Precise Lipidomics Decipher Circulating Ceramide and Sphingomyelin Cycle Associated with the Progression of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune condition that causes joint and surrounding tissue inflammation. Lipid mediators are involved in inflammation and deterioration of the joints. Despite attempts to discover effective drug targets to intervene with lipid metabolism in the disease, progress has been limited. In this study, precise lipidomic technology was employed to quantify a broad range of serum ceramides and sphingomyelin (SM) in a large cohort, revealing an association between the accumulation of circulating ceramides and disturbed ceramide/SM cycles during the progression of RA. In our investigation, we discovered that eight ceramides exhibited a positive correlation with the activity of RA, thereby enhancing the accuracy of RA diagnosis, particularly in patients with serum antibody-negative RA. Furthermore, the enzyme SM phosphodiesterase 3 (SMPD3) was found to disrupt the circulating SM cycle and accelerate the progression of RA. The activity of SMPD3 can be inhibited by methotrexate, resulting in decreased metabolic conversion of SM to ceramide. These findings suggest that targeting the SM cycle may provide a new therapeutic option for RA.

Rapid, sensitive, and high-throughput quantification of broad serological ceramides by using isotope dilution liquid chromatography-negative ion electrospray tandem mass spectrometry.

Ceramides are important intermediates in the metabolism of sphingolipids. High-throughput liquid chromatography-mass spectrometry has been used extensively for monitoring the levels of serological ceramides, but is still limited by inadequate coverage or lack of sensitivity. Herein, a rapid, sensitive, and high-throughput isotope dilution liquid chromatography-negative ion electrospray tandem mass spectrometry (IDLC-nESI-MS/MS) method was developed and verified for accurate quantification of 41 ceramides, involving ceramides with C16-20 sphingosine, dihydro-ceramide, and dehydro-ceramide. This method was validated with excellent linearity (R2 > 0.99) and good recovery in the range of 90-110%. Intra- and inter-day imprecision were below 5.57% and 7.83% respectively. The improved high-throughput quantitative method developed in this study may aid in the accurate characterization of ceramides for understanding ceramide biology and application in disease diagnosis.

Yaobitong capsules reshape and rebalance the gut microbiota and metabolites of arthritic rats: An integrated study of microbiome and fecal metabolomics analysis.

Yaobitong capsule (YBTC), a Chinese medicine compound preparation, has been demonstrated to affect multiple pathways associated with inflammation and exhibit potential anti-arthritis effect. In this study, an integrated omic approach based on UHPLC-Q-TOF MS and 16S rRNA sequencing analyses was proposed to reveal the anti-arthritis effect and possible mechanism of YBTC. The AIA rat model showed that YBTC significantly alleviated the typical symptoms of AIA rats such as weight, spleen index and pro-inflammatory cytokines. Fecal metabolomics results identified 41 differential metabolites, which mainly referred to tryptophan, bile acid and fatty acid metabolism. The gut microbiota played a crucially important role in anti-inflammatory immunity, 16S rRNA results indicated that YBTC changed the community structure and alleviated the microecological imbalance caused by rheumatoid arthritis (RA). Further ROC curve analysis demonstrated that it was reliable to identify RA by using 5 metabolites and 3 microorganisms (AUC > 0.83). In summary, it was the first time that the preventive effect of YBTC in RA was confirmed. The secretion of the microbiota-mediated metabolites was significantly improved by YBTC, through its callback effect on the disturbed gut microbiota. Thus, we have indicated a potential novel strategy for the prevention of RA via evaluation of intervention effects of YBTC on AIA rat model.

A metabolomics study of Qianliexin capsule treatment of benign prostatic hyperplasia induced by testosterone propionate in the rat model.

A metabolomics investigation of the treatment effect of Qianliexin (QLX) capsules was conducted on rats with benign prostatic hyperplasia (BPH) induced by testosterone propionate. Establishment of the BPH model was confirmed using the prostatic index. Hematoxylin and eosin (HE) staining for TGF-ß, EGFR, collagen, IL-1 ß, TNF-α was performed and changes in urine volume were measured. Urine and serum samples were collected from three groups, including a control group, a BPH model group and a QLX-treated group and subjected to metabolomics profiling based on ultrahigh-performance liquid chromatography-mass spectrometry. Pharmacodynamics analysis showed that the QLX group had significantly lower histopathological damage, fibrosis damage, and inflammation and higher urine output compared with the model group. Twenty-two potential biomarkers were identified in urine samples and 23 metabolites were identified in plasma samples. Alterations in metabolic patterns were evident in all sample types. The treatment effects of QLX appear to involve various metabolic pathways including lipid metabolism, fatty acid metabolism and purine generation and significantly reduced the pathological symptoms and related biochemical indicators of BPH and improved the level of potential marker metabolites. This comprehensive study suggested that differential markers provided insights into the metabolic pathways involved in BPH and the treatment effects of QLX.