[Effect of RORC inhibitor on HIF-1α and VEGF in nasal mucosa of allergic rhinitis of mice].

Objective: To investigate the effects of the retinoic acid receptor related orphan C (RORC) inhibitor (SR1001) on the expression changes of proteins of hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the nasal mucosa of mice with allergic rhinitis (AR) model. Methods: Thirty BALB/c were randomly divided into normal group, AR model group and RORC inhibitor group, 10 mice each group. AR model of mice was established by ovalbumin (OVA) sensitization method. RORC inhibitor group was given intraperitoneal injection of SR1001 (25 mg/kg), while AR model group intraperitoneal injection of the same volume of 0.9% normal saline. The symptom score of the mice was determined every weekend after administration. The pathological morphological changes in the nasal mucosa tissue obtained from anesthetized mice were observed by light microscope. The expression of HIF-1α and VEGF protein were detected by immunohistochemistry. IFN-γ, IL-17, and sIgE in the serum were detected by ELISA and the expression of HIF-1α and VEGF in the nasal mucosal tissue of the mice were measured by Western blot. One-way ANOVA was used for inter-group comparison. LSD method was used for inter-group comparison with equal variance, and Dunnett T3 method for inter-group comparison with unequal variance. P<0.05 was considered statistically significant. Results: The AR model was successfully established. Compared with the model group, the RORC inhibitor group significantly reduced the symptom score of AR mice (4.02±0.97 vs 8.50±1.76, t=7.050, P<0.01). The damaged mucosal epithelium appeared to be improved, the glands and dilated ducts tended to be normal, the mast goblet cells significantly reduced, and the infiltration of inflammatory cells in the inherent mucosa reduced. Meanwhile, the content of IL-17 and sIgE in serum decreased [(25.10±4.11) ng/ml vs (42.56±5.98) ng/ml, (0.875±0.244) ng/ml vs (1.982±0.365) ng/ml, t value was 14.141, 10.275, respectively, all P<0.01] and the content of IFN-γ increased [(61.32±8.83) pg/ml vs (38.94±5.97) pg/ml, t=8.133, P<0.01]. The expression of HIF-1α and VEGF protein in the nasal mucosal tissues of AR mice significantly reduced (0.92±0.08 vs 1.67±0.31, 1.12±0.21 vs 2.54±0.46, t value was 7.408, 8.880, respectively, all P<0.01). Conclusion: The RORC inhibitor has the therapeutic effect on AR by changing the content of inflammatory factors in AR mice and reducing the expression level of HIF-1α and VEGF in the nasal mucosa.

Overexpression of an alternative oxidase gene, OsAOX1a, improves cold tolerance in Oryza sativa L.

Low temperature is a major environmental stress in rice cultivating and production. The alternative oxidase 1 (AOX1) gene is potentially important for genetic engineering to increase cold adaptation. However, previous studies related to this effect have mostly focused on the dicot plants Arabidopsis and tobacco, whereas functional research on rice is limited. In this study, we cloned a rice predominant cold-response AOX1 gene, OsAOX1a. Transgenic rice plants with overexpression of OsAOX1a were obtained. We found that OsAOX1a overexpression could strongly enhance the cold growth of seedlings, especially with respect to root extension. However, growth between transgenic and control plants did not differ under normal conditions. Furthermore, the lipid peroxidation and ion leakage rate were determined after cold treatment in transgenic plants. Both factors were reduced by OsAOX1a overexpression, which revealed that OsAOX1a could reduce oxidative damage under cold stress. Taken together, our results suggested that overexpressing OsAOX1a could improve growth performance of rice under cold stress, which might be closely related to the reduction of reactive oxygen species generation and oxidative damage.

Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2.

MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.

miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1.

MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.

Acellular dermal matrix allografts to achieve increased attached gingiva. Part 1. A clinical study.

BACKGROUND: Freeze-dried acellular dermal matrix (ADM) allograft, originally used for full-thickness burn wounds, was recently introduced as an alternative to the autogenous free gingival graft (FGG) in achieving increased attached keratinized tissue. The aim of part 1 of this study was to investigate the clinical efficacy of the ADM allograft for this particular purpose. METHODS: Twelve patients, 7 males and 5 females, with attached gingiva < or =1 mm on the facial aspect of mandibular anterior teeth demonstrating a tendency of progressive marginal tissue recession, were randomly assigned to either test or control treatment. Six patients received ADM graft (test) and 6 patients received an autogenous FGG harvested from the hard palate (control). Clinical variables including plaque index (PI), gingival index (GI), probing depth (PD), attached tissue width (AT), and gingival recession (GR) were recorded immediately before surgery and at the 6-month postoperative visit. Patients were seen at 2, 4, 6, 8, and 12 weeks to monitor wound healing and oral hygiene performance (PI and GI). Graft width was also measured, in corono-apical direction, on individually involved teeth during the surgery. RESULTS: When values between baseline and 6 months were compared in both groups, there was no statistically significant difference in changes of PI, GI, PD, and GR (P>0.05) with the exception of PD in the FGG group (1.01 +/- 0.03 versus 1.27 +/- 0.20 mm, P= 0.042). There was a statistically significant (P <0.05) increase in AT in both groups. Although the ADM group received wider grafts than the FGG group (8.81 +/- 0.46 versus 6.70 +/- 0.89 mm), the AT gain was significantly smaller (2.59 +/- 0.92 versus 5.57 +/- 0.44 mm) and the graft shrinkage significantly greater (71 +/- 10% versus 16 +/- 12%) in the ADM group than in the FGG group (P<0.01). CONCLUSIONS: The results of this study suggest that in procedures aiming at increasing the width of attached gingiva: 1) the ADM allograft was less effective and less predictable than the autogenous FGG in terms of increasing attached keratinized tissue due to considerable shrinkage and inconsistent quality of the attached tissue gained and 2) the esthetic results using the ADM allograft might be better than those using the autogenous FGG.