There is a critical need for the discovery of novel biomarkers for early detection and targeted therapy of cancer, a major cause of deaths worldwide. In this respect, proteomic technologies, such as mass spectrometry (MS), enable the identification of pathologically significant proteins in various types of samples. MS is capable of high-throughput profiling of complex biological samples including blood, tissues, urine, milk, and cells. MS-assisted proteomics has contributed to the development of cancer biomarkers that may form the foundation for new clinical tests. It can also aid in elucidating the molecular mechanisms underlying cancer. In this review, we discuss MS principles and instrumentation as well as approaches in MS-based proteomics, which have been employed in the development of potential biomarkers. Furthermore, the challenges in validation of MS biomarkers for their use in clinical practice are also reviewed.

Background: Inulin-type fructans (ITF) have been used as prebiotics to alleviate glucose and lipid metabolism disorders. However, few studies evaluated the microbial mechanism of ITF in improving maternal metabolic status during pregnancy.Methods: C57BL/6J mice were fed a high-fat/sucrose diet (HFD) for 4 weeks before and throughout pregnancy to induce a model of gestational diabetes mellitus (GDM). Body weight, glycolipid metabolic parameters, and fecal short-chain fatty acids (SCFAs) were assessed in the experimental process. The effects of ITF on the fecal microbiota were analyzed by 16S rRNA gene amplicon sequencing.Results: Pregnant HFD-fed mice displayed significant insulin resistance and dyslipidemia. ITF (3.33 g/kg/day) treatment improved glucose and lipid metabolism disorder parameters in HFD-induced GDM mice and alleviated fat accumulation and glucose intolerance. The alpha diversity of the gut microbial community was increased in ITF mice, while the beta diversity returned to the level of normal chow diet (NCD) mice. Interestingly, Verrucomicrobia, Bifidobacterium, and Akkermansia were obviously enriched, while Dubosiella was obviously lessened after inulin treatment. Further analysis indicated that Dubosiella was positively correlated with markers of glycolipid metabolism disorders, whereas the ITF-supplemented diet partially reversed the changes.Conclusion: Our results suggest that the ITF treatment may alleviate glucose and lipid metabolism disorders with the mediation of gut microbiota.

A novel system for copy number variation (CNV) analysis was developed in the present study using a combination of magnetic separation and chemiluminescence (CL) detection technique. The amino-modified probes were firstly immobilized onto carboxylated magnetic nanoparticles (MNPs) and then hybridized with biotin-dUTP products, followed by amplification with ligation-dependent polymerase chain reaction (PCR). After streptavidin-modified alkaline phosphatase (STV-AP) bonding and magnetic separation, the CL signals were then detected. Results showed that the quantification of PCR products could be reflected by CL signal values. Under optimum conditions, the CL system was characterized for quantitative analysis and the CL intensity exhibited a linear correlation with logarithm of the target concentration. To validate the methodology, copy numbers of six genes from the human genome were detected. To compare the detection accuracy, multiplex ligation-dependent probe amplification (MLPA) and MNPs-CL detection were performed. Overall, there were two discrepancies by MLPA analysis, while only one by MNPs-CL detection. This research demonstrated that the novel MNPs-CL system is a useful analytical tool which shows simple, sensitive, and specific characters which are suitable for CNV analysis. Moreover, this system should be improved further and its application in the genome variation detection of various diseases is currently under further investigation.

Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.

Background: Gestational diabetes mellitus (GDM) has significant short and long-term health consequences for both the mother and child. There is limited but suggestive evidence that inulin could improve glucose tolerance during pregnancy. This study assessed the effect of inulin on glucose homeostasis and elucidated the molecular mechanisms underlying the inulin-induced antidiabetic effects during pregnancy. Method: Female C57BL/6 mice were randomized to receive either no treatment, high-dose inulin and low-dose inulin for 7 weeks with measurement of biochemical profiles. A real-time² (RT²) profiler polymerase chain reaction (PCR) array involved in glycolipid metabolism was measured. Results: Inulin treatment facilitated glucose homeostasis in a dose-dependent manner by decreasing fasting blood glucose, advanced glycation end products and total cholesterol, and improving glucose tolerance. Suppressing resistin (RETN) expression was observed in the inulin treatment group and the expression was significantly correlated with fasting blood glucose levels. The ratios of p-IRS to IRS and p-Akt to Akt in liver tissue and the ratio of p-Akt to Akt in adipose tissue as well as the expression level of GLUT4 increased significantly after inulin treatment. Conclusions: Our findings indicated improvement of glucose and lipid metabolism by inulin was to activate glucose transport through the translocation of GLUT4 which was mediated by insulin signaling pathway repairment due to decreased expression of RETN and enhanced phosphorylation of IRS and Akt in GDM mice.