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Abstract Background Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. Methods The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein–protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. Results 60 lipid metabolic genes differentially expressed in early AD patients’ cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. Conclusions AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Effective compounds isolated from Chinese herbs play an important role in the development of new candidate drugs, which can be widely used in the treatment of various diseases. Previous literature has revealed that Stellera chamaejasme L. possesses the activity of inhibiting liver cancer cells. Nevertheless, the interactions between active compounds isolated from this herb and targets related to liver cancer are still not very clear. In this study, we applied network pharmacology-based analysis to figure out these relationships. And eight compounds were predicted to have the most significant activity against liver cancer. At the same time, the binding modes between the top eight candidate compounds and the protein target Glutamine synthetase which is likely to be the most important target associated with liver cancer were identified. It is believed that the study can provide a reference for the discovery of new drug molecules. [ABSTRACT FROM AUTHOR]

Sweet cherry ( Prunus avium L.) is highly perishable and is greatly affected by orchard management and environmental conditions, such as excess rainfall before harvest. Rain-induced cracking is the major cause of crop loss in sweet cherry in most production areas of the world. Advances in understanding the physiological and molecular mechanisms involved in cracking physiology in combination with orchard management strategies to limit cherry cracking are discussed. The current opinions to explain fruit cracking is that the process initiates with water uptake by the fruit surface that results in localised bursting of cells that release malic acid into the apoplast. This results in swelling of the epidermis and weakening of the epidermal and hypodermal cells until macroscopic fruit cracking. This review focusses on management strategies such as rain cover protection, mineral sprays, anti-transpirants and growth regulators. Tree responses to growth regulators and biostimulants vary with cultivar, application frequency, concentration and type, making it hard to generalize their effects. New approaches to limit cracking are presented, including the development of tolerant cultivars, candidate mineral sprays, biostimulants and technologies for rainwater removal such as orchard air-blast sprayers or creating downwash by helicopters. [ABSTRACT FROM AUTHOR]

Drug repurposing is a method of drug discovery that consists of finding a new therapeutic context for an old drug. Compound identification arises from screening of large libraries of active compounds, through interrogating databases of cell line gene expression response upon treatment or by merging several types of information concerning disease–drug relationships. Although, there is a general consensus on the potential and advantages of this drug discovery modality, at the practical level to-date no non-anti-cancer repurposed compounds have been introduced into standard acute myeloid leukaemia (AML) management, albeit that preclinical validation yielded several candidates. The review presents the state-of-the-art drug repurposing approach in AML and poses the question of what has to be done in order to take a full advantage of it, both at the stage of screening design and later when progressing from the preclinical to the clinical phases of drug development. We argue that improvements are needed to model and read-out systems as well as to screening technologies, but also to more funding and trust in drug repurposing strategies. [ABSTRACT FROM AUTHOR]

Aim: To explore the mechanism of gastric carcinogenesis by mining potential hub genes and to search for promising small-molecular compounds for gastric cancer (GC). Materials & methods: The microarray datasets were downloaded from Gene Expression Omnibus database and the genes and compounds were analyzed by bioinformatics-related tools and software. Results: Six hub genes ( MKI67 , PLK1 , COL1A1 , TPX2 , COL1A2 and SPP1 ) related to the prognosis of GC were confirmed to be upregulated in GC and their high expression was correlated with poor overall survival rate in GC patients. In addition, eight candidate compounds with potential anti-GC activity were identified, among which resveratrol was closely correlated with six hub genes. Conclusion: Six hub genes identified in the present study may contribute to a more comprehensive understanding of the mechanism of gastric carcinogenesis and the predicted potential of resveratrol may provide valuable clues for the future development of targeted anti-GC inhibitors.

Introduction: This invention provides the screening methods of candidate compounds, the diagnostic methods and the methods of treatment of human cognitive diseases, and also gives out several potential candidate compounds. The invention establishes that the FKBP52-Tau interaction provides a new target that may be used advantageously for novel therapeutic approaches for neurological disorders involving Tau dysfunction, and especially for Alzheimer's disease., Areas Covered: The invention generally relates to neuroprotection and repair in neurological disorders involving Tau dysfunction (including Alzheimer's disease). The invention describes a direct interaction between FKBP52 and Tau, the screening methods for molecules acting on the FKBP52-Tau interaction, in order to modulate the detrimental effect of pathogenic Tau. Finally, it discusses therapeutic, diagnostic, prognostic and monitoring assays of neurological disorders involving Tau dysfunction., Expert Opinion: Several methods or techniques were used to determine the validity of screening methods, involving biochemistry, immunology, fluorescence analysis and cell experiment. Candidate compounds mentioned in the patent include FK506 derivatives, rapamycin derivatives and pipecolyl-α-keto-amid compounds. However, the mechanism, the structural similarity and the biological activity were unmentioned, which may partly reduce the practicability of the invention. The FKBP52-Tau interaction as a novel target for neurodegenerative diseases is promising. FKBP52 is capable of preventing polymerization of tubulin and maintaining axonal transport. In AD patients' brain, the high level of Tau protein phosphorylation is directly related to the decrease of FKBP52. The FKBP52-Tau interaction may provide a new critical path for treatment of neurodegenerative diseases, and new molecules will possess higher affinity and efficiency.