Global characterization of chemical compounds in Shidan granule and their metabolites in rat plasma using ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry.

Shidan granule is an in-hospital traditional Chinese medicine prescription with obvious clinical effects in the treatment of chronic atrophic gastritis. Characterizing the compounds of Shidan granule and exploring the absorbed prototype constituents and metabolites in the blood is significant to understand its effective compounds. In this work, a reliable approach based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry was performed for systematic analysis of chemical substances of Shidan granule and their metabolites in rat plasma. The compounds were rapidly characterized using integrated filtering methods, including mass defect filtering, neutral loss filtering, and diagnostic fragment ions filtering. As a result, 87 compounds were tentatively or unambiguously characterized. In rat plasma, a total of 79 components, including 21 prototype constituents and 58 metabolites, were preliminarily determined. And flavonoids-related, phenolic acids-related, saponins-related and terpenoids-related compounds were the main precursors of these metabolites. Phase I reactions (methylation, demethylation, hydroxylation, hydrogenation, and oxidation) and phase II reactions (glucuronidation, glucosidation, and sulfation) were observed as the major metabolic pathways of Shidan granule. It is the first comprehensive study on the metabolism of Shidan granule in vivo, which could offer a solid scientific basis for exploring the multiple effects and therapeutic mechanisms of Shidan granule.

Explore the effects of Shidan granules on chronic atrophic gastritis using LC-MS based plasma metabolomics study.

Shidan granule (SDG), a traditional Chinese medicine in-hospital preparation, has been demonstrated to exert good effects on chronic atrophic gastritis (CAG) in clinics. However, the underlying mechanism of SDG against CAG is still unclear. This study utilized an untargeted plasma metabolomics approach to explore the potential mechanism of SDG in CAG rats using LC-MS and pattern recognition analysis. The results indicated that SDG could effectively improve the biochemical indexes and pathology features of CAG rats. Nineteen potential biomarkers (variable importance in projection > 1 and P < 0.05) contributing to CAG progress were identified. After SDG intervention, 17 biomarkers were obviously restored to normal levels. Further metabolic pathway analysis showed that aspartate and glutamate metabolism, arachidonic acid metabolism, arginine and proline metabolism, and TCA cycle were the most related pathways for SDG treatment. Based on these findings, the main mechanisms of SDG against CAG might be attributed to the regulatory effects of energy balance, inflammatory suppression, and improvement in disturbed amino acid and lipid metabolism. This study provided information for the mechanism research of SDG against CAG and would promote its clinical application.

Comprehensive Analysis of Differentially Expressed circRNAs Reveals a Colorectal Cancer-Related ceRNA Network.

The morbidity and mortality of colorectal cancer (CRC) remained to be very high worldwide. Recently, circRNAs had been revealed to have a crucial role in cancer prognosis and progression. Numerous researches have shown that RNA sequencing technology and in silico method were widely used to identify pathogenic mechanisms and uncover promising targets for diagnosis and therapy. In this study, these methods were analyzed to obtain differentially expressed circRNAs (DECs). We identified upregulated 316 circRNAs and reduced 76 circRNAs in CRC samples, in comparison with those in normal tissues. In addition, a competitive endogenous network of circRNA-miRNA-mRNA was established to predict the mechanisms of circRNAs. Bioinformatics analysis revealed that these circRNAs participated in metabolism regulation and cell cycle progression. Of note, we observed the hub genes and miRNAs in this ceRNA network were associated with the survival time in CRC. We think this study could provide potential prognostic biomarkers and targets for CRC.

LPS promotes the expression of PD-L1 in gastric cancer cells through NF-κB activation.

Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.