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1.
Medicine (Baltimore) ; 103(25): e38315, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905402

ABSTRACT

Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the therapeutic mechanism and targets of action of GGS on alcoholic liver disease utilizing network pharmacology and bioinformatics. The active ingredients in GGS were screened in the literature and databases, and common targets of ALD were then obtained from public databases to construct the network diagram of traditional Chinese medicine-active ingredient targets. Based on the common targets, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to find target enrichment pathways, and the core targets were screened out by combining differential analysis and protein-protein interaction network analysis. Molecular docking was performed to verify the binding effect between the core targets and the corresponding active ingredients. ALD and GGS have 84 common targets, corresponding to 91 active ingredients. After subsequent differential analysis and protein-protein interaction network analysis, 10 core targets were identified. Gene Ontology and KEGG enrichment analyses showed that the main BPs corresponding to the common targets included the response to lipopolysaccharide, inflammatory response, etc. The KEGG pathways involved in the regulation of the common targets included the lipid-atherosclerosis pathway and the alcoholic liver disease pathway, etc. Further molecular docking showed that the core targets CYP1A1, CYP1A2, CXCL8, ADH1C, MMP1, SERPINE1, COL1A1, APOB, MMP1, and their corresponding 4 active ingredients, Naringenin, Kaempferol, Quercetin, and Stigmasterol, have a greater docking potential. The above results suggest that GGS can regulate lipid metabolism and inflammatory response in the ALD process, and alleviate the lipid accumulation and oxidative stress caused by ethanol. This study analyzed the core targets and mechanisms of action of GGS on ALD, which provides certain theoretical support for the further development of GGS in the treatment of ALD, and provides a reference for the subsequent research on the treatment of ALD.


Subject(s)
Computational Biology , Drugs, Chinese Herbal , Liver Diseases, Alcoholic , Molecular Docking Simulation , Network Pharmacology , Protein Interaction Maps , Liver Diseases, Alcoholic/drug therapy , Liver Diseases, Alcoholic/metabolism , Network Pharmacology/methods , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Computational Biology/methods , Medicine, Chinese Traditional/methods , Gene Ontology
2.
Molecules ; 29(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38930877

ABSTRACT

Tau protein is a microtubule-associated protein that is widely distributed in the central nervous system and maintains and regulates neuronal morphology and function. Tau protein aggregates abnormally and forms neurofibrillary tangles in neurodegenerative diseases, disrupting the structure and function of neurons and leading to neuronal death, which triggers the initiation and progression of neurological disorders. The aggregation of tau protein in neurodegenerative diseases is associated with post-translational modifications, which may affect the hydrophilicity, spatial conformation, and stability of tau protein, promoting tau protein aggregation and the formation of neurofibrillary tangles. Therefore, studying the role of tau protein in neurodegenerative diseases and the mechanism of aberrant aggregation is important for understanding the mechanism of neurodegenerative diseases and finding therapeutic approaches. This review describes the possible mechanisms by which tau protein promotes neurodegenerative diseases, the post-translational modifications of tau protein and associated influencing factors, and the current status of drug discovery and development related to tau protein, which may contribute to the development of new therapeutic approaches to alleviate or treat neurodegenerative diseases.


Subject(s)
Neurodegenerative Diseases , Protein Processing, Post-Translational , tau Proteins , tau Proteins/metabolism , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Animals , Drug Development , Protein Aggregation, Pathological/metabolism , Protein Aggregation, Pathological/drug therapy , Neurofibrillary Tangles/metabolism , Molecular Targeted Therapy
3.
Medicine (Baltimore) ; 102(48): e36238, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38050310

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by a novel coronavirus. Traditional Chinese medicine (TCM) has been proven to have a potential curative effect on COVID-19. This study preliminarily analyzed the existing TCM prescription's key components and action mechanisms for preventing and treating COVID-19 using bioinformatic and experimental methods. Association and clustering analysis reveals that the "HQ + FF + BZ" drug combination had a strong correlation and confidence in 93 TCM prescriptions and may affect the progression of COVID-19 through inflammatory pathways such as the TNF signaling pathway. Further molecular docking revealed that quercetin has a higher affinity for IL6 and IL10 in the TNF signaling pathway associated with COVID-19. In vitro experiments demonstrated that quercetin could effectively reduce the levels of the inflammatory factor IL-6 and increase the anti-inflammatory factor IL-10, alleviating inflammation impact on cells. Our results provide a new understanding of the molecular mechanism of TCM prevention and treatment of COVID-19, which is helpful to the development of new diagnosis and treatment schemes for COVID-19.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Drugs, Chinese Herbal/therapeutic use , Molecular Docking Simulation , Quercetin/therapeutic use , Computational Biology
4.
J Artif Organs ; 19(1): 70-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26280316

ABSTRACT

An attempt to maintain the three-dimensional space into restorative sites through the conveniently pack porous fillers are general used strategy. Advancement in the manufacturing protective shells in the scaffolds, which would be filled with brittle ceramic grafts for the development of highly connective pores provides the approach to solve crack problem for generating the tissues. Therefore, multilayered braided and alkalized poly(lactic acid) (PLA) composites with calcium phosphate bone cement (CPC) were synthesized and compared. The PLA/CPC composites were divided into various groups according to a series of heat-treatment temperatures (100-190 °C) and periods (1-3 h) and then characterized. The effects of 24-h immersion on the strength decay resistance of the samples were compared. Results showed that the residual oil capped on the surfaces of alkalized PLA braid was removed, and the structure was unaltered. However, the reduced tensile stress of alkalized PLA braids was due to ester-group formation by hydrolysis. Mechanical test results of PLA/CPC composites showed that the strength significantly increased after heat treatment, except when the heating temperature was higher than the PLA melting point at approximately 160-170 °C. The degree of PLA after recrystallization became higher than that of unheated composites, thereby leading to reduced strength and toughness of the specimen. Braiding fibers of biodegradable PLA reinforced and toughened the structure particularly of the extra-brittle material of thin-sheet CPC after implantation.


Subject(s)
Bone Cements , Bone Substitutes/chemistry , Lactic Acid , Materials Testing , Polymers , Calcium Phosphates , Ceramics , Polyesters
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