Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype.

Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality. Analysis of the biological characteristics of B6-Co mice demonstrated that abnormal migration of keratinocytes could affect eyelid development, but proliferation and apoptosis in B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated that in B6-Co mice, adenosine was inserted into the untranslated regions, between 3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that expression of the Hbegf gene was significantly down-regulated in the eyelids of B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1, Map3k1, and Jnk1 genes did not show any significant changes. Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice.

Regulatory role of microRNA184 in osteosarcoma cells.

Osteosarcoma is a highly malignant cancer that often appears in teenagers. It is the most frequently occurring primary bone tumor, and can easily metastasize, resulting in high mortality. MicroRNAs express abnormally in osteosarcoma, and may function as oncogenes or tumor suppressors. Recent studies showed that microRNA184 (miR-184) is abnormally expressed in multiple tumors, and is involved in tumor cell growth, differentiation, invasion, and metastasis. Nevertheless, the role of miR-184 in osteosarcoma cells remains unknown. We evaluated the expression and function of microRNA184 in osteosarcoma cells. SOSP-M osteosarcoma cells were divided into normal control, miR-184 mimic, and miR-184 inhibitor groups. Real-time PCR was applied to detect miR-184 expression. The 3-(4,5-dimethylthaizol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cell proliferation. Transwell assays were performed to detect changes in cell invasion ability. Compared with the control group, miR-184 expression was significantly increased in the miR-184 mimic group (P < 0.05). After miR-184 inhibitor transfection, miR-184 expression was obviously reduced (P < 0.05). Tumor cell proliferation was enhanced in the miR-184 mimic group (P < 0.05), whereas miR-184 inhibition suppressed cell proliferation (P < 0.05). Furthermore, tumor cell invasion increased after miR-184 mimic transfection (P < 0.05), and decreased after inhibiting miR-184 (P < 0.05). MiR-184 promotes tumor cell proliferation and invasion, and may represent a new biological target for osteosarcoma.

WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce "browning" of white adipocytes in mice.

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of "brown adipocytes" within white fat depots. All-trans retinoic acid (t-RA) and peroxi-some proliferator-activated receptor-α (PPARα) have been implicated in "browning-like" or "browning" programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the "browning" of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of "brown-ing" using western blot. All concentrations of WY14643 failed to in-duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P < 0.05). WY14643 combined with t-RA was observed to induce UCP1 mRNA expression, protein expression, and phosphory-lation of p38 MAPK (P < 0.05). SB203580 combined with WY14643 and t-RA suppressed UCP1 mRNA expression, protein expression, and p38 MAPK phosphorylation (P < 0.05). WY14643 combined with t-RA can induce the transformation of white adipocytes to brown adipocytes through activation of the p38 MAPK signaling pathway.

Correlation between MTP -493G>T polymorphism and non-alcoholic fatty liver disease risk: a meta-analysis.

Several studies have found that microsomal transfer protein (MTP) may be important in the development and progression of non-alcoholic fatty liver disease (NAFLD). In this meta-analysis, we evaluated the relationships between a common polymorphism (-493G>T, rs1800591 G>T) in the MTP gene and NAFLD risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Eleven case-control studies were included in this meta-analysis. A total of 636 NAFLD patients and 918 healthy control subjects were examined in this meta-analysis. Our results indicate that the MTP -493G/T polymorphism increases the risk of NAFLD (G allele vs T allele: OR = 1.39, 95%CI = 1.17-1.65, P < 0.001; GG + GT vs TT: OR = 1.46, 95%CI = 1.02-2.09, P = 0.038, respectively). Subgroup analyses indicated that the MTP -493G/T polymorphism was associated with an increased risk of NAFLD in population-based, hospital-based, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and large sample-size subgroups under the allele and dominant models (all P < 0.05). However, we found no association between non-PCR-RFLP polymorphism and small sample-size subgroups (all P > 0.05). Our findings indicate that the MTP -493G/ T polymorphism may contribute to the development of NAFLD. Thus, the MTP -493G/T polymorphism may be a biomarker for the early detection of NAFLD.