Introduction: Dyslipidemia is a hallmark of T2DM, and as such, analyses of lipid metabolic profiles in affected patients have the potential to permit the development of an integrated lipid metabolite-based biomarker model that can facilitate early patient diagnosis and treatment.Methods: Untargeted and targeted lipidomics approaches were used to analyze serum samples from newly diagnosed 93 Chinese participants in discovery cohort and 440 in validation cohort via UHPLC-MS and UHPLC-MS/MS first. The acid sphingomyelinase protein expression was analyzed by Western blot.Results and Discussion: Through these analyses, we developed a novel integrated biomarker signature composed of LPC 22:6, PC(16:0/20:4), PE(22:6/16:0), Cer(d18:1/24:0)/SM(d18:1/19:0), Cer(d18:1/24:0)/SM(d18:0/16:0), TG(18:1/18:2/18:2), TG(16:0/16:0/20:3), and TG(18:0/16:0/18:2). The area under the curve (AUC) values for this integrated biomarker signature for prediabetes and T2DM patients were 0.841 (cutoff: 0.565) and 0.894 (cutoff: 0.633), respectively. Furthermore, theresults of western blot analysis of frozen adipose tissue from 3 week (prediabetes) and 12 week (T2DM) Goto–Kakizaki (GK) rats also confirmed that acid sphingomyelinase is responsible for significant disruptions in ceramide and sphingomyelin homeostasis. Network analyses of the biomarkers associated with this biosignature suggested that the most profoundly affected lipid metabolism pathways in the context of diabetes include de novo ceramide synthesis, sphingomyelin metabolism, and additional pathways associated with phosphatidylcholine synthesis. Together, these results offer new biological insights regarding the role of serum lipids in the context of insidious T2DM development, and may offer new avenues for future diagnostic and/or therapeutic research.

In a series of studies on the metabolism of iridoid compounds, we investigated the metabolic fate of swertiamarin (1) in Wistar rats. Liquid chromatography/ion trap mass spectrometry detected new nitrogen-containing metabolite gentiandiol (3) in rat plasma. The structure of the metabolite was unequivocally identified by comparing the retention time as well as the mass spectrum with those of authentic compound, which was synthesized from swertiamarin (1). The transformation of swertiamarin to nitrogen-containing metabolite gentiandiol (3) in vivo was verified for the first time. Understanding of this unique metabolic pathway may shed light on clinical efficacy of swertiamarin (1) and will also assist in studies for the metabolism of other natural iridoids in vivo.

Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18–21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RT‒qPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1β expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.