TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways.

The exact mechanism by which knockout of Toll-like receptor 4 (TLR4) attenuates the liver injury remains unclear. The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation (BDL)-induced liver cholestatic injury and the underlying mechanism. Wild type (WT) mice and TLR4 knockout (TLR4-KO) mice were used for the establishment of the BDL model. Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups. The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice. The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids- and choline-related metabolites. After BDL, the amino acids- and choline-related metabolites, especially choline and 3-hydroxybutyrate, were significantly increased in WT mice (both in serum and liver), but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD. In conclusion, TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.

Non-coding RNA 886 (nc886) has been suggested to serve tumor-suppressing roles in several cancer cells. However, the expression pattern of nc886 and its function in renal cell carcinoma (RCC) has not been reported until now. The present study aimed to examine the expression of nc886 in human RCC tissues and to investigate the role of nc886 in RCC cell proliferation, apoptosis and invasion in vitro. Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling was investigated. It was demonstrated that nc886 is overexpressed in human RCC tissues compared with normal tissues, as determined by reverse transcription-quantitative polymerase chain reaction analysis. The nc886 mimic and inhibitor were transfected into the A­498 cells to overexpress or knock down nc886 expression. Cell proliferation, cell apoptosis rate and cell invasion ability were determined by MTT, flow cytometry and Transwell­Matrigel invasion assays. The results demonstrated that nc886 overexpression promotes A­498 cell proliferation and invasion, and inhibits cell apoptosis, while nc886 knockdown resulted in the opposite effects. Furthermore, nc886 could activate the JAK2/STAT3 signaling pathway in A­498 cells. AG490, an inhibitor of JAK2, could attenuate the effects of nc886 on cell proliferation, apoptosis and invasion. In conclusion, to the best of our knowledge, the present study for the first time revealed the expression profile and the tumor­promoting role of nc886 in RCC. nc886 affects RCC cell proliferation, apoptosis and invasion at least partially via the activation of JAK2/STAT3 signaling. This study may provide a useful therapeutic target for RCC.