Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS.

ObjectiveThe present study aimed to investigate circular RNA (circRNA) expression in uveal melanoma (UM).MethodsFirst, we used microarray to compare the expression profiles of circRNA in five UM samples and five normal uvea tissues. Next, bioinformatics analyses, including gene ontology (GO) analysis and pathway analysis, were applied to study these differentially expressed circRNAs to predict pathogenic pathways that may be involved. Quantitative real-time polymerase chain reaction (qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circRNA expression profiles obtained from the microarray data. Finally, we analyzed the interaction between validated circRNAs and their potential cancer-associated miRNA targets.ResultsIn total, 50,579 circRNAs [fold change (FC) ≥2.0; P<0.05], including 20,654 up-regulated and 29,925 down-regulated circRNAs, were identified as differentially expressed between UM tissues and normal uvea tissues. We used qRT-PCR to verify seven dysregulated circRNAs indicated by the microarray data, including hsa_circ_0119873, hsa_circ_0128533, hsa_circ_0047924, hsa_circ_0103232, hsa-circRNA10628-6, hsa_circ_0032148 and hsa_circ_0133460, which may be promising candidates to study future molecular mechanisms.ConclusionsThis study explored, for the first time, the abnormal expression of circRNAs in UM and described the expression profile of circRNAs, providing a new potential target for the mechanism of UM and future treatment of UM.

IntroductionMesenchymal stem cells (MSCs) are considered to play important roles in wound repair and tissue remodeling. Hypertrophic scar (HTS) is a cutaneous condition characterized by deposits of excessive amount of collagen after an acute skin injury. However, currently there is little knowledge about the direct relationship between MSCs and HTS.MethodsThe hypertrophic scar model was established on rabbit ears. MSCs were isolated from rabbit femur bone marrow and transplanted through ear artery injection. Hypertrophic scar formation was examined using frozen-section analysis, hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and scar elevation index. The role of p53 in the MSCs-mediated anti-scarring effect was examined by gene knockdown using p53 shRNA.ResultsIn this study, MSCs engraftment through ear artery injection significantly inhibited the hypertrophic scarring in a rabbit ear hypertrophic scar model, while this anti-scarring function could be abrogated by p53 gene knockdown in MSCs. Additionally, we found that MSCs down-regulated the expression of TGF-β receptor I (TβRI) and alpha-smooth muscle actin (α-SMA) at both mRNA and protein levels in a paracrine manner, and this down-regulation was rescued by p53 gene knockdown. Moreover, our results showed that MSCs with p53 gene knockdown promoted the proliferation of fibroblasts through increasing nitric oxide (NO) production.ConclusionsThese results suggest that MSCs inhibit the formation of HTS in a p53 dependent manner through at least two mechanisms: inhibition of the transformation of HTS fibroblast to myofibroblast; and inhibition of the proliferation of fibroblasts through inhibition of NO production.

Endothelial cell (EC) injury or dysfunction is believed to be mediated at least in part by lipopolysaccharide (LPS). Recent studies have shown that LPS induces apoptosis in different types of endothelium, including HUVEC. Previously we used EOLA1 (endothelial-overexpressed LPS-associated factor 1) cDNA as a bait and performed a yeast two-hybrid screening of a human liver cDNA library and identified metallothionein 2a (MT2a) as the associated protein. EOLA1 protein plays a role as a signal transduction factor. But the mechanism of EOLA1 mediated the protection of cell production of IL-6 and apopotosis in HUVEC is not known. MT2a is expressed in many kinds of cells and plays a role in inflammation. In this study, we demonstrated that LPS could induce EOLA1 expression in time-dependent and apparently contributed to the inhibition of IL-6 production and apoptosis induced by LPS treatment. We also found that deletion of EOLA1 promoted IL-6 production and apoptosis in the treatment of LPS in HUVEC. Furthermore, we demonstrated that MT2a was activated by LPS, and played a key role in LPS-induced IL-6 expression in HUVEC. We further provided the evidence that EOLA1 functioned as a negative regulator for LPS response by regulation of MT2a. These findings suggest that EOLA1 may have an important regulatory role during EC inflammatory responses.