Metabolomics represents an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of bio-systems through the study of potential metabolites that could be used as therapeutic targets and for the discovery of new drugs. Hepatitis C virus (HCV) is a leading cause of liver disease worldwide, and is a major burden on public health. It is hypothesized that an animal model of HCV infection would produce unique patterns of endogenous metabolites. Herein, a method for the construction of efficient networks is presented with regard to the proteins of bear bile powder (PBBP) that protect against HCV as a case study. Ultra-performance liquid chromatography, coupled with electrospray ionization/quadrupole-time-of-flight high definition mass spectrometry (UPLC-HDMS), coupled with pattern recognition methods and computational systems analysis were integrated to obtain comprehensive metabolomic profiling and pathways of the large biological data sets. Among the regulated pathways, 38 biomarkers were identified and two unique metabolic pathways were indicated to be differentially affected in HCV animals. The results provided a systematic view of the development and progression of HCV, and also could be used to analyze the therapeutic effects of PBBP, a widely used anti-HCV medicine. The results also showed that PBBP could provide satisfactory effects on HCV infection through partially regulating the perturbed pathway. The most promising use in the near future would be to clarify the pathways for the drugs and obtain biomarkers for these pathways to help guide testable predictions, provide insights into drug action mechanisms, and enable an increase in research productivity toward metabolomic drug discovery.
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http://dx.doi.org/10.1016/S1875-5364(13)60076-X | DOI Listing |
ACS Cent Sci
January 2025
Sarafan ChEM-H Institute, Stanford University, Stanford, California 94305-6104, United States.
Antimicrobial drug resistance (AMR) is a pressing global human health challenge. Humans face one of their grandest challenges as climate change expands the habitat of vectors that bear human pathogens, incidences of nosocomial infections rise, and new antibiotics discovery lags. AMR is a multifaceted problem that requires a multidisciplinary and an "all-hands-on-deck" approach.
View Article and Find Full Text PDFChin Med
January 2025
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Background: Bear bile powder (BBP), a unique animal-derived medicine with anti-inflammatory and antioxidant effects, is used in Shexiang Tongxin dropping pills (STDP), which is applied to treat cardiovascular diseases, including acute myocardial infarction (AMI). The efficacy and compatibility mechanisms of action of BBP in STDP against cardiovascular diseases remain unclear. This study aimed to investigate the compatibility effects of BBP in STDP in rats with AMI.
View Article and Find Full Text PDFCells
January 2025
Key Laboratory of Resource Biology and Biotechnology Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an 710069, China.
Glycosylation plays a critical role in various biological processes, yet identifying specific glycosyltransferase substrates remains a challenge due to the complexity of glycosylation. Here, we employ proximity labeling with biotin ligases BASU and TurboID to map the proximitome of MGAT3, a glycosyltransferase responsible for the biosynthesis of the bisecting GlcNAc structure, in HEK293T cells. This approach enriched 116 and 189 proteins, respectively, identifying 17 common substrates shared with bisecting GlcNAc-bearing proteome obtained via intact glycopeptide enrichment methods.
View Article and Find Full Text PDFNat Chem
January 2025
Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.
View Article and Find Full Text PDFAcc Chem Res
January 2025
Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
ConspectusA key challenge in modern chemistry research is to mimic life-like functions using simple molecular networks and the integration of such networks into the first functional artificial cell. Central to this endeavor is the development of signaling elements that can regulate the cell function in time and space by producing entities of code with specific information to induce downstream activity. Such artificial signaling motifs can emerge in nonequilibrium systems, exhibiting complex dynamic behavior like bistability, multistability, oscillations, and chaos.
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