AbstractTime-restricted feeding (TRF) confers protection against nutritional challenges that predispose obesity and metabolic risks through involvement of circadian locomotor output cycles protein kaput genes and gut microbiome, but the underlying mechanism is not clearly understood. Therefore, the present study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n 56; non-TRF, n 24) of male adults were enrolled. The TRF group provided blood at pre-TRF and post-TRF, while non-TRF one time after 25 d of trial. Serum lipid and liver profiles were determined. Real time-PCR was applied for circadian and inflammatory gene expression. The 16S rRNA genes were sequenced on the Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In the TRF group, gut microbial richness was significantly enhanced, with enrichment of Prevotellaceae and Bacteroideaceae. TRF enhanced circadian gene expression probably by activation of sirtuin-1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidaemia, as it regulates circadian rhythm associated with gut microbiome modulation.

Long non-coding RNAs (lncRNAs) play significant roles in the pathogenesis of various cancers, including lung cancer. In this study, we aimed to investigate the biological function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in cancer stem cells (CSCs). CSCs have been suggested as the main cause of tumor metastasis, tumor recurrence, and chemotherapy resistance. The copper transporter 1 (CTR1) has been the focus of many recent studies because of its correlation with cisplatin (CDDP) resistance. So far, the mechanism of how NEAT1 regulates CSCs in NSCLC remains unknown. In the current study, lung cancer stem cells were enriched from the parental NSCLC cells. We observed that NEAT1 was up-regulated while copper transporter 1 (CTR1) was down-regulated in the enriched NSCLC cancer stem cells. Knockdown of NEAT1 was able to decrease the CSC-like properties in NSCLC cells, while over-expression of NEAT1 could contribute to the stemness respectively. Meanwhile, appropriate doses of EGCG restrained the stemness triggered by over-expressing NEAT1 via inducing CTR1 expression. Wnt signal pathway and epithelial-to-mesenchymal transition (EMT) process were involved in NEAT1-induced CSCs in NSCLC. These findings may suggest a novel role of NEAT1 for NSCLC treatment.

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Non-small cell lung cancer (NSCLC) remains one of the most aggressive tumors with low life expectancy worldwide. The existence of cancer stem cells (CSCs) contributes to the failure of cancer treatment resulted from drug resistance. Altered microRNA expression has been observed in human tumors due to its role in tumor growth, progression, and metastasis. Hence, the aim of our present study was to investigate the effects of miR-485 on the CSC-like traits in NSCLC A549-cisplatin resistant cells and concentrate on the underlying molecular mechanism. It was found that CSC-like phenotypes were much more enriched in A549/cisplatin (A549/CDDP) cells compared to A549-parental cells. In addition, we observed that miR-485 was greatly decreased in A549/CDDP cells and miR-485 overexpression was able to decrease the stemness of A549/DDP cells. Meanwhile, epigallocatechin-3-gallate (EGCG), a green tea polyphenol which has been identified as an effective anticancer compound was able to increase miR-485 expression dose-dependently in A549/CDDP cells. Inhibitors of miR-485 remarkably increased CSC-like phenotypes, which could be reversed by indicated doses of EGCG. Moreover, CD44 was predicted as downstream target of miR-485 and the correlation between them was validated by performing dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Subsequently, in vivo experiments were employed to confirm that EGCG restrained CSC-like characteristics by increasing miR-485 and decreasing CD44 expression. Taken together, it was implied that stemness features and CSC population were suppressed by EGCG-modulated miR-485/CD44 axis in A549/CDDP cells.

Non-small-cell lung cancer (NSCLC) appears to be a significant threat to public health worldwide. MicroRNAs have been identified as significant regulators for the development of NSCLC. Previous reports have suggested that hsa-mir-485-5p is dysregulated in various cancers. RXRα, as a kind of nuclear receptor, is an effective target of cancer treatment. Cancer stem cells (CSCs) are recognized as the main cause for tumor metastasis, recurrence, and chemotherapy resistance. However, the mechanism by which hsa-mir-485-5p and RXRα modulate CSCs in NSCLC remains unknown. Here, we found that hsa-mir-485-5p was decreased in serum samples from patients with NSCLC and NSCLC cells. Meanwhile, epigallocatechin-3-gallate (EGCG), an effective anticancer compound extracted from green tea, can enhance hsa-mir-485-5p expression. Hsa-mir-485-5p mimics markedly inhibited NSCLC cell growth and induced cell apoptosis. However, inhibition of hsa-mir-485-5p significantly enriched CSC-like traits. Moreover, bioinformatics analysis predicted the binding correlation between hsa-mir-485-5p and RXRα, which was confirmed by a dual-luciferase reporter assay. We observed that RXRα was increased in NSCLC and EGCG could inhibit RXRα levels dose dependently. In addition, RXRα upregulation or activation expanded the CSC-like properties of NSCLC cells, whereas RXRα inhibition or inactivation could exert a reverse phenomenon. Consistently, in vivo experiments also validated that EGCG could repress the CSC-like characteristics by modulating the hsa-mir-485-5p/RXRα axis. Our findings may reveal a novel molecular mechanism for the treatment of NSCLC.