain PITX2 bound to DNA was used as a template. The simulation results indicate that the methylated CpG located at the DNA major groove can enhance the protein-DNA interactions, and the residue side-chains near the methylated CpG pair appear to have an unusually high affinity with DNA. The structural analysis and calculated energy values demonstrate that the binding-induced structural changes were further encouraged as the CpG methylation upon the complexation. Moreover, the CpG methylation may reduce the unfavorable effect of the conformational entropy and increase the electrostatic contribution to the binding free energy of DNA-PITX2. The changes in specific binding sites and the excessive affinity between DNA and protein caused by the CpG methylation could affect the gene transcriptional activity.
Assuntos
Ilhas de CpG , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Citosina/química , DNA/química , DNA/genética , DNA/metabolismo , Regulação da Expressão Gênica , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Neoplasias/genética , Ligação Proteica , Conformação Proteica , Proteína Homeobox PITX2RESUMO
The mechanisms of cycloaddition reactions between 2-azoniaallene cations and olefins have been explored at the B3LYP/6-31G level. It is found that the positive charge in 2-azoniaallene makes the reaction more complicated. For the reactions between olefins with Cl groups or CH(3) groups and 2-azoniaallene, the typical carboniums have been located along the reaction path. In addition, for the reactions between 1,1-dimethylethene and 1,3-dichrolo-2-azoniaallene, different paths and products have been rationalized and verified.
