Effect of Yinlai Decoction on the metabolic pathways in the lung of high-calorie diet-induced pneumonia rats

Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its effects on inflammation-related metabolic pathways.Methods:Lipopolysaccharides(LPS)and a special high-calorie diet were used to induce Sprague Dawley(SD)rats to simulate the intestinal state of infant pneumonia.Liquid chromatography-mass spectrometry technology(LC-MS/MS)was used to detect metabolites in each group.Supervised orthogonal partial least squares discriminant analysis(OPLS-DA)model values were used for the detection results to find the differential metabolites.The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis.Finally,the T cell receptor signaling pathway(TCR)signal conversion was analyzed by the network pharmacology method.Results:In the high-calorie diet combined with pneumonia group(M3),a total of 55 metabolites were determined to be different from the normal group(N).A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group(T1).YD had a regulatory effect on glutathione metabolism,arginine and proline metabolism,ascorbic acid and aldehyde metabolism and phenylalanine metabolism.And the small molecule metabolites could act on the FYN and lymphocytespecific protein tyrosine kinase(LCK)target proteins in the TCR signaling pathway,thereby affecting the immune function of the lungs.Conclusion:A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats,thereby creating chronic lung inflammation in young rats.YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets.Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.

TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN

We report herein that TSPAN32 is a key node factor for Philadelphia (Ph+) leukemia pathogenesis. We found that TSPAN32expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph+cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impairedleukemia stem cell (LSC) proliferation. LSCs represent an obstacle for chronic myeloid leukemia (CML) elimination, which continuallyreplenish leukemia cells and are associated with disease relapse. Therefore, the identification of essential targets that contribute tothe survival and self-renewal of LSCs is important for novel curative CML. Mechanistically, TSPAN32 was shown to interact withPTEN, increased its protein level and caused a reduction in PI3K-AKT signaling activity. We also found that TSPAN32 was repressedby BCR-ABL via the suppression of an important transcription factor, TAL1. Ectopic expression of TAL1 significantly increasedTSPAN32 mRNA and protein level, which indicated that BCR-ABL repressed TSPAN32 transcription by decreasing TAL1 expression.Overall, we identified a new signaling axis composed of “BCR-ABL-TAL1-TSPAN32-PTEN-PI3K-AKT”. Our findings furthercomplement the known mechanisms underlying the transformation potential of BCR-ABL in CML pathogenesis. This new signalingaxis also provides a potential means to target PI3K-AKT for CML treatment.