The mechanism of biological actions of quercetin was studied by using metabolomic method and biomolecular network. HPLC-MS was used to analyze the serum metabolome in rats of blank group and quercetin administration group rats, and MS data were processed by MATLAB software. With multivariate statistical analysis of serum metabolite profiles, a clear separation among blank group and quercetin administration group was achieved, potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. Four compounds, related enzymes, action targets and metabolic pathways had been confirmed, namely retinoic acid and RARbeta, arachidonate and COX-2, 3, 5-diodotyrosine and TPO, uridine diphosphate glucose and PDEs. The mechanism of quercetin enhancing ability of retinoic acid on the induction of RARbeta, activating TPO, using as COX-2 and PDEs inhibitor was approved by biomolecular network and related literatures. In this study, a mechanism of multiple biological actions of quercetin was evaluated at the level of the biomolecular network, metabolomics and biomolecular network can be used to investigate the biological effects mechanism of quercetin, which provided a new method to further revealing mechanism of drug action.
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Nature
January 2025
Laboratory of Protein Design and Immunoengineering, Institute of Bioengineering, Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland.
Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.
View Article and Find Full Text PDFNeuropharmacology
January 2025
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address:
Anhedonia, a transdiagnostic symptom prevalent in depressive and psychotic disorders, poses a significant challenge for pharmacological intervention due to its association with impaired motivation. Understanding how psychotropic drugs can modulate this pathological domain and elucidating the molecular mechanisms underlying such effects are crucial endeavors in psychiatric research. In this study, we aimed to investigate the pro-motivational properties of lurasidone in a rat (Sprague Dawley males) model of anhedonia and to unravel the interplay between lurasidone and the brain regions critical for reward processing.
View Article and Find Full Text PDFMol Biotechnol
January 2025
Enzyme and Microbial Research Center, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Glucanases are widely applied in industrial applications such as brewing, biomass conversion, food, and animal feed. Glucanases catalyze the hydrolysis of glucan to produce the sugar hemiacetal through hydrolytic cleavage of glycosidic bonds. Current study aimed to investigate structural insights of a glucanase from Clostridium perfringens through blind molecular docking, site-specific molecular docking, molecular dynamics (MD) simulation, and binding energy calculation.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Dermatology and Allergy, University Hospital of Munich, Ludwig-Maximilian-University, Munich, Germany.
Background: Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Single Molecule Analysis Group, Department of Chemistry, The University of Michigan, Ann Arbor, Michigan 48109, United States.
Single-molecule fluorescence resonance energy transfer (smFRET) has emerged as a pivotal technique for probing biomolecular dynamics over time at nanometer scales. Quantitative analyses of smFRET time traces remain challenging due to confounding factors such as low signal-to-noise ratios, photophysical effects such as bleaching and blinking, and the complexity of modeling the underlying biomolecular states and kinetics. The dynamic distance information shaping the smFRET trace powerfully uncovers even transient conformational changes in single biomolecules both at or far from equilibrium, relying on trace idealization to identify specific interconverting states.
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