There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham-operated with pair-fed as RYGB; sham-operated fed ad libitum; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham-operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.

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Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc.

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Background Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux‐en‐Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram‐negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. Methods Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham‐operated group pair‐fed with the RY group; and (c) a sham‐operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate‐dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)‐1, occludin, and claudin‐1 were assessed 10 weeks postoperatively. Results Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin‐1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO‐1, occludin, and claudin‐1 expression. Conclusions The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram‐negative bacteria.

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Although a variety of drug delivery strategies have been designed for enhancing the treatment of Triple negative breast cancer (TNBC), combating with TNBCs is still dramatically challenged by the selection of appropriate therapeutic targets and insufficient tumor accumulation or inner penetration of chemotherapeutics. To address these issues, the classical EGFR-inhibitor, erlotinib (EB), was selected as the model drug here and PLA-based nano-platform (NP-EB) was prepared for tumor site drug delivery. Given the significant role of Notch-EGFR interplay in raising severe resistance to EGFR inhibition of EB, gamma secretase inhibitor (GSI)-DAPT was further entrapped into the core of nanoparticles to inhibit the activation of Notch signaling (NP-EB/DART). For achieving the goal of tumor targeting drug delivery, we developed a new peptide CF and decorating it on the surface of EB/DART-dual loaded nanoparticles (CF-NP-EB/DART). Such CF peptide was designed by conjugating two separated peptide CREKA, tumor-homing peptide, and F3, cell penetrating peptide, to together via a pH-sensitive hydrazone bond. By this way, the tumor unspecific property of F3 was sealed and significantly reduced the site effects. However, after the nanoparticles reach the tumor site, the pH-sensitive linkage can be broken down by the unique acidic environment of tumor, and subsequently discovered the F3 peptide to penetrate into tumor cells.