A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening.

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).

A multi-omics study of the anti-cancer effect of a ferulic acid derivative FA-30.

The active ingredients of Traditional Chinese Medicine are an important source of bioactive molecules and play an important role in the research and development of innovative drugs. FA-30, which is a derivative of natural product ferulic acid, inhibited cervical cancer cell proliferation and induced apoptosis as well. To understand the underlying mechanisms of FA-30, a complementary multi-omics study was conducted. Cysteine and methionine metabolism and aminoacyl-tRNA biosynthesis pathways were significantly changed both at the metabolic level and proteomic level. This may help us to get a better understanding of cervical cancer and FA-30 at the same time.

A strategy of screening and binding analysis of bioactive components from traditional Chinese medicine based on surface plasmon resonance biosensor.

Elucidating the active components of traditional Chinese medicine (TCM) is essential for understanding the mechanisms of TCM and promote its rational use as well as TCM-derived drug development. Recent studies have shown that surface plasmon resonance (SPR) technology is promising in this field. In the present study, we propose an SPR-based integrated strategy to screen and analyze the major active components of TCM. We used Radix Paeoniae Alba (RPA) as an example to identify the compounds that can account for its anti-inflammatory mechanism via tumor necrosis factor receptor type 1 (TNF-R1). First, RPA extraction was analyzed using an SPR-based screening system, and the potential active ingredients were collected, enriched, and identified as paeoniflorin and paeonol. Next, the affinity constants of paeoniflorin and paeonol were determined as 4.9 and 11.8 µM, respectively. Then, SPR-based competition assays and molecular docking were performed to show that the two compounds could compete with tumor necrosis factor-α (TNF-α) while binding to the subdomain 1 site of TNF-R1. Finally, in biological assays, the two compounds suppressed cytotoxicity and apoptosis induced by TNF-α in the L929 cell line. These findings prove that SPR technology is a useful tool for determining the active ingredients of TCM at the molecular level and can be used in various aspects of drug development. The SPR-based integrated strategy is reliable and feasible in TCM studies and will shed light on the elucidation of the pharmacological mechanism of TCM and facilitate its modernization.

Investigation of the apoptosis-inducing effect of docetaxel by comprehensive LC-MS-based metabolomics and network pharmacology approaches.

Docetaxel is one of the clinical first-line drugs and its combination with other chemotherapy agents for advanced or metastatic cancers has attracted widespread attention. Therefore, to promote the clinical application of docetaxel alone or in combination, a comprehensive investigation of the metabolic mechanism of docetaxel is of great importance. Here, we apply an integrative analysis of metabolomics and network pharmacology to elucidate the underlying mechanisms of docetaxel. After taking the intersection of the aforesaid two methods, five pathways including ABC (ATP-binding cassette) transporters, central carbon metabolism in cancer, glycolysis and gluconeogenesis, cysteine and methionine metabolism, and arginine biosynthesis have been screened. Concerning the interaction network of these pathways and the anti-apoptosis effect of docetaxel itself, the central carbon metabolism in cancer pathway was mainly focused on. This study may help delineate global landscapes of cellular protein-metabolite interactions, to provide molecular insights about their mechanisms of action as well as to promote their clinical applications.

Development of a surface plasmon resonance biosensor for accurate and sensitive quantitation of small molecules in blood samples.

Therapeutic drug monitoring (TDM) has played an important role in clinical medicine for precise dosing. Currently, chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy. However, some problems still exist in practical applications, such as complicated operation and the influence of endogenous substances. Surface plasmon resonance (SPR) has been applied to detect the concentrations of small molecules, including pesticide residues in crops and antibiotics in milk, which indicates its potential for in vivo drug detection. In this study, a new SPR-based biosensor for detecting chloramphenicol (CAP) in blood samples was developed and validated using methodological verification, including precision, accuracy, matrix effect, and extraction recovery rate, and compared with the classic ultra-performance liquid chromatography-ultraviolet (UPLC-UV) method. The detection range of SPR was 0.1-50 ng/mL and the limit of detection was 0.099 ± 0.023 ng/mL, which was lower than that of UPLC-UV. The intra-day and inter-day accuracies of SPR were 98%-114% and 110%-122%, which met the analysis requirement. The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples; moreover, the SPR biosensor has better sensitivity. Therefore, the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.