Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post‐genome era, advanced mass spectrometry driven multi‐omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge‐based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry‐based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:331–349, 2016.

The high-pathogenicity island (HPI) is an important determinant of the pathogenicity of pathogenic Yersinia microbes. The HPI carries a cluster of virulence genes that chiefly account for the biosynthesis, transportation and regulation of a virulence-associated siderophore, yersiniabactin. This siderophore is also present in uropathogenic E. coli (UTI89) but not in non-uropathogenic E. coli. We sought to perform metabolic phenotyping and to understand how the presence of the HPI influences central carbon metabolism, which remains poorly understood, by combining targeted metabolomics with a genetic approach. Unexpectedly, our results revealed that uropathogenic E. coli (UPEC) with an HPI had superior metabolic homeostasis to a non-UPEC K12 strain without an HPI, thereby allowing UPEC with an HPI to flexibly adapt to a variety of growth environments. In this study, we elucidate the unrecognized regulatory effects of the HPI virulence genes on central carbon metabolism, in addition to their roles in directing yersiniabactin. These regulatory effects may be implicated in differentiating UPEC from non-UPEC.

Aristolochic acid (AA) is the major active component of medicinal plants from the Aristolochiaceae family of flowering plants widely utilized for medicinal purposes. However, the molecular mechanisms of AA systems effects remain poorly understood. Here, we employed a joint network analysis that combines network pharmacology, a protein–protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects. Firstly, we selected 15 protein targets (14 genes) in the PubChem database as the potential target genes and used PPI knowledge to incorporate these genes into an AA-specific gene network that contains 129 genes. Secondly, we performed biological processes analysis for these AA-related targets using ClueGO, some of new targeted genes were randomly selected and experimentally verified by employing the Quantitative Real-Time PCR assay for targeting the systems effects of AA in HK-2 cells with observed dependency of concentration. Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA. At last, we built an AA target pathway network of significant pathways to predict the system effects. Taken together, this joint network analysis revealed that the systematic regulatory effects of AA on multidimensional pathways involving both therapeutic action and toxicity.

A practical and mild method for the switchable synthesis of sulfoxides or sulfones via selective oxidation of sulfides using cheap N-fluorobenzenesulfonimide (NFSI) as oxidant has been developed. These highly chemoselective...

In vivo small molecules as necessary intermediates are involved in numerous critical metabolic pathways and biological processes associated with many essential biological functions and events. There is growing evidence that MS-based metabolomics is emerging as a powerful tool to facilitate the discovery of functional small molecules that can better our understanding of development, infection, nutrition, disease, toxicity, drug therapeutics, gene modifications and host-pathogen interaction from metabolic perspectives. However, further progress must still be made in MS-based metabolomics because of the shortcomings in the current technologies and knowledge. This technique-driven review aims to explore the discovery of in vivo functional small molecules facilitated by MS-based metabolomics and to highlight the analytic capabilities and promising applications of this discovery strategy. Moreover, the biological significance of the discovery of in vivo functional small molecules with different biological contexts is also interrogated at a metabolic perspective.