Urine LMs quantitative analysis strategy development and LMs CWP biomarkers discovery.

Coal workers' pneumoconiosis (CWP) is one of the most common inhalation occupational diseases. It is no effective treatment methods. Early diagnosis of CWP could reduce mortality. Lipid mediators (LMs) as key mediators in the generation and resolution of inflammation, are natural biomarkers for diagnosis inflammatory disease, such as CWP. The UHPLC-MRM technique was used to detect LMs in urine. The metabolic network of LMs in CWP and CT group samples was comprehensively analyzed. Screening for major difference compounds between the two groups. Aimed to contribute to the early diagnosis and treatment of CWP. Urinary levels of 13-OxoODE, 9-OxoODE, and 9,10-EpOME were significantly higher in the CWP group compared with the CT group (P < 0.05). In the model group, the area under the receiver operating characteristic (ROC) for 9-OxoODE,13-OxoODE,9,10-EpOME was 84.4%, 73.3%, and 80.9%, respectively. In the validation group, the area under the ROC was 87.0%, 88.8%, and 68.8% for 9-OxoODE,13-OxoODE,9,10-EpOME, respectively. According to the logistic regression model, the area under the ROC was 80.4% in the model group and 86.7% in the validation group. 13-OxoODE,9-OxoODE,9,10-EpOME could be used as biomarkers for early diagnosis. Significant abnormalities of LOX and CYP450 enzyme pathways were seen in CWP organisms. Changes in the CYP450 enzyme pathway may be associated with PAHs.

Novel Structure-Driven Predict-to-Hit Strategy for PC Double Bond Positional Isomer Identification Based on Negative LC-MRM Analysis.

As the predominant phospholipids in mammalian cells, phosphatidylcholines (PCs) have been demonstrated to play a crucial role in a multitude of vital biological processes. Research has highlighted the significance of the diversity in PC isomers as instigators of both physiological and pathological responses, particularly those with variations in the position of double bonds within their fatty chains. Profiling these PC isomers is paramount to advancing our understanding of their biological functions. Despite the availability of analytical methods utilizing high-resolution secondary mass spectrometry (MS2) fragmentation, a novel approach was imperative to facilitate large-scale profiling of PC isomers while ensuring accessibility, facility, and reliability. In this study, an innovative strategy centered around structure-driven predict-to-hit profiling of the double bond positional isomers for PCs was meticulously developed, employing negative reversed-phase liquid chromatography-multiple reaction monitoring (RPLC-MRM). This novel methodology heightened the sensitivity. The analysis of rat lung tissue samples resulted in the identification of 130 distinct PC isomers. This approach transcended the confines of available PC isomer standards, thereby broadening the horizons of PC-related biofunction investigations. By optimizing the quantitation reliability, the scale of sample analysis was judiciously managed. This work pioneers a novel paradigm for the exploration of PC isomers, distinct from the conventional methods reliant on high-resolution mass spectrometry (HRMS). It equips researchers with potent tools to further explore the biofunctional aspects of lipids.

A novel SPE-LC-MRM strategy for serum demethylzeylasteral quantitation developed with an 18O-labeled internal standard.

Natural bioactive compounds (NBCs) are widely used in clinical treatment. For example, Tripterygium wilfordii Hook f. is commonly known in China as Lei-Gong-Teng which means thunder god vine. This herb is widely distributed in Eastern and Southern China, Korea, and Japan. The natural bioactive compounds of this herb can be extracted and made into tripterygium glycoside tablets. It is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA), nephrotic syndrome (NS), autoimmune hepatis (AIH), and so on. However, many NBCs are difficult to reliably quantify in the serum due to the effects of matrix and RSD. In addition, the targeted compound's internal standard (IS) is rarely sold due to the complex isotope internal standard synthesis pathway. In this study, a new quantitation method for 18O labeling combined with off-line SPE was formulated. We contrasted the recoveries and matrix effects of various separation methods in order to choose the best method. Furthermore, we optimized the conditions for SPE loading and washing. An isotopic internal standard was prepared by the 16O/18O exchanging reaction in order to eliminate the matrix effects. The method's accuracy and precision met the requirements for method validation. The recovery of this method was close to 60%. The relative standard deviation (RSD) of the high-concentration sample was 2%, and the limit of detection (LOD) was 1 ng/mL. This method could be used to analyze the clinical serum concentration of demethylzeylasteral. Sixty samples were collected from 10 patients with diabetes nephropathy. The quantitation results of demethylzeylasteral in patients' serum obtained using this method exhibited a correlation between therapeutic drug monitoring (TDM) and decreased urinary protein. This work may have broad implications for the study of drug metabolism in vivo and the clinical application of low-abundance and difficult-to-quantify NBCs.

Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.