Celastrol induces lipophagy via the LXRα/ABCA1 pathway in clear cell renal cell carcinoma.

Celastrol is a triterpene derived from the traditional Chinese medicine Tripterygium wilfordii Hook f, which displays potential anticancer activity. In the present study, we investigated the anticancer effects of celastrol against clear cell renal cell carcinoma (ccRCC) and the underlying mechanisms. Using Cancer Genome Atlas (TCGA) database and genotype-tissue expression (GTEx) database we conducted a bioinformatics analysis, which showed that the mRNA levels of liver-X receptors α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) in ccRCC tissues were significantly lower than those in adjacent normal tissues. This result was confirmed by immunoblotting analysis of 4 ccRCC clinical specimens, which showed that the protein expression of LXRα and ABCA1 was downregulated. Similar results were obtained in a panel of ccRCC cell lines (786-O, A498, SN12C, and OS-RC-2). In 786-O and SN12C cells, treatment with celastrol (0.25-2.0 µM) concentration-dependently inhibited the cell proliferation, migration, and invasion as well as the epithelial-mesenchymal transition (EMT) process. Furthermore, we demonstrated that celastrol inhibited the invasion of 786-O cells through reducing lipid accumulation; celastrol concentration-dependently promoted autophagy to reduce lipid storage. Moreover, we revealed that celastrol dramatically activated LXRα signaling, and degraded lipid droplets by inducing lipophagy in 786-O cells. Finally, celastrol promoted cholesterol efflux from 786-O cells via ABCA1. In high-fat diet-promoted ccRCC cell line 786-O xenograft model, administration of celastrol (0.25, 0.5, 1.0 mg·kg-1·d-1, for 4 weeks, i.p.) dose-dependently inhibited the tumor growth with upregulated LXRα and ABCA1 protein in tumor tissue. In conclusion, this study reveals that celastrol triggers lipophagy in ccRCC by activating LXRα, promotes ABCA1-mediated cholesterol efflux, suppresses EMT progress, and ultimately inhibits cell proliferation, migration, and invasion as well as tumor growth. Thus, our study provides evidence that celastrol can be used as a lipid metabolism-based anticancer therapeutic approach.

Changes in the intestinal microbiota of healthy adults induced by brown yogurt and relationships of bacterial taxa with specific components.

Yogurt consumption shows a wide range of effects on the gut microbial composition, and correlation of components in yogurt with the changes of gut microbia remains largely uncharacterized. We aimed to determine the effect of brown yogurt (SSN) on the composition of the gut microbiota and to explore the effects of the major components. We performed a randomized study of 70 healthy adults to compare the effects of SSN and standard probiotic-containing yogurt (YJD) during a 28-day intervention and a 10-day follow-up period. The results showed that the SSN group showed significant increases in the butyrate-producer Akkermansia muciniphila, Ruminococcus, and Veillonella (p < 0.05), whereas the YJD group showed increases in the butyrate-producer Megasphaera, Anaerostipes, and Eubacterium. There were reductions in the potential pathogens Haemophilus parainfluenzae and Gemmiger formicilis in both groups (p < 0.05). The SSN group had more Faecalibacterium prausnitzii, Prevotella copri, Bifidobacterium and B. longum than the YJD group (p < 0.001), but fewer Bacteroides, unspecified Clostridiales and Coprococcus eutactus (p < 0.01). These differences might be at least in part explained by the higher concentrations of monosaccharide, palmitoleic acid, and glutamine synthetase adenyltransferase in the SSN product (p < 0.05), which were positively associated with F. prausnitzii (p ≤ 0.001) and B. longum (p < 0.05), and negatively associated with C. eutactus (p < 0.01). The single strain of starter culture and lower content of polyunsaturated fatty acids (PUFA) in the SSN product were also related to the different changes of gut microbia, and the taxa F. prausnitzii, Bifidobacterium and B. longum were negatively associated with starter culture and PUFA (p < 0.01). These findings suggested that SSN is rich in prebiotic components and might be beneficial for healthy adults. Furthermore, bacterial taxa with potential health benefits could be encouraged through improving the formulation and technology used to produce the dairy products.

[Screening and characterization of peptides specifically binding to the schistosomulum tegument of Schistosoma japonicum].

OBJECTIVE: To screen and analyze the peptides in 12 phage-display peptide library specifically binding to the schistosomulum tegument of Schistosoma japonicum. METHODS: A 12 phage-display peptide library was screened with the S. japonicum schistosomula as the target cells for biopanning by degrees, positive clones picked randomly were deduced by DNA sequencing. According the sequence seeing result, immunohistochemical staining was performed to determine the specificity of the phages to the tegument. To test their targeting efficacy, the interested phage clones were infused back to the mice infected with S. japonicum, mice were sacrificed 2.5 hours later, and the phage distribution in the liver and the tegument of schistosomula was appraised, respectively. RESULTS: After 3 rounds of biopanning, the phage recovery rate increased from 0.77 x 10(-8) to 0.75 x 10(-5), indicating that the phage library was successfully enriched in the tegument of schistosomula. Seventy-five percent (15/20) of the analyzed sequences were identical with a sequence of QHPRIRKOOOOO. The immunohistochemical stainings showed this sequence specifically binding to the tegument. In vivo titering displayed that this sequence selectively targeted the tegument. CONCLUSION: The peptide of QHPRIRKOOOOO specifically binds to the schistosomulum tegument.