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This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets.

To achieve the accurate diagnosis of tumor with the magnetic resonance imaging (MRI), nanomaterials-based contrast agents are developed rapidly. Here, a tumor targeting nanoprobe of c(RGDyK) modified ultrasmall sized iron oxide is reported with high saturation magnetization and high T 1 -weighted imaging capability, attributed to a large number of paramagnetic centers on the surface of nanoprobes and rapid water proton exchange rate (inner sphere model), as well as strong superparamagnetism (outer sphere model). These nanoprobes could actively target and gradually accumulate at the tumor site with a time-dependent T 1 -T 2 contrast enhancement imaging effect. In in vivo MRI experiments, the nanoprobes exhibit the best T 1 contrast enhancement at 30 min after intravenous administration, followed by gradually vanishing and generating T 2 contrast enhancement with increasing time at tumor site. This is likely due to time-dependent nanoprobes aggregation in tumor, in good agreement with in vitro experiment where aggregated nanoprobes display larger r 2 /r 1 value (19.1) than that of the dispersed nanoprobes (2.8). This dynamic property is completely different from other T 1 -T 2 dual-modal nanoprobes which commonly exhibit the T 1 -and T 2 -weighted enhancement effect at the same time. To sum up, these c(RGDyK) modified ultrasmall Fe 3 O 4 nanoprobes have significant potential to improve the diagnostic accuracy and sensitivity in MRI.

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BackgroundBmi1 (B lymphoma Mo-MLV insertion region 1 homolog) contributes to human tumorigenesis via epigenetic transcriptional silencing and represents a novel therapeutic target with great potentials. Here we sought to determine the therapeutic efficiency of PTC-209, a potent and selective Bmi1 inhibitor, in head neck squamous cell carcinoma (HNSCC) cells and a HNSCC xenograft model.MethodsThe mutation pattern, mRNA level of Bmi1 in HNSCC and its associations with clinicopathological parameters were determined through comprehensive data mining and interrogation using publicly available databases GENT, cBioPortal, Oncomine and TCGA. The PTC-209, a selective and potent Bmi1 inhibitor, was exploited and its effect on Bmi1 expression was measured in two HNSCC cell lines Cal27 and FaDu. The phenotypical changes of HNSCC cells were observed upon PTC-209 treatment in vitro. Moreover, the therapeutic effects of PTC-209 for HNSCC were determined in a xenograft animal model.ResultsThrough comprehensive data mining and interrogation, we found that Bmi1 mRNA was frequently overexpressed in a subset of HNSCC samples. Our data revealed that PTC-209 robustly reduced the expression of Bmi1 in Cal27 and FaDu cells presumably by post-transcriptional repression and ubiquitin-proteasomal degradation. PTC-209 treatment resulted in impaired cell proliferation, G1-phase cell cycle arrest, compromised migration and invasiveness, and increased cell apoptosis and chemosensitivity to 5-FU and cisplatin in vitro. Moreover, PTC-209 exposure reduced colony formation, tumorsphere formation and the percentage of ALDH1+ subpopulation in both Cal27 and FaDu cells. Importantly, in vivo PTC-209 administration significantly reduced tumor growth in a HNSCC xenograft model probably by Bmi1 inhibition and impaired cell proliferation.ConclusionsOur findings indicate that pharmacological inhibition of Bmi1 is a novel therapeutic strategy for HNSCC patients, especially with those with aberrant Bmi1 overexpression.Electronic supplementary materialThe online version of this article (10.1186/s12935-017-0481-z) contains supplementary material, which is available to authorized users.